University Microfilms International 300 N

8100108

Ba l o g h , D o u g l a s W a y n e

THE SYNTHESIS OF SECODODECAHEDRANE AS A POTENTIAL PRECURSOR TO THE PENTAGONAL DODECAHEDRANE

The Ohio State University PH.D. 1980

University Microfilms International 300 N. Zeeb Road, Ann Arbor, MI 48106 THE SYNTHESIS OF SECODODECAHEDRANE AS A POTENTIAL

PRECURSOR TO THE PENTAGONAL DODECAHEDRANE

DISSERTATION

Presented in Partial Fulfillment of the Requirements for

the Degree Doctor of Philosophy in the Graduate

School of The Ohio State University

Douglas Wayne Balo'gh, M. S.

*****

The Ohio State University

1980

Reading Committee: Approved By

Dr. P h ilip D. Magnus

Dr. David J. Hart ______A dviser' Dr. Leo A. Paquette Department of Chemistry ACKNOWLEDGMENTS

The author gratefully acknowledges the fbllowing individuals who have contributed in varying degrees to the project: Dr. William

Begley, Dr. Martin Banwell, Dr. David Bremner, and Dr. Robert Blanken ship. Appreciation is also expressed for the careful, concise work reported in the dissertation of the project*s initiator, Dr. Matthew

J. Wyvratt, which provided a solid foundation for the work reported h ere.

A special word of gratitude must be expressed to Dr. Leo A.

Paquette, whose overwhelming enthusiasm and continuous interest in the project proved quite contagious. His knowledge and experience provided a lim itless wealth of ideas from which to draw.

The author wishes, finally, to express appreciation to his wife and family for their encouragement, particularly to Deborah Balogh who has offered understanding and unending support throughout this work while completing her own dissertation.

i i VITA

May 22, 1952 ...... Born - Painesville, Ohio

1974 ...... B. S., Bowling Green State University, Bowling Green, Ohio

1 9 7 4 -1 9 7 6 ...... • • Teaching Assistant, Department of Chemistry Bowling Green State University, Bowling Green, Ohio

1976 ...... M.S., Bowling Green State University, Bowling Green, Ohio

1976-1977 ...... • Teaching Associate, Department of Chemistry The Ohio State University, Columbus, Ohio

1977-1979 ...... Research Associate, Department of Chemistry The Ohio State University, Columbus, Ohio

1979-1980 ...... Presidential Fellow, The Ohio State Univer sity, Columbus, Ohio

PUBLICATIONS

"Synthesis and X-Ray Crystal Structure of a (C^)-Dioxatrisecododeca- hedrane," L. A. Paquette, D. Balogh, and P. Engel, Submitted for Publi c a tio n , ( 1980).

"Unusual Photo isomerization of an "Encased" a-Diketone," D. W. Balogh, L. A. Paquette, and P. Engel, Submitted for Publication, ( 1980).

"Topologically Spherical Molecules. Transannular and Other Rearrange ment Reactions of Bishomo Dioxatrisecododecahedranes," D. W. Balogh and L. A. Paquette, J. Org. Chem., 45 ? 3038 ( 1980).

”(Cj2)-D ioxa-C 2o-°ctaquinane, a Heterocyclic Triseco Dodecahedrane," D. Balogh, W. J. Begley, D. Bremner, M. J. Wvyratt, and L. A. Paquette, J. An. Chem. Boc.. 101, 749 (1979). "Topologically Spherical Molecules. Rearrangement Reactions of Func- tionalized £2 Symmetric Hexaquinane Systems and Synthesis of (£ 2)- Dioxa-Cao-octaquinane, a Heterocyclic Triseco Dodecahedrane," L. A. Paquette, W. J. Begley, D. Balogh, M. J. Wyvratt, and D. Bremner, J. Org. Chem., 44, 3630 (1979) •

"Topologically Spherical Molecules. Synthesis of a Pair of £ 2- Symmetric Hexaquinane Dilactones and Insights into Their Chemical Reactivity. An Efficient s-Mediated 1,6-Dicarbonyl Reduction," L. A. Paquette, M. J. Wyvratt, 0. Schallner, J. L. Muthard, W. J. Begley, R. M. Blankenship, and D. Balogh, J. Org. Chem. , 44, $ 6l 6 (1979)*

FIELD OF STUDY

Major Field: Organic Chemistry

iv TABLE OF CONTENTS

Page

AC KNOWLEDOMENTS...... i i

VITA ...... i i i

LIST OF FIGURES...... v i i

CHAPTER

I. Introduction ...... 1

1-1 Theoretical Interest in the Pentagonal Dodeca hedron • •••■»*••••••••••••••• 1 1-2 General Approaches to Dodecahedrane ...... 8 I-3 Aim of This Research and Survey of the Dis s e r ta tio n ...... 12

II. Construction of the A ll-cis Fused Hexaquinane Frame work 13

II-l Introduction ...... 15 II-2 Review of the Domino Diels-Alder Reaction through the Bislactone (15) ...... 16 II-3 Avenues for Expansive Research ...... 24

III. The Bis Closed Lactol (£ 8) and Derived Molecules .... 27

III-l Introduction ...... 27 III-2 Oxidation of Bislactol j 8 ...... 28 III-3 The Bis Dihydro Pyran £4 (Reduction of Bis l a c t o l 38) ...... 29

III-3-1 Transannular Derivatives ...... 29 III-3-2 Symmetrical Derivatives ...... 35

III-4 Bis Epoxy Ether 63 ...... 36 III-5 Bis Cyclopropyl IFElier 6 4 ...... 48

IV. The Open Bismethyl Lactone (40) and Derivatives ...... 55

IV-1 Introduction ...... 55 IV-2 Lactone Ring Cleavage Reactions ...... 58

v TABLE OP CONTENTS Page

IV-3 The Open Bis Methyl Lactol (97) ...... 6 l

IV-3-1 Transannular Derivatives ...... 6 l IV-3-2 Symmetrical Derivatives ...... 68

V. Photochemistry of Carbonyl Groups (Carbon-Carbon Bond I b r m a tio n ) ...... 70

V-l Introduction ...... 70 V-2 The Two Saturated Diesters (120 and 127) ...... 72 V-3 An Unusual Decaquinane ...... 79

VI. Trisecododecahedrane Derivatives ...... 87

VI-1 Introduction ...... 87 VI-2 Methylation Products from Dissolving Metal Reduction of Dichloro Diester ^ ...... 88 VI-3 Photochemistry R evisited ...... 93 VI-4 Trimethyl Trisecododecahedrane Derivatives ...... 95 VI-5 Dimethyl Trisecododecahedrane Derivatives ...... 103 VI-6 Desmethyl Trisecododecahedrane Derivatives ...... 104

VII. Secododecahedrane ...... 109

VII-1 Introduction ...... 109 VTI-2 Dimethyl Secododecahedrane 1 6_ ...... 110 VII-3 Trimethyl Secododecahedrane 202 ...... 113 VII-4 Outlook for the Future ...... 115

SUMMARY...... 119

EXPERIMENTAL SECTION...... 124

PROTON NMR SPECTRA...... 225

LIST OF REFERENCES...... 243

vi LIST OF FIGURES

Figure Page

1. Three-Dimensional Features of Dimethyldioxa- triseco Dodecahedrane 82 as Determined by X-ray A n a ly s is ...... ^9

2. Three-Dimensional Features of a-Diketone l^J as Determined by X-ray Analysis ...... 82

5- Three-Dimensional Features of Decaquinane Diol 140 as Determined by X-ray Analysis ...... 81j-

4. Three-Dimensional Features of Triseco Dodecahedrane IpJ as Determined by X-ray Analysis ...... 96

v i i CHAPTER 1

INTRODUCTION

1-1 THEORETICAL INTEREST IN THE PENTAGONAL DODECAHEDRON

Almost 25 centuries ago Plato mathematically defined the five uni

form polyhedra, the Platonic solids in his Theaetetus, as the tetrahedron, 1 the cube, the octahedron, the icosahedron, and the dodecahedron.

Little did he realize that the fascination he must have held for them

■would be felt as strongly by modern theoretical and synthetic chemists.

The Platonic Solids: (top) tetrahedron, cube, dodecahedron; (bottom) octahedron, icosahedron.

The aesthetic appeal of the Platonic solids for the chemist lies in their envisioned molecular equivalents, i. e. with an atom of a

1 2 specific element located at each of the vertices. In this respect, the inorganic chemist is indeed fortunate. There are many examples of tetrahedral clusters (S 4, P4, Sb 4) and tetrahedral complexes (BF 4" and

C104- ). Octahedral molecules (SFq, Co(CO)e) and complexes (PFe“,

Gr(NH3)Q3+) are also very common. Even though there is only one known inorganic example of cubic symmetry [ C u q ( S2CC(CN)2 ) 12] , th e much more highly ordered icosahedron can be found occurring in all forms of ele mental boron as well as in the B 12H122- ion. There is, however, no known example of an inorganic molecule which has the structure of the 2 regular dodecahedron.

The organic chemist envisions the Platonic solids with a methine unit at each vertex, such that a CnHn hydrocarbon results. However, be cause of the tetravalent nature of carbon, he is constrained. Only the tetrahedron, the cube, and the dodecahedron can have hydrocarbon equi valents, viz. tetrahedrane, cubane and dodecahedrane. Of these, only dodecahedrane rem ains unknown.

Although the parent tetrahedrane has not yet been synthesized, two tetrasubstituted derivatives are known. The first of these derivatives, tetralithiotetrahedrane (l), was reported by the Schleyer group in 3 1978. Their approach is based on the premise that a-donating, n-accept- ing substituents such as lithium might serve to stabilize the internal strain of the system. Irradiation of dilithioacetylene in liquid am monia gave a white powder believed to be 1 , a stable entity if kept un- o der argon at -20 C. Unfortunately 1_ has defied conversion to hydro carbon tetrahedranes. 3

Li hV, U-C=C-Li ------— — ► Li NH3

-45*C

The second tetrahedrane, tetra-te rt-hutyltetrahedrane (2), was pre- 4 pared hy the Maier group, also in 1978* by a more classical synthetic sequence involving, among several other steps, four photochemical trans formations. .Amazingly, 2 exists as a stable crystalline solid which o . m elts a t 135 C (d ec).

< >

9 Cubane ( 5 ) was first synthesized by the Eaton group in 1965 *

Since then several modifications and variations on the original theme a have appeared. This exquisite structure has been confirmed by x-ray 7 crystal analysis. Despite the high strain energy of 166 kcal/m ole

(l4 kcal/mole per C-C bond), the molecule has proven to be remarkably o 5 , 8 stable and to exhibit a melting point of 130 C. Examination of the IS 3 properties of this hydrocarbon and derivatives thereof has led to some 9 } 10 interesting results.

Although cubane and substituted tetrahedranes have been realized, the perhaps most interesting of the three (and indeed the most symmetri cal) has defied synthesis. Neither the pentagonal dodecahedrane (C 20H2 0 ) 11 nor any derivative has been prepared.

Unlike tetrahedrane or cubane, dodecahedrane (4) possesses little

strain energy. Each edge (C-C bond) of the polyhedron meets each of the 0 t 12 other edges at an angle of 110 54 • Waen the idealized tetrahedral o o' angle of a carbon atom of 109 28 is considered, it must be concluded that the angle strain in 4 is very small. The source of strain in 4 then is a result of the eclipsed arrangement of each of the carbon and hydrogen atoms. Calculations have placed the total strain energy in V between 3 k2. 98 and 88. 38 kcal/mole, or only 1. k-2. 9 kcal/mole per C-C bond. 3

When these figures are compared with the strain energies of tetrahe

drane and cubane ( 2k and 14 kcal/mole per C-C bond, respectively), 14 dodecahedrane appears to be almost strain free.

The strain energy of the final product is not the reason that do

decahedrane has defied synthesis. This low strain energy in must not

be extrapolated to imply that intermediates en route share this same

characteristic. Therein lies the problem. Many examples of intermediate, molecules involved in synthetic approaches to j* are known to suffer from

serious nonbonded steric interactions.

Dodecahedrane has more to offer than serving as a molecule that

confirms or disputes the validity of enthalpy calculations. Dodeca hedrane possesses the highest possible known point group symmetry (i^,

icosahedral) and shares its membership in this exclusive club only with the icosahedral boron structures. These molecules possess 120 point

group operations (a symmetry number of 60 ) and must therefore begin to 15 assume the shape of a sphere.

Recently, adamantane derivatives have found successful biomedical 16 use. The caged hydrocarbon portion of a pharmacologically active mole

cule to which an adamantyl group has been attached promotes lipid solu

bility and aids in adsorption on, or passage through biological mem- branes. The obvious possibilities for dodecahedrane in this area

are potentially great.

Recently, the homologous cations of both tetrahedrane and cubane have been examined. Because of the symmetrical structure of each 6 of these cations a large number of degenerate rearrangements were pre

dicted. Indeed, rearrangements of this type were recently established 1 8 in the case of the homocubyl cation. The homododecahedryl cation £

would be of particular interest since the atoms in £ could exist in 19 2 .5 6 x 10 degenerate arrangements.

The concept of placing an atom in the central cavity of dodecahe drane has recently received considerable attention. The central cavity is remarkably small. Calculations based on a C-C bond length of 1. 3k h reveal that the distance between two opposite vertices along a 3- fo ld axis is 4.3 However, when a van der Waals radius of i. 60 L fo r carbon is used, the radius of the cavity is reduced to 0.55 This volume is, despite its size, felt to be large enough to hold a small atom or ion. Consequently, theoreticians have considered the stabili zation energy to the dodecahedrane molecule with various atoms or cations located at the center of the cavity.

Depending on the choice of atom for the central cavity, the calcu lations range from marked destabilization to the astonishing stabiliza- 20 tion energy of -519 kcal/mole for a neutral berylium atom. Stabiliza tion energies for various cations have also been calculated. The proton, 2+ 2 + 21 Mg , and particularly Be have all heen calculated to stabilize C 2 oH20»

It should be noted here that various authors do not necessarily agree on figures. In fact quite the opposite is observed.

Ermer has considered the vibrational frequencies for dodecahedrane and has predicted it to have eight Raman active inodes and only three - i 2 2 infrared active modes ( 2890, 1 3 1 0 and 760 cm" ). Verification of these values, of course, requires that dodecahedrane be synthesized. There are, in addition, many other aspects of dodecahedrane chemistry that await investigation once it has been realized. Dodecahedrene 6j w ith its uniquely distorted double bond, and the dodecahedryl cation 7 su rely w ill exhibit intrigui.ngly novel chemistry.

Recently, St. Pyrek has hypothesized that dodecahedrane could have 23 a natural origin and asked the question "Is it a diterpene?". In this treatise, four isoprene units were positioned on the dodecahedrane frame work in two symmetrical arrangements and a promising biogenetic-like precursor of dodecahedrane planned. This added insight into the problem has undoubtedly served as an inspiration not only to contributors to this project, but to many others as well. 8

The list of possible experiments involving dodecahedrane and its derivatives is long indeed. Because of their highly theoretical nature, many of these may never be undertaken. Nevertheless, speculation upon the results has, and ■will continue to provide many a stimulating argu ment. But speculation, however interesting, is not the real world.

The latter is what must be addressed for the evolution of progress.

1-2 GENERAL APPROACHES TO DODECAHEDRANE

There are three basic types of approaches toward the synthesis of the dodecahedrane molecule. The first approach is based on the delight fully simple concept of isomerization and arises from the premise that dodecahedrane is likely the most stable C 20H20 hydrocarbon* This is in all probability a valid assumption and constitutes the approach of 24 the Schleyer group.

What is required then is a suitable simpler C 20H20 hydrocarbon and an appropriate Lewis acid. Despite the fact that a variety of hydro carbons and Lewis acids have been utilized in these attempts, nothing resembling dodecahedrane has ever been observed. The figure below illustrates one such example.

I The second approach is also rather elegant in its simplicity. Ex

tensively investigated by Woodward, this appraoch involves dimerization

of the two "halves" of dodecahedrane, i.e. coupling of two triquinacene 25 u n its ( 8). The list of catalysts and reagents scrutinized in an ef-

fort to effect triquinacene dimerization is a long one indeed. None

have enjoyed the slightest hint of success. Realistically, it must be

recognized that the demands being placed on the two halves require them

.not only to align themselves properly, but also to interact with each

other six times (6 bonds are necessary). Such a scheme is certain to

have the laws of thermodynamics working against it.

A clever modification of this approach was put forth by the Paquette

and Woodward groups. The P aquette approach involved lin k in g two t r i - 26 quinacene units with a C-C bond to form a bivalvane structure (£).

The Woodward approach involves the placement of two trans C-C linkages 27 between the triquinacene "halves" as in 10. Even though the two halves

have been linked, the major obstacle, unfortunately, had yet to be over

come. Sterically, the form in which the two halves are aligned relative

to each other (the conformation required for dodecahedrane formation)

is much less favorable than that in which the two halves are turned

apart. This has been the downfall of both of these sequences. 10

The third "basic type of approach is a stepwise synthesis. Current ly both the Eaton group at Chicago and the Paquette group are actively involved with such strategy. The Eaton approach involves the elegant construction of the peristylane ring system (ll). At the present time, completion of the project requires installation of the four remaining 28 bonds between the "cap" and the rest of the peristylane framework. 11

The Paquette group is currently involved in two synthetic ap proaches. The first "begins with a diketone (12) that is a precursor to

Cie-hexaquinacene (l^)? a molecule that is related to dodecahedrane be- 28,30 cause of its CnHn formula and polyquinane framework. An additional

12 13

quinane ring is easily introduced by inserting a carbon atom between the two ketone groups to give 14. The project currently requires the addition of three carbon atoms and the construction of seven bonds for completion.

The latter of the two Paquette approaches involves manipulation of the structural features of a molecule already containing all 20 o f th e 31 required carbon atoms (15)* Because of the all cis-fused nature of the 12

polyquinane framework, the carbon atoms are, in addition, "fixed" in their required positions. At the time the work to be described in this dissertation began, five bonds were required to complete the project.

This dissertation will describe the installation of four of those five remaining bonds.

1-3 AIM OP THIS RESEARCH AND SURVEY OP THE DISSERTATION

When this project was taken on, the 20 carbon all-cis fused hexa quinane framework had already been constructed. The results of many preliminary experiments with a variety of the derivatives of the basic framework were already in hand and were compiled in the Wyvratt dis- 32 sertation. The task remaining then, was simply to install as many of the five remaining bonds as possible. Surprisingly, it has proved to be quite simple (in retrospect) to introduce four of the remaining five bonds and to arrive at the dimethylsecododecahedrane

16 . 15

Secododecahedrane, a decaquinane, is the highest ordered poly quinane known to date and could potentially serve as a precursor to dodecahedrane. It should be noted here that although the construction of l6_ was relatively simple, only after several years did the proper reaction sequence become apparent from facts learned in the course of less productive sequences.

This dissertation describes the successful synthesis of l£ and relates the many avenues of endeavor that are perhaps less relevant to the target molecule, but significant in terms of new chemical know ledge. Since this project began as a continuation of previous work,

Chapter II deals with chemistry in the Wyvratt treatise that serves as a foundation for the present study. Additional chemistry and modifica tions to molecules in this sequence are also described.

Chapter III deals with the chemistry of a bisdihydropyran inter mediate in which the center bond has been cleaved. The highest ordered heterocyclic polyquinane, the dioxatriseco system 1T> is also included in this section. Development of the synthetic utility of methyl block ing groups is outlined in Chapter IV, and the chemistry of a bis lactone substituted with a pair of methyl groups is discussed. Light has for many years served chemists by performing synthetic transformations unachievable by other means. Chapter V introduces photochemistry as a useful C-C bond forming reagent in the present context. Installation of two of the remaining five bonds is detailed

in Chapter VI. Three different, although related, trisecododecahedranes are included therein. Secododecahedrane and its immediate precursors are dealt with in the final chapter (VII). CHAPTER I I

CONSTRUCTION OF THE ALL-CIS FUSED HEXAQUINANE FRAMEWORK

I I - l INTRODUCTION

In order to circumvent at least some of the problems that have plagued other approaches to dodecahedrane, a scheme was desired that

■would maintain all of the 20 constituent carbon atoms "locked" into the proper configuration. In addition, a C 2 axis of symmetry -was de

sired in the synthetic design. This feature offers two significant ad vantages over a synthetic sequence which does not maintain symmetry.

The first advantage is that the number of steps to the target molecule

could in principle be reduced by a factor of two. Secondly, observa- l3 tion of the C NMR spectrum of any intermediate would quickly pro

vide a determination of whether a reaction had proceeded according to

design. The spectra of such molecules are characterized by the presence

of only one half of the lines relative to the total number of carbon

atoms.

With this in mind, the Journey began. Matt Wyvratt, the primary

contributor, and three post-doctoral researchers established an eleven-

step sequence to an all-cis fused hexaquinane lactone beginning with

the domino Diels-Alder reaction. This synthetic sequence served as the

foundation for all of the subsequent chemistry developed herein. Some

15 1 6

knowledge of this sequence and of certain recent modifications is

necessary for a deeper appreciation of the multifaceted aspects of the overall synthetic approach.

I I - 2 REVIEW OF THE DOMINO DIELS-ALDER REACTION THROUGH THE BIS-

LACTONE 1£.

The Diels-Alder reaction has been acknowledged for many years as a highly efficient method for the elaboration of an additional six-membered ring. Generalized, the Diels-Alder reaction involves the intermolecular

(jt4 + jt2) cycloaddition of a dienophile to a 1,3-diene moiety. Of par ticular utility is the fact that the new ring is always introduced with full retention of stereochemistry.

In theory then, when a molecule containing two separate 1,3-diene moieties which are linked together in some fashion is placed in the presence of an appropriate dienophile, two Diels-Alder reactions are expected to occur. The first (rt 4 + fl2) cycloaddition produces a new olefinic moiety; subsequent involvement of the newly formed olefinic

center (or the residual double bond in the dienophile if o r ig in a lly

acetylenic) in intramolecular (« 4 + Hz) bonding to the remaining 1 , 3-

diene completes the formation of four new C-C sigma bonds. This concept 33 was dubbed the domino Diels-Alder reaction.

In actual practice, 9,10-dihydrofulvalene was used as the

coupled diene and dimethyl acetylenedicarboxylate served as the dieno phile. As expected, two domino Diels-Alder products (l 8 and 19) were obtained. Selective saponification separates the mere rapidly hydrolyzed IT

COOCH3

+ * (40%) ^ N ; o OCH3 T cOOCH, COOCH, 18 COOCH3 19

isomer lj3 from diester 19.

In order to maintain a Cjs axis of symmetry through the subsequent biscyclopentenone annulation procedure, it soon became evident that re course to a bisiodolactonization step -was necessary. Hydrolysis of 19

COOCH, COOH c— 0

KOH

&c o o c h 3 COOH IS 2 0 NoOCH3, CH30 H

COOCH3 COOCH3 HO

Zn-C. IT ^ V f° 0 CHjOH I H2 S04

COOCH3 COOCH3 COOCH, 24 23 22 18 gave the diacid 20;, -which when su b jec te d to io d o la c to n iz a tio n co n d itio n s cleanly gave 21. The lactone rings in 21 were easily opened in methanol containing a catalytic amount of sodium methoxide to give 22. Jones oxi dation produced 23 which when treated with zinc-copper couple was con verted quite cleanly to the diketo diester 24.

With th e £2 symmetry axis maintained, a biscyclopentenone annulation was required. The procedure chosen by Wyvratt was a three step 34 route involving application of the Trost cyclopropylsulfonium ylide.

Diketo diester 24 reacted with the Trost reagent to give a mixture of isomeric cyclobutanones, recrystallization of which gave the desired symmetrical endo-endo isomer 25, but only in 35$ yield. Subsequent

c o o c h 3 C0 0 CH

COOCH3 C0 0 CH3 COOCH3 2 6 JA J25

3 0 %CH3 C0 ^ HOAc c h 3so 3h -10* MegSi^X\ sec-B u L i SiMe* COOCH* COOCH3 0 NaOCH3, CH CH® CH CH,0 H ^ CH, Si Me3 SiMe COOCH COOCH3 CH-CH 27

29 19

Baeyer-Villiger oxidation of 25_ yielded 2£ which, when followed by an intramolecular Friedel-Crafts acylation effected with % phosphorous pentoxide in methanesulfonic acid, provided the bisenone 27.

In an attempt to improve the yield of these steps an alternate route to 2(5 was examined. Recently, Magnus and coworkers developed a 35 spirolactone annulating procedure involving silane chemistry. Treat ment o f 2k with the lithium salt of trim ethylallylsilane at -45°C gave the diol 28. At warmer temperatures, the undesired bislactone 2g was obtained which could be converted by treatment with sodium methoxide in methanol back to 28. Oxidation of 28 with peracetic acid did lead to the desired 2d, but in disappointingly small quantities.

Catalytic hydrogenation of bisenone 2J proceeded smoothly to deliver diketo diester 30 in quantitative yield. Wyvratt and coworkers have shown quite adequately that diketo diester ^preferentially enolizes 31 32 toward the bridgehead position. Thus, attempts to functionalize the cyclopentanone ring in results firstly in tertiary bridgehead functionalization; only subsequently is the secondary O-position functionalized.

Thus, attention was directed to the functionalization of a mole cule at an earlier stage of development. For this purpose, bisenone

27 proved to be a pivotal molecule. It was felt that if the bridgehead position in ^0 were blocked, enolization would be forced to occur toward . the secondary position. With this in mind, bisepoxyketone ^1 was pre pared. Unfortunately, ^ did not lend itself to useful and recog nizable chemistry. 20

COOCH3 0.

C00CH

c o o c h 3 NdoCO 27

COOCH3 31

Lead tetraacetate in refluxing benzene has teen shown to be an efficient oxidizing agent for enone systems, functionalizing them in 36 the a-position. When 27_was so treated, two products (the symmetri cal and the unsymmetrical were obtained in an equal ratio. The position of the acetoxy groups in 32^ could not be defined unequivocally; therefore, the position a to the carbonyl groups was assumed on the 36a basis of literature precedent.

The symmetrical isomer ^2 was reduced catalytically and gave ^ in excellent yield. Unfortunately, the spectral data obtained for 2it also shed no definitive light on the question of the exact location of the acetoxy groups. All additional attempted manipulation of the func tionality within 3^ led only to complex mixtures. A more well behaved substituent was therefore sought. 21

coochj COOCH3 PbCOCOCHj^ 27 MOCOCH3 toluene | > OCOCc\ooo^(j CH3CO COOCH* COOCH, 32 ,NBS lCCI4, hv

COOCH3 COOCH3 CH3C0 OCOCH3

COOCH3 COOCH, 34

The symmetrical dibromide 35 vas next prepared from bisenone 27 37 with UBS in carbon tetrachloride. Surprisingly, none of the unsymmetrical product was obtained. Comparison of reported spectral data for a- and p-bromo cyclopentenones suggested that ^ 5 _ vas the symmetri- 38 cal P,S-isomer. Unfortunately, 35_ decomposed during attempted con version of the bromide substituents to a variety of other functional groups and during attempted reduction of the double bond.

In light of these failures, efforts were channeled directly into the chemistry of diketo diester ]50. In addition to the list of reactions in v o lv in g £0 that Wyvratt has previously discussed, two new successful 22

reactions have been uncovered. Sterically hindered bisketal was prepared by heating 3£ and ethylene glycol with £-toluenesulfonic acid

as a catalyst. In addition to spectral data, the strongest proof of

the structure of 36 was obtained via simple acid hydrolysis, which re

tu rn e d £0. Unfortunately, attempts to cleave the center bond in or to reduce the ester moieties with hydride reagents gave rise only

to complex mixtures.

N0BH4

Palladium chloride converted 3£ into the bisenone £7 in 3856 y ie ld .

In bisenone £7> each position that ultimately will require a C-C bond in the completed dodecahedrane molecule contained functionality. This, however, may have been a case o f too much too soon. W yvratt has shown 23

that diketo diester 30 when treated with sodium cyanoborohydride is

converted cleanly into the closed bislactone 15. However, when 37 was

treated with hydride reducing agents, under conditions analogous to

those used by Wyvratt to convert 30 in to 15 , only complex mixtures were

o b tain ed .

With these possibilities exhausted, a possible route to new chemis

try via the c lo s e d bislactone 15 was next examined. The term "closed"

refers to the presence of the central bond that links the two sides of

the molecule. This bond, although unwanted in the final product, had

served its purpose well by maintaining a norbornyl type of framework

in all the molecules so far in the sequence. Drawn another way, the

norbornyl structure of 15 is quite evident. Thus, many of the reactions

that led up to lactone 1^ enjoyed direct precedent from the chemistry of simpler norbornane systems.

The molecules in which this bond has been cleaved have been dubbed

’’open" molecules. Cleavage of this bond allows the molecules to attain a more dodecahedrane-like shape and introduces new flexibility into the molecular structure. 2k

I I - 3 AVENUES FOR EXPANSIVE RESEARCH

The closed bislactone Improved to be the pivotal molecule for all further chemistry. Bislactone 15_underwent three different types of reactions. Each led down a totally different avenue of research.

In the first instance, hydride reduction of 15 fbrmed lactol 3p*

Lactol j58 or one of its derivatives was anticipated to undergo one or

more e th e r rin g opening re a c tio n s v ia th e mechanisms shown in Scheme 39 I. At this level of oxidation, the resulting "open” molecules could lead to some useful chemistry. 25

Scheme I

a - x t - ct

/ _ / x r f cpc o c Nu' 0 H OH 0

Direct cleavage of the center "bond in 15 ^ resulted in formation of open bislactone 59_or open bismethyllactone 40^ depending upon condi tions. These molecules provided the second major avenue. Surprising ly, the behavior both of 29. (reported by Wyvratt) and 4(3 (described herein) provided striking contrasts to the behavior of l^when treated under identical reaction conditions.

The third major avenue resulted from lactone ring cleavage reac tions. Despite deployment of many different techniques and reagents, only two reactions have resulted in the successful cleavage of both lactone rings. Trimethyloxonium tetrafluoroborate at elevated tempera tures converted 15^ to a mixture of isomeric diene diesters 4l. Hydro gen chloride in methanol gave the dichloro diester 42.

Interestingly, later developments have shown that the two reactions which provide 4l^ and 42^ could not be repeated with the open reactions

22, and ii£* In fact, these two reactions represent the only two processes in which both carbon-oxygen ether linkages could successfully be cleaved 2 6 in symmetrical fashion ! Nonetheless, these tvo molecules and in parti c u la r k2 have led to some most exciting chemistry. CHAPTER I I I

THE BIS CLOSED LACTOL 38 AND DERIVED MOLECULES

I I I - l INTRODUCTION

One strikingly obvious feature of lactol 38 (o r some d e riv a tiv e in which the hydroxyl functions are converted into good leaving groups) is its potential for ring opening as depicted in Scheme I and discussed in

Chapter II. Easily prepared by stirring ^8 in thionyl chloride, bischloroether fits well into this scheme of things. Not only are the

27 28 chloro substituents good leaving groups, but the departure of chloride ions can be accelerated in the presence of silver ions. In particular, we had special designs on acquisition of the diene dialdehyde 44.

Suitable treatment of was projected as a route to trisecodo- 40 41 decahedranes 45_ or 46 depending upon the reaction conditions uti lized. Wyvratt and coworkers had previously investigated all obvious reactions of this type with 38 and 43. At no tim e was any p roduct ex- 48 hibiting the properties expected for 44 ever isolated. An example of the frustration they felt can perhaps be best illustrated by the reaction of bischloroether 43 with silver perchlorate in benzene.

Instead of the desired conversion to 44^ the transannular perchlorate

4j[ was obtained. Recourse therefore had to be made to either an oxi dation or reduction of bislactol 3j3 or bischloroether 43.

III- 2 OXIDATION OF BISLACTOL 38

A procedure for oxidizing unactivated C-H bonds consists of treat- 43 ing an alcohol with a solution containing lead tetraacetate and iodine.

The iodine serves to capture the initially formed carbon radical before it can be oxidized by a lead(lll) or lead(lV) derivative. Application of this mechanistic rationale to lactol 38 suggested that the product in which the neighboring methylene group would be oxidized (i.e ., W3) might be fbrmed.

At the experimental level, the bislactol ^13 underwent fragmentation to deliver the bisiodo formate 49. Because of the exo orientation of the 29

I 2 , Pb(0Ac)4

l2,Pb(0Ac)4 CoC03» hv

KOH H20,CH^)H H.

hydroxyl groups in a steric factors take control. The iodine is prohibited from entering the cavity and a free radical ^-fragmentation occurs. Saponification of ^9 transforms it to the iodoalcohol jjO.

This transformation completes a three-step decarbonylation procedure

for j58. Although no practical use could be found for 50^ the carbonyl

group extrusion sequence was filed for later use should such methodology become necessary.

I l l - 5 THE BISDIHYDROPYRAN £4 (REDUCTION OF BISLACTOL ^8)

III-5-1 Transannular derivatives

With the oxidation of lactol 58 having gone astray and the chemis t r y o f 43. having led only to undesired products, reduction studies on 50

38 and -were pursued n ex t.

Not surprisingly, lactol 3j3 underwent clean reduction with sodium

and ethanol in liquid ammonia to give tetraol 51. This was easily con

verted into the tetraacetate 5£ with acetic anhydride in pyridine. An

acetate pyrolysis is a commonly employed technique for the introduction 44 of a double bond. Such a pyrolysis of ££ might be expected to give

the diene diacetate 53; Disappointingly, only complex mixtures of pro

ducts were obtained.

CHjCOtL 0C0CH3

N o , NH3 S3 c^ 5oh OCOCH3

GHj COO

OCOCH

Bischloroether 4^ also can be reduced with sodium in liquid ammonia.

In this instance, the chlorine atoms are positioned in a 1,4-relation

ship properly aligned for cleavage of the central C-C bond. Indeed,

when this reaction was performed (reported in the Wyvratt dissertation) 51 the bisdihydropyran was obtained alongside the simpler reduction product 55 (m inor).

Bisether 55_ either proved to be inert or to decompose in the 45 presence of a variety of ether ring cleavage reagents. As a con

sequence, attention was focused on the bisdihydropyran £4. The Wyvratt work had demonstrated quite well that bisdihydropyran was labile to

Scheme I I

HCI

-H

5 4 I

56 acid. Treatment of 5^ with hydrochloric acid resulted in transannular interaction of the two it systems with resultant formation of chloroether

56 . This process presumably operates via the mechanism depicted in

Scheme II. More recently, it was found that certain batches of silica gel quite efficiently rearranged 5 j+ into the aldehyde 57 > presumably via an analogous pathway.

Molecules containing dihydropyran moieties have been shown to react 46 with N-bromosuccinimide in methanol to give a-bromo acetals. But, be cause of the ionic nature of this reaction it came as no surprise that

5k did not undergo conversion into a-bromo acetal 58 . Instead, the transannular bromo acetal 59^was obtained. When N-iodosuccinimide was used, iodo acetal 6 £ resulted.

Although these two molecules were not as glamorous as the symme t r i c a l 58 would have been, they did possess substituents in potentially interesting locations. Silver(l) ion has for many years been utilized as an agent to remove halide ions. More recently, Paquette has shown that silver perchlorate in benzene also can induce the ionization of 47 ^ methyl ethers. Halides 59_ and 60 contain both of these substituents . and therefore could potentially be converted to the diene dialdehyde 33

44 by a carbonium ion mechanism. A major question in this plan was

Scheme H I

£9.R = Br 60# R* I CH30V o CHOL

44 54

■whether the transannular "bond could be induced to return to its original

symmetrical position. Scheme III summarizes the mechanistic considera

tio n s .

Although iodo acetal 6(3 decomposed in the presence of silver re

agents, bromo acetal 59 reacted with silver perchlorate in benzene to

deliver bromo aldehyde 6 l and bismethylacetal 62 _ in approximately equal

amounts. The formation of symmetrical bismethylacetal 62 was exciting.

Although 62 previously had been prepared by Wyvratt via a much simpler

sequence, its formation by this approach demonstrated that the position of the transannular bond was not fixed and could, in fact, be manipulated advantageously back to a symmetrical position. 35

In addition, the perfect molecule -with -which to demonstrate the u tility of the new discovery was in hand. The second product, bromo- aldehyde 61 , appeared to be properly constructed to undergo the bond migration reaction upon treatment with silver ion. The ensuing cation was expected to give diene dialdehyde 44. Disappointingly, 6 l proved to be inert to silver ion under mild conditions. Forcing conditions returned only complex mixtures.

Ill-3-2 Symmetrical derivatives

It was now obvious that in order to obtain a symmetrical derivative of the bisdihydropyran 54, a reagent was required that would function through a non-ionic mechanism or through an ionic mechanism which would not allow for participation of the second olefinic bond in the rate- determining step. Reactions fitting into the former category include free radical additions of bromine or thiophenol. Fortunately, two reagents that fit into the second category were found.

