Xerox University Microfilms

INFORMATION TO USERS

This material was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted.

The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction.

1. The sign or "target" for pages apparently lacking from the document photographed is "Missing Paga(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity.

2. Whan an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. You will find a good image of the paga in the adjacent frame.

3. When a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It is customary to begin photoing at the upper left hand corner of a large sheet and to continue photoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again — beginning below the first row and continuing on until complete.'

4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. Silver prints of "photographs" may be ordered at additional charge by writing the Order Department, giving the catalog number, title, author and specific pages you wish reproduced.

5. PLEASE NOTE: Some pages may have indistinct print. Filmed as received.

Xerox University Microfilms 300 North ZMb Road Ann Arbor, Michigan 40100 75-19,455 JAKES, Donald Richard, 1948- SEMIBULLVALENE AND HYPOSTROPHENE: SYNTHETIC AND CHEMICAL ASPECTS OP SOME FLUXIONAL MOLECULES. The Ohio State University, Ph.D., 1975 Chemistry, organic

J Xerox University Microfilms , Ann Arbor, Michigan 48108

THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED. SEMIBULLVALENE AND HYPOSTROPHENE: SYNTHETIC AND CHEMICAL

ASPECTS OF SOME FLUXIONAL MOLECULES

DISSERTATION

Presented in Partial Fullment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University

Donald Richard James, B.S.

A * i t * *

The Ohio State University 1974

Reading Committee: Approved by

Dr. Gideon Fraenkel

Dr* John Swenton ~ Adviser \5 Dr. Leo Paquette Department of Chemistry ACKNOWLEDGMENTS

I wiBh to express my gratitude to the fine chemists associated with the Department of Chemistry at The Ohio State University for their assistance in my training, but particularly to Professor

Leo Paquette who provided the guidance and drive to carry me through to the end. To my parents, who helped me through college, 1 say thanks. To my wife Elaine and daughter Jessica, who have aided and comforted me from beginning to end, I give my deepest appreciation.

To Elaine, who typed my dissertation, I dedicate this manuscript and finally, I thank those agencies which provided me with financial support: The Ohio State University, The Goodyear Tire and Rubber

Company, and my w ife .

ii VITA

December 3, 1948. . . Born - Frackville, Pennsylvania

1970 B.S., Urslnus College, Collegeville, Pennsylvania

1970-1973 Teaching A ssistant, The Ohio State University, Columbus, Ohio

1973-1974 Goodyear Tire and Rubber Company Fellow

PUBLICATIONS

"Rearrangements Attending Attempts to Form the lrDibenzosemibull- valenylcarblnyKl-Dibenzotrlcyclo[3.3.0.0 * ]octadienylcarbinyl) Cation." S.J.C ristol, G.C.Schloemer, D.R.James, and L.A.Paquette, J. Ore. Chem., 3J, 3852 (1972).

"A Simple Route from Cyclopentadiene to Hypostrophene." L.A.Paquette, R.F.DavIs, and D.R.James, Tetrahedron L ett., 1615 (1974).

"Equilibrium Displacements Resulting from Substitution of the Semibull- valene Nucleus." L.A.Paquette, D.R.James, and G.H.Birnberg, J. Amer. Chem. S o c .. in p re ss, 1974.

"Direct and Indirect Trapping of Isomeric Monosubstituted Blcyclo[4.2.0]- octadienes with Triazolinediones. Photocyclization and Ag(I) Catalyzed Rearrangement of the Derived Adducts as a Route to Functionalized 9,10-Diazasnoutanes." L.A.Paquette, D.R.James, and G.H.Birnberg, ibid., in press, 1974.

"Cheletropic ^2 + ^-2 +

FIELDS OF STUDY

Major Field; Organic Chemistry

i l l TABLE OF CONTENTS

Page ACKNOWLEDGMENTS...... 11

VITA ...... H I

LIST OF TABLES...... V

LIST OF FIGURES...... v i

PART

I. Rearrangement: of the 1-Dibenzosemibullvalenylcarbinyl Cation.

Introduction ...... 1

R e su lts ...... 5

Discussion ...... 8

Experimental ...... 14

II.Equilibrium Displacements Resulting from Substitution of the Semibullvalene Nucleus.