Bisdihydropyran 54_was observed to undergo epoxidation with m- chloroperbenzoic acid to yield the symmetrical bisepoxy ether 6 ^ 4 8 1 quantitatively. The simplicity of the H ((CDCI 3 ) 6 9 .6 6 ( s , 2 ) , 13 4.70 (m, 2) and 3.60-1.40 (m, l 8)) and C RMR spectra ((CDCI 3) 205-51,

103.43, 92.53, 6 3 .5 0 (2C), 61.72, 57.95, 49.20, 34.15, and 29.73 PPm) o f 63 confirm the retention of a molecular £2 axis in this heterocyclic octaquinane derivative. Interestingly enough, J?4 could also be cyclo- propanated quantitatively to biscyclopropyl ether 64, when Simmons-Smith 48 conditions involving the zinc-silver couple of Conia were used. When 3 6

results with this particular reagent proved to be somewhat difficult to

reproduce, recourse was made to the ethylzinc iodide procedure of 50 Inouye. The latter methodology also provided 6k quantitatively.

^CPBA CHgl2 c h 2ci2 Zn-Cu > -h

£3

The purpose of the epoxy and cyclopropyl groups was two-fold. Since the double bonds were removed from the molecule, unwanted transannular

interactions were expected to be eliminated. In addition, both epoxy

groups as well as cyclopropyl groups were known to open under a variety of conditions, thus enabling the continuation of work in this series.

I I I - 4 BISEPOXY ETHER 6 ^

When subjected to bases, acids, reducing agents, or Lewis acids,

the epoxide functional group undergoes conversion to a variety of deri

vatives. Each of these types of reagents was applied to bisepoxy ether

6p. Disappointingly, 6 ^ proved to be inert to strong bases such as 51 sodium hydride or lithium diisopropylamide.

Conversely, it was felt that a dissolving metal certainly would

react with 63 . One of two possible products was expected, depending on 37

52 ■which bond of the epoxide ring -was reduced. Should reduction of the

epoxide C-0 bond occur toward the carbon that was bonded to two oxygen atoms, then bishydroxy ether 65 would be formed. Cleavage of the other

epoxide C-0 bond would yield the open bislactol 66 that had previously been prepared by Wyvratt.

N o, NH3 S.CH3CH2OH

CH3CH2OH

The results obtained when 6£ was treated with sodium in liquid

ammonia were surprising indeed. Mot only were neither 6%_ nor 66 ob

served, but the center bond had been reinstalled across the center of

the molecule. A transannular interaction had again manifested itself.

In the absence of a proton source the reduction of 65 o ccu rred only at one of the epoxide moieties. This generated an anion which 38 attacked the second epoxide ring from across the cavity to yield the closed bislactol 38. This mechanism i s shown in Scheme IV.

Scheme IV

The presence of ethanol in the reaction mixture allowed the re duction to proceed further to the stage of tetraol 51? similarly ob tained from the dissolving metal reduction of 38.

Bisepoxy ether 63 proved also to be labile to treatment with acid in an alcoholic solvent. When subjected to methanolic hydrogen chlo ride, the epoxide rings in 63 were both opened and bishydroxy acetal

67 was obtained. Since lactol functionality is rapidly converted to acetal groups in the presence of an acidic alcoholic medium, the alternative structural assignment resulting from epoxide ring opening 39

in the other direction, i.e. 68^ was ruled out. Disappointingly, the

action of silver ion on 67 gave only complex mixtures.

Lewis acids converted 63 to yet another product. Certain batches of silica gel rearranged 63 , via the mechanism proposed in Scheme V, to

the dioxatriseco dialdehyde 69 in 48$ y ie ld .

Scheme V

silica gel

f t 4o

When consistent results on silica gel became difficult to obtain, a v a rie ty o f o th e r media •which would perform th e rearrangem ent were sought. Boron trifluoride etherate, strong acids and certain silver salts decomposed the epoxy compound. Weak Lewis acids and acidic, neutral, or basic alumina had no effect on 63 . Tonally silver perchlorate-benzene solutions were found to transform 63 . into the bisaldehyde 69^ in acceptable yield.

( - 2 CO)

CHO 17

Close examination of 6 ^, revealed that it was a trisecododecahedrane containing eight all-cis fused quinane rings. The axis of symmetry of this molecule along with the complex polyquinane framework make it 53 the highest ordered heterocyclic polyquinane yet observed.

Decarbonylation of this material was expected to give the parent molecule, viz. dioxatriseco compound 17. The x-ray crystal structure o f 1£ would indeed be an interesting trophy to hang on the mantel above the fireplace. Recently, rhodium catalysts have been used quite success- 54 fully as aldehyde decarbonylation agents. However, when Wilkinson’s catalyst was applied to 6%_ under a variety of conditions, only decom position occurred. 4 l

Recourse was then made to a more traditional method. Eaton and

coworkers have successfully decarbonylated carboxylic acids by thermal 55 decomposition of their corresponding te rt-butyl peresters.

Bisaldehyde 69 was therefore oxidized with some difficulty through 56 use of silver oxide to the dicarboxylic acid JO. Treatment of 70.

with thionyl chloride followed by careful addition of tert-butyl

hydroperoxide afforded the bis-tert-butyl perester 71* Although the

CC>3C(CH3)3

perester groups in 71 could be thermally decomposed (evident because of the evolution of carbon dioxide as tiny bubbles), none of the desired parent molecule could be detected.

Recourse was finally made to a procedure involving direct decar bonylation of 6 ^ with light. Cohen and coworkers observed clean de

carbonylation of aldehydes upon treatment with light at elevated tem peratures in a solvent mixture containing a radical transfer agent and 57 a photosensitizer. When the bisaldehyde 69 was dissolved in ethyl benzoate (solvent), mixed with acetophenone and benzyl mercaptan, and heated to l4o°C with simultaneous irradiation from a UV sunlamp, clean 42

decarbonylation occurred. By means of this technique, the dioxatri-

seco compound ( 17) could routinely be obtained in yields greater than

9<# after chromatography.

hv, PhCOCH? PhCHgSH,

PhCOO^Hjj

Once obtained, the dioxatriseco molecule was characterized by its 13 simple nine line C NMR spectrum. The proton and infrared spectra were

rather featureless as expected. Although a nicely crystalline molecule,

17 could not be coaxed into developing a single crystal suitable for an x-ray crystal structure determination. Rather, the molecule preferred to crystallize in the form of delicate flowers.

Progress could not stop for want of a crystal. The dioxatriseco

derivative itself contained no features that were suitable for further

chemistry so recourse was made to bisaldehyde 69 .

Expectedly, 69 could be converted to bismethylacetal 72 with an acid

catalyst in methanol. However, 72_ was not found to give rise to new and

useful derivatives. Bisaldehyde 6

sodium borohydride to yield diol 73 which proved to be a serviceable

intermediate. (CH30 )£ H

CHjOH tHgsq^)

CH(OCH^2 22. 73

HOCH2 H2NCH2 N3CH2 0

H2 i cot No n -: HMPA

c h 2nh 2 CHgOTt 76

The ultimate goal of this route remained cleavage of the ether linkage and obtention of a molecule -with functionality suitable for installation of a new C-C bond. A carbonium ion at the position held 44 by the hydroxyl group possibly could induce ether ring opening with formation of an ene epoxide.

A convenient method for the generation of such carbonium ions 58 under controlled conditions is via decomposition of diazonium ions.

Toward this end, ditosylate j4 was prepared by stirring diol 73 with

£-toluenesulfonyl chloride in pyridine. The tosyl groups in 74 were found to be reluctant to undergo displacement with sodium azide in 59 common solvents such as acetone or dimethylformamide. However, with recourse to hexamethyl phosphoramide (HMPA) as the solvent, the dis placement proceeded smoothly to yield bisazide 75; Catalytic hydrogena tion quantitatively converted bisazide 75_ to the bisamine 76. Unfor tu n a te ly , when 76 was subjected to nitrous acid deamination, no ole fin containing product was observed.

A lte rn a tiv e ly , (3-bromo e th e rs have been shown to undergo re d u c tiv e 60 ether ring cleavage upon treatment with zinc. The reaction proceeds through reduction of the bromine moiety accompanied by displacement of the adjoining C-0 bond. An example is shown in Scheme VI.

Scheme VI

This scheme should apply directly to this series of molecules if the dibromide could be obtained. Reports of conversion of alcohols to ^5 bromides by treatment of the corresponding tetrahydropyran with tri- 61 phenylphosphine dibromide have claimed excellent yields. The bis- tetrahydropyran ether 77 was formed from diol 7£ under the usual condi - 62 tions. However, triphenylphosphine dibromide reacted with 77 to give only complex reaction mixtures, ibrtunately, the more cumbersome pro cedure of sodium or lithium bromide in HMPA did result in displacement of the tosyl groups in 7^- to deliver dibromide j8.

CH^OTHP

CH20 THP

TS0CH2

With dibromide 7j3 in hand, the next step was to open the ether linkages with zinc to obtain diene diol 79 * The projected synthetic

strategy was to involve oxidation of the hydroxyl groups and subsequent 46 reduction of the double bonds to give diketone 80. Photochemical excita tion of the carbonyl groups might then be expected to induce cyclization to form the trisecododecahedrane 8l -which contains two additional five- 63 membered rin g s . T his sequence o f re a c tio n s i s shown in Scheme VII.

Scheme V II

Lo]

i Ho* cat

.OH

■4-----

81 ft©

Zinc reduction of dibromide 78 in methanol did indeed proceed to give diene diol 79. However, the conditions required for the reaction proved to be quite sensitive. In the presence of ethylenediaminetetraacetic acid (EDTA), diene diol 79 "was obtained in yields varying eoa from 50 to SOjo. Without EDTA present to complex the zinc ion, none of the desired product was obtained. Instead, apparent simple reduction ^7 of the bromine moieties ■was observed and the dimethyldioxatriseco compound 82 was obtained.

OH BrCHg o CHg'

EDTA, ;oh CH-OH

CHg •

Zn, CH3 OH

Several examples of caged molecules containing both hydroxyl and exocyclic methylene groups have been reported. In each of these cases, the molecules were shown to be very sensitive to a variety of reagents 64 rapidly forming cyclic ethers. Diene diol 79 proved to be no dif ferent and, in fact, exhibited extreme sensitivity to electrophilic re a g e n ts.

Any attempt to reduce the olefinic bonds via catalytic hydrogena tion resulted in the formation of 82. Treatment of 79 with protic or

Lewis acids also resulted in the formation of 82. Because of this sensitivity and the low yield encountered in the formation of 79, further work in this area was discontinued.

This study was not without some success however. Dimethyldioxa triseco dodecahedrane 82 crystallized from ethyl acetate as octahedral prisms which proved quite suitable for x-ray crystal structure deter- 65 mination. At long last, the x-ray we had sought was in hand. 48

.Apparently for steric reasons, the oxygen atoms in 82 are puckered

slightly into the center of the cavity. This conformation offers the

four methylene groups relief from a sterically crowded environment caused

hy their mutual interaction across the gap in the molecule. The steric

repulsion between these methylene groups evident in the x-ray (shown in

Figure I) has undoubtedly been an influential factor in facilitating

the transannular interactions in molecules both previously discussed

and to be presented subsequently.

I l l - 5 BISCYCLOPROPYL ETHER 6^

Because the chemistry of bisepoxy ether 63 did not lead to our ultimate goal, attention was focused on the biscyclopropyl ether 64.

Precedented in large part by the earlier findings of "Wenkert, acid 36 hydrolysis of 64 was investigated. Wenkert and coworkers treated

0 II

£3 M

64 JB& 49

Figure 1

Three-Dimensional Features of Dimethyldioxatriseco Dodecahedrane

82 as Determined by X-ray Analysis 50

cyclopropyl ethers of the type 83 with hydrochloric acid and obtained a-methyl carboxaldehyde products (e.g., 84) via transient oxonium ions.

Should the intervening oxonium ions derivable from 64 experience ring opening to produce ene aldehyde units, the highly attractive hexa-

quinane 85^ would result. However, when 64 was treated with hydrogen

chloride, the marked preference for kinetically controlled transannular bonding was again manifested. Treatment of 64^ with anhydrous hydrogen

chloride in dichloromethane at room temperature provided a-chloroether

HCI

ch 3 07

CHjpH

CH3O

87 in quantitative yield. The corresponding methyl acetal 88 was ob tained through methanolysis of 87. Bromination of 64 analogously 51 provided dibromide 89. As before, methanolysis gave bromo acetal go, thereby confirming the structural assignment.

The most plausible mechanism for these results is illustrated in s tru c tu re 86 . Because of steric constraints, the interior of the mole cule is devoid of solvation. As a result, functional groups on the opposite side of the molecule become particularly energetic toward the reaction center and participate at an extremely accelerated rate.

Thus, only products formed by transannular bonding may be expected for an ionic reaction of 64.

In anticipation of the fact that free radical reactions would pro ceed without this complication, 64 was treated with N-bromosuccinimide in carbon tetrachloride solution with simultaneous irradiation with a

UV sunlamp. The symmetrical dibromide 91 resulted. Characterized by its simple C spectrum (12 lines observed), 91 was immediately treated with tr i-n_-butyItin hydride which provided clean conversion to the sym- 1 metrical bismethyl imide g2. Clearly identified by its H MMR ((CDC13) 13 3.9k ( s , 2) , 5 .9 1 ( s , 2 ), 3. 3- 1 .3 (m, 18)) and C MR spectra ((C D C I3 )

178.42, 78.70, 72.75, 65 . 26 ( 2 ), 51.12, 50.15, 49.03, 44.52, 28. 01,

33. 50 , 28. 30, 26 . 12), 92^ was clearly an "open” analogue of the closed b i s la c to l 38. Without the center bond contained in 38 and with methyl groups blocking the positions a to the reactive functionality of the m olecule, 92 was expected to be free of transannular complications.

The entire spectrum of reactions that were carried out on ^8 could presumably be repeated on £2. Entirely different, hopefully more pro ductive results were anticipated. The succinimide groups on 92 were, however, somewhat less than desirable substituents with which to pur

sue the chemistry already demonstrated by 38. The simple bisamino

ether ^ was projected to be more suitable for these needs. Loss of

ammonia in this case might be expected to give the highly desirable 85 .

.\ ‘St CHO I ^

NH,

93 85

Alkaline hydrolysis, however, only did half of its job, quantita

tively opening the succinimide rings to the biscarboxylic acid 9^*

The second hydrolysis of each of the succinimide groups clearly was 55 expected to be more difficult. Each of these groups new contained a carboxylate anion, which undoubtedly provided an electronic deterrent for approach of a hydroxyl anion to the second amide carbonyl carbon.

To circumvent this problem, 9£_ was treated with both hydrazine and methylamine. Again, cleavage of the second amide linkage did not occur and the derivatives 95 and 9 6 , respectively, were formed.

R-NHC0(CH2)2C00H 94

H2NNH2

\ 3 2 CH NH

3 c h 3 ch NHC0CCH2)2C0NHNH2 FT* NHC0(CH2) 2 C0NHCH3 96 35

It had become clear that more forcing conditions were required to carry out the desired transformation of to bisamine 93. At this 54 point in time, a much less cumbersome procedure provided access to the corresponding open bismethyl lactol 97- Because of the close analogy between the new conveniently prepared lactol 9£ and 92, further work with 92 was discontinued. As additional time at the bench revealed, l a c t o l 97 and its derivatives did indeed lead to some most exciting new chemistry. This chemistry comprises the bulk of the next chapter (Chap t e r IV). C H A P T E R IV

IV-1 INTRODUCTION

The last chapter was concerned with the chemistry of closed lactol

58. This compound represented the first of the three major research avenues derived from the closed bislactone 1£, viz. reduction of the lactone carbonyl groups. Much of this chemistry was plagued by the now familiar transannular reactions. One possible solution to this prob lem, removal of the central bond at an early stage, was next investi gated. Comparison of models indicated that an "open” lactone would enjoy a much more flexible framework and may be expected therefore to be the source of many yet uncovered chemical transformations.

The simplest open lactone, i. e. ^ was obtained by Wyvratt upon reduction of 15 _ with sodium in toluene containing trim ethylsilyl chloride. Methanolysis of the initially formed trimethylsilylenol acetal yielded 59. Open bislactone ^9 proved to be a disappointing intermediate. Its periphery contains two acidic hydrogens a to the lactone carbonyl groups. The possibility of intramolecular condensa tions within 59 "were therefore present, thereby setting the stage for serious complications. Wyvratt demonstrated .that this was precisely the case. Treatment of ^ with sodium hydride transformed the

55 56

symmetrical to unsymmetrical keto lactone via an intramolecular

Dieckmann condensation. In addition, a variety of other reagents gave rise to similar products.

In order to continue the chemistry of the open lactone series of molecules, it soon became apparent that the lactone must be made de void of a-protons. The first obvious choice involved utilization of methyl groups as blocking agents. While investigating this possibility,

Wyvratt found that 1£underwent clean reductive cleavage with sodium in liq u id amm onia. The use of excess methyl iodide as a quenching agent yielded the open bismethyl lactone 40 in high yield. Because of time lim itations, Wyvratt proceeded no further.

CH-

<*3

J5 57

Methyl groups symmetrically disposed on the periphery of such mole cules offer three distinct advantages. The most immediate of these is, of course, the deprivation of unwanted intramolecular Dieckmann conden sations. The last two are somewhat more subtle, but nevertheless just as important. The methyl protons provide a characteristic "handle" in the ^ NMR spectra of these molecules. This feature instantly converts a ^ NMR spectrum into an efficient tool for determination of the sym metry or dissymmetry of a reaction product. The final advantage is to be found in the added crystallinity and higher melting points imparted to the molecules. This feature was used to great advantage in the case of the dioxatriseco (lj) and dimethyl dioxatriseco dodecahedranes ( 82).

The disadvantage of methyl blocking groups lies in their relative permanency. The alkyl-free nature of our ultimate goal (dodecahedrane) made the choice for methyl blocking groups less desirable. As an al ternative, thiomethyl groups as the new blocking agents seemed to be the obvious selection. Molecules containing such groups should not only exhibit all the advantages found with the simple methyl groups but also be subject to ready removal, a problem to be encountered at a later stag e.

Unfortunately, when 1£ was reduced with sodium in liquid ammonia and the intermediate bisenolate quenched with dimethyldisulfide, two products were obtained. The major product, transannular thiomethyl la c to n e 100, apparently results because of the lower reactivity of dimethyldisulfide compared to methyl iodide. This reduced reactivity allows the intermediate anion to have a significant lifetime, this resulting in the intramolecular Dieckmann reaction observed previously.

Bisthiomethyl lactone 101 -was obtained only as the minor product.

CH3SSCH3

Neither the reaction time nor reaction temperature proved critical

to the product ratio. Despite the previously stated disadvantage of

the methyl blocking group, its utilization was considered essential to

unlocking future synthetic pathways.

17-2 LACTONE RING CLEAVAGE REACTIONS

Clearly the most direct approach to an attractive trisecododecahedrane derivative with retention of £2 symmetry would involve retrograde 59

Baeyer-Villiger ring contraction of lactone ko. Acid-promoted elimina tion and intramolecular acylation in concentrated acid are recognized 67 simple conditions for performing such operations. When 4(3 "was stirred

■with 8j& phosphorous pentoxide in methanesulfonic acid, polyphosphoric acid, or sulfuric acid, the highly desirable 102 was not obtained.

Rather, a unique isomerization resulted. The infrared carbonyl

stretching frequency (1760 cm-1) of the new substance coupled with the lack of downfield *H NMR absorption (characteristic of X3H-0C0-) infer the product to be the structurally interesting but useless lactone 10^.

CH 3A ^O

CH3S03H

Recourse was then made to milder conditions. Decomposition of lactone tosylhydrazones frequently results in the formation of retro- 66 grade Baeyer-Villiger products via oxycarbenes. Such a process would produce the highly desirable 104. Because of the proximity of the hy drogens ( 6 ) on the adjacent cyclopentane rings to the carbenic center, intramolecular hydrogen transfer might also be expected to occur re sulting in formation of ether 105 . 104 105

Since lactone tosylhydrazones are most conveniently prepared from ortholactones, the corresponding bisortholactone of 40^-was required.

Exposure of 40 to trimethyloxonium tetrafluoroborate at room tempera tu r e fo r 16 hr, followed by direct treatment -with a sodium methoxide in methanol solution resulted in clean conversion only to the mono ortholactone 106. Methylation of the first carbonyl group generates

(CH3)30 +BF4 CH^CIg R.T.

40 106

CH;

CHj

106 107 6 l

a carbocation intermediate, Apparently the juxtaposition of this bisoxy-

carbocation and the second transannularly disposed carbonyl group func

tions as a deterrent to a second electrophilic attack. In addition, the

loss of symmetry made it impossible to determine, based on spectroscopic

data alone, if the monoortholactone had not undergone a deep-seated

structural rearrangement. This doubt was dispelled when mild acid

hydrolysis of 106 returned 40.

Increased temperatures did not force the formation of the symmetri

cal bisortholactone. Rather, both 40 and 106 were converted to ester

lactone 107. The lack of vinyl protons in the 1H NMR of this obviously unsymmetrical molecule implied that the initially formed olefinic bond had rearranged under the reaction conditions to the presumably more

stable tetrasubstituted position. This result was disappointing. Not only had the carbene insertion reaction been eliminated from the syn thetic plan, but the cyclopentene ring no longer possessed functionality in the key 6 -position formerly occupied by the lactone oxygen atom. Ul timate cleavage of both lactone rings was accomplished in trichloro- ethylene solution where a molecule tentatively assigned the structure

108 was formed.

IV -5 THE OPEN BISMETHYLLACTOL 97

IV-3-1 Transannular Derivatives

An alternative assault on the lactone rings involved reduction of the lactone carbonyl groups. The resulting masked aldehyde 97 was obtained in excellent yield from 40 by reduction with lithium aluminum 62 hydride at -78 C. As previously observed for lactols of this type, 97 is the product of thermodynamic control. The kinetically favored endo, endo isomer rapidly equilibrates to the more stable exo,exo isomer 3l}453,69 during workup and/or isolation.

CH 3,0^0. ch 3 , ; \

Li Al H4

92 [HCl]y [HCI] CH^OH/2-3 hr. CH30H

Lactol 2X was much more accessible than the closely related £2 p re viously discussed in Chapter III and therefore served as the key com pound in the open masked aldehyde series of molecules.

Initial characterization of ^8 was based upon the observation of a pair of hemiacetal protons as a singlet in the 1H NMR (pyridine) at

6 4. 80. The chemical shift of these did not change appreciably upon conversion to the much more soluble methyl acetal 109 (6 4.52 in CDCI 3).

Conveniently prepared by the short-term action (2 hr) of methanolic hy drogen chloride on 97; 109 results from solvent capture by the inter mediate oxonium ion on the exterior of the molecule. In each case, 13 the simplified "C NMR spectrum (ll lines for and 12 lines for 109)

substantiated the C 2 symmetry of these substances.

The phrase short-term was emphasized above. Long-term treatment

(2 days) o f £7 o r 109 in methanolic hydrogen chloride resulted in a unique intramolecular oxidation-reduction reaction which cleanly pro duced the unsymmetrical ether lactone 110. Titanium trichloride in chloroform proved equally efficient in providing 110 from o r lOff.

The structure of 110 was substantiated by the presence of an infrared

carbonyl stretching frequency at 1710 cm-1 (characteristic of similar

6 -lactones) and a widely spaced AB absorption at 6 3.86 (d , J = 12 Hz) and 2 .9 8 (d, J = 12 Hz) typical of an ether methylene group fixed in a 42y 53 rigid spherical framework.

The most reasonable rationale for this interesting reaction involves a transannular hydride migration across the hydrophobic cavity to a carbocation center generated by the loss of methanol or water subsequent to protonation. A related, although distinctly different example of intramolecular hydride transfer as an equilibrium between a 1,4-hydroxy 70 ketone has recently been reported by Craze and Watt. Substantiation * of this explanation was obtained more concretely by lithium aluminum deuteride reduction of g7 to the dideuterio lactol Ilia. The standard

short-term methanolic hydrogen chloride conditions yielded dideuterio 6k methylacetal 111b. Long-term treatment of either substance gave ether

la c to n e 112 -which now co n tain ed both deuterium s u b s titu e n ts gem inally positioned. - Again, infrared spectroscopy demonstrated the presence o f a 6 -lactone carbonyl group at 1710 cm"1. The “hi NMR spectrum of 112 was identical to that obtained for 107 except for the conspicuous ab

sence of the ether methylene group AB pattern. Scheme VIII depicts the mechanism involved in this transposition.

Scheme V III

R0 CHJno

[hci ] CH-OH

c h 3 i!!a, r - h

R - c h 3 -RX

112

Lactol 97 proved surprisingly susceptible to yet another unusual o transannular interaction. The lactol (stable below 160 C) melts at an elevated temperature with the evolution of tiny gas bubbles (H 2O).

When th is experiment was conducted in an NMR tube, the XH NMR spectrum 65 clearly indicated that an unsymmetrical aldehyde had "been formed -which exhibits two distinct methyl signals at 6 1 .18 and 1. 04 and a single aldehyde signal at 9-85 (s, 1H). The 21 line l3 C NMR spectrum confirmed the dissymmetry of the substance and aided the assignment of the acetal aldehyde structure 113 to the substance.

This transannular ether migration presumably occurs through loss of hydroxide ion as catalyzed by agents on the surface of the glass

(Scheme IX). Were this the case, then a more appropriate catalyst might be expected to' perform this transposition under milder conditions.

Scheme IX

H^ol © CHO CH;

180 C L.J

ch3 66

Aprotic conditions were deemed to be required. Eor this purpose, lead

tetraacetate buffered with calcium carbonate in cyclohexane performed

admirably, converting efficiently into II 3. These results pro

vided an interesting contrast to the iodoformate ^9 obtained from the

closed lactol ^8 when so treated in Chapter III. The distinct dif

ference in chemical reactivity of the open versus the closed lactones

and lactols is once again emphasized.

The effect of catalytic quantities of hydrochloric acid in tetra-

hydrofuran on 97 was also examined. When so treated, lactol 9J_ y ie ld e d

a mixture of II 3 (6<$), 110 (29$) and unidentified substances (1$) af

ter two days.

Since acetal aldehyde 113 and ether lactone 110 had now been ob

served together on two occasions in crude reaction mixtures, the ques

tion of their interconvertibility arose. The answer came quickly.

Methanolic hydrogen chloride completely isomerized 11^ to 110 at room temperature. Apparently, the closely proximate carboxaldehyde exhibits

in protonated form an electrophilicity sufficient to be attacked by an

acetal oxygen and produce an oxonium ion intermediate. This inter

mediate, identical to one previously observed for the formation of

110, then proceeds down the path of known chemistry (Scheme IX).

Similarly, when 113 was treated with triphenylmethyl tetrafluoro-

borate, a mixture of 110 (2$) and a new substance (6$) exhibiting a

XH NMR signal at 6 2. 09 characteristic of a methyl ketone resulted.

An infrared carbonyl band at 1710 cm "1 confirmed the aliphatic nature of the ketone group. Although the mechanism remains shrouded, the reagent apparently induces a Wagner-Meerwein methyl migration result

ing in the formation of isomeric keto acetal lljf-. The driving force

is presumed to he the alleviation of steric congestion in the central

c a v ity o f 113.

With ether lactone 110 as the common terminating point in this

series of reactions, quantities of this substance were beginning to

accumulate. A mild ring opening procedure involving the lactone group

might now yield a desirable ether ene aldehyde derivative. To this

end, lactol 113a and methyl acetal 113b were prepared by procedures

similar to those previously discussed. When treated with a catalytic

quantity of £-toluenesulfonic acid under conditions where methanol

was continuously removed, 113b was transformed into bisether ll6. This

second example of a 1,2-Wagner-Meerwein methyl shift product was obtained

as an isomerically pure substance. Although the exact position of the

olefinic moiety has not yet been ascertained, the XH (by the absence of vinyl absorption) and l3C NMR spectra (with lines at 1^2.78 and

132.93 PPm) confirm the tetrasubstituted character of the bond. The 68

LiAIH4 (TsOH)

H§ o , R s H Li Al H b, R =CH3

CHgOH

118

H NMR spectrum reveals that one of the methyl groups is now bonded to a secondary carbon (d, J = 7 Hz), demonstrating the Wagner-Meerwein shift and the reluctance of the heterocyclic ring to undergo cleavage.

Lithium aluminum hydride at room temperature reduced 110 com pletely to yield diol 117. Thermal decomposition of 117 at 170°C led to cyclic dehydration and formation of the Cg symmetric bishomo dioxatrisecododecahedrane l l 8 in low yield. Examination of the aH

MMR (methyl groups coalesced) and l3C NMR spectra (only 11 lines ob served) recorded for ll 8 confirmed the structure.

IV-3-2 Symmetrical Derivatives

The impression should not be held that all derivatives of lactol

9J are subject to transannular rearrangement. One exception was noted 69 upon treatment of gT with thiophenol in tetrahydrofuran containing an acid catalyst. Clean formation of the bisthio hemiacetal 119 resulted.

The relatively simple MR (a singlet at 6 5. ^3, s, 2H, assigned to

>CH-S-) and l3C MMR spectra (l4 lines) substantiate the Cg symmetry of the product. Treatment of ll^ with alane provided a highly efficient

PhS. CH3Q'*, CH3 V ,0 . CH

AIH3

I.J

c h 3 119 118

synthesis of bisether ll8. No cleavage of the C-0 linkage adjacent 71 to the thiophenyl moiety was observed.

Unfortunately, 11.8 proved to be extremely resistant to ether ring 45,72 cleavage procedures. Such conditions either returned ll8_ un changed or led to complex mixtures accompanied by decomposition. CHAPTER V

PHOTOCHEMISTRY OF CARBONYL GROUPS (CARBON-CARBON BOND FORMATION)

V -l INTRODUCTION

Eor more than two decades the photochemistry of carbonyl compounds has been receiving a great deal of attention as an efficient means of functionalizing unactivated positions on an alkyl chain. More pre cisely, the photoexcited Jt# n carbonyl groups has been found capable of Y"Hydrogen abstraction in a process sometimes called a Norrish II re a c tio n . Commonly, th e in te rm e d ia te has two choices: r a d ic a l c o lla p se to 63, 73 form cyclic alcohols (frequently cyclobutanols), or bond scission

(Scheme X). Aldehydes have also been observed to undergo these pro- 74 c esses.

SCHEME X

JO , u OH

TO 71

In addition, many examples of cyclopentane ring formation have 75 appeared. These seem to occur particularly in cases where the y C-H 76 77 bonds are lacking or where the C-H bond is appreciably activated.

One more group of compounds of particular interest to photochemists

are the a-dicarbonyls. They tend to exhibit low lying triplet states

and act as excellent quenchers. Hydrogen abstraction is also, as in the

case of simple ketones, commonly found to occur in such compounds. This

abstraction process again has found significant synthetic u tility in 78 cyclobutanol synthesis (Scheme XI).

Scheme XI

The fact that only cyclobutanols have been observed is apparently

due largely to the accessibility of the y-hydrogens. Cyclic pseudo

six-membered transition states have been recognized for many years as

being strain-free and therefore preferred.

With photochemistry in mind, an attractive molecule was thought to be the closed diester 120. Ketones derived from 120 cannot enjoy a pseudo six-membered ring transition state, since the y-hydrogens are

sterically inaccessible to the ketone moieties. Examination of models 72

indicates, however, close proximity between 8-hydrogens and the ke

tone groups. Cyclopentanols might be expected to result photochemi-

cally (Scheme XII). Were this the case, 120 could serve as a pivotal

Scheme XII

molecule for a variety of photochemical transformations through ap propriate manipulation of the closed diester functionality. Modifica

tion of the photochemically unreactive esters to photochemically reac

tive ketones or aldehydes would then lead to the formation of new quin-

ane rin g s .

V-2 THE TWO SATURATED DIESTERS (120 and 127)

Previously, Wyvratt had reported the formation of dichloro diester

k2 by treatment of the bislactone 15 with saturated methanolic hydrogen

chloride. Obtained in 5$ yield, had also been treated with tri-n-

butyltin hydride to give Wyvratt saturated diester 120 in hjfo y ie ld .

Clearly a higher yielding procedure was necessary if 120 was to be used

as a precursor to photochemically active ketones. Ibr this purpose, 79 the Corey modification of this procedure -was utilized. A catalytic

quantity of tri-n-butyltin chloride along -with sodium borohydride worked admirably to increase the yield of 120 to 9$.

Despite the high yielding chloride reduction procedure, the overall yield for the two steps was only kjfo. Alternatively, a completely dif ferent and less troublesome synthesis of 120 was sought. Wyvratt had previously shown that one of the lactone rings in bislactone 15 could be opened with trimethyloxonium tetrafluoroborate in methylene chlo ride at room temperature to yield ene ester 121. Although the effect of increased temperature (70°C and above) had been investigated, no product in which both lactone rings had been opened had been observed.

S u rp ris in g ly , when reco u rse was made to a p re v io u sly u n in v e stig a te d

solvent, 1,1-dichloroethane, a 5$ yield of diene diester 4l was ob tained along with 4<$ of 121. That diene diester 4l had been produced

as a mixture of isomers was deduced from the appearance of a m ultiplet at 6 5.42 (4H) and the coalescence of the methyl ester signals in the

■•■H NMR spectrum (CDC13). The 1:^C NMR spectrum proved to be of little use, revealing several olefinic lines. The most convincing structural proof was obtained through catalytic hydrogenation of 4l which quanti tatively gave 120. Eor practical purposes, the crude mixture of 121 and 4l was not separated, but reduced together before purification to give 120 (5$). The remaining material contained ester lactone 122

(4C$) which could be re subjected to the above conditions to provide an additional 29$ of 120 to bring the total yield to 73$.

With 120 efficiently in hand, its conversion to diketone 12j3 was investigated. Photolysis of 12^ might be expected to yield the highly desirable diol 124. Diketone 123 "was envisioned to be available from a double addition of methyllithium to the corresponding dicarboxylic 80 a c id 125 or lithium dimethylcuprate addition to the corresponding 81 acid chloride 126 (Scheme XIII).

Scheme X III

CHjOv^O so Cl* HMPA or PCI,

120 125 127

i ; LiH \soci2 2.;CH3 Li X 3 ^ 0 CIv^O

hv (CH^CuLi

124 123 126

D ieste r 1 2 0 proved to he resistant to alkaline hydrolysis even at elevated temperatures. Resort was then made to sodium cyanide in

HMPA which gave diacid 125 in fair yield. The infrared spectrum of

125, exhibits characteristic carboxylic acid absorptions and the NMR spectrum closely resembles that obtained for 12 0 . Unfortunately, the biscarboxylate of 125 proved to be inert to methyllithium even at 76

elevated temperatures. In addition, 125 could not be transformed into

bisacid chloride 126. Instead, a variety of standard reagents including

thionyl chloride, phosphorous pentachloride, and oxalyl chloride simply

dehydrated 125 to give anhydride 12J. Anhydride 127 "was also inert

to organocuprates. Apparently the center bond in 125 contributes to

anhydride formation since cyclic five-membered anhydrides are quite 31, 72b readily formed. These facts prompted the preparation of open

dimethyl diester 128.

Treatment of closed diester 120 with sodium in liquid ammonia

followed by methyl iodide as the quenching agent gave the open bismethyl ester 128 in 60fa yield. Diester 128 was identified by its XH

CHjjO HO

120 129

PCC

HO.

CH3

J2L 130 77

NMR spectrum (C D C I3) which exhibited two singlets at 6 3.60 and 1.40 13 ( 6 H each). The simple C NMR spectrum (9 lines) confirmed the C 2V symmetry. Diester 128 was reduced with diisohutylaluminum hydride

(DIBAL-H) to give diol 129 in excellent yield. Interestingly, lithium aluminum hydride failed to reduce diester 128. A large hydroxyl absorp tion in the infrared spectrum and a simple 8-line l3C NMR spectrum con firmed structure 129. Pyridinium chlorochromate (PCC) cleanly oxidized

129_to bisaldehyde 1^0 which because of its symmetry was also easily identified by l3C NMR (8 lines) and XH NMR spectroscopy (CDC13, 5 9-98

( s , 2H, -CHO)).

The literature compiled on aldehyde Norrish II processes, although not as vast as that amassed on ketone photochemical processes, indicates a distinct preference for decarbonylation in cases where the radical 74a formed by loss of carbon monoxide is particularly stable. Such was expected to be the case in J 2 Sr Not only would the ensuing radical be tertiary, but there was also expected to be a considerable relief of steric interactions between groups on the central cavity upon ejection of carbon monoxide. It was not a great surprise then that photolysis o f 130 led not to trisecododecahedrane 131 but to a complex mixture of substances that mass spectrometry revealed had lost CO.

In an attempt to bypass this complication, aldehyde 150 was treated with methyllithium at -J8°C to give a mixture of two epimeric diols

( 132) (Scheme XIV). Although these could be separated by preparative

TLC, they were usually oxidized together with PCC to give a single bismethyl ketone lffi. Again the now familiar shape of the methine and 78

Scheme XIV

CH3CH0H

methylene envelope in the 1H NMR spectrum (CDC13) and the absorptions a t 6 2.11 ( s , 6 H) and 1 .2 8 ( s , 6 H) along with an infrared carbonyl band a t 1700 cm-1 substantiated structure 1 3 3 • Photochemical cycliza- tio n o f 133 might be expected to give the attractive trisecododecahedrane 13k. Appropriate loss of water followed by ozonolysis would y ie ld I 35 . An additional photolysis would quickly generate secododecahedrane 136 (Scheme XIV).

Although the literature abounds with examples of ketone Norrish II processes, the Norrish I process, i.e. radical disproportionation of the 79

73 R-COB' bond, is also a realistic possibility. When put to the test, the latter option proved to be all too favored. Irradiation of dike tone lpp produced no substance identifiable as diol lph. Instead only products identified by mass spectrometry as possible Norrish I products were obtained. Apparently steric congestion about the carbonyl groups again provides a significant driving force for deacetylation to occur.