Introduction ...... 19

Results and Discussion ...... 34

Experimental ...... 80

III.Synthesis and Chemistry of Hypostrophene

Introduction ...... 106

Results and Discussion ...... 112

Experimental ...... 133

REFERENCES...... 153

I LIST OF TABLES

Page Table I . A G ^ f o r Cope Rearrangem ents ...... , 31

Table II. Results of Direct and Indirect Addlton of PTAD to Various Monosubstituted Cydooctatetraenes. . . 48

Table III. Results of Photochemical Cyclizations ...... 51

Table IV. Results of Ag*-Catalyzed Rearrangements ...... 57

Table V. Physical Data for the 7,8-Diazatrlcyclo[4.2.2. 0 * ]deca-3,9-diene-7,8-dlcarboxamides ...... 87

Table VI. Physical Data for the 9,10-Diazabasketanes. . . 93

Table VII. Physical Data for the Diazasnoutanes...... 97

Table VIII. Variable Temperature Pmr Shift Data for 91-CH3 ± ; 92-CH3 ...... 102

Table IX. Variable Temperature Pmr Shift Data for 91-C6H5^ j»2-C6H5...... 103

Table X. Variable Temperature Pmr Shift Data for 1 3 9 -C H .^ 140-CH3 ...... 104

Table XI. Variable Temperature Pmr Shift Data for 139-Ff^:140-F ...... 105

i LIST OF FIGURES

Page Figure 1. Selected variable-temperature pmr spectra of l(5)-methylsemibullvalene (60 MHz, CS£ solution), 65

Figure 2. Selected variable-temperature pmr spectra of l ( 5 )-phenylsemibullvalene [100 MHz, CD.C1„~ Freon 11 solution (1:1)] ...... 69

Figure 3. Selected variable-temperature pmr spectra of 2(4)-methylsemibullvalene (60 MHz, CLCl, sol ution at 80° and 99 ; CS„ solution at +52 and b elo w ) ...... 73

Figure 5. Selected variable-temperature pmr spectra of 2(4)-fluorosemibullvalene (60 MHz, CS 2 s o lu tio n ) . 74

Figure 5. Alcohols synthesized from hypostrophene...... 127

vi Part I: Rearrangement of the 1-Dibenzoaemiballvalenylcarblnyl Cation.

Introduction

The 8emibullvalene molecule (1), a structurally compressed homotro- pilidlne, undergoes Cope rearrangement with the lowest known activation energy for this type of reaction.* The highly fluxional character of this hydrocarbon results in the rapid equilibration of carbon atoms

2 and 4 , 6 and 8, and 1 and 5 (3 and 7 remain unchanged). A reactive functionality such as, for example, a -CHj* group at could consequently

experience exchanges between and C,. before its ultimate involvement in chemical reaction. Thus the observable experimental results with such intermediates may not be easily rationalizable due to multicenter reactivity, i.e ., the presence of two reactive intermediates in com petitive self-annihilation. The differences in hybridization and chemical environment at various positions in semibullvalene would govern in large part the percentage of reaction occurring from each substituent position. The semibullvalene molecule thus provides an interesting case for study of the effects of hybridization on reactivity. In order to understand the possibly complex nature of reactions t pursuant to generation of unstable semibullvalene Intermediates, we were led to study first certain nonfluxional model compounds. The dibenzosemlbullvalene molecule ( 2) provides a suitable candidate for these studies since the benzo fusion does not permit operation of the

Cope rearrangement which is inherent in 1.

In this connection, 5 -dibenzosemlbullvalenylcarboxaldehyde tosylhydrazone (3) had previously been shown to decompose in base under 2 aprotic conditions to give 2,3-benzofluorene (4) a reaction which 3 almost certainly proceeds through a carbenic intermediate.

b a s e diglyme

Paquette and Blrnberg have presented evidence derived from deuterium labeling experiments which indicates that a 1, 2-phenyl migration to 2 the carbene center la responsible for the rearrangement to 4. When 3 this reaction was carried out in the protlc solvent ethylene glycol, a new product ^5} was obtained in addition to 4.

ethylene glycol HOCM^HaP

Typically, carbene precursors generate dlazonlum ions in protlc media and a difference in behavior is therefore expected when such a change from protlc to aprotic solvent is made.^ The new product (5) was considered to arise from solvent trapping of the intermediate formed subsequent to 1,2 phenyl migration to the initially formed cation center. This conclusion is supported by the observation that

the perchlorate salt of 5-dlbenzosemibullvalenylmethylamine ( 6) undergoes deamination in acetic acid containing sodium nitrite to

give only acetate 7.