V-3 AN UNUSUAL DECAQUINANE

Twice the Norrish I photochemical reaction has been observed to occur in these systems instead of the desired insertion reaction. It was becoming obvious that for the desired cyclization to occur the compound would necessarily require features locking the carbonyl groups in place. This could be best accomplished by linking the carbonyl moieties together to form an a-dicarbonyl system. Such substances are known to undergo analogous photochemical cyclizations as mentioned pre viously. Acyloin cyclization of 128 followed by an oxidative workup would be expected to yield diketone 13X - Irradiation of 137 would yield the highly desirable trisecododecahedrane 138. Oxidative cleavage of the glycolic bond should be easily accomplished at this stage giving the very attractive diketone 1^5 (Scheme XV).

Esters have been shown to undergo clean acyloin cyclizations with 82 sodium in liq u id ammonia in e x c e lle n t y ie ld , but when 128 proved inert to these conditions, recourse was made to the more reactive po tassium in liquid ammonia. Instead of the acyloin, however, only 8o

Scheme XV

C O 0 CH3 ' I.N o,M e3SiCI toluene '*«0 r • ^ 7 7 2. FeClj, HCI, ether

138

K.NH 3 Pb( 0 Ac) 4 ; py

139

diacid l ffi was obtained. This unusual cleavage provided an indication of the steric congestion about the ester moieties. Ebr a successful acyloin condensation to occur, the ester carbonyls must orient them selves in a parallel geometry. Apparently, the 6 -hydrogens in 128 supply sufficient through-space steric interactions to the ester groups that the coupling reaction is prevented from occurring. Since conforma tional flexibility was expected to increase with thermal energy, recourse was made to sodium-potassium alloy in toluene with trimethylchlorosilane .81

83 at the reflux temperature, these conditions cleanly converted 128 into the desired bistrim ethylsilyl enol ether, oxidation of which -with ferric chloride in ether yielded the desired a-diketone 13J ( 63 $ ). T his yellow solid exhibited a characteristic IR absorption at 1690 cm-1 and

UV maxima (isooctane) at 260, 310, and 4^0 nm characteristic of an a- diketone. Conclusive proof was obtained by x-ray crystal structure 84 analysis. The shape of the molecule, which is clearly £ 2 symmetric and p ro je c ts an 0=C-C=0 d ih e d ra l angle o f 19. 7°» i s given in F igure I I .

On this basis, 1$J was expected to be very responsive to photoexcita- ta. tx . . o n . 833,85 ’

Irradiation of 157 in a benzene-acetone-tert-butyl alcohol (3:1:1) solution (a wide variety of solvents actually yielded the same product) with a 450W Hanovia lamp afforded a highly crystalline diol ikO (13$).

The chemical shifts of key proton and carbon resonances and the simpli fied l3C NMR spectrum (ll lines) clearly indicated that £2 axial symmetry had been maintained. In addition, the vicinal nature of the hydroxyl groups was confirmed by oxidative cleavage to the symmetrical diketone 86 l4l with lead tetraacetate in pyridine.

c h 3 OH

• 4

141 F igure 2

Three-Dimensional Features of a-Diketone as

Determined by X-ray Analysis The structure of this diketone (thought at that time to be 155) was questioned -when H/D exchange could not be effected at the a-carbonyl positions despite forcing conditions. Even more astonishingly, l4l ~was reconverted to diol ljj-Q (91$ yield) by a unique intramolecular pinacol reduction -with lithium diisopropylamide (LDA) in tetrahydrofuran at

25°C. The reductive capability of LDA has been previously demonstra ted, but no examples of an intramolecular pinacol reaction had been re p o rte d . 87 While diketone 15!? was expected to be capable of under

going pinacolization, the relative ease in which l4 l was reduced placed

doubt on the assigned structure. In addition, the off-resonance de coupled l3C NMR spectrum revealed the presence of three quaternary

carbons (only two lines are expected for 1 38). These combined findings led to the assignment of ljf _0 as the structure of the diol photoproduct

and of l4l as the corresponding diketone. The new assignments subse

quently were proved correct by x-ray crystal structure analysis of 84 diol l40 (Figure III).

The photochemical transformation of 157 into diol lft-0 is most un usual. The initial step in the rearrangement is undoubtedly abstraction o f th e 6 -hydrogen by the oxygen of the excited carbonyl group. Pre

sumably because of the long lifetim e of the a-dicarbonyl radical, re

combination does not immediately occur. Rather, the secondary alkyl radical is sufficiently long-lived that a 1 , 5 -hydrogen shift to forming a more stable tertiary radical can occur. Subsequent radical recombi nation gives rise to 1^2 which could also be isolated from the photolysis mixture in kOfo yield (Scheme XVI). Repetition of the above abstraction, migration, and recombination sequence with 1^2 gives diol 1^0. 8h

F igure 3

Three-Dimensional Features of Decaquinane Diol l40

as Determined by X-ray Analysis 85

Scheme XVI

/ OH CH

fl*

ch 3 CH3

140 142

Although photoexcitation of l p j led to some novel chemistry, the elusive dodecahedrane was no closer to being synthesized. However, the conversion of diketone 13J to diol lAO had convincingly demonstrated the potential of carbonyl photochemistry as a convenient C-C bond form ing reaction to an unactivated methylene moiety. With knowledge of the geometrical requirements for excited-state intramolecular hydrogen abstraction-recombination reactions and the structural dimensions of the dodecahedrane intermediates (x-ray data), an appropriate carbonyl containing compound was sought. 86

However, there existed no suitable carbonyl compound in all existing dodecahedrane chemistry which would permit utilization of this new tool.

It has been said that every keyring contains at least one key fitting no lock. The dodecahedrane keyring certainly contained many such keys.

Somehow the latest key on the ring seemed different; it could not be fo rg o tte n . CHAPTER VI

TRISECODODECAHEDRANE DERIVATIVES

VI-1 INTRODUCTION

Many examples of open and closed lactone, lactol, chloroether, methylacetal and simple ether derivatives have been discussed in the previous chapters. In each of these cases, the one paramount problem not effectively solved had been ether ring cleavage. Of all the deri vatives known to date, only two examples of such cleavage had been ob served, viz. formation of diene diester 4l and diehloro diester j*2. The

CH30 ^ 0

reluctance of this ether linkage to undergo ring opening at various stages of development made it clear that efforts must be concentrated more on the two molecules in which successful ether ring cleavage had been effected.

Unfortunately, jjl was obtained only as a mixture of double bond isomers, thus reducing the yield of the desired C 2 symmetric isomer to

8 7 88 a minor fraction of the overall yield for the reaction. This would obviously be disadvantageous where later chemistry was concerned. At tention, therefore, was focused on dichloro diester 42.

V I-2 METHHiAIION PRODUCTS FROM DISSOLVING METAL REDUCTION OF DICHLORO

DIESTER 42

On structural features alone, b2_ seemed ideal for reductive cycli zation between the chlorine moieties and the ester groups. Indeed, a few examples of metal promoted tu-halo ketone cyclizations have been 33 reported. Although no cu-halo ester cyclizations were known, it was hoped the proximity of the two interacting groups would prove con ducive to such chemistry. Disappointingly, Wyvratt found that carbanionic centers at the originally chlorinated carbon atoms in 42 led most frequently to simple reduction and formation of diester 120 as the only recognizable product. Techniques used to generate these

4 2 120

carbanionic centers had included powdered magnesium and sterically hindered alkyllithiums. 88 These results clearly indicated such an approach was futile. 89

Only after several years had elapsed was such a process to he

examined again. Confident that reduction of the chlorine atoms would

lead only to frustrating results, a method of reduction that would

initially attack the ester groups was viewed as an alternative approach.

The most convenient procedure expected to accomplish this appeared to

be the dissolving metal reduction of 42 in liquid ammonia. Such con

ditions were expected to generate the radical anion lhp_ (Scheme XVII).

Radical anion 143 was further expected to undergo one of two possible reactions. The first of these, viewed as less likely, was center bond cleavage. For this process to occur, the ester groups necessarily need be aligned perpendicularly to the central bond for proper orbital interaction. The steric demands (through-space interaction of 6 - hydrogens and the ester groups) encountered during this process might be expected to cause a reduction in the rate of center bond cleavage.

On the other hand, the second possible interaction does not require alignment of the ester groups and furthermore would proceed with the initially formed radical anion in the sterically most favored position.

This process was expected to be displacement of chloride ion to yield the intermediate 144.

Further reduction of the ketone carbonyl in 144 would be expected to cleave the center bond and deliver ultimately, after cleavage of the second chlorine and protonation by solvent, the bisenolate l4j?_. Al ternatively, initial reduction of the ester group in l44 could yield two products resulting either from center bond cleavage to give 145

or from chlorine displacement followed by center bond cleavage to give Scheme XVII 91

bisenolate 146. It was also felt that the ratio of 145 to 146 would

depend in large part upon the particular stage in the reduction se

quence during which the second chlorine atom underwent simple reduction-

p ro to n a tio n by th e re a c tio n medium.

In our initial investigations of this process, 42^was treated with

sodium in liquid ammonia followed by rapid addition of methyl iodide to

quench the reaction mixture. In this case, one major product, the keto

ester 147 yield), and two minor products, transannular hydroxy

ester 148 ( 2$ ) and a substance tentatively assigned the structure of

diketone l4ff (l$), "were identified (Scheme XVII). Presumably, 14-7 re

sults from in itial quenching of bisenolate 145 with two molecules of

methyl iodide followed by a-methylation of dimethyl keto ester 150

during workup. On the other hand, if only one methyl iodide molecule

can reach 145 before transannular Dieckmann reaction occurs, then hydroxy

ester 148 results. Diketone l4j? apparently results from the less likely

second chloride displacement reaction.

Obviously, the overall reduction comprises a delicate balance of

several competing reactions. Ibr example, when lithium was sub

stituted for sodium in later investigations and the reaction was worked

up immediately after the ammonia had evaporated, dimethyl keto ester

150 could be isolated as the major product.

An unfortunate aspect of the overall reaction is the loss of 2 of

dichloro diester 42 as the transannular product 148. Hydroxy ester 148,

although a novel heptaquinane, is of no further synthetic use as long as the transannular bond is present. Hydroxy ester 148 exhibits a 92 1 characteristic hydroxyl singlet in the H NMR spectrum (CDC13) "which disappeared with a D 2O shake, and shows a strong infrared hydroxyl band

( 3^80) and remarkably low ester carbonyl (1690 cm-1) stretch (due to the large intramolecular hydrogen bonding component). At this point, the question of the reversibility of the transannular process arose. In ini tial attempts to accomplish this feat, l48 was treated with sodium hy dride in the presence of methyl iodide, the idea being to trap the re verse Dieckmann product. Unfortunately, only the product of O-alkyla- tio n ( 151 ) was formed.

CH3O CH3°>

148 151

DIBAL-H

CH2 0H CH2 OTs

t-BuOK

t-BuOH

ch3 ch3 ch3

J§2 153 J54

Seduction of the ester group in 148 proceeded smoothly with DIBAL-H to give diol 132 . Treatment of 132 with £-toluenesulfonyl chloride in 93

pyridine yielded tosylabe 133. Grob fragmentation of 153 with potassium

te rt-butoxide provided the enone 154, which was characterized by an exo-

cyclic methylene pattern in the 1H IflMR spectrum and an infrared carbonyl

stretch at 1730 cm"1 (characteristic of a cyclopentanone carbonyl

group ) . 90 The reversibility of the transannular process had been

demonstrated. Further experiments designed to functionalize the dou

ble bond in 154 are in progress.

More importantly, attention was focused on keto esters l4j and

150. Both have lost symmetry and the l3C NMR spectra of these two molecules were useful only in confirming the existence of the ketone

and ester carbons. Infrared carbonyl bands at 1730 cm "1 demonstrated that a new cyclopentanone ring had been formed.

Although later investigations demonstrated that dimethyl keto

e s te r 150 could be obtained as a major product from the lithium in

ammonia red u c tio n o f 42, many o f th e e a rly experim ents on tris e c o d o -

decahedranes were performed on the trimethyl series of molecules be

ginning with l4j. For this reason, the chemistry of 147 merits initial

discussion. Thus, with tetrasecododecahedrane 147 in hand, the next task was to install yet another C-C bond. At this point, we opted,

literally, to shine light on the problem.

V I-5 PHOTOCHEMISTRY REVISITED

In Chapter V, the synthetic u tility of carbonyl photochemistry as a C-C bond forming tool was discussed in some detail. The ideal mole cule with which to demonstrate the effectiveness of this tool, i. e. 14?, had now "been obtained. The remaining question, -was whether the radical

rearrangement observed for the a-diketone 157 "would occur in the case of

l4j. Such proved not to be the case. Photoexcitation of the ketone

carbonyl groups in l4j through pyrex in a solvent system comprised of

2($ tert-butyl alcohol in benzene yielded trisecododecahedrane Ipp in

> 89$ yield. Usually the presence of several drops of triethylamine

in the photolysis mixture prevented spontaneous dehydration of the

newly formed tertiary alcohol. Hydroxy ester Ipjj underwent facile

(TsOH) 0 *6**

CH3 CH5

157 156

acid catalyzed dehydration to give the ene ester lp6 in excellent yield.

Ene e s te r Ip6 proved inert to catalytic hydrogenation even at 1^00 psi of hydrogen, but was cleanly reduced with diimide to give trimethyl 95

91 ester 137 in > 9$ yield. At this point, any doubts about the struc tu re o f 197 were dispelled when an x-ray crystal structure determina- 92 tion confirmed our proposal for 157, (Figure IV).

The x-ray crystal structure confirmation of 1^7 was certainly welcome news. In molecules which had lost symmetry, clear-cut identi fication of new substances had become difficult. The entire HMR spectrum of each new molecule, although characteristic, consisted of a broad aliphatic envelope between 6 3-5 and 0. 8. In addition, the newly obtained substance (l^j) had just been carried through four steps without the benefit of a symmetry element to aid in structural assign ment. The confirmatory x-ray data provided a new base from which sub sequent molecules could be accurately assigned individual structures.

Close examination of Figure IV reveals that considerable through space non-bonding interactions are experienced in 137. The opposing methylene group carbon atoms are only 3. 3 1. apart. Likewise the dis tance between methylene group carbons and the ester carbonyl carbon is on ly ca 3. 2 I. In other words, the yet uncyclized rings are pushing strongly against each other. This steric repulsion provides a sig nificant driving force for several unanticipated reactions involving trisecododecahedranes.

V I-4 TRMETHYL TRISECODODECAHEDRANE DERIVATIVES

It is quite obvious that the opposed methylene groups in 1J?7, where a bond is ultimately required, are unfunctionalized. It was felt that a carbonyl group at either of these positions would lead to Figure 4

Three-Dimensional Features of Trisecododecahedrane

as Determined by X-ray Analysis a quick synthesis of dodecahedrane by means of additional photochemis try. In an effort to correct this situation, epoxide 1^8 -was prepared.

CH3O

■CH' MCPBA CHpClg

157

While proving inert to alkaline epoxide ring opening procedures, epoxide 158 -was opened readily ■with boron trifluoride in benzene to

K BF3 -Et2Q PCC CHgClg C6H6 HO >.4 R.T. R.T. CH3 160 MCPBA, rPCC c h 2 ci2 c h 2ci2 98

give allylic alcohol ljjffi in 50f> y ie ld . 93’94 The tertiary alcohol un

fortunately did not respond in a prototypical fashion to chromium based 95 oxidants. Instead of delivering the 1,5-transposed enone, 159^re

acted •with such reagents to give epoxy ketone l 6 o. Although l60 con

tained an additional epoxide group, one of the methylene groups had

been successfully functionalized. While oxidations of this type have

been reported, there existed no conclusive evidence that l 60 was indeed 95 . __ the correct structure and not an isomer thereof. While the NMR

spectrum (CDC13) of l60 clearly showed ketone (217-92), ester ( 176 . 66 )

and epoxide (84.84 and 84.11 ppm) carbons and the infrared spectrum

revealed two carbonyl absorptions at 1732 and 1718 cm-1, the absolute position of the ketone group could not be established by spectroscopic methods.

To provide confirmation of structure l60, allylic alcohol lj?ft •was

epoxidized -with m-chloroperbenzoic acid and the resulting epoxy alcohol

16 1 -was treated with boron trifluoride etherate in benzene. An interest ing and unusual epoxy alcphol-epoxy alcohol rearrangement resulted to

a ffo rd 162 . The driving force for this reaction has not been posi

tively established. Apparently the epoxide ring in rearranged epoxy

alco h o l 162 aids in opening the cavity, thus lessening non-bonded

steric interactions between opposing methylene hydrogens to a greater

degree than that present in epoxy alcohol l 6 l .

Jones oxidation of either l 6 l (with concurrent rearrangement) or

162 led directly to epoxy ether 160 as anticipated. 99

Unfortunately, l60 contained an extra epoxide ring that did not

fit into the synthetic strategy. Nevertheless, deoxygenation of l60

■was expected to give enone l 6p. Reduction of the a, P-unsaturated car

bonyl system would give l 6ji, which when follow ed by a C laisen condensa tion might be expected to give diketone l 6jj. A double-barreled photoly

sis would then produce dodecahedrane diol 1 66 (Scheme XVIII).

Scheme XVIII

OCH; ch § y i

CHj

164

H0<

CH:

166

Recent reports of epoxide deoxygenations were quite encouraging.

But when l60 was heated along with zinc-copper couple in refluxing ethanol, only a low yield of a substance with properties resembling 100

9 *7 those expected for 16 $ was obtained. Increased tenperature had a deleterious effect leading to isolation of an unidentified substance that was isomeric with l60 . 9 8 Epoxy keto ester l60 also proved inert to the cobalt octacarbonyl deoxygenating procedure of Dowd, and like wise was unreactive in in itial investigations with tungsten(lll) and

(17). " ,1 0 0

Despite the presence of the unwanted epoxide moiety, a Claisen con densation analogous to that proposed for 16k would still give the de sirable diketone 167 . Unfortunately, 160 could not be induced to

167

cyclize under a variety of basic conditions. Instead, complex mixtures were obtained.

Recourse was then made to the more reactive and sterically less demanding aldehyde group. Epoxy alcohol 1^2 -was reduced with diisobutylaluminum hydride to give epoxy diol l 68 . Pyridinium chlorochromate oxidized 168 to the corresponding keto aldehyde l 6 ff. When t h i s sub stance was treated with potassium tert-butoxide, the desired aldol condensation occurred cleanly. However, instead of delivering the de sired f3-hydroxy ketone, the cyclization was accompanied by loss of 101

•water and formation of disecododecahedrane 1J0. Epoxy enone 1J0 was

characterized by a doublet in the NMR spectrum (CDCI3 ) a t 6 6.2b

CH3* CH2OH HO1 ho * a \ | CH toluene

162

|c h 2 c i2

CHj CHO

t-BuOK t-BuOH

(J = 3 Hz, 1H), typical of P-hydrogens in a,P-unsaturated carbonyl sys tems. Additional structural confirmation was obtained through examina tion of the infrared spectrum of lJO which showed an intense carbonyl

stretch at 1728 cm"1 and an olefinic stretch at 1603 cm-1 .

The loss of water to give 170 was unfortunate. Without the P- hydroxyl group, oxidation to the 1 , 3-dicarbonyl system could not be performed, thus ruling out the double-barreled photolysis that would have led to the dodecahedrane nucleus. Because of this, the low yield obtained on several steps, and the difficulty expected in later 102 processing of the.epoxide moiety, further examination of this series of molecules was, perhaps prematurely, discontinued.

In lieu of the predescribed route, the sequence of reactions that would allow a more rapid installation of the remaining bonds was sought.

Conversion of the ester moiety in 157 to an aldehyde group followed by photoexcitation-insertion of the carbonyl group was expected to be re warding, provided that decarbonylation was not encountered to an over whelming extent.

To this end, 157 was treated with diisobutylaluminum hydride and triseco alcohol 171 was obtained quantitatively. Oxidation to alde hyde 172 was carried out, again in excellent yield, with pyridinium chloro chromat e.

ch 3 c h 2 0H

ch 3DIBAL-H toluene

Because of the lack of symmetry, trimethyl trisecododecahedrane aldehyde 172 exhibited a 21 line (2 carbons overlap) 3C NMR spectrum

(CDCI3) with the aldehyde carbon seen at 204.21 ppm. The appearance of aldehyde absorptions in the infrared (1712 cm-1) and in the XH NMR s p e c tra (6 9*92, s, 1H) contributed additional proof of aldehyde forma tion. Irradiation of aldehyde 172 was expected to give rise to a 103 combination of four possible alcohols not including decarbonylation products. Indeed, initial attempts to photolyze 172 disappointingly led only to complex mixtures.

V I-5 DIMETHYL TRISECODODECAHEDRANE DERIVATIVES

A symmetrical aldehyde analogue of 172 ■would be expected to yield only two disecododecahedrane alcohols upon irradiation, i. e. the endo and exo isomers. One such symmetrical aldehyde was easily prepared

Scheme XIX

CH3°x

(TeOH)

^6 H6 » (CHstfOH

c h 3 J 5 2 173

HN-NH,

c h 3 o h

CH*0H CH* 0CH*

PCC, PfBAL-H c h 2c i2 toluene

ch 3 ch 3 ch 3

i l l 176 175 104

from dimethyl keto ester 150 via the identical five step sequence used to convert 147 into aldehyde 172 (Scheme XIX).

Photolysis of 150 yielded the C s symmetric hydroxy ester 17Jj>.

Acid-catalyzed dehydration of Ijp gave ene ester 174. Diimide reduc tion of this substance returned the Cs symmetry and provided dimethyl 13 trisecododecahedrane ester 1J5. The simplified 15 line C NMR spectrum of 175 exhibited an ester carbon signal at 177« 40 ppm and confirmed the reassumption of planar symmetry. Piisobutylaluminum hydride re duction cleanly converted the ester group in 175 the equally sym metric alcohol 176 , oxidation of which under the usual conditions gave a quantitative yield of dimethyl trisecododecahedrane aldehyde 1JJ_.

The XH NMR (CDC13) spectrum of 1J7 contained a sharp aldehyde singlet a t 6 9*98 (IB) and two methyl singlets at 1 .2 0 ( 5 H) and 1.12 ( 3H) in addition to the usual aliphatic envelope. The infrared spectrum of

1J7 provided the additional information required to correctly assign the structure of 172 (aldehyde group absorptions at 2690 and 1718 cm-1 ).

This symmetrical aldehyde is clearly of substantial interest as a po tential dodecahedrane precursor.

V I-6 DESMETHYL TRISECODODECAHEDRANE DERIVATIVES

The dodecahedrane molecule possesses, of course, no methyl sub

stituents. Because of the difficulty expected to be encountered during demethylation of alkyl dodecahedranes, the desmethyl analogue of triseco

dodecahedrane aldehyde 177 is a highly desirable entity. 105

One of the later modifications of the reduction of dichloro diester b-2 involved quenching the reaction mixture with a proton source. In in itial investigations, only the transannular hydroxy ester 178 r e sulting from the intramolecular Dieckmann reaction could be isolated.

Mechanistically, 1?8 was presumed to arise via base-catalyzed cyclization of keto ester 179. Certainly the reaction medium contained suf ficient base to induce such a process. A change in reaction conditions to sodium sand in tetrahydrofuran had no effect on the outcome of this 101 process; ljB was obtained only in low yield.

CH,0 n CU-n « CH30 v : 0

L i , NH3

4 2 179 178

I. Li , NH3 ,,2.C ^ 50 H

180 181

This problem was nicely circumvented by maintaining a sufficient concentration of lithium metal in the reaction mixture such that 106 reduction of the ester group occurred immediately after protonation of the bisenolate anion. With the ester group reduced to the alcohol level, no transannular Dieckmann reaction could occur. This procedure was not without a drawback, however. Partial reduction of the ketone

carbonyl group also occurred, leading to a mixture of hydroxy ketone l 80 ( 31$) and diol l 8l ( 26 $). Tbrtunately, the primary hydroxyl group

in 181 could be selectively acetylated with acetic anhydride in pyridine to give acetal 182. Oxidation of 182 with pyridinium chlorochromate gave ketone l8 p which could be hydrolyzed with potassium hydroxide to return the desired l80. This procedure increased the overall yield o f l 80 significantly.

CH3 COO

GCH3C0)2O

i £ l I&2 PCC CHgClg

CH3 COO

180 103 107

Hydroxy ketone lj30 was converted to the trisecododecahedrane diol l84 through the now familiar photoinduced carbonyl abstraction- recombination procedure (Scheme XX). As in the methylated cases, diol l84 underwent clean acid-catalyzed dehydration to unsaturated alcohol

Scheme XX

h*,CcH6 - (TsOH) tart-BuOH

h2n n h2

CHO

182 186

185 , which was reduced with diimide to give hydroxy trisecododecahedrane

186 . The beautifully crystalline 186 sported a simple 12 line l3C NMR spectrum consistent with the proposed Cs symmetric structure.

Now, however, the sim ilarity between methylated and unmethylated analogues ended. Pyridinium chlorochromate oxidation of 186 did not provide the expected aldehyde l 8j. Instead a mixture of ene aldehyde io 8 j-88 and olefin 189 was obtained. Both of these unforeseen products apparently result because of the steric crowding around the periphery of the central cavity. This crowding effect, which tends to force the hydroxyl groups outward from the cavity is relieved in the formation of anc* In the methylated cases, the a-position is blocked,

IfiS 188 189

thus preventing these strain-relieving processes from occurring. This problem has not yet been adequately resolved, and the action of a variety of oxidizing agents on 186 is being actively investigated.

Although the symmetrical desmethyl trisecododecahedrane alde hyde 187 could not be obtained, the dimethyl aldehyde 177 bad been successfully synthesized. Trimethyl aldehyde 172 was also in hand.

With high expectations, we proceeded. CHAPTER V II

SECODODECAHEDRANE

V II-1 INTRODUCTION

There are many examples of successful aldehyde Norrish II abstrac- 74,102 tion-recombination processes in the literature. Unfortunately, this earlier -work and our findings in Chapter V indicate a strong preference for photodecarbonylation in cases -where the radical formed by loss of CO is particularly stable. As concerns dimethyl dialdehyde

130, ho-wever, there -were t-wo such groups. This feature -was expected,

of course, to cut already low yields in half. In addition, the two aldehyde groups in I 30 were capable of mutual interaction. While the consequences of such an interaction remains unknown, the potential for problems attributable to this factor seems quite real.

In trisecoaldehydes 172 and 177, only one aldehyde group is present.

There were also many variables such as solvent, wavelength, and tempera ture which required investigation. 109 110

V II-2 DIMETHYLSECODODECAHEDRME l6

Of the two aldehydes, 1JT "would be expected to yield the simplest photolysis mixture because of its symmetry. Both endo and exo isomers of the alcoholic product were expected as well as products arising from decarbonylation. Aldehyde 172, on the other hand, was expected to yield four alcoholic products. Two would depend upon which side of the molecule experienced free radical insertion; the endo and exo iso mers of each would bring the total to four. In addition, if decar bonylation proceeded through a process that involved one or the other side of the molecule, another set of isomeric products would result.

In itial photochemical experiments were performed on milligram quantities of both 1_J2_ and 177 and were monitored by thin layer chro matography. Decarbonylation clearly accounted for the bulk of the re action mixture, and this product was observed as a non-polar spot which moved slightly behind the solvent front. Such experiments indicated that the solvent system chosen for the reaction had little effect on its outcome. Likewise, the wavelength of the exciting lamp appeared to have no effect on the reaction. Finally, the old standby solvent system of 20$ t'ert-butanol in benzene was chosen for the preparative scale reaction. Irradiation of 177 through pyrex at 25°C in this solvent mixture indeed gave the expected endo and exo isomers of al cohol 190, but in only 1C$ yield. The remainder of the isolated ma terial was the result of decarbonylation and was not further identified.

A 10$ yield clearly presents problems when further chemistry is to be conducted. There was, however, one additional variable to be I l l

toluene CgHgOH -7fl*C

investigated. Although no reference had been made in the literature to a low temperature photolysis, the effect of increased temperature was 57 known to accelerate the rate of decarbonylation of aldehydes. Con versely, low temperatures might slow the rate of decarbonylation. When

177 was irradiated at -78°C in 1C$ ethanol-9C$toluene through pyrex, the desired alcohol lj?0 was obtained in 21$ yield, decarbonylation re mained the major reaction pathway.

The endo and exo isomers of 190 could be separated chromatogra- phically on silica gel. However for practical purposes, the combined isomers were directly oxidized with pyridinium chlorochrornate to give dimethyl ketone 191. Photolysis of 191 in 2C$ te rt-butanol-8C$ benzene again proceeded cleanly to return Cg symmetry and yield hydroxy secododecahedrane 192. As in the cases of the tr-iseco derivatives, 192 was dehydrated with £-toluenesulfonic acid in benzene delivering the olefin lffi. Diimide reduction of 193 gave the beautifully crystalline dimethyl secododecahedrane l6._

Secododecahedrane 16 is a unique high melting (235-240°C, subl.) substance possessing a C 2v symmetry element. As expected, the NMR 112

ch 3 c h 3

191 192 (T*OH)

h 2 n n h 2

h 2 o 2

194

spectrum (CDC13) exhibits a broad aliphatic absorption ranging from 6 i s 3.8 to 0.7 (2CH) and a sharp methyl singlet at 1.18 ( 6H). The C NMR spectrum (CDC13) of 16 has only the 8 lines expected for symmetry

(78.40, 70.15, 68 . 16 , 60 . 08, 58.97, 52.29, 33-64, and 32.58 ppm) -with values consistent -with those expected for the assigned structure. The infrared spectrum of 1(5 reveals only aliphatic absorptions with an un usually high absorption at 3150 cm-1, assumed to be caused by the sterically compressed opposed methylene hydrogens.

Examination of models of this highly rigid molecule reveals that the opposed methylene groups must experience substantial steric repulsion 113

and undoubtedly exist in a skewed orientation. Oxidative conversion of

l 6 to dimethyl dodecahedrane l$ b would certainly be expected to be an

exothermic process based on this evidence. One might hope that an ap

propriate catalyst would facilitate such an energy releasing process.

However, perliminary efforts have yet to be successful. Nevertheless,

this problem is under active investigation.

V II-3 TRIMETHYL SECODODECAHEDRANE 202

There was yet another secododecahedrane to be made. This one,

though, was less glamorous as it contains three methyl substituents

and hence was without symmetry (Scheme XXI). Low temperature photoly

sis of aldehyde 172 gave the endo and exo isomers of alcohols 195 and

196 ( 28$ combined yield). As in the dimethyl case,these were not

separated but oxidized together to give the two isomeric ketones 197_

and 198. Preliminary investigations by NMR appear to reveal that one

of the two isomers predominates to a large degree. Again these were

not separated but were photolyzed together under the standard condi

tions to give a single hydroxy secododecahedrane 199. Acid-catalyzed

dehydration of 199 in benzene, as usual, proceeded smoothly to give two

isomeric olefins (200 and 20l). These isomers, which likewise could

not be separated, were reduced together with diimide to yield trimethyl

secododecahedrane 202 (Scheme XXI).

As the trimethyl analogue of 16 ^ 202 contained no symmetry ele ment. Not yet obtained in crystalline form, 202 was characterized on

the basis of its XH NMR spectrum (6 3.8 -0 . 5 (m, 19H)» 1.26 ( s , 3*0, n U

Scheme XXI

CH3 « 0

C6H6- !4Ei-BuOH

196

PCC. ch 2c i2

CH,

c h 3 c h 3 198 J2? (T*OH) \^6H6

+ H302

CH3 2 0 0 201 115 and 1.18 (s, 6 H)). Although time and material did not permit further characterization of 202, the close analogy between the reactions lead in g up to 202 and 16 permits the structural assignment of 202 to be made w ith confidence.

V II-4 OUTLOOK FOR THE FUTURE

There exists, obviously, a wide variety of different methods for the installation of the final bond. It is impractical to discuss all the possibilities already conceived. Surely the ideas yet unconceived will fill a future volume. So we must be restricted to a few of the more promising and interesting possibilities.

The olefin l^p_ is isomeric with the dodecahedrane lgft. There have been numerous methods for olefin migration reported in the literature

103 which utilize transition metal catalysts. These methods as well as direct acid catalysis could conceivably migrate the double bond and perhaps form the final product by an appropriate protonation-deprotona- tion sequence (Scheme XXII). Initial investigations with such catalysts as rhodium(lll), palladium on carbon, and mineral acid unfortunately have not yet met with success. Such chemistry remains under active in vestigation.

A procedure with a much lower hit-or-miss air about it involves functionalization of the position beta to the carbonyl group in 191.

Eaton and coworkers have demonstrated that in peristylane ketones this beta position can be readily functional!zed via organoselenium 28b,X04' chemistry in high yield. Such a procedure \Haen applied to Iff! 116

Scheme XXII

J 2 3 i f

could produce the 3-acetoxy derivative 20p. The usual photolysis, dehydration, and reduction operations -would provide acetate 20k.

H ydrolysis o f 20fe follow ed by o x id a tio n and p h o to ly sis -would give hydroxy dodecahedrane 205 (Scheme XXIII).

There are other possible methods for functionalizing the P-keto position in 1£1 , such as bromination-dehydrobromination, chloranil, 105,106 dichlorodicyanoquinone and selenium dioxide. Analogous 117

Scheme XXIII

CHgCOO,

I. PhStCI 'zYoxf 3.N002CCH3

I 2 . - H 2 0 3. H N -N H

L HO 2. PCC 3. hv

c h 3

£ 0 4

application of these procedures to the keto ester 1J50 could also lead to the appropriate functionality with which to complete the synthesis.

c h 3 118

Clearly, the route developed In this thesis to sedodocecahedrane is not a dead end. Rather, many different approaches for installa tion of the final bond await investigation. Further work at the bench w ill without doubt require modifications to even the best laid of these p la n s. SUMMARY

The preceding chapters have seen the gradual progression of ideas and manpower culminate in the successful synthesis of secododecahedrane l 6 , only one bond short of dodecahedrane itself. The research project began more than eight years ago when a synthetic route to this most complex of the Platonic solids was conceived in these laboratories.

The first two chapters followed the development and progression of this idea from diester obtained from the domino Diels-Alder reaction, into the all-cis fused hexaquinane lactone 15 . Lactone 15

10 STEPS

15.

functioned as the pivotal molecule from whence three significantly dif ferent synthetic strategies evolved. Chapter II introduced the first line of synthetic assault on 15 . This procedure involved hydride re duction of the lactone carbonyl groups to give bislactol 38. Unfor tunately, many of its derivatives were plagued by transannular inter actions which led to many products which contained an unwanted unsymmetrical C-C bond between the juxtaposed labile functional groups.

119 120

This work did, however, ultimately yield dioxatrisecododecahedrane 17? 53 the highest ordered heterocyclic polyquinane yet known.

The second of the synthetic strategies involved derivatives formed by central bond cleavage within lactone 15 . Although free from the type of transannular interactions seen in Chapter III, the molecules discussed in Chapter IV found a different way to experience trans annular behavior. Instead of the migration of electrons to form new

C-C bonds, atoms were now transposed. Thus, lactol §7; when treated with acid, yielded ether lactone 110 in which a hydride shift had occurred across the cavity. This reaction constitutes a fascinating example of an intramolecular oxidation-reduction. Under thermal conditions, la c t o l 9£ transferred an ethereal oxygen atom to yield yet another transannular substance, the acetal aldehyde 11^. Unfortunately, these undesirable side reactions could not be overcome and it became necessary to redirect our interests to the two lactone ring cleavage reactions that could be successfully performed on lactone 1£.

The lactone rings in 15^could be cleaved with Meerwein's reagent to give diene diester 4l. In Chapter V the synthetic utility of 121

[ h c Q t 15 CH30H

c h 3

180 C

CH3* CHO

carbonyl photochemistry was demonstrated when 4l was converted into a- diketone 1 37 and this product was irradiated. Although the desired

IS 41

4 STEPS

c h 3

140 122 photoproduct -was not observed, the potential of such a method -was es tablished when l^J, was converted by photoexcitation to diol l40.

In Chapter VI, the dichloro diester 42, also obtained from the bislactone 1^ was successfully reduced with lithium in ammonia. De pending on the conditions, three tetraseco dodecahedrane ketones could be obtained. The lesson learned in Chapter V paid off hand somely when another bond was installed photochemically in each of these three ketones yielding trisecododecahedranes. Shown are keto ester 150

c h , o CHaO^o

1.Li ,NH3 15 2. CH3I

CHj m

122 122 123 and hydroxy ester l j p as representative examples of this process. In anticipation of future photochemical success, 173 was converted to aldehyde 177-

Our expectations and efforts were rewarded in the final Chapter

(V II) when aldehyde 177 was converted into dimethyl secododecahedrane

16 . Eor those interested in such things, the synthesis of 16 re q u ire d

23 chemical transformations and was obtained in an overall yield of

0. 78ft> (an average of 8l$ yield per step) from the in itial domino Diels-

Alder product.

Work cannot stop here, however. With only one bond remaining, surely the ultimate reward, dodecahedrane (4), is not far down the road.

A EXPERIMENTAL SECTION

Melting points are. uncorrected. Proton magnetic spectra were ob ta in e d w ith Bruker HX-90 and V arian A-60A, HA-100, T-60, EM- 360 and

EM-390 spectrometers; apparent splittings are given in all cases.

Carbon spectra were recorded with Bruker "WP-80 and HX-9° spectrometers.

Infrared spectra were determined on a Perkin-EImer Model 467 instrument.

Mass spectra were recorded on an AEI-MS9 spectrometer at an ionization potential of 7° eV. Elemental analyses were performed by the Scandi navian M icroanalytical Laboratory, Herlev, Denmark.

Decahydro-3, 6 -bis[3-(trim ethylsilyl)allyl]-lH- 6 ,4,5,7b-(epoxy- ethanylylidyne)cyclopenta[ 2 , 3]pentaleno[ 6 , 1-b c ]fu ra n - 1 , 9-dione ( 2g ).

A solution of allyltrim ethylsilyl

anion was prepared by adding sec- SiMe, I 3 CH =CH CH=CH butyllithium in cyclohexane ( 6 .3 8

SiMe mmol) to dry tetrahydrofuran ( 3° ml)

with stirring under nitrogen at -78°C.

Tetramethylethylenediamine (740 mg, 6 . 38 mmol) and allyltrim ethylsilane

(73° mg, 6 .3 8 mmol) were introduced and the solution was kept at -20°C for 3° min. After cooling to -4o°C, 500 mg (l. 6 U5 mmol) o f 2k was added.

Stirring was maintained for 1 hr and the reaction mixture was kept at

-20°C for 1 hr. Following the addition of solid ammonium chloride, the

124 125 solution was allowed to warm to 0^ poured onto water (3 0 ml), and ex tracted with ether (3 x 30 ml). The combined organic extracts were washed with water (2x) and brine prior to drying. Evaporation of the solvent left 880 mg of a yellow oil which was subjected to preparative layer chromatography on silica gel (elution with 2($ ether in hexane).

There was isolated 200 mg ( 23$) of 28 and 80 mg (lC$) of 2g. Recrystal lization of the bislactone from benzene-hexane afforded white needles, mp 176-1T7°C;v^ 2955, 1750, 1615, 1332, and 840 cm-1; MR ( 6 , CDCI3)

5.95 (d of t, J = 19 and 6 Hz, 2H), 5-71 (d, J = 19 Hz, 2H), 3.1 -2 .2

(m, 10H), 2.25 (d, J = 19 Hz, 2H), 1.7 (d of d, J = 19 and 3-4 Hz, 2H), and 0.15 (s, 18H); l3 C NMR (ppm, CDC13) 171. 03, 139-17, 137-70, 89. 67 ,

65 . 02, 59- 77, 54. 90, 49. 28, 4 5 .1 1 , 33- 79, and - 1. 23; m/e calcd 468. 2150 , obs 468,2164.

Anal. Calcd for CaeHaeO^Sia: C, 66 .6 2 ; H, 7* 74. Ibund: C, 66 .6 0 ;

H, 7-84.

Dimethyl 0ctahydro-l, 5 -dihydroxy- 2 ,5-bis[3~(trim ethylsilyl)allyl]-

3,4,7-metheno-lH-cyclopenta[a]pentalene-7,8(7aH)-dicarboxylate ( 28).

Method A.

A solution of sec-butyllithium in COOCH3 HQ tetrahydrofuran was prepared from

CH = CH 2. 64 mol of sec-butyllithium dis

SiMe, solved in cyclohexane, 5 nil o f

cooch 3 tetrahydrofuran, and 310 mg (2 .6 4 mmol) of tetramethylethylenediamine at -78^ under nitrogen. To this mixture was added allyltrim ethylsilane (301 mg, 2.64 mmol) and th e 126 solution was warmed to -20^ with stirring for JO min. After cooling to

-45°C, 200 mg (0.66 mmol) of 24_was introduced, stirring was maintained for 1 hr, solid ammonium chloride (l g) was added, and the solution was allowed to warm to 0°C. The solution was poured into water (10 ml) and extracted with ether (3 x 10 ml). The combined organic extracts were washed with water (2x) and brine before drying. Solvent removal under reduced pressure gave 360 mg of yellow oil which was subjected to pre parative layer chromatography on silica gel (elution with JOjo e th e r- TTRy* hexane). There was obtained 130 mg (29$) of 28^ mp 108-109°C; vmax

5507, 2955, 175 O, 1615 , 855 , and 850 cm"1; XH NMR ( 6 , CDCI3) 6 .1 0

(d of t, J = 19 and 6 Hz, 2H), 5-70 (d, J = 19 Hz, 2H), 3-73 (s, 6 h ),

2. 8-1. 5 (series of m, l 6 H), and 0.1 (s, l 8H); l3C NMR (ppm, CDCI3)

173. 85 , 142.00, 134.53, 77.3^, 66 . 85 , 59 . 18, 58 . 85 , 52 . 04, 49.91,

48.26, 37.43, and -I. 16 .

Anal. Calcd for C 2 aH4406 S i2: C, 63 . 12; H, 8. 31. Ibund: C, 62.73;

H, 8.45.

Method B. A so lu tio n o f 29_ (100 mg, 0.21 mmol) in dry m ethanol

(4 ml) under nitrogen was treated dropwise with a solution of sodium methoxide in methanol until the pH was approximately 10. After being s tir r e d fo r 4 h r a t 25 ^3^116 reaction mixture was poured into water

(10 ml) and extracted with ether (3 x 10 ml). The combined organic layers were washed with water ( 2x) and brine, 'dried, and evaporated to give 105 mg (94$) of pure 28. 127

Oxidative Cyclization of 28. Ptormation of Bisspirolactone 2 6 .

To a solution of 28 (100 mg, 0 .1 8 8

mmol) in acetic acid (3 ml) under

nitrogen -was added 286 mg ( l . 50

mmol) of peracetic acid and 6

C00CH3 drops of sulfuric acid. After being stirred for 4 hr at room temperature, the acidic solution -was

neutralized -with saturated sodium bicarbonate solution, extracted

■with dichloromethane (3 x 10 ml), 'washed with sodium thiosulfate solu

tion, water, and brine, then dried. Removal of solvent under reduced pressure left 50 mg of a clear residue. Trituration with ether afforded

19 mg ( 21*86) o f 26 .

Dimethyl Octahydro-1,5-dioxo-5H,8H-3a,9a: 4b,7a-diepoxy-4, 8,9 - metheno-lH-cyclopenta[l,2-a:4,3-af]dipentalene-4,ll(4aH)-dicarboxylate

( a ) '

COOCH-a A solution of 2£ (100 mg, 0.263 0. mmol) in 9% eth an o l (5 ml) was

treated with a solution of sodium

carbonate (32 mg, 0.302 mmol) and

COQCH3 hydrogen peroxide (0.13 ml, 1.5

mmol) in water (l ml). The reaction mixture was stirred at 50°C fo r 10 min prior to dilution with water (10 ml). The precipitated solid was

separated by filtration and recrystallized from ethyl acetate-dichloro- ...... KBr methane. There was obtained 82 mg (7Qp) of ^1? mp 304-305 j vmax -^50

and 1320 cm"1; ^ NMR (6 , CDC13) 3-60 ( s , 6 h ) , 3.25-3-0 (m, 4H), and 128

2.7-2.5 (m, 10H); l3C NMR (ppm, CDC13) 205.48, 170.04, 67.50, 62.51, ’

62 . 48, 56 . 82, 56 . 51 , 51.76, 45.92, 58 .4 6 , and 21. 61 .

Anal. Calcd for C 22HacPaS C, 64.08; H, 5*84. Ibund: C, 65 . 9^»

H, 4 .9 k

Dimethyl 1,2,5,5b,4a,5, 6 , 7 , 8, 8a , 8b,9-Dodecahydro-l,5-dihydroxy-

2,6-dioxo-4,8,9-metheno-4H-cyclopenta[l,2-a:4,5-a']dipentalene-4,10- dicarboxylate diacetate ($2).

Biscyclopentenone 2£ (590 mg, 1.55 COOCH* mmol) was d isso lv e d in 50 ml o f

1OCOCH3 toluene under nitrogen in a 100

ml flask equipped with a reflux

COOCH3 condenser. Lead tetraacetate

( 2 .7 6 g, 6 .2 mmol) was added and the mixture was heated at the reflux temperature for 10 hr. The mixture was then allowed to cool to 25°C and filtered. The filtrate was washed with 25 ml of saturated sodium bicarbonate solution, water, and brine prior to drying over magnesium sulfate. Removal of the solvent left a yellow o il which was chroma tographed on Florisil. Elution with chloroform gave benzyl acetate

(a byproduct of the reagents used). Elution with 2C$ ethyl acetate- chloroform gave pure product. Continued elution, followed by elution with pure ethyl acetate gave a mixture of both the symmetrical product believed to be the (a,a) isomer and the (a, 6 ) product. Repeating the chromatography with fractions enriched in the symmetrical isomer in creased the yield to 270 mg (55$) of 32. Recrystallization from ben zene or chloroform-carbon tetrachloride gave the analytically pure 129

m a te ria l, mp 212. 5-2. 3 -5°C; IR ( KEr, cm"1) 1760, 1640; *11 HMR ( 6 , CDC13)

5.20 (d of d, = 6 .6 Hz, JBX = 3.4 Hz, 2H), 3.52 (s, 6 H), 3-7-2.2

(m, 10H), 2.12 ( s , 6 h ); l3 C HMR (ppm, CDCI 3) 193- 35(s), l 8l . 9 l ( s ) ,

170. 22(b ), 169 . 92( a ) , 144.89(b), 76.34(d), 70.94(a), 62 . 81(d ), 62 . 20(d ),

58 . 99(d), 52.28(q), 33.98(t), 20.75(q); a/e 496 .

Anal. Calcd for C 26 H24O10: C, 62.90; H, 4.84. ibund: C, 62 . 70;

H, 4.85.

Dimethyl Hexadecahydro-1,5 - dihydro xy- 2, 6 - dio xo - 4 , 8,9-metheno-4H-

cyclopenta[l, 2- a : 4, 3-af]dipentalene-4, 10-dicarboxylate diacetate (34).

a,a'-Bisacetoxycyclopentenone 3j-_

CH3 COO (100 mg, 0 .2 0 mmol) was dissolved OCOCH3 in 10 ml of ethyl acetate and

0.05 g of 1C$ Pd/C catalyst was C 00C H , added. The mixture was hydrogena

ted at 40 psi for 8 hr at 25°C. The reaction mixture was filtered

through Celite and the filtrate was evaporated to give the crude 34

(100 mg, 10C$), which was recrystallized from benzene-hexane to give

pure product; mp l89-191°C; v^ y 1740, 1234 and 1118 cm 1; HMR ( 6 ,

CDCI3) 5.15 (d of d, = 6 .8 Hz, JBX = 4.6 Hz, 2H), 3 .6 3 ( s , 6 h ),

3 .6 -1 .5 (m, l4H), 2.05 (s, 6 h) ; l3 C NMR (ppm, CDC13) 212.22(b), 171.44(b),

169.74(b), 7 8 .5 3 (d ), 62 . 32( d ), 62 . 02(d), 57.17(a), 5l.83(q), 49. 58 (d ),

37. 26 (d ), 29. 7 4 ( t) , 20. 6 o (q ); m/e calcd for CaeHaaPio 500 . 1682 , obs

500 .1694. 130

Dimethyl 1 ,5-Dibromo-l,2,3, 3b,^a,5, 6 , 7 , 8, 8a , 8b,9-dodecahydro-3,7- dioxo - 4 , 8, 9-metheno - 4H- cyclop ent a[ 1,2-ja: 4 ,3-a 1 ] dipent alene-4,10-di car boxylate (j 55 ).

Biscyclopentenone 2J_ (100 mg,

C00CH 0. 263 mmol) was d isso lv e d in c a r

bon tetrachloride (18 ml) along

with N-bromosuccinimide (9 8 mg,

COOCH3 0. 552 mmol). The m ixture was heated at the reflux temperature for 20 min with concurrent irradiation from a 275W UV sunlamp. The mix ture was cooled and concentrated at reduced pressure. The residue was subjected to preparative tic on silica gel (ether elution) and 105 mg

(7*$) of crude ^5, was obtained. Recrystallization from ethyl acetate , o CDClo gave the analytically pure material, mp 204 C dec; vmax 1730, 1705, and 1618 cm-1; ^ MR ( 6 , CDC13) 5-28 (m, 2H), 4. 0-2.7 (m, 10H), and

3.55 ( s , 6 H); l3C MR (ppm, CDC13) 196.14(b), l8 l.l5 (s), 169 . 95 ( a ) ,

148.47(a), 71.43(s), 64 . 36 (d), 6l.4l(d), 58. 96 (d), 5 2 .4 0 (q ), 51 . 0l ( t ) ,

39.42(d); m/e 538.

Anal. Calcd for C 2aHi6Rr206: C, 49.10; H, 3. 37. Ibund: C, 49.10;

H, 3.49.

Dimethyl 1 ,3a, 3b, 4a, 4b, 5 ,7a, 8, 8a , 8b, 9 ,9a-Dodecahydro-l, 5-dioxo-

4,8,9-metheno-4H-cyclopenta[ 1,2-a: 4,3-a*]dipentalene-4, 10-dicar boxylate (ZD- A solution of diketo diester ^0 (50 mg, 0.1 3 mmol) in degassed aqueous dioxane (is 1, 5 ml) was treated in one portion with palladium 1 5 1

chloride (l 62 mg, 0 .91 mmol) and

pu n *0 the resultant solution was heated at the reflux temperature under a

nitrogen atmosphere for 80 hr.

The cooled reaction mixture was

concentrated ,in vacuo. diluted with water (15 nil) and extracted with dichloromethane (5 x 10 ml). The

combined organic phases were dried, filtered, and concentrated _in vacuo

to give a clear colorless oil. Preparative TLC (ethyl acetate elution)

afforded a single major and chromophoric hand (Rf = 0. 28) Recrystal

lization of this material from ethyl acetate afforded diene dione 2 L

(18.8 mg, 50$) as white crystals, mp 225-227°C (dec); \ > ^ 13 1725,

1699 cm"1; XH MMR ( 6 , CDC13) 7-^5 (d of d, J = 5-6 and 6.0 Hz, 2H),

5.95 (d of d, J = 6 . 0 and 2.0 Hz, 2H), 5-55 (s, 5H), 5-55-2.50 (br m,

10H); 13C NMR (ppm, CDC13) 207.1*3, 170.22, l 6 l . l 8, 155-65, 60.8l , 60.02,

56 . 98, 52 . 51 , 50 . 92, 4 9 . 16 , 1*6 . 75 ; n^e calcd 580 . 1260 , obs 580 . 1261 *.

Anal. Calcd for C 22H20O6 ! C, 69-1*6; H, 5- 51- Pound: C, 69 . 2l*;

H, 5- 36.

Catalytic Hydrogenation of Diene Dione Diester Reformation of

D iketo D ie ste r 50.

Diene dione diester (22.2 mg, O. 06 mmol) was dissolved in ethyl

a c e ta te (3 ml) and 1($ palladium on carbon was added. The mixture was

hydrogenated in a Parr apparatus for 16 hr and filtered. The filtrate

was concentrated in vacuo to leave a white crystalline solid. Prepara

tive TLC on silica gel (ethyl acetate elution) gave 17-3 mg (71$) o f 152 poire diketo diester £0 which was identical spectroscopically to an authentic sample.

Dimethyl Tetradecahydrodispiro[l,3-dioxolane-2,l'-[4, 8,9]-metheno-

[ top cyclopenta[1,2-a: 4, 5-a' ] dipent alene-5' ( 2 *H), 2"-[ 1,5] dioxolane] -

4 ,10-dicarboxylate ( 3§ ).

A solution of diketo diester 30

(250 mg, O.6 5 mmol) in dry benzene

^ (6 0 ml) containing freshly dis

tilled ethylene glycol (5 ml) and

£ -to lu e n e su lfo n ic a c id mono

h y d rate (6 0 mg) was heated at the reflux temperature for 63 hr under a nitrogen atmosphere in an apparatus containing a Dean-Stark trap. The cooled reaction mixture was poured into saturated sodium bicarbonate solution (100 ml) and the organic phase was separated. The aqueous phase was extracted with dichloromethane (3 x 50 ml) and the combined organic phases were washed with water (2 x 100 ml), dried (MgSO^), filtered, and concentrated in vacuo to give an oily solid. Recrystallization of this material from ethyl acetate afforded diketal 36 (250 mg, 83$) as white crystals, mp 214-

216^ (dec); 1765 cm"1; h . AMR ( 6 , CDCI3 ) 5- 80 (s, fib), 3 .6 2 ( s ,

6 H), 2.96-2.12 (br m, 12H), 1.75-1.22 (m, 6 h ); l3 C NMR (ppm, CDC13)

171. 68 , 87.93, 66.39, 64.99, 64 . 27, 62.75, 56 . 38, 50.73, 50.37, 49. 03,

39- 99, 33- 62 , 22. 39; m/e calcd 472.2097, obs 472. 2108.

Anal. Calcd for C2eH320s: C, 66 . 08; H, 6 . 83. ibund: C, 65 . 87;

H, 6.84. 155

Acid Hydrolysis of Bisketal 36 . Reformation of Diketo Diester

52 ? To a stirred solution of diketal diester 36 . (20 mg, 0. 04 mmol) in dry tetrahydrofuran (2.5 ml) -was added 25 drops of 1C$ aqueous per chloric acid solution. The resultant solution was stirred in a stoppered flask at ambient temperature for 43 hr, then poured into satutated so dium bicarbonate solution (15 ml) and extracted with methylene chloride

(3x5 ml). The combined organic phases were washed with water (l x

15 ml), dried, filtered, and concentrated in vacuo to give a clear color less oil. Preparative TI£ on silica gel (ethyl acetate elution) af forded a single major band (R^ = 0. 3) which yielded diketo diester ^0

( l4 mg, 8Qfo) identical in all respects with an authentic sample.

Hexadecahydro-1,5-diformyloxy-4,10-diiodo-4, 8,9-metheno-IH- cyclopenta[ 1 , 2- a : 4 ,3-a*]dipentalene (49).

0 Calcium carbonate (0. 80 g, 8 mmol) 11 and lead tetraacetate ( 0. 896 g,

2. 02 mmol) was refluxed in cyclo

hexane (lOO ml) with stirring for II 0 10 min. At this point, dilactol 38 (226 mg, 0. 8l mmol) together with io d in e (823 mg, 3*24 mmol) were added and the heating continued for 1 .2 5 hr with simultaneous irradiation of the reaction mixture by a sunlamp.

After cooling, the inorganic salts were separated by filtration and washed with a small amount of ether. The combined filtrates were washed with aqueous sodium thiosulfate solution, dried, and evaporated to leave 134

380 mg (8l$) of white crystalline solid. Recrystallization from

benzene-hexane gave pure 4g^as colorless plates, mp 248-249°C dec

beginning at 200°C; v1®^ 1725 and 1710 cm"1; ^ NMR ( 6 , CDCI3) 8.1 3 max (d , J = 1 Hz, 2H), 5.10 (m, 2H), and 3. 30-1. 0 (br m, 10H); l3C NMR

(ppm, CDCI 3) 161.16(d), 75.86(d), 67 . 98(d), 65.77(d), 51.80(d),

46.94(a), 45.32(d), 40.95(d), 30. 38( t ) , and 20. 07( t ) ; m/e 580 .

Anal. Calcd for C 20H22I 2O4: C, 4 l. 4 l; H, 3. 82. Pound: C, 41.48;

H, 3-88.

Hexadecahydro-1,5-dihydro xy-4,10-diiodo-4, 8,9-metheno-lH-

cyclopenta[ 1 , 2-a: 4 , 3-a/]dipentalene (£ 0).

A 170 mg (0 .2 9 3 mmol) sample o f

H kp was suspended in 10 ml o f 18$

aqueous methanol and treated with

potassium hydroxide ( 9 8 .6 mg,

I .7 6 mmol). The mixture was

stirred at room temperature for

2-3 hr until a clear solution resulted. The solvent was evaporated and

the residue was recrystallized from methanol to give 142 mg (93$)

JjO as long colorless needles, mp 179-l80°C; vmqv 3480 and jhOO cm"1; 1 1 3 TI NMR ( 6 , CDCI3) 4.33 (b r m, 2H) and 2 .9 0 -1 .2 5 (b r m, 2QH); C NMR

(ppm, CDCI3) 75-64 (d), 6 9 .2 8 (d), 66.20 (d), 51.80 (d), 49. 53 ( s ) ,

47.26 (d), 41.00 (d), 33-40 (t), and 20. 50 (t); m/e 524 (M+).

Anal. Calcd for C 18H22I 2O2: C, 41.24; H, 4.23* Pound: C, 41.23;

H, 4.17. 135

Octadecahydro-4, 8-dihydroxymethyldipentaleno[l, 2,3-cd: 1*, 2*, 3* -£h]- p en talen e 1 , 5 - d io l (%1).

To 15 ml of anhydrous liquid am

monia cooled to -T 80C "was added ho 150 mg ( 6 .5 2 mg-at) of sodium

metal followed by 2 ml of absolute

ethanol. Bislactol (100 mg,

O.3 0 5 mrrol) in dry tetrahydrofuran

(5 ml) was introduced dropwise during a 15-20 run and stirring at -33 0 was continued for 1 hr prior to the addition of solid ammonium chlo rid e . The ammonia was removed and th e re sid u e added to 75 ml d i-

chloromethane. The organic solution was washed with water (l x 25 ml)

and brine prior to drying over magnesium sulfate. The filtered solu

tion was evaporated to dryness to give 50 mg (50$) of tetraol 51 which

could be recrystallized from pyridine-dichloromethane and obtained as

small prisms, mp 268-272° dec; IR (KBr, cm-1) 3380; ^ NMR ( 6 , pyridine-

d5) 7.29 (s, 2H), 5 .53, 5*48, 5.44, and 5-38 (X part of ABX, 2H), 4. 73,

4.68, 4.59, 4.54, 4.44, 4.34, 4.31, and 4.21 (AB part of ABX and m, 6 h ),

and 2.69-1.48 (br m, l 8H); l3C NMR (ppm, pyridine-d5) 74. 96 (d), 59*72

( 2C, t and s ) , 59 . 23(d), 54.8l(s), 50 . 30(d), 48.11(d), 42. 38(d), 35*83

( t ) , and 23.0l(t); m/e_ 332 (M+, 3$)s 31^ (M -H2O, 1 0 ($ ), and 296 (M -

2H.SP, 6 $ ) .

Anal. Calcd for C 2 oHg^ 04: C, 72.26; H, 8. 49. Ibund: C, 71*96;

H, 8.45. 1 5 6

Dimethyl Hexadecahydro-1,5-dihydro-3, 7-dioxo-4, 8, 9-metheno-4H- cyclopentaC 1 , 2-a: 4, 3 -a 1 ] dipentalene-4, 10-bis( acetoxymethyl) diacetate

(52).

T e tra o l ^ 1 .(6 0 mg, 0 .1 8 mmol) was

CHjCOOv OCOCH3 dissolved in pyridine (4 ml) along

■with acetic anhydride (368 mg,

3* 6 l mmol) and 4-dimethylamino- OCOCH3 p y rid in e (5 mg). The resulting

solution was stirred for 12 hr at 25°C, poured into 3° rol 3 H hydrochloric acid, and extracted with dichloromethane (3 x 10 ml). The combined organic extracts were washed w ith 1 N hydrochloric acid (l x 10 ml) and saturated sodium bicarbonate solutions prior to drying over magnesium sulfate. The filtered solu tion was concentrated in vacuo to give a clear oil which was crystallized from ethyl acetate-hexane and obtained as colorless crystals of pure

52, mp 190-195°C; h i MR ( 6 , CDC13) 5-0 (m, 2H), 4.64 ( i ABq, J = ***** "“AB 12 Hz, 2H), 4.30 ABq, = 12 Hz, 2H), 3. 2-1.0 (m, l 8H), 2.10 (s,

6 H), and 1 .9 6 ( s , 6 H).

2 ,3 ,3a, 3b, 4a, 4b, 7 ,7a, 7b, 7c, 7d, 8, 8a, 8b-Tetr adecahydro-1,4, 8- (epoxymetheno) dipentalenof 1.2.3- cd: 1 1,2*, 3* -gh]pentalene-4( 1H) -carboxaldeh.yde (57^

In certain instances, varying lots

of silica gel were found to convert

bisdihydropyran 54 to £ 7, when elu

tion through the column was made •

with ether; IR (KBr, cm-1) 2740 137 and 1710; ^ NMR (6, CDC13) 9 .8 3 (s, III), 5-78 (m, IH), 5-50 (m, 1H),

4.79 (s with fine splitting, 1H), 3*9^ (s, 1H), and 3-^0_l*00 (br m,

17H); l3C NMR (ppm, CDCI 3) 207.24(d), 133. 87(d), 129.99(d), 71.25(d),

68 . 70(d), 62.93(s), 59.05, 57.65, 54.50 (2C), 53.53, 53-04, 48.31,

46.67, 43.45, 42.18, 38. 84, 38. 11, 33. 68 , and 24.64; m/e 294 (M+, weak),

266 (M+-C0, base peak).

Anal. Calcd for C 20H22O2: C, 8l. 60; H, 7* 53* ibund: C, 8l . 5I 5

H, 7.55.

8-Bromohexadecahydro-4x-methoxy-4H-7,4a, 8-( epoxymetheno)-IH- 3- oxacyclopenta[ cd]pentaleno[ 1 ', 2 ', 3 ': 3,4]pentaleno[ 2, 1 , 6 -hia]indene (£ 2 ).

The bisdihydropyran ^4_(106 mg,

0.361 mol) was dissolved in 25

ml of dry methanol (freshly dis

tille d from magnesium methoxide)

under a nitrogen atmosphere. The o solution was cooled to -10 C and

N-bromosuccinimide (65 mg, 0.37 mmol) was added slowly in portions with

stirring. After 5 rain (deposition of white crystals noted), the re- o action mixture was allowed to warm to 25 C and stirred for an additional

2. 5 hr. The volume was reduced to ca 8 ml and the resulting crystals were filtered off and air dried to give 90 mg of pure 5£» rap l88-190°C.

The filtrate was evaporated to near dryness and filtered again to pro vide an additional 3° rag of product (total yield 9$), IR (KBr, cm-1)

108l and 995; NMR ( 6 , CDCI3) 5-05 (s, IH), 4.90 (br s, 1H), 4.48

(br s, 1H), 3-42 (s, 3H), and 3.0 -1 .5 (m, 19H); l3 C NMR (ppm, CDC13) 158

101. 15 , 71.85 , 70.95, 66.51, 58.74, 56.07, 55-95, 54-08, 55-89, 52-55,

48. 79, 48.51, 47.97, 46. 56 , 4 6 .4 l, 4o. 10, 57- 67 , 25 . 84, and 22.72

( 20th signal not observed and may overlap); m/e_ 406,404.

Anal. Calcd for C 2 iH25 Br03: C, 62.22; H, 6.17. Found: C, 62.24

H, 6.51.

8-Iodohexadecahydro-4a-methoxy-4H-7,4a, 8-( epoxymetheno) - lH - 5 - oxacyclopenta[cd]pentaleno[ 2 , 1 , 6 -hia]indene ( 60 ).

The bisdihydropyran 54.(101.5 mg,

CH-aQ. 0. 545 mmol) -was dissolved in dry

m ethanol (20 ml) under nitrogen

and N-iodosuccinimide ( 7 8 .8 mg,

0. 55 mmol) was added in portions

at 25°C. After 1 hr, the volume

of solvent ■was reduced to ca 7 ml and the white crystals were separated

by filtration to give 120 mg of pure 60, mp 155-155^0 dec. Further

concentration afforded an additional 55 mg o f 60 (total yield 99$ ) ;

1080 and 992 cm"1; NMR ( 6 , CDC13) 4.99 (s, IH), 4.87 (br s, IUcUl IH), 4.72 (br s, IH), 5.40 (s, 5H), and 5 .2-1.5 (br m, 19H); l3C NMR

(ppm, CDCI 3) 101.07, 76.66, 71.66, 70.64, 60.88, 57-14 ( 2C), 55-95,

54 . 55 , 54.04, 52 . 92, 49. 05 , 4 8 . 51 , 48.21, 47. 68 , 46 . 56 , 40.00, 57 . 65 ,

25 . 69 , and 22. 87; m/,e calcd 452. 0850 , obs 452. 0858.

Anal. Calcd for C21H25IO3: C, 55-76; H, 5-57- Found; C, 55-72;

H, 5.51. 139

Exposure of 29a to Silver Perchlorate. 8-Bromo-2,3,3aj3t>,4a,4b,

7,7a, 7b, 7c,7d,8,8a,8b-tetradecahydro-1,4,8-(epoxymetheno)dipentaleno-

[1,2,3-cd; 1 ',21,3*-gh]pentalene-4(lH)-carboxaldehyde (6l).

To a solution of bromo acetal 59^

I (133 mg, O.3 2 8 mmol) in dry ben- CH zene (10 ml) was added 1. 48 ml o f

0. 222 M silver perchlorate in

benzene ( 0 .3 2 8 mmol). The mixture Br was stirred for 30 an<^ p laced

directly on a Florisil column (tetrahydrofuran elution) to give 120 mg of crude product. This material was subjected to purification on pre parative TIC (silica gel, 1 C$ ether in hexane). There was isolated

58 mg (4-$) of 61 , mp 138-139. 5°C; v™* 2930, 1710, 108l, 710, and

674 cm"1; 1H NMR ( 6 , CDCI3) 9-93 ( s , IH ), 5. 80 (m, IH), 5-50 (m, IH),

4.85 (br m, IH), 4.55 (br m, IH), and 3. 7 -1 .0 (m, l 6 H); n/e 372.0725,

obs 372.0732.

Anal. Calcd for C 2 OH2iBr02: C, 64. 35; H, 5- 67 . Found: C, 64. 04;

H, 5-75. Obtained as well was 25 mg (21$) of 62 with spectral properties

identical to those of the authentic sample.

Hexadecahydro-4aH, 8aH -l,4,5 . 8-tetraoxabisc.yclopenta[ cd]oxireno[ g]-

p e n ta le n o [ 2, 1 , 6 -hia:5.4,3-hti ,at]diindene ( 63 ).

To a stirred solution of 54, (200 mg, 0.68 mmol) in dry ether (15

ml) was added m-chloroperbenzoic acid (280 mg o f 89$ p u r ity , 1 .3 8 mmol)

and epoxidation was allowed to proceed for 3 hr at room temperature. i4o

The reaction mixture was trans

ferred to a separatory funnel

where it was washed with 1($ so

dium carbonate solution (4 x 20

ml) and water (2 0 ml) prior to

drying. Concentration gave a white solid which was triturated with a small amount of warm hexane to remove residual m-chloroperbenzoic acid. There was obtained 150 mg

( 67$) o f 6 ^ small colorless needles from ethyl acetate-hexane, mp 197-

200°C dec; NMR ( 8, CDCI3) 5 -B26 (s , 2H), 4.046 (m, 2H), and 3. 30-

1.^5 (br m, l 8H) ; l3C NMR (ppm, CDC13) 81.27, 71. 03, 62.18, 53-45,

48. 38, 47. 30, 45. 79, 45. 09, 38.29, and 21. 84; m/e 308 (M+-H20) and

297 (M+-HC0).

Anal. Calcd for C 20H22O4: C, 75* 60; H, 6 .79* Pound: C, 73* ^-2;

H, 6 . 8l .

Reduction of 63 with Sodium in Liquid Ammonia. A. In the Absence of a Proton Source.

Sodium metal (28 mg, 1.23 mg-at) was dissolved in freshly dis tilled (from sodium) ammonia under an inert atmosphere. A solution of

63 (50 mg, 0.152 mmol) in anhydrous tetrahydrofuran (3 ml) was intro duced dropwise at -33°C. Upon completion of the addition, the mixture was stirred for 2 hr prior to the addition of solid ammonium chloride until loss of the blue color. Evaporation of the ammonia was followed by quenching with 50 ml of 10f!> hydrochloric acid. The mixture was ex tracted with dichloromethane (3 x 10 ml) and the combined organic layers i h l were washed with water, dried, and evaporated. There remained 50 mg

(IOO56 ) of product, whose spectra were identical to those of which were reported in the Wyvratt dissertation.

B. In the Presence of Ethanol as a Proton Source

To 15 ml of anhydrous liquid ammonia cooled to -78°C was added 150 mg ( 6 .5 2 mg-at) of sodium metal followed by 2 ml of absolute ethanol.

Diepoxyether 63 . (100 mg, 0. 306 mmol) in dry tetrahydrofuran (^ ml) was introduced dropwise during 15-20 min and stirring at - 33°C was continued fo r 1 hr prior to the addition of solid ammonium chloride and workup as described above. There was isolated 50 mg (5$) of the very in soluble tetraol £L which was identical in every way with an authentic sample.

Hexadecahydro-4,8-dimethoxy-5 37-dioxodicyclopentaC cd,c 1d*]pentaleno-

[ 2 ,1 , 6 -hia: 5. 3-h* i 1 a 1 ] diindene-^a, 8a( 4h, 8H) - d io l ( 67 ).

Bisepoxyether 6 3 (50 mg, 0.153

mmol) was added to dry m ethanol

(5 ml) containing 5 drops o f 0 .2 N

methanolic hydrochloric acid solu-

tion. The mixture was stirred for

1 hr and concentrated to dryness in vacuo to leave a white foam, which crystallized upon the addition o f e th e r ( 6 0 mg). Recrystallization from ether gave pure bishydroxy- _ A D I 1 acetal 67, mp 172-180 C (d); vmax 5550 and 1050 cm"1; H NMR ( 6 , CDC13)

4.71 (s, 2H), 3.93 (m, 2H), 3-^5 (s, 6 h ), 3-2-1. 3 (m, l 8H), 3-04 ( s , 2H); l3c KMR (ppm, CDCI3) 98.75, 81. 32, 68.11, 63. 1b, 60.39, 55-34,

54 . 18, 51.75, 48.26, 37. 58 , 27.04; m/e no M+, 298 (base peak, M+-

2xCH30H and -CO).

Anal. Calcd for C 22H30O6 : C, 67 . 67 ; H, 7-74. Ebund: C, 67 . 78;

H, 7.79.

Hexadecahydro-3, 6 -dioxabiscyclopenta[3,4]pentaleno[ 2, 1 , 6 - cde:

2*,1*,6l-ghla]pentalene-3a,6a-dicarboxaldehyde ( 69 ). A. Rearrangement o f 63 , on Silica Gel.

A 250 mg ( 0.766 mmol) sample o f 0 63 . was taken up in dichlorome-

thane and adsorbed onto silica

gel. The substance was allowed

to remain on the column for 2 h r CH0 before elution (CH 2CI2) was i n i tiated. There was obtained 110 mg (44$) of dialdehyde 69 , colorless prisms from benzene-hexane, mp 190-200°C dec; IR (KBr, cm"1) 2790,

2690 , and 1725; RMR ( 6 , CDC13) 9 .6 6 3 (s, 2H), 4.70 (s, 2H), and 3. 60 -

I.40 (br m, l 8H); l3C MMR (ppm, CDC13) 205-51, 103-43, 92.53, 63 .5 0 (SC),

61 . 72, 57.95, 49.20, 34.15, and 29.73; no M+, 297 (base peak, M+-HC0).

Anal. Calcd for C 20H22O4: C, 73-60; H, 6 . 79. Ebund: C, 73-83;

H, 6.91.

B. Silver Catalyzed Rearrangement of 63 .

Bisepoxyether 63 (600 mg, 1.84 mnol) was dissolved in 10 ml of benzene under nitrogen. To this was added a solution of silver lk 3 perchlorate in "benzene (0 .1898 M, 19.4 ml, 5-68 mmol). After 2 hr, the reaction mixture "was added to 100 ml of water and extracted with dichloromethane (3x). The combined extracts were washed with water, brine, water, and brine prior to drying over magnesium sulfate. The filtered solution was concentrated in vacuo and placed atop a silica gel column. Elution with dichloromethane gave 320 mg (51$) of pure bisaldehyde which exhibited spectral properties comparable with those of the authentic material.

Hexadecahydro-3, 6 -dioxabiscyclopenta[3? 4]pentaleno[2,1, 6 -cde:

2 1,1*,6l-ghia]pentalene-3a,6a-dicarboxylic Acid (JO).

Silver oxide was freshly pre

pared by addition of a solution

of sodium hydroxide (l84 mg, 4. 6

mmol) in 5 ml of water to a solu

tion of silver nitrate ( 39° mg,

2 .3 mmol) in 25 ml o f w ater. The brown precipitate was stirred for 5 min under nitrogen at which time

155 mg (0.475 mmol) o f 69 dissolved in tetrahydrofuran (5 ml) was in troduced dropwise. The mixture was stirred for 7 hr at 25°C and fil tered. The filtrate was acidified with 2 N hydrochloric acid and ex tracted with dichloromethane (4 x 25 ml). The combined organic layers were washed with water and brine before drying. Solvent removal left

50 mg ( 29$) of dicarboxylic acid mp 24o°C dec (from methanol-ethyl acetate); NMR ( 6 , CDCI3 ) 6 .0 -5 . 0 (b r m, 2H), 4.62 (m, 2H), 4.18 (m,

2H), and 3 .9-1.5 (br m, l 6 H); m/e 313 (M+-C0OH). ib k

Anal. Calcd for C 2 oH220 6: C, 67 . 04; H, 6 . 15 . Hound: C, 66 . 68 ;

H, 6. hi.