HOtJo CH

one 7 4

Similarly, 5-tosyloxymethyldibenzosemlbullvalene ( 8) undergoes s o l- ***** volysls In buffered acetic acid to give acetateJ7 along with some 2 starting material.

The dichotomy of responses to carbene vs. carbonium ion genera tion observed in the (^-substituted derivatives is not observed in the protic/aprotlc base-induced decomposition of 1-dibenzosemlbull- 5 valenylcarboxaldehyde tosylhydrazone (9). The observed rearrangement is virtually independent of base or solvent and gives 3,4-behzofluorene

( 10) and a lle n e 11 in a ratio*of 2 : 1.

tf-H H T s

Presumably 10 and 11 arise from the common intermediate 12. l t3- ' yv+t w"* ^ Phenyl migration (path a) ultimately provides 3,4-benzofluorene (10), while ring opening with acetylene formation (path b) and subsequent

1 , 3-pro to tropic shift** gives allene 11.

-> Products

a At this point, we were led to examine the interaction of a cation

center with the dibenzosemlbullvalene nucleus to determine any simi

larity to the observed carbene rearrangement.^

Concurrent with the present study, Cristol carried out the silver

ion-assisted solvolysis of 1-bromomethyldibenzosemibullvalene (J^)

in acetic acid and provided some information on the rearrangement

pathways available to this carbonium ion . 7 The results of Cristol*s work w ill be presented later.

At Ohio State, the protic and aprotlc deaminations of 1-aminomethyl- dibenzosemibullvalene were investigated and the results are presented below. For convenience and maximum clarity, the deamination results are discussed in tandem with the solvolytlc behavior of 13 observed Q by C ristol and Schloemer.

R esults. ,

Fhotoisomerization of readily available dibenzobarrelene 1A 9 according to the procedure of Ciganek afforded 1-carbomethoxydl-

benzosemibullvalene (15) in good yield. Hydrolysis of ljji with

aqueous sodium hydroxide gave acid 16 which was converted efficiently

to amide 17 by stepwise reaction with thionyl chloride and saturated

ethereal ammonia. Reduction of 1£ with diborane in refluxlng tetrahydrofuran"^ afforded l-amlnomethyldlbenzoBomibullvalene (18)

in high yield.

When 18 was treated in glacial acetic acid with sodium nitrite

(protic deamination), immediate nitrogen evolution ensued with formation of a mixture of several acetates and alcohols along with 3,4-benzo-

fluorene (10). Separation of hydrocarbon 10 from the more polar acetates and alcohols was achieved by column chromatography on silica

gel. The hydrocarbon was characterized by comparison of its pmr

spectrum and melting point with the available literature data.^ The acetate-alcohol mixture was separated into four components by pre parative thick layer chromatography on silica gel. The reaction mixture was thereby found to contain in relative percentages, 16% unrearranged acetate 19-OAc, 12% the corresponding alcohol 19-OH,

24% exo acetate 20-OAc, 40% exo alcohol £0-0H, and 8% 10. 7

n 1.0

Alcohol 19-OH was characterized by comparison of its physical pro perties with those of an authentic sample prepared by lithium aluminum hydride reduction of ester ,15. Conversion of 19tOH t0 a c e ta te

(19jOAc) with acetic anhydride in pyridine provided proof for another of the products of deamination. Alcohol 2O7OH and acetate j^-OAc Q were Independently synthesized by Cristol and Schloemer and a com parison of proton magnetic resonance data provided convincing confirmation of their structural assignments. Of particular signi ficance is the fact that no endo products^ 21_nor [ 2 . 2. 2] products

22 and 23 were found.

cH, U

X X b 21 XL Deamination of amine ^18 vith isoamyl n itrite in diglyme contain ing one equivalent of acetic acid led to a mixture containing 33% 19,-OAc,

51% 20-0Ac and 16% 10. Again* no endo products nor [2.2.2] bicyclics were noted.