D i-tert-butyl Hexadecahydro-3 5 6 -dioxabiscyclopenta[3,i0pentaleno-

[ 2, 1 , 6 -cde: 2 f , 1 *, 6 ' -gh'alpentalene^a, 6 a-dipercarboxylate (£L) •

Dicarboxylic acid (290 mg, 0. 8l

thionyl chloride (25 ml) fo r 3 fcr

under nitrogen. The excess re

C03C

pressure, benzene (25 ml) was added, and the evaporation repeated. The residue ■was finally placed under high vacuum for 3° min prior to being dissolved in dry ether o (25 ml) and tetrahydrofuran (5 ml) then cooled to 0 C. Pyridine (0. 75 ml) was added followed by te rt-butylhydroperoxide (510 mg, 5*67 mmol).

This mixture was stirred for 2 hr and filtered. The filtrate was washed with cold $ aqueous sulfuric acid solution, cold 5$ sodium car bonate solution, and ice water. The organic phase was dried and con centrated to give tert-butyl perester (50 mg, 1*$) which was used without further purification.

Oct adecahydro-3,6-dioxabi scyclopent a[3 »^Opentaleno[2,1, 6 - cde:

2 , , l , , 6 ,-g]h|ji]pentalene ( 17).

Dialdehyde 69 (100 mg, 0. 31 mmol) was placed in a 0. 5 ml flat- bottomed reaction vessel along with acetophenone ( 7-^ mg, 0. 06 l mmol), benzyl m ercaptan ( l mg, 0. 008 mmol), and ethyl benzoate (3 drops) as 145

solvent. The mixture -was stirred

magnetically, heated to l4o°C un

der argon, and irradiated with a

275W sunlamp. The immediate evolu

tion of carbon monoxide was noted.

After 2 hr, an additional mg of benzyl mercaptan was added to again promote gas evolution which had subdued. Two hours later, the mixture was allowed to cool and product purification was achieved by preparative TLC on silica gel (elution with 4<$ ether in hexane). There was isolated 80 mg ( 9$) of 17 as a fluffy white solid, mp 156-158°C (from methanol); v ^ r 2940, 2842, IO 85 , max 1026, and 896 cm-1 ; ''n NMR ( 6 , CDC13) 4.55-4.0 (m, 4H) and 5 .3 -1 .5 (b r m, i 8h ); 13C MMR (ppm, CDC13) 91. 08, 90.30, 62 . 68 , 62 . 29, 61 . 36 , 56.22,

49. 57 , 34. 08, and 28. 84; m/e calcd 270. 1620 , obs 270. 1613 .

Anal. Calcd fo r CigtffeaOa: C, 79*96; H, 8.20. Hound: C, 79* 80;

H, 8. 13.

Hexadecahydro-3, 6 -dioxabiscyclopenta[3,4]pentaleno[2,1, 6 - cde:

2 1. l 1.6f-ghta]pentalene-3a,6a-dicarboxaldehyde Bisdimethylacetal (72).

A solution of 6 ^ (3 0 mg, 0. 092

mmol) in dry m ethanol (5 ml) con

ta in in g 1 drop of concentrated

sulfuric acid was stirred at room

CHtOCH^g temperature for 2 hr. The result

ing precipitate was separated by filtration and recrystallized from methanol to give 30 mg ( 78$) o f J2} 146 mp 193-195°C; IR (KBr, cm"1) 1200, 1170, and 1090; ^ HMR ( 6 , CDC13)

4 .8 0 (m, 2H), 4.02 (s, 2H), 3-46 (s, 6 h), 3-43 (s, 6 h), and 3-40-1.60

(b r m, i 8h ); 13C MR (ppm, CDCI 3) 109. 28, 102.58, 92.00, 62.77, 62. 09,

61 . 80, 58 . 26 , 57- 72, 54.13, 50 . 25, 33. 90, and 29. 00.

Anal. Calcd for Ca^Ha^e: C, 68. 87; H, 8. 19. ibund: C, 68 .7 1 ;

H, 8.13.

3a,6a-Bis(hydroxymethyl)hexadecahydro-3j6-dioxabiscyclopenta[3,4]- pentaleno[2,1, 6 -cde:2',1*, 6 *-gh*a]pentalene ( Jp ) ♦

Dialdehyde 6 g_ (70 mg, 0.215 mmol)

H0CH2 0 was dissolved in dry methanol (8

ml) at 0°C. Sodium borohydride

(64 mg, 1 .7 2 mmol) was added and

the reaction mixture was stirred

at room temperature for 18 hr.

After acidification with dilute acetic acid, the product was extracted in dichloromethane (3 x 10 ml) and the combined organic layers were washed with water, saturated sodium bicarbonate solution, and brine prior to drying and evaporation of solvent. The residual white solid was chromatographed on silica gel to give 50 mg ( 7$ ) of the highly in>

soluble diol mp > 26o°C; IR (KBr, cm"1) 3400, 2940, 1190, 1110, 1075,

and 1035; ^ MR ( 6 , CDC13) 4.68 ( t , J = 5-5 Hz, 2H), 3.60 (d , J = 10. 8

Hz, 2H), 3. 3O (d , J = 10.8 Hz, 2H), and 3- 8-1.5 (m, 2QH).

Anal. C alcd fo r CaoHaeO^ C, 72.70; H, 7 .93» Sbund: C, 72.54;

H, 7- 98. 3a, 6a-Eis(£-toluenesulfonyloxymethyl)hexadecahydro-3,6-dioxadicy- c lo p e n ta [ 3 j^]pentaleno[ 2 , l , 6 -c d e :2 * ,l f , 6 '-g lf[a ]p e n ta le n e (T^O•

£-Toiuenesulfonyl chloride (500

T«CV' U- mg, 2 .6 2 mmol) was added slowly

to a cold (0°C) solution of 75

(185 mg, O.5 6 mmol) in 10 ml o f

c h 2 o t* pyridine under a nitrogen atmos

phere. The mixture was stored overnight at 0°C, after which time a few ice chips were added and the mix ture was poured into ice water (50 ml). The product was extracted into dichloromethane (4 x 20 ml) and the combined organic layers were washed with water (2x) and brine prior to drying. Removal of solvent left a solid residue, recrystallization of which from benzene gave pure Jk 0 I (225 mg, 7$) which decomposes at 129. 5-156 C; IR (KBr, cm” ) 1362

1172, 968, 662, and 557; ^ UMR ( 6 , CDC13) 7-68 and 7-26 d of d,

-AB = - AB = 7 ,7 HZj AVAB = 28 Hz’ 805» k' k9 (tr s> 205» 5 ,7 7 ( s ’ 4H) 3.4-1.5 (series of m, l 8H), and 2.^1 (s, 6 H).

Anal. Calcd for C 34H3gPsS2i C, 63 . 95 ; H, 5*96. Ibund: C, 63*75;

H, 5 .9 ^

3a, 6 a-Bi s( a zidomet hy l) o ct adecahy dro - 3 3 6 -dioxabi scyclopenta[ 3, - pentaleno[ 2 , 1 , 6 - cde: 2 *, l f , 6 *-gha]pentalene ( 75 ).

Ditosylate (150 mg, 0. 235 nmol) was d isso lv e d in 6 ml of dry

HMPA under nitrogen. Sodium azide (155 mg, 2.35 mmol) was added and the mixture was heated at 8o°C for 12 hr, allowed to cool to 25°C, and added to 40 ml of ether. The

ether phase was washed with water

(4x) and dried over magnesium sul

fate. The solution was filtered

c h 2 n 3 and the ether removed to give a

semi-crystalline solid. Prepara tive TLC on silica gel (2C$ ether-hexane) gave bis-azide (72 mg,

8l$) as a crystalline solid. The analytical sample was obtained as colorless needles, rap 101. 5-102.5°C, upon recrystallization from me thanol; IR (KBr, cm'1) 2940, 2875, 2100, 1450, 1294, and 1025; NMR

( 6 , CDC13) 4.71 (br s, 2H), 5 .5 5 (i'A B q, = 11 Hz, 2H), 5 . l4 (g-ABq,

J = 11 Hz, 2H), 5-5-1* 2 (m, l 8H); m/e no mass ion observed, base =

526 (M+-2N2).

Anal. Calcd for C 20H24N6 S C, 65.14; H, 6 . 36 . Pound: C, 63 .12;

H, 6.52.

Octadecahydro-3, 6 -dioxabiscyclopenta[3,4]pentaleno[ 2 , 1 , 6 - cde:

2 *, 1 *, 6 t-gha]pentalene- 3a , 6 a-diraethaneamine ( 76 ).

B is-a z id e (40 mg, 0.105 mmol)

was dissolved in 5 ml of dry ethyl

acetate. Platinum oxide (3 nig)

was added and the mixture was

hydrogenated at 50 p s i fo r 8 h r c h 2 n h 2 a t 25°C. The re a c tio n m ixture was filtered through Celite and the filtrate was evaporated to give pure 149 diam ine 76 as a crystalline solid (40 mg, 100$); H NMR ( 6 , CDC13)

4.58 (m, 2H), 5*^-1. 0 (series of m, 26H).

5a, 6 a-Bi s( bromomethyl)oct adecahydro-3, 6 -dioxadicyclopenta[ 5? 4] - p e n ta le n o [ 2 , 1 , 6 - cde: 2 * 1 16 1 -ghfa]pentalene (j 8).

To a so lu tio n o f 74 (150 mg, 0. 255

mmol) in 6 ml of anhydrous hexa-

methylphosphoramide was added so

dium bromide (250 mg, 2 .5 5 mmol)

CHgBr and the mixture was heated to

8o°C with stirring for 15 hr.

The cooled reaction mixture was added to ether (40 ml) and the ether layer was washed with water (4 x 10 ml), dried, and evaporated. The resulting semi-solid was triturated with pentane to give 100 mg (90$) o f mp 158 . 5-l60°C (from hexane); IR (KBr, cm *) 2958, 1033, 1014,

990, and 652 ; ^ MR ( 6 , CDC13) 4.8-4.5 (br t, 2H), 5 .40 (s, 4H), and

5 -4 -1 .5 ( s e r ie s o f m, l 8H); l3 C MR (ppm, CDC13) 99* ^ 6 , 91*15, 65 . 96 ,

62.45 (2C), 56.01, 50.01, 39. 52 , 55 . 92, and 28.28; m/e calcd 454.0144, obs 454.0153.

Anal. Calcd for C 2 oH24Br2 : C, 52 . 65 ; H, 5-26. Ibund: C, 52 . 89;

H, 5.32.

0ctadecahydro-4, 8-bis(methylene) dipentaleno[l, 2, 3-cd: 1 *, 2 *, 5 ' -jgh] - pentalene-l, 5 -diol (72).

A suspension of zinc and ethylenediaminetetraacetic acid was pre pared by adding sodium hydroxide (200 mg, 4.9 mmol) to 4 ml of methanol 150

followed by EDTA disodium salt

(925 mg, 2.5 mmol). Subsequently,

sodium iodide (30 mg, 0 .2 5 mmol)

and zinc dust (216 mg, 3*3 m g-at)

were introduced. This slurry was

added to a solution of (40 mg,

0 .0 9 mmol) in 10 ml of benzene and 2 ml of methanol and the mixture was heated at the reflux temperature under nitrogen for 30 hr, cooled, and filtered through Celite. The filtrate was added to dichloromethane

(50 ml) and washed with water, saturated sodium bicarbonate solution, water, and brine before drying. Solvent evaporation left 25 mg ( 92$) o f 7£ as a colorless crystalline solid; IR (KBr, cm'1) 33^0, 1632 , 1093, and 903; *2 M l ( 6 , CDCI3) 5-25 (br s, 2H), 4.9 (br s, H), 4.25 (hr s,

2H), and 3 . 6 - 1 . 0 ( s e r ie s o f m, 2CH); m/e c a lc d 298. 1933, obs 298.1940.

3a,6a-Dimethylhexadecahydro-3, 6 -dioxadicyclopenta[3,4]pentaleno-

[2,l,6-cde:2,, l ,,6*-ghJJ_a]pentalene ( 82). A. Direct Reduction of jS.

A ctiv ated zin c (240 mg, 3*55 m g-at)

rH, 0 "was added under nitrogen to a solu

tio n o f 78 (40 mg, 0. 088 mmol) in

10 ml of methanol and 1 ml o f

tetrahydrofuran. The mixture was

heated at the reflux temperature for 20 hr, cooled, and filtered through Celite. The filtrate was added to water (10 ml) and extracted with dichloromethane (5 x 15 ml). The combined organic phases were washed with water and brine, dried, and 151

evaporated. Preparative layer chromatography of the residue on silica

gel (elution with 1C$ ether in hexane) gave two major hands. The hand

■with Rf. = 0.75 proved to he 82 (12 mg, 46$). The second hand, = 0.2

(9 mg), was not identified.

B. Acid-Promoted Cyclization of (79).

To a solution of 7^. (30 mg) in methanol (5 ml) was added one drop o f 1 N methanolic hydrogen chloride and the mixture was stirred at 25 °^!

for 12 hr. Evaporation of solvent left a yellowish oil which was puri

fied as ahove to give 25 mg ( 83$) o f 82. Recrystallization from hexane

afforded colorless prisms, mp 210-215°C; IR (KBr, cm”1) 2920, 1055> and

1031; 1H MR ( 6 , CDCI3) 4.65 (m, 2H), 3 . 8-1. 0 (series of m, 18h), and

1.23 ( s , 6H); l3C MR (ppm, CDCI 3) 97-14, 89. 28, 67.34, 62 . 63 , 62 . 31*,

61 . 32, 1*9. 91, 34.08, 27. 96 , 27. 28; m/e calcd 298. 1933, ohs 298. 191*0.

Anal. Calcd for C 2oH2e02: C, 80.1*9; H, 8. 78. Itound: C, 80.0 6 ;

H, 8. 36 .

E i co s ahy dro -1*, 8- dioxahi s cyclop ent a[ cd] cy clopr opa[ g] p ent ale no [ 2 , 1 , 6 - hia;5,4,3-hli ,al]diindene (64). A. Cyclopropanation via the Zinc-

Silver Couple.

Silver acetate (44 mg) was dis

solved in hot acetic acid (15 ml)

under nitrogen. To this solution

was added zinc dust (l. 098 g,

1 6 .8 mg-at) and the mixture was

stirred for a few min. The acetic 152

acid was decanted off and the zinc-silver couple was washed with acetic

acid (15 ml) and then ether (4 x 15 ml). Ether (15 ml) and methylene

io d id e ( 5*0 g, 11*2 mmol) were added and the suspension was refluxed

fo r 50 min under nitrogen. At this point, 165 mg (0. 560 mmol) o f J>4 was introduced prior to overnight heating at the reflux temperature.

The cooled supernatant was decanted into a separatory funnel and the

residue was thoroughly washed with ether. The combined ether solu

tions were washed with 1 C$ hydrochloric acid (2 x 20 ml), aqueous so

dium thiosulfate (20 ml), and saturated sodium bicarbonate solutions

(20 ml) prior to drying and concentration. There remained 180 mg

(l0<$) of 64 judged to be pure by 1H NMR analysis. Recrystallization

from methanol gave colorless prisms, mp l 8l - l 86 ° dec with prior soften

ing a t 165 °C; 3120-3000 cm"1; NMR (6,CDC13) 5 . 056 , 5.014, 4.975,

4.929 (X part of ABX system, 2H), 3-700, 3-664, 3 .6 2 8 (t, 2H), 3-3-1-3

(br m, 18H), 0.749, 0.703, 0.681, O .6 3 5 (B part of ABX, 2H), 0.459,

O.387, 0.374, and O.3 0 6 (A part of ABX, 2H); l3C NMR (ppm, CDC13)

68.14, 60.54, 57-57, 52.50, 48. 83, 47-57, 47. 10, 38. 63 , 21. 85 , 20. 93, and 9 * 12; m/e_ 322.

Anal. Calcd for C 22H26 02: C, 81. 95 ; H, 8. 13. Ibund: C, 81. 53 ;

H, 8. 13.

B. Cyclopropanation via Ethylzinc Iodide.

Zinc dust (6.1 g, 94.0 mg-at) was stirred in 15 ml of ether along with cuprous chloride ( 0. 92 g, 9.4 mmol) and the mixture was heated at the reflux temperature for 30 min. After cooling to 25°C, 60 ml of ether was added along with ethyl iodide (13*4 g, 94.0 mmol). The mixture was stirred for 12 hr and allowed to settle. The clear color less supernatant solution was assumed to be 1 M in concentration. To a 20 ml aliquot of this solution (20 mmol) was added diiodomethane

( 2 .7 3 1 0 .2 mmol) and the mixture was heated at 35 °C under nitrogen fo r 1 h r. The bisdihydropyran £4.(500 mg, 1 .7 mmol) was next i n tr o duced as a solution in 5 nil o f a 50:50 mixture of ether-tetrahydrofuran.

The reaction mixture was heated to 45°C for 2 hr, cooled to 25°C, quenched by the dropwise addition of water, added to 500 ml of ether, and washed with dilute hydrochloric acid solution, sodium thiosulfate solution, water, and brine. The ether solution was dried over mag nesium sulfate and concentrated in vacuo to give 530 mg ( 9T$) o f crystalline cyclopropyl ether 64. The spectral properties of this material were identical to those of the authentic sample.

Acid-Promoted Ring Opening of ££. A. 9-Methyloctadecahydro-kx- methoxy-lH- 8, 5 a, 9- ( epoxymetheno) - 3-oxacyclopenta[ cd]pentaleno[ 1 *, 2 *, 5 *:

3,4]pentaleno[2,l,6-ija]azulene ( 88).

A suspension of 64^ (88 mg, 0.273

mmol) in a 5 $ solution of con

centrated hydrochloric acid in

m ethanol (5 ml) was heated at re-

flux with stirring for 5 ° min. CM3 The resulting dark colored solu tion was cooled, diluted with water (20 ml), and extracted with di chloromethane (5 x 15 ml). The combined organic extracts were washed with saturated sodium bicarbonate solution (15 ml), dried, and 154 evaporated. The residual dark oil (90 mg) was chromatographed on s ili ca gel (elution with 1C$ ether in hexane) to give TO mg (j£ o f 88, colorless needles from hexane, mp l4l°C; Hi MR (8, CDCI 3) 4.789 ( s ,

1H), 4.518, 4.469, 4.4l4, 4.565 (X p a r t o f ABX, i n ) , 4 .0 8 1 (m, 1H),

4.045 (m, IB ), 5.555 (s, 5H), 2.75-1.50 (hr m, 20H), and 1.082 (s, 5H); m/e calcd 554.2195 , obs 554. 2200.

Anal. Calcd fo r.C 23H3o03: C, 77-95; H, 8. 55 . Found: C, 77-58;

H, 8.47.

B. Two-Step Procedure.

Biscyclopropyl ether 64 (5 0 mg, 0. 095 mmol) was dissolved in di chloromethane which had been saturated with hydrogen chloride (2 m l).

After being stirred at room temperature for 5° min, the solution was evaporated to dryness to provide a quantitative yield of 87, mp 155 ”

155° dec with prior softening at 150°C; XH MR ( 8, CDC13) 5-65, 5-58,

5.48, and 5-40 (X part of ABX, 1H), 4.68 (hr m, IH), 4.29 (br m, 1H),

4.08 (m, 1H), 5 . 52 -I .5 5 (br m, 2CH), and 1.0J (s, 5H); m/e calcd

558 . 1699, obs 558 . 1706 .

The above product was suspended in dry methanol (2 ml) and stirred at room temperature for 24 hr during which time dissolution occurred.

Removal of the solvent under reduced pressure left a white solid whose spectral characteristics were identical to those of 88 isolated earlier.

Bromination of 9-(Bromomethyl)octadecahydro-4a-methoxy-1H, 8,

5 a , 9-(epoxymetheno)- 5 -oxacyclopenta[cd]pentaleno[lf, 2 ', 5 *: 5 -4]pentaleno-

[ 2 , 1, 6 -i j a] a zulen e (go).

A solution of 64^ (50 mg, 0.095 mmol) and bromine (9-84 y l, 0.191 155

mmol) in carbon te tr a c h lo r id e (2

ml) was refluxed for 1 hr. The

cooled reaction mixture was evapo

rated to dryness under reduced

pressure and the residue was re

crystallized from benzene-hexane to give pure 8g as fine white needles, mp 225-226°C dec with prior softening at ~ 200°C.

A sample of this material (l 6 mg, 0.033 mmol) was s ti r r e d in dry m ethanol (2 ml) for 24 hr prior to removal of the solvent under reduced pressure and recrystallization of the residue from methanol. There was

isolated 10 mg (720) of go, mp l88-l89°C dec; NMR ( 6 , CDC13) 4.916

(m, 1H), 4.535, 4.486, 4.430, 4.382 (X part of ABX, 1H), 4.11-4.0 (br m,

2H), 3.762 (s, 2H), 3.541 (s, 3H), and 2.83-1.40 (br m, 20H); m/e calcd 432.1300, obs 432. 1308.

Anal. Calcd fo r C23H29Br03: C, 63.74; H, 6.74. Found: C, 63.41;

H, 6.80.

1 ,1 * -[4 a , 8a-Bis(bromomethyl)eicosahydro-3,7-dioxadicyclopenta[cd,

cJ[djJpentaleno[ 2 , 1 ,.6 -h ia : 5 ,4 , 3-h,i lat] diindene-4, 8-diyl]bis[ 2 , 5 - pyrrolidinedione] (^i).

The biscyclopropylether 64_ (163

BrC?2\v0 mg, 0. 51 mmol) and N-bromosuccini- r mide (185 mg, 1 . 04 mmol) were heated at reflux in carbon tetra- ■

BrCHgO' ch lo rid e (10 ml) w hile 156 simultaneously irradiated with a 275W UV sunlamp for 1 hr. The mixture

•was cooled and concentrated in vacuo to give a slightly yellow crystal line solid. Recrystallization from benzene gave 285 mg ( 83$) of pure

91; vmnY 1780, 1705 cm"1; NMR (6, CDC13) 5. 80 (s, 2H), 3- 3$ (£ ABq,

= 1 0 .4 Hz, 2H), 3. 08 ABq, = 10.4 Hz, 2H), 4. 0-1. 0 (m, 20H),

2.64 ( s , 8h); l3C NMR (ppm, CDCI3) 177.60, 128.41 (from the benzene complex with the sample), 77- 01, 72. 52 , 62 . 26 , 58 * 26 , 50 . 98, 49.76,

4 9 .0 3 (2C), 46.42, 37.55, 28. 34, 25.91; m/e 678.

1,1' -[ Eicosahydro-4a, 8a- dimethyl - 3,7-dioxadicyc lop e nt a[ cd., c 1 d* ] - pent aleno[ 2 . 1 , 6 -h ia : 5 .4 , 3^ * 1 * at]diindene-4<8-diyl]bis[2,5-pyrrolidinedione] ( 92).

The bisbromoimide 91_ (285 mg,

0.420 mmol) was dissolved in ben

zene (1 0 ml) along with tri-ri-

butyltin hydride (428 mg, 1.47

mmol). This mixture was heated

at the reflux temperature and irradiated with a 275W UV lamp through pyrex for 3 hr, cooled, and concentrated under reduced pressure to give a crystalline semi-solid.

This material was washed with benzene, filtered, and dried under vacuum

at 80°C for 12 hr to give 194 mg ( 89$) of 92. Recrystallization from benzene gave the analytical sample as colorless prisms, mp 310°C (d);

1775 and 1705 cm"1; NMR ( 6 , CDCI3) 5-91* (s, 2H), 3 .9 1 (m, 2H), IUcLX 3.0-1.3 (m, 18H), 2.70 (s, 8H), 0.90 (s, 6 H); l3 C NMR (ppm, CDC13)

178.42 (s), 128.41 (from the benzene complex with the sample), 78.70 157

(s), 72.75 (a), 6 3 .2 6 (4c), 51-12 (d), 50.15 ( d ), '4 9 .0 3 (d), 44.52 (s),

38.01 ( t ) , 33-30 (q ), 2 8 .3 0 ( t ) , 26.12 ( t ) ; m/e 520 .

Anal. Calcd for C 30H36 N2O6 • 2 CeH6: C, 74.53; H, 7.15* Hound:

C, 74.11; H, 7.03.

Treatment of §£ -with Potassium Hydroxide. Synthesis of Diacid g4.

Bismethyl succinimide (30 mg,

0. 058 mmol) -was suspended in 7$

aqueous methanol. To this was

added potassium hydroxide (40

mg, 0 .7 mmol). The m ixture R-NHCOCCH^COOH ■was stirred for 2 hr, acidified w ith 10$ hydrochloric acid solution and filtered to give 25 mg ( 83$) of 94; IR (KBr, cm"1) 3500-2400, 1720, 1660, 1530, and 1070.

Treatment of with Hydrazine. Synthesis of Bis Amide 95*

The bism ethyl imide 92^(50 mg,

0. 096 mmol) was suspended in V. f t eth an o l (3 ml). To this mixture

was added hydrazine hydrate (15

c h 3 mg, 0 .2 9 mmol) and th e so lu tio n R'= NHC0CCH2>2C0NHNH2 was heated at the reflux tempera ture for 10 hr. The solution was then cooled and concentrated in vacuo to give an oil. Crystallization and recrystallization from ethanol- ethyl acetate gave colorless needles (4l mg, 73$) of mp 220-221°C

(sealed tube); IR (KBr, cm"1) 3440, 3300, 1660 , and 1530. 158

Treatment of 92 -with Methylamine. Synthesis of Bis Amide

The bismethyl imide §2_ (30 nig,

c h 3, \ JO 0. 058 mmol) was d isso lv e d in 3

ml of tetrahydrofuran and treated

with 1 ml of methylamine (k&jo

c h 3 in water). The resulting solu Pf* NHC0(CH 2)2C0NHCH3 tion was stirred for 12 hr and concentrated under reduced pressure to give white crystals of 96

(10$); IR (KBr, cm'1) 3^20, 3320, 1660 , and 1530.

Reductive Cleavage of 1£_ in Sodium-Liquid Ammonia. Synthesis of

5,9-Dimethyloctadecahydro-4a, 8a-bis(methylthio) -3, T-dioxadicyclopenta-

[cd.cld,]pentaleno[ 2 , l , 6 -hia: 5,^,3-hti tat]diindine-4,8-dione (lOl) and

Keto Lactone 100.

CH,S

s c h 3

A solution of bislactone 15 (llO mg, 0.307 mmol) was dissolved in

15 ml of tetrahydrofuran and added dropwise to a stirred solution of liq u id ammonia (40 m l), te tra h y d ro fu ra n (3 0 ml) and sodium (5 0 mg, 2 .2 gr-at) at -T8°C. After 15 min, dimethyl disulfide (0.3 ml) was added and stirring was continued for 30 additional minutes. The reaction mixture was quenched with saturated ammonium chloride solution, and 159 freed of ammonia. The resulting solution was added to water and ex tracted with chloroform (3 x 50 ml). The combined extracts were washed with water, dried over calcium sulfate, filtered, and concentrated in vacuo to give a yellow solid. Recrystallization of this material from ethyl acetate gave 71 mg of 100 ( 67$) of a white solid, mp 268-270°C;

IR (KBr, cm'1) 3420, 1740, 1705; NMR ( 6 , CDG13) 5.20 (m, 1H), 4.05

(m, 1H), 3-55-0.9 (m, 19H), 2.02 (s, 3H); l3C NMR (ppm, CDC13) 200. 98,

169.90, 87.24, 76.02, 66 . 26 , 65.77, 60.27, 59.13, 58.27, 54.71, 54.49,

54 . 01, 50 . 61 , 48.99, 48. 56 , 40.79, 39* 06 , 36 . 80, 23. 15 , 21. 53 , 8. 52 ; m/o^ calcd 372.1395, obs 372.1400.

Anal. Calcd for C21H24O4S: C, 67-72; H, 6 . 49. Ibund: C, 67-32;

H, 6 . 47.

The mother liquors from several runs were combined and chromato graphed on silica gel (chloroform elution). The first material off the column was the symmetrical disulfide 101 (34 mg). Recrystallization from ethyl acetate gave analytically pure material, mp 240-24l°C; IR

(KBr, cm’ 1) 1710, 1205, and 1075; XH NMR ( 6 , CDCI3 ) 4.72 (m, 2H), 4 .6 -

I .1 (m, 18H), 2.22 ( s , 6 h ); m/e 572 (M+-CH2S).

Anal. Calcd for CzsRsqO^z: C, 63 .13; H, 6.26; S, 15-32. Ibund:

C, 62.86; H, 6.29; S, 15.13.

Acid-Catalyzed Isomerization of 40.

A solution of 4£ (80 mg) in concentrated sulfuric acid (3 ml) was heated at 78-80°C for 20 hr. The reaction mixture was poured into water

(20 ml) and extracted with chloroform (3 x 25 ml). The combined organic layers were washed with water (2 x 20 ml), dried, and evaporated. The residual solid (5 8 mg) was r e

crystallized from ethyl acetate

to give 103 as colorless needles,

mp 20T-209°C; IR (KBr, cm"1) 1760

XH NMR (6 , CDCI3) 3. 90- 3 .2 6 (m,

2H), 3- 08-2. 36 (hr m, 4h), 2.4-

1.55 (br m, l4H), and 1 .3 6 ( s , 6 h); l3C NMR (ppm, CDC13) 179-^0, 104.99

65 . 34, 65 . 18, 61 . 29, 6 l . 13, 5 4 .66 , 40.47, 34. 91, 26 . 06 , and 25 . 90; m/e

calcd 354.1831, obs 354. 1836 .

Anal. Calcd for C 22H26 O4: C, 74.56; H, 7-59- Ibund: C, 74.42;

H, 7.45.

0ctadecahydro- 8,8-dimethoxy-4a, 8a-dimethyl-3,7-dioxadicyclopenta-

Ccd,c'dl]pentaleno[ 2 , l , 6 -hia:5.4,3-hli ta*]diinden-4(lH)-one (106)*

To a magnetically stirred solu

tion of 40, (50 mgj 0.14 mmol) in C H *n n dry dichloromethane (4 ml) which

was maintained under a nitrogen

atmosphere was added 100 mg ( 0 .6 8 CH3 mmol) of trimethyloxonium tetra-

fluoroborate. After 16 hr at room temperature, a solution of sodium

methoxide in methanol -was added and a color change from red to pale

yellow was noted. The mixture was poured into water and extracted with dichloromethane (3*). The combined organic layers were washed

twice with water, shaken with brine, and dried. Upon removal of sol

vent, a yellow crystalline residue remained. Preparative thin layer l 6 l

chromatographic (TLC) purification on silica gel (elution -with 1($

ether in hexane) gave *+0 mg ( 73$) o f 106 as colorless crystals, mp 15 *+-

157°C; XH NMR ( 6 , CDCI3 ) *+. 6 -*+.l (m, 2H), *+.0-0.8 ( s e r ie s o f m, 18H),

5 . 6 *+ ( s , 5 H), 3.25 (s, 3H), 1.38 (s, 3H), and 1. 06 (s, 3H); m/e calcd

*+00. 22*+0 , obs *+ 00. 2256 .

H ydrolysis o f 106.

A solution of 106 (*+0 mg, 0.1 mmol) was dissolved in 6 ml of aqueous

tetrahydrofuran ( 5 $ ) and treated with three drops of 3$ hydrochloric

acid. The mixture was stirred at room temperature for 2*+ hr and the

product was extracted into dichloromethane. After drying and solvent

evaporation, bislactone 40 was recovered whose spectra proved identi

cal to those of the authentic sample.

M ethyl 2 ,2 a ,*+,*+a,*+b, 5 , 6 , 7 , 7 b , 8, 8a, 8b , 8c , 8d, 8e , 8f-hexadecahydro-

*+a, 8-dimethvl-*+-oxo-lH-5-oxacyclopenta[ cd]pentaleno[ 1* ,2 ’ ,3 ’: 3,*+]- pentaleno[2,1, 6 -hia]indene- 8-carboxylate (107). A. . Cleavage of 40.

B islacto n e *+0 (5 ° rogj 0.1*+ mmol)

CH, was dissolved in dry 1 , 1-dichloroethane (5 ml) with stirring under

nitrogen. Trimethyloxonium fluoro-

CH3 b o ra te (200 mg, 1*35 mmol) was

added and the mixture was heated

at reflux for 18 hr. After cooling, a solution of sodium methoxide in methanol was added and a color change from orange to milky white was

noted. Workup as described above afforded 50 mg of a clear oil. 162

Preparative TLC purification on silica gel (ether elution) furnished

35 nig (68^) of 10J as a colorless crystalline solid, mp 135-138°C;

IR (KBr, cm-1) 2940, 1730, 1272, 1133, H l 8 , and 9 96 ; XH NMR ( 6 , CDC13)

5 .0 0 -4 .7 (m, 1H), 4. 0- 3.3 (m, 2H), 3-67 (s, 3H), 3* 3-1-0 (seris of m,

16H), and 1. 36 . ( s , 6 h ); l3 C NMR (ppm,. CDC13) 206.71, 176 .l4, 149.14,

148.46, 84. 67 , 78. 65 , 75 . 45 , 63 . 31, 60 . 69 , 58 . 26 , 56 . 80, 54 . 57 , 52 . 04,

51.75, 50 . 98, 49.42, 46.12 , 39. 03, 32.92, 30. 88, 28. 35 , 28. 06 , and

25.92; m/e_ calcd 368 . 1987, obs 368.1994.

Anal. Calcd for 023*12304: C, 74.97; H, J. 66 . ibund: C, 75- 01;

H, 7. 79.

B. Cleavage of 106.

A mixture containing 30 mg (0. 08 mmol) of 106 and 20 mg (0. 056 mmol) o f 40 and 5 nil of dry 1 , 1 -dichloroethane -was heated at reflux -with magnetic stirring for 18 hr. The usual -workup afforded 34 mg ( 68 $) o f

107 as a colorless solid, mp 135-138°C.

Double Lactone Cleavage in 40.

A so lu tio n o f 40 (50 mg, 0. l4 mmol)

and trimethyloxonium tetrafluoro-

b o rate (150 mg, 1 .0 mmol) in

ethylene trichloride (1 0 ml) -was

CH, heated at the reflux temperature

under nitrogen for 24 hr. The orange-colored solution was cooled, treated -with methanolic sodium methoxide, and poured into water. The product was extracted into 163 dichloromethane and the combined organic layers were processed as be fore to give mg of a clear oil. Preparative TLC purification on

silica gel (elution with ether-hexane (l:l)) afforded 15 mg (28j6 ) o f

108; ^ NMR ( 6 , CDCI3 ) 3.61 (s, 6 H ), 3. 8-0. 8 (series of m, l 8H), and

1.15 ( s , 6 h); 13C MR (ppm, CDC13) 178. 22, 167 . 1 2 , 66 . 52 , 57-98, 55-90,

53-05, 51 . 82, 51-55, 49.26, 47.36, 41.20, 41.01, 38.ll, 25.70, and 23-90* m/e c alcd 382.2144, obs 382. 2150 .

Anal. Calcd for C 24H30O4: C, 75-56; H, 7-91- Ibund: C, 75-52;

H, 7. 89.

Eicosahydro-4a,8a-dimethyl- 3, 7-dioxadicyclopenta[cd,cf d 1]pentaleno-

[ 2 , 1 , 6 -h ia : 5 ,4 , 3-h,i ta*]di indene-4, 8- d io 1 ( £J) -

A so lu tio n o f 40 (400 mg, 1.13

mmol) in dry te tra h y d ro fu ra n (45

ml) was cooled to - 78°C and l i

thium aluminum hydride (120 mg,

3 .1 6 mmol) was added with stir- c h 3 ring. After 4 hr at this tempera ture, the progress of reaction was arrested by addition of water. The mixture was allowed to warm to 25°C whereupon it was added to 400 ml of dichloromethane. The resulting solution was washed with 50 ml of water containing a small amount of hydrochloric acid, water ( 2x) and brine before drying. Removal of solvent left 4l0 mg of a colorless oil which crystallized upon the addition of dichloromethane. The solid was filtered, washed with additional dichloromethane, and dried to give

390 mg (97$) of 2X as a colorless solid, mp 171-173°C dec (loss of H 2O); IR (KBr, cm-1) 3390, 2920, 1118, 1050, and 750; XH WMR ( 6 , pyridine-d5)

8. 3-6. 0 (m, 2H), 4 .8 0 (m, 2H), 4. 3- 1 .0 (series of ra, 2CH), and 1.30

( s , 6 h); 13C NMR (ppm, CDC13) 100.45, 78.45, 64 . 30, 57-09, 54.93, 51-63,

50.12, 49.20, 38. 33, 36 . 27, and 30-95; m/e (M+-H 20) calcd 340. 2038, obs

340. 2043.

Eico sahydro-4,8-dimethoxy-4a, 8a-dimethyl-3,7-dioxadicyclopenta-

[ cd, c 1 d']pentaleno[ 2 , 1 , 6 -h ia ; 5 ,4 , 3-h 'i * a*]diindene ( 109) -

To a stirred solution of 97 (lOO

mg, 0 .8 mmol) in dry m ethanol (30

ml) maintained under a nitrogen

atmosphere was added 1 -2 drops o f

a saturated methanolic hydrogen

chloride solution. After 10 min, a white precipitate appeared. Stirring was continued for 3 hr, where upon the reaction mixture was concentrated and the colorless solid fil tered off to give 108 mg (9^) of pure 10g, mp l84-l86°C (from acetone);

IR (KBr, cm'1) 2940, 1170, 1108, 1045, and 950; *H NMR ( 6 , CDCI3) 4.52

(s, 2H), 4. 0-3.4 (m, 2H), 3-28 (s, 6 h ), 3.2 -0 .9 (series of m, l 8H), and

0 .9 8 ( s , 6 H); 13C NMR (ppm, CDCI 3) 100.98, 67 .05, 64.23, 60.78, 55.05,

50 . 30, 49.57, 49-33, 46.61, 37- 82, 35 - 00, and 27. 28; m/e 386 ( l$ ) , 371

(M+-CH3) calcd 371.2222, obs 371-2228.

Anal. Calcd for C 24H3406: c, 74.58; H, 8. 87. Bbund: C, 74.45; 165

Octadecahydro-4a,8a-dimethyl-5< T-dioxadicyclopentaT cd,c 1d '] - pentaleno[2,1, 6 -hia;5 ,4,3-h 1i * a*1diinden-4(lH)-one (llO). A. Isomeri zation of £ 7^

A so lu tio n o f (100 mg, 0. 28

mmol) in dry m ethanol (25 ml) -was

treated -with a small amount of

hydrogen chloride under nitrogen

^h3 and the reaction mixture was

stirred at room temperature for

5 days. Concentration of the resulting solution gave a semi-solid

■which was purified by preparative TLC on silica gel (ether elution).

There was isolated 82 mg ( 8256 ) of 110 as colorless crystals, mp 186 - l 88°C (from ethyl acetate); IR (KBr, cm"1) 2920, 2850 , 1710, 1450, and

1095; MR ( 6 , CDCI3) 4.9-4.65 (m, 1H), 4.2-5-4 (m, 5H), 5 .8 6 (d,

J = 12 Hz, 1H), 3-4-1.1 (series of m, l 6H ), 2 .9 8 (d, J = 12 Hz, 1H),

1.43 (s, 3H), and 0.95 (s, 3H); l3C MR (ppm, CDCI 3) 176*91, 83. 16 ,

76.32, 71.27, 65.49, 63.70 ( 2C), 59.76, 54.33, 52.38, 50.35, 50.25,

49. 76 , 48.55, 4?.24, 42.38, 39. 81, 38. 1 6 , 38. 01, 35 . 83, 28. 11, and

27.14; m/e calcd 340. 2038, obs 340.2043.

Anal. Calcd for C 22H28O3: C, 77* 6 l ; H, 8. 29. Ibund: C, 77.43;

H, 8.25.

B. Rearrangement of lOff in Acidic Methanol.

A so lu tio n o f lQft (50 mg, 0.13 mmol) in dry m ethanol (10 ml) was treated with 1 drop o f 2 N methanolic hydrogen chloride and stirred un der nitrogen for 3 days. Removal of the solvent in vacuo left 50 mg 166 of crude 110. Preparative TLC o.n silica gel furnished ^5 mg (9$) of

colorless crystals, mp l 86 - l 88°C.

C. Titanium Trichloride Promoted Isomerization of lOg.

A solution of lOg (10 mg) in 0. 5 ml of CDCI 3 "was placed in an NMR tube. To this tube was added 8 mg of titanium trichloride. After 1 hr,

a spectrum showed a mixture of 10g, 110, and llg to be present. After

2. 5 hr, only 110 and 11$ were present. After 7 hr, the tube contained

essentially pure 110,

D. Acid-Catalyzed Isomerization of 11/1

A solution of 11£ (50 mg, 0 .15 mmol) was dissolved in methanol

(10 ml) under a nitrogen atmosphere. One drop of 2N methanolic hy

drogen chloride was added and the reaction mixture was stirred at room temperature for ^8 hr. The solvent was removed in vacuo and the resi due was purified by preparative TLC on silica gel (ether elution).

There was obtained 40 mg ( 8($) of ether lactone 110.

Ei co s ahydro-4 . 8- dp-^ a . 8a-dimethyl-5,7-dioxodicyclopenta[ cd^d* ] — pentalenoL2.1. 6 -hia; 5A.5-hti tat]diindene-4.8-diol (ilia ).

A 100 mg (0 .2 8 mmol) sample o f ^ 0

dissolved in 10 ml of dry tetra

hydrofuran was cooled to -78°C

and while stirred was treated with

CHa 53 mg ( 0. 79 mmol) o f lith iu m alum- num deuteride as described earlier.

There was obtained 100 mg ( 9^ ) of Ilia as a colorless solid, mp 171- 167

173°C dec (loss of H20 ); IR (KBr, cm"1) 3^20, 2920, 1175, 1120, and

1055; m/;e M+ not observed, 3^2 (M+-Ha0).

Eicosahydro-4,8-dimethoxy-4a, 8a- dimethyl-3,7-dioxadicyclopenta-

[c d ,c *d 1]pentaleno[ 2, 1, 6 -h ia : 5 , 5 - h 1i 1 a'] diindene-4, 8-dg (lllb ).

B is la c to l I l i a (70 mg, 0.19^ mmol)

0 was dissolved in dry methanol (30 CHi,( ''/lv ml) and treated while being stirred

under nitrogen with 1 drop o f me-

thanolic hydrogen chloride. After

2 hr, ■the precipitated solid was

filtered to give 50 mg ( 68$) of lllb as colorless crystals, mp 188-

190°C; IR (KBr, cm'1) 2925, 1173, 1115, IO 65 , 10U5 , and 908; ^ MR

( 6 , CDCI3) 3.81 (m, 2H), 3-35 (s, 6 H ), 3. 3- 1. 2 (m, l 8H), and 1 . 02 ( s ,

6 H); m/e M ( 388) not observed, 373 (M+-CH3).

0ctadecahydro- 8,8 -d g -4 a, 8a-dimethyl- 3 , 7-dioxadicyclopenta[ cd,ctdf ]-

pentaleno[2,1, 6 -hia:5.^.3-hfi 1 a 1]diinden-^(1H)-one (ll2 ).

An approximate 1:1 mixture of Ilia

^ 3, 0^ 0^ and (70 mg) dissolved in me

th a n o l (3 0 ml) containing a drop

of methanolic hydrogen chloride

was stirred at room temperature

for a period of 3 days. The

solvent was removed in vacuo and the resulting solid was purified by

preparative TLC on silica gel (ether elution). There was obtained 60 mg of il2, mp l8T-l89 0C; IR (KBr, cm-1) 2930, 1710, 1160, 1130, and

1088; WMR (6 , CDCI3) 4 .9 -4 .6 5 (m, IH ), 4 .2- 3.4 (m, 4h ) , 3* 4 -1 .1

( s e r ie s o f m, 16 H), 1.43 (s, 3H), and 0 .9 5 (s, 3H); l3C HMR (ppm,

CDCI3) 176.91, 83.I 6 , 76.22, 70.44, 65.50, 63.65 ( 2C), 59.76, 54.33,

52 . 38, 50.35, 50.25, 49. 76 , 4 8 . 56 , 47.19, 42.19, 39. 81, 38. 16 , 38. 01,

35 . 78, 28. 11, and 27. l4 ; m/e calcd 342.2164, obs 342. 2170.

0ctadecahydro-4a, 8-dimethyl-4,7-epoxy-lH-3-oxacyclopenta[cd]- pentaleno[l' , 2 *, 3 ': 3,4]pentaleno[2,l,6-hia]indene-8-carhoxaldehyde ( l l j i ) .

A. Thermal Dehydration of 9.7-

A 100 mg (0. 28 mmol) sample o f £ £ o •was heated under nitrogen at 175 C

for 4 min. The evolution of -water,

as noted by the formation of tiny

c h 3 gas bubbles in the melt, had

stopped at the end of this time.

The re s id u e , -which s o lid if ie d upon co o lin g , was p u r if ie d by p re p a ra tiv e

TLC chromatography on silica gel (elution with 5$ ether in hexane) to give 50 mg (53^) of 11£ as colorless crystals, mp l44-l46°C (from ether).

A second band of lower (0.45 vs 0.2) proved to be ether lactone 3JL0

(15 mg). Eor 113, IR (KBr, cm”1) 2931, 2700, 1715, 1454, 1092, and

1050; XE HMR ( 8, CDCI3) 9 .8 5 (s, IH), 4.86 (s, 1H), 4. 5-0 .9 (series of m, 20H), 1.18 (s, 3H), and 1 .0 9 (s, 3H); l3C KHR (ppm, CDC13) 204.15,

95.64, 76.95, 71.67, 61 . 90, 61 . 54 , 60.99, 59.59, 58 . 50 , 56 . 13, 55 . 34,

52 . 98, 51.58, 51.04, 47. 34, 45.51, 40.84, 35 . 56 , 3 1 .6 8 ( 2C), 28. 58 , and 23. 79; m/e calcd 340. 2038, obs 340.2044. 169

Anal. Calcd for C22H2& 3: C, 77*61; H, 8. 29. Round: C, 77*38;

H, 8.27.

B. Reaction of 97 "with Lead Tetraacetate.

A mixture of lead tetraacetate (155 mg, 0.55 mmol), calcium carbo nate (l40 mg, 1.4 mmol) and cyclohexane (5 ml) was stirred at reflux for 10 min. Bislactol 2X. (50 mg, 0. l4 mmol) and iodine (l42 mg, 0. 56 mmol) were added and heating was continued with concomitant irradiation from a 15 OW sunlamp. After 1. 5 hr, the dark mixture was cooled and the inorganic solids filtered off. The filtrate was diluted with ether (30 ml) and the organic phase was washed with sodium thiosulfate solution, water, and brine prior to drying. Removal of solvent gave 40 mg of an oil whose MR spectrum showed it to be essentially pure 113.

C. Rearrangement of 'with Hydrochloric Acid in Tetrahydrofuran.

A solution of §7 (50 mg, 0.14 mmol) in dry tetrahydrofuran (5 ml) was treated with 1 drop of dilute hydrochloric acid and stirred under nitrogen for 2 days. The solvent was removed in vacuo to give 50 mg 1 of an amorphous solid. H MR analysis of this material showed it to consist of 113 (6($), 110 (29$), and an unidentified substance (—1^).

Octadecahydro-4a-methyl-4,7-epoxy-lH-3-oxacyclopenta[cd]pentaleno-

[ l * , 2 *, 3 ‘:4]pentaleno[2,l,6-hia]indene-8-ethanone (114).

To a solution of 11 5, (100 mg, 0.29 mmol) in benzene (5 ml) was added triphenylmethyl tetrafluoroborate (120 mg, 0. 35 mmol) and th e mixture was stirred for 10 min. After water (5 drop ) had been added slowly, the reaction mixture was poured into 10 ml of water. The 170

aqueous solution was extracted

Q ^H3 with methylene chloride (3 x 20

ml) and the combined organic ex

tracts were washed with water ( 2x)

and brine prior to drying over

magnesium sulfate. The filtered solution was evaporated to dryness to give 182 mg of a clear oil. Pre parative TLC on silica gel (elution with 5$ ether in hexane) gave ll4

(60 mg, 6 $ ). Recrystallization from ethyl acetate gave tiny prisms, mp l65-l64°C; IR (KBr, cm’ 1) 2925 , 1710, 1149, and 1032; *11 MMR ( 6 ,

CDCI3) 4.93 (s, IH), 1.0-4.4 (m, l 8H), 2.09 (s, 3H), 1.07 (s, 3H); m/e calcd 340.2038, obs 340. 2044.

Anal. Calcd for C 22H29O3: C, 7 7 .6 l ; H, 8. 29. Ibund: C, 77.57;

H, 8.25.

Obtained as well was 25 mg ( 29$) of 107 with spectral properties identical to those of the authentic sample.

Eicosahydro-4a,8a-dimethyl- 3 ,7-dioxadicyclopenta[cd,cld,]pentaleno-

[ 2 , 1 , 6 - h ia : 5 . 4 . 3-h* i * a*]diinden-4-ol (l! 5 a ) .

A s t i t r e d so lu tio n o f 110 (100 mg,

HO 0 .2 9 mmol) in dry tetrahydrofuran

(5 ml) was cooled to -78°C and

treated under nitrogen with 0. 315

mmol of 1 M diisobutylaluminum c h 3 hydride dissolved in hexane.

After 3 hr at this temperature, water was introduced, a small amount 171 of dilute hydrochloric acid was added to dissolve the a l uminum s a lt s , and the mixture was extracted with dichloromethane. The combined or ganic extracts were washed with water ( 2x) and brine before drying.

Removal of solvent left 100 mg of crude 115a which was utilized with out further purification.

Eicosahydro-4-methoxy-^a, 8a-dimethyl-3,7-dioxadicyclopenta[ cd, c * d 1 ] - pentaleno[ 2, 1 , 6 -h ia : 5 . 5 - h* i * a* ] diindene (l l j b ) .

The crude lactol prepared above

was dissolved in methanol (10 ml)

and treated with 1 drop o f 2 N

methanolic hydrogen chloride.

The solution was stirred at 25°C CH3 fo r 10 hr and evaporated. Fre- parative TLC purification of the resulting clear oil (elution with 5$ ether in hexane) afforded 60 mg ( 92$ overall) of 115 b as colorless crystals, mp 157-l60°C (from acetone); IR (KBr, cm"1) 2930, 1^55, 1170,

1095, 10k2, and 975; *H MR ( 6 , CDC13) k.6 5 ( s , IH ), k. 3- 3.3 (m, 4H),

3 .9 6 (d , J = 13 Hz, IH ), 3.5 5 (s, 3H), 3-3-0.9 (m, 16 H), 2.97 (d, J =

13 Hz, IH), 1.02 (s, 3H), and 0 .9 2 (s, 3H); m/e calcd 356 .2351, obs

356. 2358.

Anal. Calcd for C 23H320 3: C, 77* ^9j H, 9* °5. Found: C, 77- 06;

H, 8.92.

Acid-Promoted Rearrangement of 115b.

A solution of 115b (100 mg, 0 .2 8 mmol) and £ -to lu e n e su lfo n ic acid 172

mo no h y d rate (5 mg) in "benzene

(3 0 ml) was heated to reflux for

40 hr, during which time methanol

was slowly removed through a modi

fied Dean-Stark trap. The darkened

reaction mixture was added to water and extracted with ether. The combined organic layers were washed with water, dried,, and evaporated to furnish a yellow o il (100 mg) which was purified by preparative TLC on silica gel (elution with 2($ e th e r in hexane). There was obtained 60 mg ( 66 £) of 116 as colorless crystals, mp l l 6 - l l 8°C (from ethyl acetate); IR (KBr, cm-1) 2930, 1450, 1175,

1090, and 992; ^ MR ( 6 , CDCI3) 5- 0 -4 .0 (m, 3H), 4 .0 (d , J = 12 Hz,

IH), 4. 0-1.0 (series of m, 17H), 3. 05 (d, J = 12 Hz, IH), 1.22 (d,

J = 7 Hz, 3H), and 1. 0 (s, 3H); l3C KMR (ppm, CDC13) 142. 78, 132-95,

76.76, 75.50, 75.94, 68 . 21, 63 . 78, 62.77, 54.96, 55-99 ( 2C), 52 . 68 ,

50.05, 49.47, 42.92, 40.78, 37.82, 35.78, 35.49, 30.05, 23.25, and

22. 38; m/e calcd 324. 2089, obs 324. 2094.

Anal. Calcd for CZ2EZ^)2: C, 8 l.4 4 ; H, 8. 70. Pound: C, 81.44;

H, 8. 78.

0ctadecahydro-7-hydroxy-4a, 8- dim ethyl- IH- 5-o xa cyclop e n t a[ c d] - pentaleno[ l 1,2 ', 3*: 5 ,4]pent aleno[ 2 , 1 , 6 -hia] in dene- 8-m ethanol (117) •

A 200 mg (0.59 mmol) sample of 110 was reduced with lithium alumi

num hydride (40 mg, 1 mmol) in te tra h y d ro fu ra n (1 0 ml) a t - 78°G fo r 3 hr. The usual workup afforded 180 mg (9$) of 117 as a white solid, 173

mp l45-l47°C (from ethyl acetate);

CH«OH IR (KBr, cm-1) 3575, 2910, 1450, CH3 HO. 1178, 1100 and 1045; NMR (fi,

CDCI3) 4.40 (d, J = 6.2 Hz, IH),

4. 3- 0 .8 (series of m, 20H), 3*88 ch 3 (d, J = 12 Hz, IH), 3.20 (d, J =

6.2 Hz, IH), 2.93 (d, J = 12 Hz, IH), 1.14 (s, 3H), and 0.90 (s, 3H).

Eicosahydro-4a, 8a-dimethyl-3,7-dioxadicyclopenta[cd,c 1d ']pentaleno

[2,1,6-hia: 5.4,5-hti taf]diindene (l l 8). A. ALane Reduction of 11J.

ALuminum chloride (l47 mg, 1.1

mmol) was cooled to 0^ and 4 ml

of dry tetrahydrofuran followed

by lithium aluminum hydride ( 10. 4

mg, 0 .2 8 mmol) ■were added -with

stirring under nitrogen. After 15 min, 119 (100 mg, 0 .1 8 mmol) -was added as a slurry in ether to the alane.

The reaction mixture was heated at reflux for 24 hr, cooled, quenched with water, and added to ether. The customary workup including pre parative TLC purification on silica gel (elution with 1C$ ether in hexane) gave 55 mg (9<$) o f l l 8 as colorless crystals, mp 104-106°C

(from hexane); IR (KBr, cm’1) 2930, 2860 , 1105, 1098; ^ NMR ( 6 , CDC13)

4. 2 -3-3 (m, 2H), 4 .0 (d , J = 12. 5 Hz, 2H), 3* 3-1* 0 ( s e r ie s o f m, I 8H),

2.95 (d, J = 12. 5 Hz, 2H), and 0 .9 2 ( s , 6 h ); l3 C MMR (ppm, CDC13)

76 . 27(d ), 71. 12(t), 64.86(d), 60 . 10( d ), 52 . 77(d), 50.97(d), 49.91(d)

42. 72(s), 3&63('t), 38.46(q), and 26 . 8o(t); m/e calcd 326 . 2246, obs 326 . 2252 . 174

Anal. Calcd for C 22H3o02 : C, 80.94; H, 9-26. Hound: C, 8l . 06;

H, 9.21

B. Thermal Cyclization of 11J.

A 10 mg sample of 117 was placed in an MR tube and heated at

170°C fbr 5 min under a nitrogen atmosphere. Gas evolution was noted as melting occurred. The tube was cooled and CDCI 3 (0. 5 ml) was added.

The bis ether 118 was seen to be produced in 7$ yield based upon ap propriate integration of the MR spectrum. The other 3$ was not identified.

E i co s ahydro- 4a, 8a-dimethyl-4, 8-bi s(phenylthio) - 3,7-dioxadicyclo- p enta[ cd , c 1 d 1 ]pentaleno[ 2 ; 1 , 6 - h ia : 5 «4 , 3-hll ,at]diindene llj).

To a so lu tio n o f 97_(lOO mg, 0.28

mmol) in dry te tra h y d ro fu ra n ( l ml)

was added 500 mg (6 .4 mmol) o f

thiophenol. After 1 hr at 25°C,

the formation of a white precipi

tate was noted. The mixture was stirred for an additional 4 hr, poured into dichloromethane (125 ml), and washed with 1<# sodium hydroxide solution ( 2x), water, and brine prior to drying. Removal of the solvent furnished 130 mg ( 86f>) o f 119 as a colorless crystalline solid, mp 227-232°C (sealed tube, gradual decomposition above 200°C) (from dichloromethane); IR (KBr, cm-1) 2925 ,

1564, 1479, 1437, 1068, 900, and 730; XH MR ( 6 , CDCI3) 7 .7 -7 .0 (m,

10H), 5 .8 3 ( s , 2H), 4. 5 -4 .2 (m, 2H), 4 .2- 3 .3 (m, 2H), 3 -3 -0 .9 ( s e r ie s 175 of m, 14h), and 1.17 (s, 6 h); l3C MR (ppm, CDCI 3) 136.75, 129-99,

128. 72, 125 . 86 , 87. 69 , 68.27, 64.21, 62 . 93, 50.37 ( 2C), 49.52, 47.15,

57.69, 37.26, and 27.19; m/e, 542.

Anal. Calcd for 03411330282! C, 75*23; H, 7 . 06 . Jbund: C, 74.83;

H, 7.17.

Dimethyl Hexadecahydro-4, 8,9-metheno-4H-cyclopenta[ 1,2-a:4,3-a*]- dipentalene-4,10-dicarboxylate (120). A. Catalytic Tin Hydride Re duction of 42.

To a solution of dichloro diester

42 (520 mg, 1 .2 3 mmol) in 25 ml

of glyme was added tri-ii-butyltin

c h lo rid e (8 0 mg, 0.246 mmol), so

dium borohydride (117 mg, 3*07

mmol) and AIM (20 mg). The mixture was heated at the reflux temperature fbr 36 hr. When cool, the solution was added to 500 ml of ether and washed with water, aqueous potassium fluoride solution, water, and brine. After being dried over magnesium sulfate, the filtered solution was evaporated to dryness in vacuo, placed atop a silica gel column, and eluted with 9$ e th e r in hexane. Early fractions contained alkane impurities. Continued elu tion gave pure diester 120 (407 mg, 95$) whose spectral properties were consistent with those of the authentic material.

B. Catalytic Hydrogenation of 4l.

The mixture of diene diesters 4l (l40 mg, 0.40 mmol) was dissolved in 20 ml of ethyl acetate and 5 ° mg o f 5$ palladium on carbon catalyst 176 was added. The mixture was treated with hydrogen at atmospheric pres sure for 8 hr, filtered through Celite, and evaporated to dryness in vacuo. The desired diester crystallized upon standing to give l40 mg

(lOC$) o f pure 120.

Cleavage of the Lactone Rings in 15. Synthesis of Dimethyl 1,3a,3b,

4a, 4b, 5,7a, 8,8a, 8b, 9> 9a-dodecahydro-4,8,9-metheno-4H-cyclopenta[ 1 ,2-a_:

4,3-a^]dipentalene-4,10-dicarboxylate (ijl) and Lactone Ester 121.'.

Bislactone 15 (100 mg, 0.31 mmol) was dissolved in dichloromethane

15 ml) along with trimethyloxonium tetrafluoroborate (200 mg, 1 .3 mmol).

The mixture was heated at the reflux temperature for 24 hr under nitro- o gen, cooled to 25 C, treated with 10 H sodium hydroxide solution until a pH o f 8 .5 was obtained, added to water, and extracted with ether (3*).

The combined ether extracts were washed with water (2x) and brine, then dried over magnesium sulfate. The filtered solution was concentrated in vacuo to give an orange colored oil. Preparative TI£ on silica gel

(lC$ ether in hexane elution) gave two products. At R^ = 0. 3 th e is o meric diene diesters 4l_ (4l mg, 35$) were obtained which were recrystal lized from ethyl acetate, mp l46-l49°C; IR (KBr, cm"1) 1760 , 1692 , 1075, ITT

and T62; xH MR ( 6 , CDC13) 5-42 (m, 4H), 3.6 0 ( s , 6 h ) , 3 -5 5 -1 .3 (m, l4H); m/e calcd 352. l6T4, obs 352 . 1680 .

Anal. Calcd for C 22H24O4: C, T4. 98; H, 6 . 86 . ibund: C, T4. T9;

H, 6.84.

At = 0.1 the ene lactone ester 121 (52 mg, 5 $ ) r e s u ltin g from a single cleavage step was obtained. Spectral properties of this ma terial were identical to those of the authentic material. This sample could be recycled to give an additional 35 nig of 41, thereby increasing the overall yield to T$.

Catalytic Hydrogenation of 121. Formation of Ester Lactone 122.

Ene lactone ester 121 (100 mg,

0. 3 mmol) was d isso lv e d in 20 ml CH4OOC ' ' of ethyl acetate and 30 nig o f 5$

palladium on carbon catalyst was

added. The mixture was treated

with hydrogen at atmospheric pres

sure for 8 hr, filtered through Celite, and evaporated to dryness in vacuo. The product, ester lactone 122, (100 mg, 10C$) was recrystallized

1 o from ethyl acetate to give the analytically pure material, mp 1T2-1T4 C;]R

(KBr, cm"1) 1T42, 1105, and 10T0; 1H NMR ( 6, CDC13) 4.8 (m, IH), 3-6 (s,50, and 3.0-1.0 (m, 20H); l3C MR (ppm, CDC13) 1T4. 32, 1T2.44, 84. 98, 64.96

62 . 64 , 6 0 .9 T , 5 8 . 9T ( 2C), 53-58, 52.34, 51 . 42, 50 . 55 , 45.48, 43. 54 , 43. 16 ,

42.68, 37. 66 , 29. 03, 28. 92,26 . 22, 23. 36 ; m/e c alcd 340.16T4, obs 340. 1680 .

Anal. Calcd for C21H24O4: C, T4.09; H, T. 11. Ibund: C, T3-T3;

H, T. 06 . 178

Hexadecahydro-4, 8,9-metheno-te- cyclopent a[ 1,2-_a: 3“£’ ^dipentalene-

4,10-dicarboxylic Acid (l25)>

To a solution of diester 120 (110

mg, 0.31 mmol) in HMFA (b ml) was

added sodium cyanide ( 26 k mg,

5 .39 mmol) and th e m ixture was

h eated to 8o°C fo r 3° h r under

nitrogen. The cooled mixture was treated with 25 ml o f 1 N sodium hydroxide solution and the alkaline reaction mixture was extracted with dichloromethane ( 3x) then acidified with concentrated hydrochloric acid. The now milky solution was ex tracted with dichloromethane (bx), and the combined organic extracts were washed with water (2x) and brine. The dried and filtered solu tion was evaporated to dryness to leave 55 mg ( 51 $) of diacid 125 , no mp dec over 190°C; IR (KBr, cm-1) 3700-2^00, 1690 , 1600, and 965 ; ^

KMR ( 6 , CDCI3) 10.2-8.9 (br s, 2H), 3.2-1.0 (m, 22H); m/e calcd 328. 167 ^, obs 328.1679-

Hexadecahydro-4,8,9-metheno-4H-cyclopenta[l,2-a:4,3-^,]dipentalene- b, 10-dicarboxylic Anhydride (127).

The d ia c id 125 (55 mg, 0 .1 7 mmol)

was dissolved in 10 ml of thionyl

chloride and heated at the reflux

temperature for 3 hr. The mixture

was cooled; benzene (10 ml) added

and removed _in vacuo to give 53 mg (10$ ) of anhydride 127. Recrystallization from ethyl acetate gave pure 179 m aterial, mp 192-194°C; IR (KBr, cm-i) 1820, 1775, 1260, and 877;

*H NMR ( 6 , CDCI3 ) 3. 5-2.1 (m, 10H), 2.1-1.1 (m, 12H); m/ £ calcd

310. 1569 , obs 310. 1563 .

Dimethyl 0ctadecahydro-4,8-dimethyldipentaleno[l,2,3-cd:1' ,2r,3*- gh]pentalene-4, 8-dicar boxylate ( 128).

A solution of diester 120 (500

CH3P mg 1. 4 mmol) in 20 ml of tetra- CH3. v ° hydrofuran was added to a solu f t tio n o f d i s t i l l e d ammonia (250

ml) containing 50 ml of tetra

hydrofuran and sodium (320 mg,

14 mg-at) and stirred at -78°C for 30 min. Methyl iodide (3 ml) was introduced and the ammonia evaporated. The remaining organic solution was added to 500 ml of ether and washed with sodium thiosulfate solu tion, water, and brine before drying over magnesium sulfate. After

filtration and evaporation of solvent in vacuo, there was obtained

500 mg of crude crystalline diester. Recrystallization from ethyl

acetate gave pure diester 12j3 (300 mg, 6 C$), mp l69-171°C; IR (KBr,

cm'1) 1730, 1140, and 1105; 1H NMR ( 6 , CDC13) 3.9 -0 .8 (m, 22H), 3-60

( s , 6 h), 1.40 (s, 6 h) ; 13C NMR (ppm, CDC13) 176 . 96 , 60.14, 57.83,

55 . 22, 51 . 58 , 50.79, 39.93, 30.53, 29. 98; m/e calcd 386.2457, obs

386 . 2461 .

Anal. Calcd for C 24H3404: C, 74.58; H, 8. 87. Ibund: C, 74.46;

H, 8.79. i8o

0ctadecahydro-4,8-dimethyldipentaleno[l,2,3-cd: 1*, 2f, 5' -ah] - pentalene-4,8-dimethanol (l2£).

A solution of diester 128 (100 mg, HO 0 .2 8 mmol) in to lu en e (1 0 ml) was

cooled to -78°C under nitrogen.

A solution of Dibal-H (1 M in

hexane, 1 .7 mmol) was added v ia

a syringe. The mixture was allowed to warm to 25°C where it was stirred for 8 hr. The progress of reaction was quenched by dropwise addition of methanol and the mixture was poured into 100 ml of methylene chloride, washed with dilute hydrochloric acid solution, saturated sodium bicarbonate solu tion, water, and brine. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo to leave 90 mg (10C$) of crude diol 12ff. Recrystallization from ethyl acetate gave pure diol

129, mp 132-134°C; IR (KBr, cm’1) 3310, 2905, 1445, and 1005; ^ NMR

( 6 , CDC13) 4 .1 -0 . 8 (m, 24h), 3-92 (s, 4h), and 1.10 (s, 6 h ); l3 C NMR

(ppm, CDC13) 66.22, 61.44-, 55-95, 55-81, 52.46, 37-16, 30. 27, 28.795 m/e, M+ not observed.

Anal. Calcd for C 22H3402i C, 79- 95; H, 10.37- Pbunds C, 79- 72;

H, 10.54.

0ctadecahydro-4,8-dimethyldipentaleno[l,2,3-cd:lf ,2* ,3*-gh]- pentalene-4,8-dicarboxaldehyde ( 150 ).

A solution of diol lgff (200 mg, 0.6 mmol) in dichloromethane (2 ml) was added in rapid dropwise fashion to a stirred suspension of pyridinium l 8 l

chlorochrom ate (400 mg, 1 .9 mmol)

in dichloromethane (25 ml). After

2 h r , e th e r (25 ml) was added and

the organic solution was decanted

from the brown salts. The salts

were triturated with additional ether (2x) and the organic layers were combined and washed with dilute hydrochloric acid solution, saturated sodium bicarbonate solution, water, and brine prior to drying. The filtrate was concentrated in vacuo to give 200 mg of crude aldehyde which was recrystallized from ethyl acetate to give l 8o mg ( 90$) of pure bisaldehyde 1 $0 , mp 137-

138°C; IR (KBr, cm"1) 2?6o, 1712, 1702, 1375, and 955; ^ NMR (6,

CDCI3 ) 9.85 (s, 2H), 4.2-1.0 (m, 22H), 1.20 (s, 6 h); l3C NMR (ppm,

CDCI3 ) 203. 90, 63 .1 1 , 61 . 66 , 57.10, 51.46, 34.17, 31.10, and 29.7 4 ; m/e calcd 326.2246, obs 326 . 2252 .

Anal. Calcd for C 28H30O2: C, 80.94; H, 9. 26. Ibund: C, 80. 8l ;

H, 9.23.

Octadecahydro-aja* ,4 , 8-tetram ethyldipent aleno[ 1 ,2,3-cd: 11, 2*, 3' - gh]pentalene-4, 8-dimethanol (l/£ 2).

Dialdehyde 150 (100 mg, 0.3 1 mmol)

Cu _CH3CH0H was dissolved in ether (15 ml)

and cooled to -78°C with stirring

c M3 choh under nitrogen. To this solu

ch3 tion was added methyllithium ( 0 .9 3 mmol) v ia a sy rin g e and s tir r in g i8e

■was maintained for 3 hr prior to quenching -with methanol, warming to

25°C, and pouring into 100 ml of ether. The ether layer was washed with water (2x) and brine prior to drying over magnesium sulfate. The filtered solution was concentrated in vacuo to leave a clear oil con taining the diastereomers of alcohol 1^2 (110 mg). Eor practical pur poses, this material was used without purification. The diastereomers could be easily separated by preparative TLC on silica gel (5$ ether in hexane). Exhibiting = 0.55 and at Rf = 0. 5, the two diols were obtained in quantities of 46 mg and 55 mg, respectively. Recrystalliza tion of the less polar diol from ethyl acetate gave the analytically pure m aterial, mp 195-210°C; IR (KBr, cm-1) 3^20, 2420, 13^5, and 1175;

XH MR ( 6 , CDCla) 4.79 (q , J = 6 Hz, 2H), 4. 0-3.5 U , 2H), 3- 8

(m, 22H), 1.20 (d, J = 6 Hz, 6 h), 1.09 (s, 6 h); m/e, (M+ not observed).

Anal. Calcd for C 24H3^02: C, 80.39; H, 10. 68 . Eound: C, 80.42;

H, 10.66.

4,8-Diacetyloctadecahydro-4, 8-dimethyldipentaleno[ 1 , 2, 3-cd: 1*, 2 ', 3* - gh]pentalene (l^ 5 ).

A solution of the diastereomeric

alc o h o ls 152 (30 mg, 0. 09 mmol)

in dichloromethane (l ml) was

added dropwise to a suspension

of pyridinium chlorochromate (60

mg, 0. 28 mmol) in 5 nil of dichloro methane. After 2 hr, ether was added and subsequently decanted from the salts. The salts were triturated with ether two additional times and 1 8 3

all the ether extracts -were combined, washed with dilute hydrochloric

acid solution, saturated sodium bicarbonate solution, water, and brine.

The organic phase was dried over magnesium sulfate, filtered and evapo rated in vacuo to give 26 mg ( 87$) of crystalline diketone ljg. Re

crystallization from ethyl acetate gave the analytically pure material, mp l82-l86°C; IR (KBr, cm"1) 2930, 1700, 1352, and 1085; NMR ( 6 ,

CDCI3) 4. 0 -0 .7 (m, 22H), 2.11 ( s , 6 H), and 1.28 (s, 6 h); l3C NMR (ppm,

CDCI3) 210.88, 66 . 70, 60.44, 55 .3 4 , 51 .6 4 , 38. 60 , 30. 58 , 30. 16 , and

27.57; a/e calcd 354.2559, obs 354.2564.

Anal. Calcd for C 24H34O2: C, 81.09; H, 9*55. Ibund: C, 81. 31;

H, 9.67.

Dimethyl 0ctadecahydro-4, 8-dimethyldipentaleno[1,2,3-ed:1*,2*,3’- jgh]pentalene-4, 8-dicarboxylic Acid (139).

Diester 128 (5 0 mg, 0.1 3 mmol)

in 5 ml of tetrahydrofuran was

added a t - 33°C to 60 ml of liquid

ammonia co n tain in g sodium (50 mg,

CH3 2 .1 mg-at) and potassium (50 mg, 1 .2 5 mg-at) over a period of 10 min. The ammonia was allow ed to r e flu x fo r 2.5 h r p r io r to quenching with solid ammonium chloride. The ammonia was then removed and water was added. This basic aqueous solution was extracted with methylene chloride and acidified. Methylene chloride extraction (3x) followed by drying of the organic extract gave 40 mg ( 8j$) of diacid 1^£, no mp but gradual dec over 220°C; IR (KBr, cm'1) 3500-2400, 1690 , 1310, and 184

1295; XH NMR (6, C5D5N) 8.0-7.0 (to s, 2H), 3-7-0.9 (m, 22H), 1.4 (s,

6H); m/e calcd 358 . 2152 , obs 358 . 2143.

Octadecahydro-4,8-dimethyl-4,8-ethano dipent aleno[1,2,3-cd:1*,2*, 3r-

gh]pentalene-9,10-dione ( 137).

To a d isp e rsio n o f sodium (400 mg,

17.4 mg-at) and potassium (400 mg,

10. 3 mg-at) in 175 nil of dry

toluene was added trim ethylsilyl

c h lo rid e (5 m l, 39*0 mmol) f o l

lowed dropwise by diester 128

(400 mg, 1. 04 mmol) in 10 ml of toluene. The mixture was heated at

reflux for 48 hr under nitrogen, cooled, filtered through Celite, and

concentrated in vacuo. The residue (which crystallized on standing)

was redissolved in 10 ml of benzene and added dropwise to a stirred

solution of anhydrous ferric chloride (500 mg, 3 .0 8 mmol) in 40 ml o f

dry ether containing 5 drops of concentrated hydrochloric acid. The

solution was refluxed gently for 0 .5 hr and treated with 20 ml of satura

ted ammonium sulfate solution. The layers were separated and the aqueous

layer was extracted with ether (2 x 75 ml). The combined organic ex

tracts were washed with water ( 2x) and brine before drying over sodium

sulfate. The solution was filtered and freed of solvent to give 375 mg of a yellow oil which partially crystallized on standing. Chroma

tography on Florisil with 10ft ether in hexane first gave an unidenti

fied material (40 mg) followed by the yellow band of desired diketone

137 (l80 mg, 55$). Recrystallization from ethyl acetate gave yellow 185 prisms, mp l82-l83°C; IR (KBr, cm"1) 2950* 1690 , 1088, and 965; UV

(isooctane) 260 (e 165 ), 510 (55), and 430 nm (47); NMR ( 6 , CDC13)

3.5 -0 .8 (m, 22H), 1.32 ( s , 6 H); l3C NMR (ppm, CDCI3) 201.96 , 61.29,

60 . 08, 57 . 23, 4 8 . 91, 32.4-1, 26 . 03, and 24.88; m/e c a lc d 324. 2089, obs

324.2094.

Anal. Calcd for C 22H2802: C, 8l . 44; H, 8.70. Ibund: C, 8l . 18;

H, 8. 59.

Hexadecahydro-4, 8-dimethyl-3a, 8,4,7b-ethanediylidenedipentaleno-

[l,2,3-cd:l,,2,,3'-gh]pentalene-9,10-diol (l4o). A. Photolysis of a-Diketone 1 $J.

D iketone IpJ (100 mg, 0.3 1 mmol)

CHa ^0H was dissolved in 5 nil of a de

gassed solution of benzene, ace

tone, and tert-butanol in a 3: 1 :1

ratio. The mixture was irradiated

■with a 450W Hanovia lamp for 10 hr. The solvent was removed in vacuo and the yellow residue was puri fied by preparative TLC (lC$> ether-10^ methylene chloride- 8c^ hexane) on silica gel to give 12 mg of diol l40 (R^ = 0. 3) , 15 mg of diketone

137 (Rf = 0.35), and 30 mg of keto alcohol 142 (R^ = 0.55). The latter two bands could be combined and irradiated again to give an additional

8 mg of diol. Total yield = 20 mg (2C$). Recrystallization from ethyl acetate gave pure l40, mp l42-l43°C; IR (KBr, cm-1) 3560, 2950 , 2925 ,

1168, and 1098; hi NMR ( 6 , CDC13) 3 -0 -0 .8 (m, 22H), 1 .1 6 ( s , 6 h ); l3 C

NMR (ppm, CDCI 3 ) 96 . 3 7 (s), 71. 85 (s ), 6 5 .5 4 (d ), 60 . 87(d ), 60 . 56 ( d ), 186

59.17(a), 55.41(d), 32.10(t), 23.9l(t), 23.73(b), 20.63(q); m/e calcd

524.2089, obs 324.2097.

Anal. Calcd for Css^s^s: C, 8l . 44; H, 8. 70. Bound: C, 81.33;

H, 8.70.

B. Reduction of Diketone l4l -with Lithium Diisopropylamide.

A solution of LDA "was prepared by dissolving diisopropylamine (0. 56 ml, 4.4 mmol) in 3 nil of tetrahydrofuran. After cooling of the solution to -78°C, n-butyllithium (3*33 ml, 4.0 mmol) -was added via syringe. The cooling bath was removed and the mixture allowed to warm to 25°C for

0. 5 h r. The LDA so lu tio n was now brought to 0°C and a s o lu tio n o f d i ketone l4l (120 mg, 0. 373 mmol) in 5 ml of tetrahydrofuran was added. o The solution was warmed to 25 C and stirred for 6 hr before being quenched with water and added to 75 ml of ether. The organic layer was washed with dilute hydrochloric acid solution ( 2x), water, and brine prior to drying. Removal of solvent gave 140 mg (97%) of diol which was recrystallized from ethyl acetate to give 90 mg of pure l40.

Hexadecahydro-4,8-dimethyl-4, 8b :4 a , 8-dimethanodipentaleno[1,2,3- c d :l* , 2 *, 3 f-gh]pentalene- 9, 10-dione (l4i).

D iol l4 0 (80 mg, 0.25 mmol) was

dissolved in 12 ml of pyridine

with stirring under nitrogen.

Lead tetraacetate (400 mg, 0.9

CH3 mmol) was added and the resulting orange-red mixture was stirred at 25°C for 1 hr, then treated ■with oxalic acid (120 mg) and 4 drops of water. After being stirred for 5 min, the yellow mixture was filtered through Celite and the residue was rinsed with ether. The combined filtrates were concentrated under reduced pressure to give a gummy solid.

Preparative TLC (lC$ ether-lC$ methylene chloride- 8C$ hexane) on silica gel gave 72 mg (91$) of diketone l4l. Recrystallization from ethyl ace tate gave pure l4 l, mp 176-177* 5°C; IR (KBr, cm-1) 2962 , 2905, 1758?

1448, and 952; XH NMR ( 6 , CDC13) 3.7-3-1 (»> 2H), 3-1-0- 8 (»» 1 & ),

1 .1 6 ( s , 6 h); 13C NMR (ppm, CDC13) 215.56(b), 69 . 67 (a), 60.75(d),

60 . 50 (d ), 57 . 83(d ), 53 . 77(d), 51.64(a), 29. 6 l(t), 22.27, 22.15, 21. 60 ; m/e c alc d 322. 1933, obs 322. 1939.

Anal. Calcd for Os ^ i 2 eO Z i C, 81. 95 ; H, 8. 13. Ibund: C, 81. 85 ;

H, 8.14.

Reductive Cyclization of 42_ in Sodium Liquid Ammonia. Synthesis of

Methyl 0ctadecahydro-2a, 3a,7-trimethyl-3-oxo-lH-cyclopenta[ 3j^Pen,fcaleno-

[ 2 ,1 , 6 -gha]pent alenoC1,2,3-cdlpentalene-7-carboxylate (l47), Methyl Hexa- decahydro- 9-hydroxy- 8-methyl-l,4, 8-methenodipentaleno[ 1 , 2 , 3-c d :1 *, 2 *, 3 *- gh]pentalene-4(lH)-carboxylate (l48) and Octadecahydro-2a,3a,5a,6a- tetramethylbiscyclopenta[ 3 ,4]pentaleno[2,1,6-cde:2',1*,6*-ghalpentalene-

3 , 6 -dione (l4g). 188

Dichloro diester |j^(800 mg, 1. 89 mmol) was dissolved in 25 ml of tetrahydrofuran and added in rapid dropwise fashion to a stirred solu tion of sodium (800 mg, 34.8 m g-at)in 250 ml o f liq u id ammonia and 50 ml of dry tetrahydrofuran cooled to -78°C. After 15 min under nitrogen, methyl iodide (20 ml) was added at a rapid rate. The ammonia was al lowed to evaporate and the remaining solution added to ether (700 m l).

The organic phase was washed with water, sodium thiosulfate solution, water, and "brine prior to drying over magnesium sulfate. The solution was filtered and, upon removal of the solvent, keto ester lVf crystal lized (500 mg, 45$). The mother liquors contained a mixture which was separated by preparative TI£ on silica gel (lC $ dichloromethane-

15$ ether-75$ hexane). Additional 147 (110 mg) was obtained at R^ =

0 .5 thereby bringing the total yield of 147 to 410 mg ( 6 l$ ). Re crystallization from ethyl acetate gave the analytical material, mp l60-l62°C; IR (KBr, cm-1) 1730, 1450, 1140, and 1120; 1H NMR ( 6 , CDCI3)

4 .4 -0 .8 (m, 20H), 3 .5 6 (s, 5H), 1.3 6 (s, 3H), 1.21 (s, 3H), 1.10 (s,

3H); 1SC NMR (ppm, CDCI3) 231. 50 , 176 . 87, 65 .15 , 64.18, 62.02, 61.75

61 . 38, 60 . 96 , 59-41, 59 . 20, 56 . 68 , 55.98, 53-16, 50.88 ( 2C), 50 . 58 ,

43. 24, 38. 72, 34. 98, 31. 62 , 31. 31, 30. 16 , 27. 85 , and 24. 85 ; m/e calcd

368 . 2351 , obs 368.2340.

Anal. Calcd for C 24H32O3: C, 78.2 2 ; H, 8. 75 . Eound: C, 77.9 7 ;

H, 8. 78.

At Rf = 0.5, hydroxy ester 148 (105 mg, 15$) was o btained. Re crystallization from ethyl acetate gave pure §2^ mp 108-109°C; IR (KBr, cm-1) 3480, 2950, 1700, 1190, and 1115; % NMR ( 6 , CDC13) 5.25 ( s , IH ), 189

24. 22, and 19- 47; m/e calcd jhO. 2038, obs 340. 2046.

Anal. Calcd for 0221*2803: C, 77- 6 l ; H, 8. 29. Ibund: C, 77-51;

H, 8. 30.

At Rf = 0.2, diketone ljjj?_ was obtained (15 mg, 1. 9$); 1®® ( 8,

CDCI3) 4. 0-0 .9 (m, l 8H), 1.23 (s, 6 H), 1.10 (s, 6 H); m/e calcd 350.2247, obs 350.2253.

Methyl Hexadecahydro-9-methoxy-8-methyl-l,4, 8-methenodipentaleno-

[1,2,3-cd:! 1,2* >3*-gh]pentalene-4(lH)-carboxylate (1^1).

Hydroxy ester l48 (50 mg, 0.154

mmol) was d isso lv e d in 5 ml o f

dry benzene. Sodium hydride (10

mg oil free) was added along with

1 ml of methyl iodide. The mix

ture was heated at the reflux temperature for 24 hr, cooled, quenched with water, and extracted with

ether. Preparative TLC on silica gel ether-hexane) separated the

ether l48 (R^ = 0.25) from the hydroxy ester l48 (R^ = 0.2 ). There was obtained 3° mg ( 5 ^ , 9$ based on recovered 148) of product, mp

178-l80°C (from ethyl acetate); IR (KBr, cm”1) 2940, 1730, l l 8o, 1130, and 1076; 1H NMR ( 6 , CDC13) 3. 65 - I . 0 (m, 21H), 3.60 (s, 3H), 3.45 (s,

3H), 1.16 (s, 3H); l3C MR (ppm, CDCI 3) 175-21, 87.00, 62.00, 6 l . 46

(2C), 59.58, 58.55 (2C), 57.58, 52.48, 50.95 (2C), 50.05, 48.65, 48.40 190

(2C), 32.77, 26.75 (2C), 26 . 26 , 25 . 83, 20.20 ( 23rd signal not observed and may overlap); m/e. calcd 354.2195, obs 354.2203.

Anal. Calcd for C23H30O3: C, 77*93; H, 8.53* Ibund: C, 77*84;

H, 8.49.

Hexadecahydro-9-hydroxy- 8-methyl-l, 4,8-methenodipentaleno[l,2, 3- cd:l*,2* ,5l-gh]pentalene-4(lH)-methanol (152).

Hydroxy ester 148 (500 mg, 1.47

mmol) was d isso lv e d in 20 ml o f

toluene and cooled to -78°C. Di

isobutyl aluminum hydride (l M

in hexane, 3 * 7 m l, 3 * 7 mmol) -was

added (fizzing noted) and the mixture was warmed gradually to 25°C. After 6 hr, TLC analysis showed that some starting material remained. LiAlH 4 (50 mg) and AICI 3 (60 mg) were added along with 10 ml of ether and the mixture was stirred for 60 hr. The reaction mixture was quenched with water and extracted with dichloromethane. The combined organic extracts were washed with dilute hydrochloric acid, water, and brine, then dried over magnesium sulfate. Upon removal of solvent, the desired diol 152 crystallized on standing. Beerystaliization from ethyl acetate-ether gave a color less solid, mp 133-135°C; IR (KBr, cm"1) 3400, 2930, 1383, 1122, and

IO38; XH NMR ( 6 , CDCI3) 4.14 (| ABq, J = 11 Hz, IH), 3 .7 8 ( i ABq, J =

11 Hz, IH), 2.9-0.9 (m, 23H), 1.12 (s, 3H); l3C NMR (ppm, CDC13) 83.6 0 ,

62.97, 59*43, 58.72, 56.61, 56.17 (2C), 56.00, 54.96, 54.59, 51.32,

50 . 22, 47.94, 47.87, 47.16, 28. 33, 27.67, 27.31, 26.17, 25.39, and 19.27; m/e calcd (M+-H 20 ) 294. 1985, obs 294. 1991. 191

Anal. Calcd for CsiHaaOs: C, 80.73; H, 9- 03. ibund: C, 80.84;

H, 9 -0 2 .

Hexadecahydro-9-hydroxy- 8-methyl-l,4, 8-methenedipentaleno[1,2,3- cd: 11,2*, 3 '-ghlpentalene-4(111) -methanol 4-(4-Methylbenzenesulfonate)

(133).

D iol ljj>2 (1 0 0 mg, O.32 mmol) was CH2 0 TS dissolved in pyridine (5 ml) and

cooled to 0°C. To this solution

was added j>-toluenesulfonyl chlo-

r id e (69 mg, 0.3 6 mmol) and 4-N,N-

dimethylaminopyridine (20 mg, 0.16 mmol). The mixture was allowed to stand at 0°C for 3 days. Ice chips were added and the mixture was added to dichloromethane and washed with water (2x) and brine prior to drying over magnesium sulfate. The fil tered solution was evaporated in dryness in vacuo to give 62 mg (42$) of the purified tosylate; IR (KBr, cm-1) 3538, 1355} H73> 845, and

665 ; 1H KMR ( 6 , C5 D5 N) 7. 9^ (£ ABq, = 8 Hz, 2H), 7.26 (£ ABq, =

8 Hz, 2H), 5.91 (s, IH), 4.78 ( | ABq, = 10.5 Hz, IH), 4.71 (i ABq,

-AB = 10,5 Hz» ^ 3-2-0. 7 (m, 21H ), 2.18 ( s , 3H ), l . l 8 ( s , 3H); m/e

294 (M+-Ts0H).

0 ctadecahydro- 3a-m ethyl- 7-methylene- 3H-cyclopenta[ 3,4]pentaleno-

[ 2, 1 , 6 -gha]pentaleno[l, 2 , 3-cd]pentalen- 5 -one (154)•

Hydroxy tosylate 15? (5 0 mg, 0 .1 1 mmol) was added as a slurry in tert-butyl alcohol to a solution of potassium tert-butoxide in tert- butyl alcohol (prepared by adding

potassium hydride (10 mg) to 5 nil

of dry tert-butyl alcohol). The

mixture was stirred under nitrogen

ch3 for 5 hr, added to water, and ex

tracted with ether (jx). The com bined ether extracts were washed with water (2x) and brine. The solution was filtered and the filtrate was concentrated in, vacuo to give a clear oil. Preparative TLC on silica gel (lC#> methylene chloride-10^) ether-

8056 hexane) separated two components. At % = 0. 3 , 10 mg of an un identified product was obtained which decomposed on standing. At Rf =

0. 35 j desired enone 154 was obtained (15 mg, 3^ ) > ER (KBr* cm-1 ) 1730?

1635 , 887, and 880; *2 NMR (6 , CDCI3) 5.08 (br s, IH ), 4 .7 8 (b r s, IH),

3 .6 -0 .8 (m, 21H), 1.21 (s, 3H); m/e calcd 294. 1983, obs 294.1975*

Methyl Octadecahydro-3b-hydroxy-3a, 6 d, 7-trim ethyl-l, 6 -methano- c.vclopent aT 3 .4]pent aleno[ 2 . 1 , 6 - cde]pent aleno[ 2 , 1 , 6 -ghajpent alene- 7- carboxylate ( 155 ).

Eeto ester 147 (100 mg, 0 .2 8 mmol)

was dissolved in 10 ml of dry de

oxygenated benzene-tert-butanol

solution (4:1) and irradiated with

a 450W Hanovia lamp for l 6 h r un

der nitrogen. The now slightly yellow solution was concentrated in vacuo to give 100 mg of crude crystalline 155. Recrystallization from ethyl acetate afforded 85 mg 193

( 85$) of pure 90; no mp, gradual dec over l80°C; IR (KBr, cm"1) 3560,

3520, 2920, 1720, and 1 1 1 0 ; KMR ( 6 , CDC13) 4. 0-0.8 (m, 20H), 3.63

(s, 3H), 1.31 (s, 3H), l.l4 (s, 6h) ; 13C MR (ppm, CDC13) 177.14,

98.25, 79.07, 69 . 24, 67 . 18, 65 . 96 , 63 . 90, 63 . 48, 6 3 .1 7 ( 2C), 62 . 72,

59.^7, 59-05, 57-59, 52.13, 50.98, 50.07, 41.51, 39. 20, 31. 62 , 30.58,

30.16, 29. 55, 28. 70; m/e calcd for M+-H20 350.2246, obs 350. 2253 .

Methyl 1,la,lb ,2, 3 ,3a,4,5,5a,6,6a,6b,6c,6d,6e,6f-Hexadecahydro-

3a , 6 d, 7-trim ethyl-l, 6 -methanocyclopenta[ 3 ,4]pentaleno[ 2 , 1 , 6 -cde] - pentaleno[ 2 , l , 6 -gha]pentalene- 7-carboxylate ( 156 ).

Hydroxy ester lj5_ (l60 mg, 0.43

mmol) -was d isso lv e d in 15 ml o f

dry benzene and p-toluenesulfonic k ch 3 acid (10 mg) was added. The mix

ture was heated at the reflux

temperature with continuous re moval of water for 6 hr. The benzene was evaporated iri vacuo to leave a yellow oil which crystallized upon standing. Preparative TLC (15$ ether-hexane) of the mixture gave l40 mg (92$) of lp6. Recrystalliza tion from ethyl acetate gave the analytically pure material, mp l4l- l42°C; IR (KBr, cm"1) 2920, 1730, 1260, and 1110; ^ MR ( 6 , CDCI3)

3.70-1.10 (m, 21H), 3.64 (s, 3H), 1.40 (s, 3H), 1.36 (s, 3H), 1.26 (s,

3H); l3c MR (ppm, CDC13) 177- 28, 142.47, 140.60, 79.84, 69.81, 67.14,

62.82, 62.55 , 62.00, 59.62, 59.52, 58.94, 57.38, 53.72, 50.86, 50.03,

48. 31, 40. 83, 40. 03, 29. 03, 28.67, 28. 47, 25.24, 24. 78; m/e calcd

350.2246, obs 350.2254. 194

Anal. Calcd for C 24H30O2: C, 82.24; H, 8. 63 . Pound: C, 8l . 90;

H, 8. 56 .

Methyl Hexadecahydro-4b,7d, 8-trimethyl-l,7-methanocyclopenta[ 3*, 4*3 - pentaleno[ 2 ’, 1 *, 6 *: 1 , 6 , 53pentaleno[ 6 ,,, 1M, 2": 2 ,3,43pentaleno[ 1 , 2-b ]- o x ire n e - 8-carboxylate (15 8) - A. Peracid Oxidation of 156 .

Ene e s te r 15 6 (190 mg, 0.54 mol)

CHdO ■was dissolved in 15 ml of dry me CH?,V° thylene chloride and m-chloroper-

benzoic acid (115 mg o f 89$ p u r ity ,

0. 56 mmol) was added with stirring.

After 15 min, the mixture was added to 100 ml of ether and washed with sodium bisulfite solution,

1($ Na£C03 solution ( 2x), water, and brine, then dried over magnesium sulfate. After filtration and removal of solvent in vacuo, there was obtained 200 mg (10C$) of crude epoxy ester 158. Recrystalliza tion from ethyl acetate gave the analytically pure material, mp l 8l -

182°C; IR (KBr, cm”1) 2933, 1730, 1265, and 1115; ^ NMR ( 6 , CDC13)

4 .0 -1 .0 (m, 18H), 3 .6 8 (s, 3H), 1.40 (s, 3H), 1.26 (s, 3H), 1.21 (s,

3H); l3 C HMR (ppm, CDC13) 176 . 96 , 86 . 66 , 83. 56 , 68 . 1 5 , 66.21, 65 . 36 ,

63 . 30, 62 . 99, 59 . 78, 58 .6 8 ( 20), 57.96, 57.71, 51 . 40, 51 . 04, 49.64,

48.06, 40.17, 38.23, 28.64, 27-37, 24.40 (2C), and 22.89; m/e calcd

366 . 2195 , obs 366 . 2201.

Anal. Calcd for C 24H30O3: C, 78.65; H, 8. 25 . Found: C, 78.29;

H, 8. 4 l. 195

B. Dichromate Oxidation of 156 .

Ene ester lj ?6 (10 mg, 0.03 mmol) -was dissolved in 5 ml of acetone and cooled to 0°C. To this was added h drops of Jones reagent (pre pared by adding 200 g of sodium dichromate dihydrate to 272 g o f con centrated sulfuric acid and 600 ml of water) and the mixture was warmed to 25°C. After being stirred for 2 hr, the mixture was added to water and extracted with methylene chloride (3X)* The combined organic ex tracts were washed with saturated sodium bicarbonate solution, water, and brine prior to drying over magnesium sulfate. The solution was filtered and evaporated at reduced pressure to leave 10 mg o f a crystalline solid which ^-H MR showed to be pure epoxide 138.

C. Pyridinium Chlorochromate Oxidation of 136 .

Ene ester 1 p6 (50 mg, 0.1^3 mmol) was added to a suspension o f pyridinium chlorochromate (100 mg, 0.46 mmol) in 4 ml o f dry methylene chloride with stirring under nitrogen. After being stirred at 25°C for 48 hr, the oxidation proved not complete. The mixture was then heated at reflux for 12 hr and cooled. Ether was added to precipitate the chromium salts and the organic layer was washed with dilute hy drochloric acid, saturated sodium bicarbonate solution, water, and brine. The solution was dried over magnesium sulfate, filtered and evaporated in vacuo to give 55 mg o f pure 15j3 (10C$).

Methyl 1,la,lb ,2, 3 ,3a,3b,5,5a,6,6a,6b,6c,6d,6e,6f-Hexadecahydro-3b- hydroxy- 3a , 6 d , 7-trim ethyl-l, 6 -methanocyclopenta[3,4]pentaleno[ 2 , 1 , 6 -c d e ]- 196 p e n ta le n o [ 2 , l , 6 -gha]pentalene- 7-carboxvlate (j- 59 ).

Epoxy e s te r ljffi (200 mg, 0. 55 mmol)

was dissolved in 15 ml of dry ben

zene. Boron trifluoride etherate CH3 (3 drops) was added and the mix HO ture was stirred at 25°C for 8 CH3 hr, added to 200 ml of ether, and washed with water (2x) and brine. After being dried over magnesium sulfate, the solution was filtered and evaporated to leave 300 mg o f a yellow oil. Preparative TLC on silica gel (5<$ ether-hexane) gave three bands. The first (Rf = 0.6) was a mixture of two unidentified compounds (50 mg). The second band (Rf = 0.4) was recovered epoxide

(40 mg). The third band (R-f = 0.25) "was the allylic alcohol (90 mg,

45$). The recovered starting material was recycled to give an addi tional 20 mg thereby bringing the total yield of 159 to 110 mg (55$).

Recrystallization from ethyl acetate gave the analytically pure ma teria l, mp l67-l69°C; IR (KBr, cm-1) 3555, 2920, 1720, and 1120; XH

MR ( 6 , CDCI3) 5 .3 0 (m, IB), 4.2-0.9 (m, 17H), 3-60 (s, 3H), 1.33 (s,

3H), 1.20 (s, 3H), 1.02 (s, 3H); 13C MR (ppm, CDCI3) 176.48, 156 . 81,

119. 92, 97. 00, 80. 30, 69 . 42, 65 . 98, 65 . 44, 62 . 87, 62.29, 61 . 32, 60 . 20,

59.13, 58.45 , 57 . 87, 52 . 82, 50 . 78, 47.43. 42.77, 40.68, 39. 03, 31. 70,

27.04, and 18. 25 ; m/e calcd 366 . 2195 , obs 366 . 2203.

Anal. Calcd for C24H3o03: C, 78.6 5 ; H, 8 . 25 . Found: C, 78.6 4 ;

H, 8.29. 197

Methyl Hexadecahydro-4b,7d,8-trimethyl-3-oxo-l,7-methanocyclopenta-

[ 3' , 1+1 ]pentaleno[ 2 ’ , 1 1, 6 1 : 1 , 6 , 5 ]pentaleno[ 6 ", 1", 2": 2, 3,4]pentaleno[ 1, 2-h ]-

o x ire n e - 8-carboxylate (l 6 p). A. Pyridinium Chlorochromate Oxidation of

i22r Allylic alcohol 139 (100 mg, 0.33

mmol) was added as a solution in

5 ml of methylene chloride drop- CH3 wise to a suspension of pyridinium

chlorochromate (170 mg, 0. 8 mmol)

in 10 ml of methylene chloride.

The mixture was stirred under nitrogen for 48 hr. Ether was added to precipitate the chromium salts and the solution was decanted from the brown salts. The salts were triturated with ether and the combined

ether extracts were washed with dilute hydrochloric acid, saturated

sodium bicarbonate solution, water, and brine. After being dried over magnesium sulfate, the solution was filtered and evaporated in vacuo to

give 75 nig of a yellow oil. Preparative TLC (5$ ether-hexane) gave

epoxy keto ester l 60 (Rf = 0. 2). Becrystallization from ethyl acetate

gave pure l60 (54 mg, 53$), mp 196-197°C; IR (KBr, cm"1) 1732, 1718,

1118, and 1108; XH NMR ( 6 , CDC13) 4.2-1. 0 (m, 14h), 3.70 (s, 3H), 2.07

Cl ABq, = 12 Hz, Av^ =8.1 Hz, 1H), I .9 8 (k ABq, = 12 Hz, Av^ =

8.1 Hz, 1H), 1.46 (s, 3H), 1.28 (s, 3H), 1.21 (s, 3H); l3C NMR (ppm,

CDCI3) 217. 92, 176 . 66 , 84.84, 84.11, 69 .OO, 64.69, 63 . 42, 62 . 51 , 61.54,

61.35, 59-59 ( 2C), 57-77, 57.65, 55 . 22, 51.34, 47.27, 40.96, 40.05, 39.57,

26 . 52 , 24.64, 23. 91, and 16 . 08; m/e calcd 380. 1987, obs 380. 1992. 198

Anal. Calcd for Cs^iseP^i C, 75- 76; H, 7- ^2. Sbund: C, 75* 65;

H, 7.^1.

B. Dichromate Oxidation of 159.

Allylic alcohol 1^9 (3° mg, 0.08 mmol) was dissolved in 5 ml of

acetone and cooled to 0°C. To this was added 280 mg of a stock solution of Jones reagent (prepared by adding 200 g of sodium dichromate dihydrate,

272 g of concentrated sulfuric acid and 600 ml of water) dropwise over

a period of 0. 5 hr. The mixture was warmed to 25°C and stirred an addi tional 2 hr. The mixture was then added to water and extracted with methylene chloride (3x). The combined organic extracts were washed w ith saturated sodium bicarbonate solution, water, and brine. After being

dried over magnesium sulfate, the solution was filtered and the filtrate

concentrated in vacuo to give a slightly yellow oil (25 mg). Prepara

t iv e TLC ( 5 $ ether-hexane) gave 17 mg of pure 160 (53$)»

C. Pyridinium Chlorochromate Oxidation of l62.

The epoxy alco h o l 162 (10 mg, 0.0 3 mmol) was dissolved in 1 ml of

methylene chloride and added to a stirred suspension of pyridinium

chlorochromate (20 mg) in 2 ml of methylene chloride. After 2.5 hr,

ether was added and the reaction worked up as before to give 10 mg o f

pure 160 .

D. Dichromate Oxidation of l 6 l .

The epoxy alco h o l l 6 l (40 mg, 0.10 mmol) was d isso lv e d in 5 ml o f

acetone and cooled to 0° in an ice bath. Jones reagent (1 0 drops, pre

pared as before) was added dropwise over a period of 20 min. After 2 199 o hr at 0 C the reaction was added to water and extracted with methylene ch lo rid e . Workup as b efo re gave 55 Kg o f pure l6 0 (92$).

Methyl Hexadecahydro-5‘b-hydroxy-5c, 6 d,7-trimethyl-1, 6 -methano-lH- cyclopenta[ 3",4"]p ent aleno[ 2", 1" 6 ": 3 ' , 4 ' }5 ' ]pentaleno[ 6 , , l ’ , 2 ,: 5 , 6 , l ] - pentaleno[l, 2-b]oxirene- 7-carboxylate (l 6 l ) .

A lly lic alco h o l lj>9_ (60 mg, 0. l 6

mmol) was d isso lv e d in 10 ml o f

methylene chloride with stirring

under nitrogen. To this solution

HO was added m-chloroperbenzoic acid ch3 (40 mg o f 8$ p u r ity , 0 .1 9 mmol) and the mixture was stirred for 10 min, added to 50 ml of methylene chloride, washed with sodium thiosulfate solution, 1 C$ sodium carbonate solution, water, and brine, dried with magnesium sulfate, filtered, and evaporated in vacuo to give 60 mg of crystalline epoxy alcohol l 6 l ;

XH NMR ( 6 , CDCI3) 4.09 (d , J = 4 Hz, 1H), 4. 0 -0 .9 (m, 2GH), l.k2 ( s ,

3H), 1.24 (s, 3H), 1.00 (s, 3H); m/e 382.

Methyl Hexadecahydro-3-hydroxy-5b,7d, 8-trimethyl-l,7-methanocyclo- pentaC 3 ' ,4,]pentaleno[2,,l,,6,:l,6,5]pentaleno[6",l",2l,:2,3,4]pentaleno-

[l,2-b3oxirene-8-carboxylate ( 162 ).

Epoxy alcohol l 6 l (20 mg, 0.0 5 mmol) was d isso lv ed in 4 ml o f dry benzene. Boron trifluoride etherate (l drop) was added with stirring under nitrogen. After 1 hr, the mixture was added to 30 ml of ether and this solution was washed with water ( 2x) and brine, dried over 200

magnesium sulfate, filtered, and

concentrated to give 20 mg o f a HO' slightly yellow oil. Preparative

TLC (70$ ether-hexane) gave 11 mg

CH3 o r pure 122 (R^ = 0. 21, 53 $ ); IR (KBr, cm"1) 3500 , 1720, 1270, and

1115; MMR ( 6 , CDCI3) 4 .2 -0 . 8 (m, 17H), 4 .0 (d , = 4 .0 Hz, 1H),

5.68 (s, 5H), 1.57 (s, 5H), 1.24 (s, 6 H).

Hexadecahydro-3-hydroxy-4b, 7d, 8-trim ethyl-l, 7-methanocyclopent a-

[ 3 ',4 ']pentaleno[ 2 1, 1 ’, 6 *: 1,6,5]pentaleno[6M,1",2":2, 3 ,4]pentaleno-

[ l , 2-b]oxirene- 8-methanol ( 168 ).

Hydroxy ester 162 (30 mg, 0. 08

CHS<> CH20H mmol) was dissolved in 4 ml of dry toluene and cooled to - 78°0 .

To this solution was added di

ch 3 isobutyl aluminum hydride (l M in hexane, 500 (il, 0. 5 mmol) and the mixture was gradually warmed to 25°C, stirred for 24 hr under ni trogen, quenched with methanol, and poured into 40 ml of methylene chloride. This solution was washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, water, and brine prior to drying over magnesium sulfate. The solution was filtered and concentrated in vacuo to give 3° mg of 168 as a clear o il, the ^-H MMR of which showed to be about 70$ pure; MMR ( 6 , CDCI3) 4.62 (s, OJH), 4.17 (? ABq, 201

= 11 Hz, 1H), 3-92 (i ABq, = 11 Hz, 1H), 4. 0-0. 8 (m, l8H),

1.23 ( s , 6H), and 1.14 ( s , 3H).

Hexade c ahydro - 4b, Td., 8-trim ethyl-3-oxo-l, 7-methanocyclopenta[ 3*, 4' 3- pentaleno[ 2* ,1 ’, 6*: 1 ,6 ,5Jpentaleno[ 6ll,l" , 2": 2, 3 ,4]pentaleno[ 1,2-b]- o x ire n e - 8-carboxaldehyde ( 169 ).

Epoxy diol I 68 ( 7$ pure material)

CH3 CHO •was dissolved in 1 ml of methylene

chloride and added to a suspension c h 3 of pyridinium chlorochromate (50

ch 3 mg, 0 .2 3 mmol) in 4 ml of methylene

chloride. After 2 hr, ether was

added and the organic layer -was decanted from the salts. This solution was washed with dilute hydrochloric acid, saturated sodium bicarbonate

solution, water, and brine, then dried over magnesium sulfate. The

solution was filtered and concentrated to give 25 mg of a slightly

yellow oil. Preparative TLC (5$ ether-hexane) gave pure epoxy keto

aldehyde l 6 g_ ( l l mg, Rf = 0. 15)5 ^ ( 6 , CDCI3 ) 9-98 (s, 1H), 4.0-

0 .8 (m, 16H), 1 .3 2 (s, 3H), 1.24 (s, 3H), 1 .2 2 (s, 3H); m/e 350 . 1882,

obs 350 . 1889.

1 ,4 b ,5 j 6 , 7,7a,7b,8,8a,8b,8c,8d,8e,8f-Tetradecahydro-l,4b, 8f -

trim e th y l- 1 , 7,8-metheno-3H-cyclopenta[ 3*»4']pentaleno[ 1 ' , 6 ’ , 5 ': 2, 3 ,4 ] -

pentaleno[l",2", 3” :1 , 6]pent aleno[ 1 , 2-b ]o x iren- 3-one.

Epoxy keto aldehyde 169 (10 mg, 0. 03 mmol) was d isso lv e d in a mix

ture of potassium tert-butoxide in tert-but.yl alcohol (prepared by adding 202

5 mg of oil-free potassium hydride

to 4 ml of dry tert-butyl alcohol)

and the mixture was stirred at CH 25°C for 12 hr. The mixture was

c h 3 poured into water and extracted

with methylene chloride ( 3x ).

The combined extracts were washed with water (2x) and brine before dry ing over magnesium sulfate. The solution was then filtered and evapora ted in vacuo to give a clear oil. Preparative TLC (5$ ether-hexane) gave pure 170 (Bf =0.3, 6 mg); IR (KRr, cm-i) 1728, 1603 , and 900;

^ RMR (5 , CDCI3) 6.24 (d , = 3 Hz, IH ), 4. 0-0. 8 (m, 15H), 1.32 ( s ,

3H), 1.22 (s, 3H), 1 .1 5 (s, 3H); m/e calcd 332.1776, obs 332. 1784.

Methyl 0ctadecahydro-3a,6d,7-trimethyl-1,6-methanocyclopenta[ 3 ,4 ] - p e n ta le n o [ 2 , 1 , 6 -cde]pentaleno[ 2, 1 , 6 -gha]pentalene- 7-carboxylate (lj> 7).

Ene e s te r 156 (100 mg, 0. 29 mmol)

was dissolved in 10 ml of a mixture

of methylene chloride-methanol c h 3 (1:3)* Hydrazine (97$, 600 |jl1)

CH3 was added at -10°C. Hydrogen per oxide (2.l4 ml) was added dropwise to the cooled reaction mixture over a period of 45 min. The mixture was stirred at 0°C for 2 hr and at 25°C for 12 hr before being added to ether and washed with water (2x) and brine. After drying over magnesium sulfate, filtration, and removal of solvent in vacuo gave 100 mg of a semicrystalline solid. Preparative TLC gave pure 157* Recrystallization 203 from cold ethyl acetate gave the analytically pure material, mp ll4-

115°C; IR (KBr, cm"1) 2925, 1732, 1260, 1118, and 1115; XH MMR (5, -

CDCI3) 3-7-0.70 (m, 23H), 3 .6 6 (s, 3H), 1.31 (s, 3H), 1.28 (s, 3H), and 1.12 (s, 3H); l3C MMR (ppm, CDCI 3 ) 177-45, 78.95, 72.76, 66 .75 (2C),

m/£ calcd 352.2402, obs 352.2409.

Anal. Calcd fo r C24H3202: C, 81.77; H, 9-15* Ibund: C, 81.47;

H, 9-04.

Octadecahydro-3a,6d,7-trimethyl-l,6-methanocyclopenta[ 3, 4 ]p en ta- le n o [ 2 , 1 , 6 -cde]pentaleno[ 2 , 1 , 6 -gha]pentalene- 7-methanol (171).

A solution of ester 157 (65 mg,

O.185 mmol) in 5 nil of toluene CH3 c h 2 0H was cooled to -78°C and diiso

butyl aluminum hydride (l M in

c h 3 hexane, 1 m l, 1. 0 mmol) was

added. The mixture was stirred at -78°C for 2 hr and allowed to warm to 25°C for 1 hr. After the excess hydride had been quenched with methanol, the reaction mixture was added to 50 ml of methylene chloride and the organic layer was washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, water, and brine. After being dried over magnesium sulfate, the solution was filtered and concentrated in vacuo to give 60 mg o f alcohol 171. Recrystallization from cold ethyl acetate gave the analy tically pure material, mp 78-79°C; hi MMR ( 8, CDC13) 4.20 ( | ABq, = 204

10.5 Hz, Av^ = 9 Hz, 1H), 4.05 (I ABq, = 10.5 Hz, Av^ = 9 Hz, 1H),

4 .0 -0 .8 (m, 21H), 1.39 (s, 3K), 1.12 (s, 6 H); l3 C NMR (ppm, CDC1S)

78. 89, 75-41, 68 . 60 , 67.43, 66 . 22, 65.59 ( 2C), 65 . 40, 64.72, 59-15,

58 . 70, 58 . 06 , 57 . 00, 52.54, 51.90 ( 20) , 40.34, 38. 16 , 35. 59, 5^* ^7,

31. 12, 30.9 5 , 50 . 29; m/e calcd 324.2453 , obs 324.246l.

0ctadecahydro- 3a , 6 d ,7-trim ethyl-l, 6 -methanocyclopenta[3,4]penta- le n o [ 2, l , 6 -cde]pentaleno[ 2, l , 6 -jgha]pentalene- 7-carboxaldehyde ( 172).

A so lu tio n o f alco h o l 171 (60 mg,

0. l 8 mmol) in 1 ml of methylene

chloride was added to a suspension

of pyridinium chlorochromate (60

mg, 0 . 28 mmol) in 5 nil of methylene

chloride with stirring under ni trogen. After 1.5 hr, ether was added and the organic layer was decanted and washed with dilute hydrochloric acid solution, saturated sodium bi carbonate solution, water, and brine. The solution was dried over mag nesium sulfate and filtered. Concentration of the filtrate gave 60 mg

(10C5&) o f 172 as a clear oil which crystallized upon standing. Re crystallization from ethyl acetate at 70°C gave pure aldehyde, mp 96-

98°C; IR (KBr, cnr1) 2905 , 2665 , 1712, 1450, and 1375; ^ NMR ( 6 ,

CDCI3) 9.92 (s, 1H), 4.2-0. 8 (m, 20H), 1 . 30 (s, 3H), 1.16 (s, 3H), and

1.10 (s, 3H); l3C NMR (ppm, CDCI 3) 204.21, 78.59, 73-07, 67 .0 6 (2C),

66 . 45 , 65 . 90, 64 . 81, 64.21, 64 . 08, 59 - 78, 59.47, 58.93, 52.37, 51 . 40,

50 . 25 , 40.72, 35-99, 34.71 ( 20) , 31. 86 , 30. 83, 29.43; m/e calcd 322. 2297, obs 322. 2303. 205

Anal. Calcd for C 23H30O: C, 85 . 66 ; H, 9* 38- Pound: C, 85 .'75;

H, 9. %

Photolysis of Aldehyde 172. Synthesis of Octadecahydro-3a,6,7- trim ethyl-1,6,7-metheno-lH-cyclopenta[ 3 ,4]pentaleno[2,1,6-gha]pentaleno-

[l,2,3-cd]pentalen-2-ol (195) and Isomeric Alcohol ( 196 ).

Aldehyde 172 (100 mg) -was dissolved in 8 ml of a 9s 1 toluene- ethanol solution. The mixture was cooled to -78°C under nitrogen and irradiated with a 450W Hanovia lamp through pyrex. After 2 hr, o the solution was warmed to 25 C and the solvent was removed under re duced pressure. Preparative TLC (l($ methylene chloride-1^ ether -

75$ hexane) on silica gel gave three bands. The major band (Rf = 0. 8) was a mixture of decarbonylated materials (50 mg). The other two bands

(R f = 0.4 and 0. 3 ) comprised mixtures of the four expected alcohols, epimeric lg£ and 196 (^0 mg, IR (KBr, cm-1 ) jKOO, 2920, 1365 , and 1083; m/e calcd 322. 2297, obs 322. 2303.

Oxidation of Alcohols 195 and 196 . Synthesis of Octadecahydro-

3a, 6 ,7-trimethyl-l, 6 ,7-metheno-2H-cyclopenta[ 3, Hpentaleno[ 2,1, 6 - gha] - 206 p e n ta le n o [ 1 ,2 ,5-cd]pentalen-2-one (197) and Isomeric Ketone ( 198).

CH CH

CH ch3

The mixture of crude epimeric alcohols 199 and 196 (40 mg, 0.12 mmol) was d isso lv ed in 1 ml of dichloromethane and added under nitrogen to a stirred suspension of pyridinium chlorochromate (35 nig, 0 .1 6 mmol) in dichloromethane (5 ml). After 2.5 hr, ether (15 ml) was added and the liquid was decanted from the brown salts. The salts were tri turated with ether ( 2x) and the combined ether extracts were washed with dilute hydrochloric acid solution, saturated sodium bicarbonate solution, water, and brine. After being dried over magnesium sulfate, the ether solution was filtered and concentrated in vacuo to give 37 mg (92$) of a slightly yellow oil. Preparative TIC on silica gel (l(# ether in hexane elution) gave a mixture of the two ketones 197 and 198

( 2 8 .5 mg). One isomer apparently predominates by NMR but the particular isomeric structure could not be assigned to the respective ketones; IR

(CDCI3, cm’1) 2925, 1715, and 1368 ; ^ NMR ( 6 , CDC13) 3.9 -0 . 6 (m, 19H),

1 .2 6 ( s , 3H), 1 .1 8 (s, 3H), l.lfc (s, 3H); m/£ calcd 320. 21^0, obs

320. 21U8. 207

Hexadecahydro-2,6d,7-trimethyl-l,6,2,5-ethanediylidenecyclopenta-

[ 5< 4]pentaleno[ 2 ,1 ,6-cde]pentaleno[ 2 ,1 ,6-gha]pentalen-3~b( 1H) -ol (lg9) •

A mixture of isomeric ketones 197

and 198 (10 mg, 0. 031 mmol) was

dissolved in 3 ml of a solution of

benzene ( 8($) and tert-butyl alco

h o l ( 20$) and irradiated with a CH3 45 OW Hanovia lamp for 1 6 hr through pyrex. The solvent was removed in vacuo to give a yellow o il which was subjected to preparative TLC on silica gel (l($ ether and 1<$ dichloro methane in hexane) to give 9 mg ( 9$ ) of pure alcohol 199? ® (KBr* cm"1) 3410, 29^0, 11)48, 1005; XH MMR ( 6 , CDC13) 4. 0-0.8 (m, 19H), 1.29

(s, 3H), 1.25 (s, 3H), 1.17 (s, 3H); m/e calcd 320.2140, obs 320. 2132.

Dehydration of 199. Synthesis of 1,la,lb ,2,3,3c,4,5,5a>6, 6 a , 6 b , 6 c,

6 d ,6 e,6f-Hexadecahydro-2, 6 d,7-trim ethyl-l, 6 ,2 ,5-ethanediylidenecyclopenta[3«4]pentaleno[2,1, 6 -cde]pentaleno[2,1, 6 -gha]pentalene (200) and Iso mer 201.

.CH

ch3 ch 3

To a solution of alcohol 199 (9 mg, 0. 028 mmol) in 3 ml of benzene was added one crystal of £-toluenesulfonic acid and the mixture was 208 heated at the reflux temperature fbr 15 min. The mixture was cooled to

25°C, added to 20 ml of ether, and washed with saturated sodium bicar bonate solution, water, and brine prior to drying over magnesium sul fate. The solution was filtered and evaporated to dryness under re duced pressure to give 8 mg of a clear oil containing a mixture of iso meric olefins 200 and 201 which could not be separated; NMR (6, CDCI3 )

5 . 8-0.6 (m, 17H), 1.21 (s, 9H); m/e 302.

Hexadecahydro-2, 6 d,7-trim ethyl-l,6,2,5-ethanediylidenecyclopenta-

[ 3>^]pentaleno[ 2 , 1 , 6 -cde]pentalene[ 2, 1 , 6 -gha]pentalene ( 202 ).

A solution of olefins 200 and 201

(15 mg, 0 .0 5 mmol) was dissolved

in 5 ml of ethanol to which 1 ml

of ethanol had been added to aid

in dissolution. The mixture was

cooled to -10°C and hydrazine

(200 yd, 6.25 mmol) was added. Chilled hydrogen peroxide ( 3$ , 680 yd) was added dropwise over a period of min and the resulting solution was stirred for 6 hr while being allowed to warm to 25°C. The reaction mixture was added to water and extracted with pentane (3 x 15 ml). The combined pentane extracts were washed with water ( 2x) and brine before drying over magnesium sulfate. The solution was filtered and evaporated to dryness in vacuo to give 13 mg ( 86£) of trimethylsecododecahedrane

202; hi NMR ( 6 , CDC13) 3. 8-0.5 (m, 19H), 1.26 ( s , 3H), l . l 8 ( s , 6 h ); m/e 3

Reductive Cyclization of 42 in Lithium-Liquid Ammonia. Synthesis of Methyl 0ctadecahydro-3a,7-dimethyl-3-oxo-lH-cyclopenta[3,4]pentaleno-

[ 2 ,1 , 6 -gha]pentaleno[1,2,3-cd]pentalene-7-carboxylate (150), Trimethyl

Keto Ester 147 and Hydroxy Ester 148.

Dichloro diester 42^(600 mg, 1.42

mmol) was dissolved in 25 ml o f

tetrahydrofuran and was added

dropwise to 250 ml of liquid am

monia a t - 78°C which contained ch 3 lith iu m (150 mg,. 21.4 m g-at) and

50 ml of dry tetrahydrofuran. Upon completion of the addition of the dichloride, the reaction mixture was stirred at -78°C for 10 additional min, then quenched by the rapid addition of methyl iodide (10 ml). The ammonia was allowed to evaporate and the resulting organic solution was immediately added to ether (500 ml). This solution was washed with water, sodium thiosulfate solution, water, and brine prior to drying over magnesium sulfate. The solution was filtered and the ether was removed to leave 560 mg of a clear oil. Preparative TKJ (l($ methylene chloride- 15 ^ e th e r - 75$ hexane) gave keto ester 150 (R^ =

0 .2 5 , 260 mg, 5256 ). Recrystallization from ethyl acetate gave pure

150, mp 179-180^; IR (KBr, cm"1) 2950, 1730, 1720, 1271, and 1130;

NMR (6 , CDCI3) 4.0-0.8 (m, 21H), 3.62 (s, 3H), 1-39 (s, 3H), 1.21 (s,

3H); l3 C NMR (ppm, CDCl3) 228. 73, 1 7 6 .90, 64.51, 63 . 96 , 63 . 72, 62.45,

59.47 ( 2C), 56 . 62 , 56 . 50 , 55 . 95 , 55.04, 52 . 86 , 50.86 ( 2C), 50 . 55 , 58 . 90,

34. 96 , 34.04, 30. 95 , 30. 71; m/e calcd 354.2195, obs 354.2203. 210

Also obtained from this reaction were keto ester lk j (Rf = 0. 3,

100 mg, 1$ ) and hydroxy ester l48 (R^ = 0. 5 , 100 mg, 22$ ).

Methyl 0ctadecahydro-3b-hydroxy-6d,7-dimethyl-l, 6 -methanocyclo-

p e n ta [ 3,^]pentaleno[ 2 , l , 6 -cde]pentaleno[ 2, l , 6 -^ha]pentalene- 7-carboxylate

(173).

Keto ester lpO (100 mg, 0. 3 mmol)

was dissolved in 10 ml of a solu

tio n o f 2056 tert-butanol in ben

zene which was subsequently de

oxygenated with nitrogen. Two

drops of triethylamine were added

and the mixture was irradiated with a tyjOW Hanovia lamp through pyrex

for 16 hr. The solvent was removed in vacuo to leave crude crystalline hydroxy ester ljp (100 mg). This material was not purified; IR (KBr,

cm"1) 3500, 1708, 1130, and 1000; ^ MMR ( 6 , CDC13) k. 0 -0 .8 (m, 21H),

3 .6 3 (s, 3H), 1.38 (s, 3H), 1.11 (s, 3H); m/e calcd 35^.2195, obs

35^. 2203.

Methyl 1,1a,lb,2, 3, 3a, 5 ,5 a ,6 , 6 a, 6 b, 6 c , 6 d ,6 e , 6 f-hexadecahydro- 6 d ,7-

dim ethyl- 1 , 6 -methanocyclopenta[ 3,^]pentaleno[ 2 , 1 , 6 -cde]pentaleno[ 2 , 1 , 6 -

gha]pentalene- 7-carboxylate (l 7j+).

Crude hydroxy ester 1£5 (100 mg, CH*0 0 .2 8 mmol) was d isso lv e d in 10 ml

of benzene along with ^toluene-

sulfonic acid (3 mg). The mixture

was heated at 8o°C fb r 0 .5 h r th en 211 freed of solvent. Preparative TLC (l($ ether in hexane) on silica gel gave 67 mg (71$) of pure 174. Recrystallization from ethyl acetate gave analytically pure m aterial, mp 127-128°C; IR (KBr, cm-1) 1730?

1258 , and 1115; NMR ( 6 , CDC13) 3- 7-0.6 (m, 19H), 3.6 1 (s, JH), 1.3 6

(s, 3H), 1.17 (s, 3H); 13C NMR (ppm, CDC13) 177.25, 140.36, 139.19,

79-57, 67.58, 62.73 (2C), 62.34, 59.67 (2C), 58.9^, 57.00, 50.88, 48.84,

48.16, 45.54, 41.12, 30.25, 28.79, 28. 35 , 25.49, 24.37; m/e calcd

336 . 2089, ohs 336 . 2095 .

Anal. Calcd for C 2^H2££>2: C, 82.10; H, 8. 30. ibund: C, 82.11;

H, 8. 47.

Methyl Hexadecahydro- 6 d, 7-dimethyl-l, 6 -methanocyclopenta[ 3,4] - p e n ta le n o [ 2 , l , 6 -cde]pentaleno[ 2 , l , 6 -_ghn]pentalene- 7-carboxylate ( 175 ).

To a solution of ethanol (10 ml)

ch3.°vI1§ and tetrahydrofuran (2 ml) contain

ing o le f in 174 (lOO mg, 0 .3 mmol)

was added hydrazine (800 |xl, 25

mmol) and the mixture was cooled o , to 0 C. Hydrogen peroxide (J.2 g o f 3$ ) was added dropwise over a 45-min period and the mixture was al lowed to gradually warm to 25°C where stirring was maintained for 6 h r.

The solution was added to ether (100 ml) then washed with water (2 x

25 ml) and brine. The dried ether solution was filtered and evaporated in vacuo to give 100 mg (100$) of crude crystalline ester 175. Re crystallization from ethyl acetate gave pure ester, mp 138-l40°C; IR

(KBr, cm-1) 1725, 1130, and 1118 cm"1; Hi NMR ( 6 , CDC13) 3.6 5 ( s , 3H), 212

Hexadecahydro- 6 d,7-dimethyl-l,6-methanocyclopenta[3 5 43pentaleno-

[ 2 , 1 , 6 -cde]pentaleno[ 2 , 1 , 6 -gha]pentalene- 7-methanol ( 176 ) •

To a solution of ester 17^ (100 ing,

0 .3 mmol) in to lu e n e (1 0 ml) cooled

to - 78°C was added diisobutyl alumi

num hydride (l M in hexane, 2 ml,

2.0 mmol) via a syringe. The mix c h 3 ture was stirred at -78°C for 5 min, warmed gradually to 25°C, and stirred for 3 br. The excess reagent was quenched with methanol and the mixture was added to ether (100 m l).

The ether solution was washed with dilute hydrochloric acid solution, saturated sodium bicarbonate solution, water, and brine. The dried solution was filtered and evaporated to dryness in vacuo to give 89 mg

(97$) of the desired alcohol 176 . Recrystallization ftom ethyl acetate gave pure alcohol, mp l44-l46°C; IR (KBr, cm"1) 3350? 1020, and 1010;

^ MR ( 6 , CDCI3) 4.20 (br s, 2H), 3-9-0. 8 (m, 22H), 1.21 ( s , 3H), 1.13

(s, 3H); m/e calcd 310.2297, obs 310. 2305 .

Hexadecahydro- 6 d, 7-dimethyl-l, 6 -methano cyclopenta[ 3? 4]pentaleno-

[ 2 , 1 , 6 -cde]pent aleno[ 2, 1 , 6 -gha]pent alene- 7-carboxaldehyde ( 177)»

To a suspension o f pyridinium chlorochrom ate (100 mg, 0.46 mmol) in dichloromethane (10 ml) was added a solution of alcohol 176 (100 mg, 0. 3 215

mmol) in dichloromethane (2 m l).

The mixture was stirred for 1 hr

and ether (15 ml) was added. The

organic solution was decanted and

the salts were leached two addi- ch3 tional times with ether. The com bined ether layers were washed with dilute hydrochloric acid solution, saturated sodium bicarbonate solution, water, and brine, prior to dry ing over magnesium sulfate. The filtered solution was evaporated to dryness in vacuo to leave 95 mg of crude crystalline aldehyde 177. Re crystallization from ethyl acetate gave pure aldehyde, mp 132-13^°C;

IR (KBr, cm"1) 2692 , 1718, 1382; ^ NMR ( 6 , CDC13) 9-98 (s, 1H), 3. 8-

0 .7 (m, 21H ), 1 .2 0 ( s , 5 H), 1 .1 2 ( s , 3H); m/e calcd 308. 2140, obs

508 . 2150 .

Oct adecahydro-5a, 7-dim ethyl-l, 6 , 7-metheno-lfi-cyclopent a[ 5 , ^3 - pentaleno[ 2 , 1 , 6 -gha]pentaleno[ 1 , 2 ,3- c d3 pentalen-5-ol (122.) •

Aldehyde 177 (100 mg, 0. 3 mmol) was

dissolved in 10 ml of a toluene-

ethanol (9:l) solution. Triethyl-

amine ( 0.25 ml) was added and the

solution was deoxygenated with ni- CH3 trogen, cooled to -78°C under ni trogen, and irradiated with a ^50W Hanovia lamp for 2 hr through pyrex.

The mixture was warmed to 25°C and concentrated in vacuo to give a crystalline solid. Preparative TLC on silica gel (l<$ ether-1C^ 21k

dichloromethane in hexane) gave three products. At = 0. 75, the de-

carbonylation products were obtained (^5 mg). The structures of these

products have not been determined. At Rf = 0.2, the endo alcohol was

o b tain ed (9 mg) while the exo alcohol materialized at R^ = 0 .1 (12 mg).

These two alcohols were combined to give 21 mg ( 21$) of epimeric IgO

IR (CDC13, cm-1 ) 3380, 2920, 1H 5 , and 1010; m/e calcd 308.21^0, obs

308. 2150 .

0ctadecahydro- 3a, 7-dimethyl-l, 6 , 7-m etheno- 3H-cyclopent a[ 3, ^ -

p e n ta le n o [ 2 , 1 ,6-gha3pentaleno[ 1 , 2, 3-cdlpentalen- 3-one ( 191)•

The epimeric mixture of alcohol IgO

(21 mg, 0 .0 6 8 mmol) was d isso lv e d

in 1 ml of dichloromethane and

added slowly to a suspension of

pyridinium chlorochromate (20 mg,

0. 093 mmol) in 5 ml of dichloro methane. The mixture was stirred for 2. 5 bar at 25°C at which point

ether (10 ml) was added and the organic solution decanted. The salts

were leached two additional times with ether and the combined organic

layers were washed with dilute hydrochloric acid solution, saturated

sodium bicarbonate solution, water, and brine prior to drying over magnesium sulfate. The solution was filtered and evaporated to dry

ness in vacuo to give 19 mg ( 91$) of crude crystalline ketone 191.

Recrystallization from ethyl acetate gave the pure material; 1H NMR

( 6 , CDCI3) 3*9-0*8 (series of m, 20H), 1.19 (s, 6 H). 215

Hexadecahydro-6d,7-dimethyl-l,6,2,5-ethanediylidenecyelopenta-

[ 3, 4jpentaleno[ 2,1,6-cde]pentaleno[ 2,1,6-gha]pentalen-3b(lH)-ol (192) •

Ketone 191 (19 mg, 0. 062 mmol) -was

dissolved in 5 nil of a solution

containing 2(# tert-butanol in ben

zene. After suitable deoxygenation

with nitrogen, triethylamine (2

drops) was added and the mixture

■was irradiated with a 450W Hanovia lamp through pyrex under nitrogen

for l6 hr. The solvent was removed in vacuo to give crude alcohol

192. This material was not further purified.

1 ,l a , l b , 2, 5 ,Ja,4,5,5a,6 , 6 a , 6 b , 6 c , 6 d ,6 e ,6 f-Hexadecahydro- 6 d ,7- dimethyl-1,6,2,5-ethanediylidenecyclopenta[ 5 ,4]pentaleno[2,1,6-cde]- p e n ta le n o [ 2 , 1 , 6 -gha]pentalene ( 195 )-

A sample of alcohol 192 (obtained

from the photolysis without puri

f ic a tio n , 19 mg, 0. 062 mmol) was

dissolved in 5 ml of benzene. A

CH3 crystal of £-toluenesulfonic acid

was added and the mixture heated to 80°C. After 0. 5 hr, the mixture was cooled to 25°C and concentrated in vacuo. The resulting yellow oil was subjected to preparative TLC on silica gel (hexane elution) to give 15 mg ( 735&) of the olefin 195 ;

1H NMR ( 6 , CDCI3) 4 .0 -0 .6 (m, I 8H), 1.21 (s, 5H), 1 .1 1 ( s , 5H). 216

Octadecahydro- 6 d ,7-dimethyl-l, 6 , 2 , 5 -ethanediylidenecyclopenta-

[3,4]pentaleno[ 2 , 1 ,6-cde3pentaleno[ 2 , 1 , 6 -gha]pentalene ( 16 ).

A solution of olefin 193 (13 mg,

0.045 mmol) was dissolved in 5 ml

of ethanol to which 1 ml o f d i

chloromethane had been added to

aid in the dissolution. The solu-

tion was cooled to -10°C and an hydrous hydrazine (200 p.1, 6.25 mmol) was added. Chilled hydrogen peroxide ( 3$ , 680 pi) was added dropwise over a period of 45 min and the resulting solution was stirred for 6 hr while warming to 25°C.

The reaction mixture was poured into water and extracted with ether

(3x). The combined ether extracts were washed with water (2x) and brine. After drying over magnesium sulfate, the solution was filtered and concentrated in vacuo to give 12 mg ( 92$) of crystalline mono- secododecahedrane l 6 . Recrystallization from hexane (-10°C) gave the analytically pure m aterial, mp 235-250°; IR (CDC 1 3 , cm"1) 3150, 2925,

1447, and 1375; ^ MMR ( 6 , CDC13) 3. 8 -0 .7 (m, 2QH), l . l 8 ( s , 6 h ); l3 C MMR (ppm, CDCI 3) 78.40 (s), 70.15 (d), 68 .1 6 ( d ), 66 . 08 (d), 58.99

(d ), 52.29 (d), 33.64 (d), 32 .5 8 (t); m/e calcd 290.2034, obs 290. 2026 .

Methyl Hexadecahydro-9-hydroxy-l,4, 8-methenodipentaleno[1,2,3-cd;

1 * , 2*,3f-gh]pentalene-4(lH)-carboxylate ( 178).

Bischloro ether 42_ (10 mg, 0.14 mmol) was dissolved in tetrahydro furan (5 ml) and added dropwise to a solution of sodium (65 mg, 2. 82 mg-at) in liquid ammonia (15 ml) at -33°C. The solution was stirred 217

for 10 min at -33°C. During this

tim e, a second so lu tio n o f ammonia

(50 ml) containing ammonium chlo

ride (l g, 18. 7 mmol) was prepared

and cooled to -78°C. The reaction

mixture was transferred to the second ammonia so lu tio n v ia a cannula and th e ammonia was evaporated.

The residue was added to 30 ml of water and extracted with dichloro methane (4 x 20 ml). The combined organic extracts were washed with water (jx), dried over magnesium sulfate, and filtered. Evaporation of the solvent left a clear oil which was placed directly on a pre parative TLC plate (silica gel). Elution with 2($ ether in hexane gave the product (Rf = 0. 5) as a clear oil (40 mg, 87$). Two additional purifications on silica gel ( 2C$ ether in hexane elution) gave hydroxy e s te r 178 as a crystalline solid, mp 75-76°C; IR (KBr, cm-1) 3450 and

1690; NMR (5 , CDCI 3) 5.15 (s, 1H), 3 .6 8 ( s , 3H), and 2 .9 -1 .1 (m,

22H); l3 C NMR (ppm, CDC13) 178. 37, 80.10, 60. 54 , 60.20, 59 . 96 , 56 . 80,

56.17, 52.98, 51.80 (2C), 51. 4l, 49.37, 48.55 (2C), 48. 26 , 32.58,

27. 82, 25. 78, 25.49, 24. 52 ; m/e calcd 326 . 1882, obs 326 . 1888.

Anal. Calcd for C 21K26 O3: C, 77- 27; H, 8. 03. Pound: C, 77.22;

H, 7.98.

Reductive Cyclization of 42 in Lithium-Liquid Ammonia. Synthesis of

Oct ade c ahydro-7-(hydro xymethyl)-3H-cyclopenta[ 3,4]pentaleno[2 ,1 , 6 - gha]- pentaleno[l,2,3-cd]pentalen-3“One (1 80) and 0ctadecahydro-3-hydroxy-lH- c.yclopenta[3<^]pentaleno[g,l,6-Kha]pentaleno[l,2,3-cd]pentalene-7' methanol (l 8l ) .

A solution of lithium (91 mg, 13*2 mg-at) in distilled ammonia (30 ml) was cooled to -80°C (dry ice/ether) under nitrogen. A solution of dichloro diester 42^ (400 mg, 0.94 mmol) in tetrahydrofuran (3 ml) was added in dropwise fashion. After 10 min, a solution of 2($ tetrahydro furan in ethanol (5 ml) was added rapidly and the resulting mixture was stirred for an additional 30min at -8o°C. S o lid ammonium ch lo rid e

(3.0 g) was added and the ammonia was evaporated. The residue was added to water (30 ml) and extracted with dichloromethane (3 x 20 m l).

The combined organic extracts were washed with water (l x 10 ml), dried over magnesium sulfate, and filtered. Evaporation of the solvent in vacuo gave a clear o il which was subjected to preparative TLC on silica gel (lC$ ether in dichloromethane elution). At = 0. 5, hydroxy ke tone l80 was obtained: 71 mg {2%). Recrystallization from ethyl ace tate gave pure l 8o, mp l65-170°C; IR (CDC13, cm-1) 36 OO and 3400; *11 MMR

( 6 , CDCI3 ) 4 .0 (d , Jpft = 7. 5 Hz, 2H), and 3. 8- 1 .1 (m, 24h); ^ NMR (ppm,

C5D5N) 225.23, 66 . 69 , 61 . 38, 60.94, 59-10, 57.15, 55.56, 54.49, 53-73,

53 . 16 , 52.59, 51.33, 51 . 20, 50 . 70, 48. 17, 35.46, 31*93, 30.59, 29. 96 , and 28. 13; m/e calcd 298. 1933, obs 298. 1927. 219

Anal^ Calcd for C 2OH2s0 2: C, 80. 50 ; H, 8. 78. Ibund: C, 80.45;

H, 8. 85 .

At Rf = 0. i+5, d io l l 8l was obtained. Recrystallization from ethyl acetate gave the analytically pure material, mp 230-232°C; IR (KBr, cm-*-) 3600 , 3430, and 3350; MR ( 6 , C5D5N) 5 .6 (s, 1H), 4.3 (m, 22H), and 3.4 -1 .0 (m, 25H); l s C MR (ppm, C 5D5 N) 79- 47, 66 . 66 , 61.75, 61 . 03,

59.72 ( 2C), 58.94, 58,36, 53 - 74, 52 . 82, 52 . 48, 51 . 80, 51-17, 50 - 54 ,

48. 06, 34. 71, 31. 80, 30. 58 , 28. 84, and 24. 56 ; m/e no M+ observed, 282

(M+-H20).

Anal. Calcd for C 20H20Q2: C, 79- 95; H, 9-39- S o u n d : C, 79* 77;

H, 9-36-

Octadecahydro-3-hydroxy-7-acetoxymethyl-lH-cyclopenta[ 3, 4]pent a- le n o [ 2 , 1 , 6 -gha]pentaleno[ 1 , 2 , 3-cd]pentalene (l 82).

To a solution of diol l 8l (150 mg,

0 .5 mmol) in p y rid in e (5 ml) was CH3 COO added 4-dimethylaminopyridine (5

mg) and acetic anhydride (108 mg,

1.1 mmol). The mixture was stirred

at 25°C for 5 hr, cooled to 0°C, and acidified with 5 N hydrochloric acid. The resulting aqueous solu tion was extracted with dichloromethane (3 x 10 ml). The combined or ganic extracts were washed with 5 N hydrochloric acid and saturated

sodium bicarbonate solution prior to drying over magnesium sulfate.

The filtered solution was evaporated in_ vacuo and subjected to prepara

tive TLC on silica gel (elution with 5<$ ether in hexane). The desired 220 product, hydroxy acetate 182^ was obtained at = 0. 3 : 90 nig ( 53 $ ).

Recrystallization from ethyl acetate-hexane gave the pure material, mp 152-153°C; IR (CDC13, cnr1) '3600 and 1725; XH RMR ( 6 , CDCI3) 4.42

(m, 2H), 4.13 ( t , J ^ , =7-5 Hz, 1H), 3. 70-1.20 (m, 24h), and 2.04 ( s ,

3H); m/e 342.

0ctadecahydro-7-(acetoxymethyl)-3H-cyclopenta[3,4]pentaleno[2, 1 , 6 - gha]pentaleno[1,2,3-cd]pentalen- 3- 0 ne ( 183).

To a stirred suspension of pyri-

dinium chlorochromate (85 mg, 0.394

mmol) in dichlorom ethane (5 ml)

was added a solution of 1 82 (90

mg, 0 .2 6 mmol) in dichlorom ethane

(6 ml). After 2 hr, ether (15 ml) was added to precipitate the inorganic salts and the resulting solution was filtered. The filtrate was concentrated and applied directly to a preparative TLC plate (silica gel). Elution with 50$ ether in hexane

gave keto acetate 183 at R^ = 0.5: 67 mg (79$); IR (CDC13, cm-1) 1725;

XH MR ( 6 , CDC13) 4.41 (d, J =7-9 Hz, 2H), 3.8 -0 .1 (m, 23H), and 2.05 AB ( s , 3H); m/e calcd 340.2038, obs 340. 2033.

Alkaline Hydrolysis of 183. Synthesis of Keto Alcohol I 80.

Keto acetate 183 (67 mg, 0.20 mmol) was d isso lv e d in 2C$ aqueous m ethanol (5 ml) and potassium hydroxide (33 mg, 0 .6 0 mmol) was added.

After being stirred for 1.5 hr, the mixture was concentrated to dryness

and water (10 ml) was added. The aqueous solution was extracted with

dichloromethane (3 x 10 ml) and the combined organic extracts were 221 washed with -water (l x 10 ml) and dried over magnesium sulfate. The filtered solution -was concentrated in vacuo and applied to a prepara tive TLC plate (silica gel). Elution -with 5$ ether in hexane gave

50 mg ( 85$) of hydroxy ketone l 80 a t R^ = 0. 5 which was identical in all respects with the authentic sample.

0ctadecahydro- 3b-hydroxy-l, 6 -methanocyelopenta[3,4]pentaleno[ 2 , 1 , 6 - cde]pentaleno[ 2, 1 , 6 -gha]pentaleno- 7-methanol (184).

Hydroxy, ketone l80 (71 mg, 0.24 mmol)

was dissolved in a solution of 2C$ HO. tert-butyl alcohol in benzene (8

ml). One drop of triethylamine was HO' added and the mixture was irradiated

fo r 10 hr through pyrex with a 4-5 OW

Hanovia lamp. The crystalline material which had formed was filtered and dried to yield 46 mg ( 66 $) of pure 184, mp 240°C dec; IR (KBr, cm-1)

3400 and 3260 ; m/e ealed 298. 1933, obs 298. 1940.

Anal. Calcd for C 20H26 O2; C, 80.50; H, 8. 78. Ibund: C, 80.21;

H, 8.80.

1 ,l a , l b , 2 , 3 ,3a,4,5,5a,6,6a,6b,6c,6d,6e,6f-Hexadecahydro-l,6- methanocyclopenta[ 3,4]pentaleno[ 2, 1 , 6 -cde]pentaleno[ 2, 1 , 6 -gha]penta- le n e - 7-methanol ( 185 ).

To a suspension of diol 184 (80 mg, 0.27 mmol) in benzene (30 ml) was added a single crystal of £-toluenesulfonic acid. This mixture was heated to 60°C for about 1 hr until complete dissolution occurred. 222

The mixture was cooled, concentra

ted in vacuo, and applied direct

ly to a preparative TLC plate

(silica gel). Elution with 50$

ether in hexane gave the desired

product: 73 nig ( 95$ ) a t R^ = 0. 6 .

Recrystallization from ethyl acetate-hexane gave pure 185 , mp 300°C dec; TR (KBr, cm"1) 3370; NMR ( 8, CDC1S) 4.1 (d, = 7. 5 Hz, 2H),

3.73 (m, 2H), and 3- 6-1.3 (m, 20H); l3C NMR (ppm, CDC13) 139-72, 137.34,

74.96, 72.24, 70.35, 64.42 ( 2C), 61 . 56 , 54.23, 53-70, 53-45, 51-70,

50 . 25 , 4 9 . 08, 48. 84, 46. 75 , 30. 25 , 28. 74, 27. 53, and 24. 03; m/e calcd

280. 1827, obs 280. 1835 .

Anal. Calcd for C 20H24O: C, 85 . 67 ; H, 8. 63 . Sbund: C, 85 .4 4 ;

H, 8.79-

Octadecahydro- 1 , 6 -methanocyclopenta[ 3 ,4]pentaleno[ 2, 1 , 6 - cd e]- p e n ta le n o [ 2 , 1 , 6 -gha]pent alene- 7-methano 1 ( l 86 ).

Hydroxy olefin 1 85 (40 mg, 0.14

mmol) was dissolved in 4 ml of a

solution composed of 25 $ dichloro

methane in ethanol. The solution

was cooled in -10°C and anhydrous

hydrazine (352 (j,l, 10.4 mmol) was added, followed by the dropwise addition of cold 3$ aqueous hydrogen peroxide (l. 1 ml of 3°$, 1° mmol) over a period of 1.5 hr. The tem perature was increased gradually to 25°C and stirring was continued 225 fo r 8 hr. The mixture was added to water (10 ml) and extracted with dichloromethane (5 x 10 ml). The combined organic extracts were washed with water (2 x 10 ml), dried over magnesium sulfate, and filtered.

Evaporation of the solvent gave 40 mg (lOC$>) of crude l 86 . P rep ara tive TLC on silica gel (5 0f> ether in hexane elution) gave the pure alcohol at Rf = 0. 5; mp > 250°C; 1H NMR ( 6 , CDC13) 4.28 (d, = 7-5

Hz, 2H) and 3-7-1.4 (m, 24H); l3C MMR (ppm, CDC13) 80. 69 , 70.25, 67 .0 9 ,

65.49, 61.51, 58.45, 55.59, 51.70, 51.56, 51.46, 31. 5 6 , and 31. 02.

Anal. Calcd for C 2dH280: C, 85 .06; H, 28. Ibund: C, 84.66;

H, 9. 54.

Oxidation of 186 with Pyridinium Chlorochromate. Synthesis of

0ctadecahydro-7-methylene-l,6-methanocyclopenta[3,4]pentaleno[2,l,6- cde]pentaleno[ 2, 1 , 6 -gha]pentalene ( 189) and a , 6 -Un sa tu ra te d Aldehyde 188.

To a suspension o f pyridinium chlorochrom ate ( l4 mg, 0. 064 mmol) in dry dichloromethane (l ml), was added a solution of the alcohol 186

(12 mg, 0. 042 mmol) in dichloromethane (2 ml). After 3° min, ether (5 ml) was added and the organic solution was decanted from the salts, concentrated, applied directly to a preparative TLC plate (silica gel), and e lu te d w ith 5 $ e th e r in hexane. The band a t R^ = 0. 8 co n sisted 224 of the olefin 189 (6 mg, 5 $ ) ; ^ NMR (6 , CDCI3) 4.90 (br s, 2H) and

3. 6-1. 5 (m, 22H); rn/e calcd 264 . 1878, obs 264.1885. A second band

(R^ = 0.6) consisted of the a,f3-unsaturated aldehyde 188; IR (KBr, cm-1) 1660 and 1615; XH NMR ( 6 , CDC13) 10.2 ( s , 1H) and 4. 0 -1 .4 (m,

21H); 13C NMR (ppm, CDC13) 186 . 97, 172. 96 , 137-80, 69 . 97, 68 . 70, 67.42,

63 .ll, 57.96, 57-41, 54.92, 53-95, 51 . 83, 51-10, 49.64, 4 8 .9 7 ( 2C),

33. 68 , 30. 95 , 29- 98, and 28. 28. PROTON NMR SPECTRA

COOCH3

MOCOCH3 CH3 COO*

COOCH

-iujiL lL i ^ .jijujuM. m “ I FfWTWH|TCV^“ F W ^ iy*yn ii>*»v

COOCH

COOCH3

A > in»ii

W*N

J 0 8 225 226

4 .(

05 • 1 i 1 * :|l=i|: ‘ 1 ‘ IHPi . t: 227 • ::!jrr '&M liti - - — iPlh:

___ ----- — t - t 1 . 1 .. J •Jiliii."* 1 ~ pj;;; - J~ i Wm r. J i ••jjijji: :• :•••: ?. •: . i rtfJTT* r :• |i ■::! i:i Uilii Ihlii 1 n/iflhJl' • ::?•••:} • a p e 1 S t e •' y 1

' I os 228

‘OH

CH2

7 6 5 4 3 2 | os 'SyM 230

CH3 .OH 233

c h 3

c h 2

0 5

ro o o

"* r j k J

I ■ K i . .

......

••4

ijM ** ch 3 ch 2 oh pNV*

i r,

C H .yo

f t I' ^ C«3 . v 3

CH3 H 0 r

CH3 coo 2k2

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