D iscussion g When CrlBtol and Schloemer solvolyzed bromide 1^ in acetic acid containing silver acetate either at room temperature or at 100° * they obtained four acetates and the hydrocarbon 3,4-benzofluorene

(10). Pmr analysis of the acetate mixture indicated the presence of

30% 20-OAc, 6% 21-OAc, 24% 22-OAc, and 23% 23-OAc. 3,4-Benzofluorene waB p re se n t to th e e x te n t o f 16% and no unrearranged 19-OAc was detectable. Treatment of a mixture of the four acetates with 0.5 M

HCIO^ in acetic acid gave rise to 22jOAc as the only product. Cristol haB interpreted this finding to be an indication of the kinetic nature of the four acetates generated in the solvolysis. Endo acetate

21-OAc is more stable than its exo counterpart to acid catalyzed , rearrangement* a result consistent with the behavior of similar 8 12 compounds. " Acetate 19rOAc is also readily converted to 22-OAc by add catalysis.

The four acetates were thought to be derived from Intermediate benzyllc ion either by direct solvent trapping in both exo and endo fashion (exo predominating) or by rearrangement to allylic ion 2£ prior to capture by solvent (Scheme 1 -see next page). The absence of products from solvent attack on ion v24 would appear to suggest that 24 is unstable and may even be bypassed to give ion ^25 directly as the result of cydopropyl assisted departure of the

bromide ion. The conclusion is also drawn that S^2 displacement of

bromide by solvent is non-existent.

Scheme I

OO-OAc <-

a a - o f l c <- ■> 0 5 - 0 f\c

An analysis of the solvolysis study of Cristol and Schloemer necessarily relates to the discussion of the deaminations of amine w'N18. The protlc deamination results are outlined in Scheme II (next 13 page). The presently accepted mechanism for deamination involves production of an unstable diazohydroxide (28). Ionization of the Scheme II

HON*NcHfc

L NX Ofle 11

N-0 bond (29) followed by solvent exchange produces the new ion pair

'30. Carbon-nitrogen bond cleavage and loss of nitrogen (energetically favorable), if sufficiently rapid, produces the tight ion pairs 31 and

32. Collapse of these tight ion pairs to products requires that exo stereochemistry occurs. This rationalization explains the absence endo products. Furthermore, the probability that a high energy diazonium ion (energy lowering Interactions with the solvent have not 13d yet developed) decays to products via a transition state that is very much like reactants explains the observation that the thermo dynamically more stable compounds 22-X and 23-X are not formed.

The high percentage of alcohols which arise during protlc de amination is consistent with Scheme II. When the diazonium ion is long lived, solvent exchange occurs, and the product is largely that

Involving solvent (an acetate in acetic acid). On the other hand, the suggestion has been made^ that, when the carbonlum ion resulting from loss of nitrogen is a stable one, decay to products occurs com petitively with solvent exchange of the hydroxide giving a higher percentage of alcoholic products. Cristol and coworkers have also shown that the high alcohol yields in deamination reactions cannot 14 be explained in terms of the amount of water present in the solvent.

Reasonably, the diazonium ion produced from aminet18 must exist long enough to permit some solvent exchange of the counterion but decay to products remains fast enough to compete with the exchange process giving a large quantity of alcohol 20-0H. Also, trapping of io n 3 5 probably occurs from a tight ion pair, thereby precluding collapse from the endo direction. Rearrangement of t25 to 2f^ i s 12

Apparently slow compared to collapse of 25 to products. The solvolysis reaction (Scheme I), on the other hand, Involves solvent separated ion pairs whose decay to give products Is somewhat slowed, permitting the rearrangement of 25 to 26 to become competitive.

The formation of 3,4-benzofluorene (10) cannot be readily ac counted for, although several possible mechanisms are available. The intermediate cation 25 can be discounted as a progenitor of hydro carbon ^10. Cristol showed that 20-Br, 21-Br, 22-Br, and 23-Br do not 15 yield any of 10 upon solvolysis. This fact certainly Indicates the

Incursion of a second mechanism separate from that in Scheme II. For instance, a 1,2 bond shift of an edge cyclopropyl bond in_2£ (the possibility of concerted nitrogen expulsion and bond reorganization is not considered here although it is as likely a process) gives cydobutyl cation 34* King opening to benzyllc cation^ followed by minor restructuring produces 10.

Along similar lines,.a 2,8 bond shift leads to cation 36, a relative of 34. Cyclopropyl ring opening again gives 35, a possible direct precursor of 10. Finally, migration of a phenyl group in a 1,3-fashion (see reference 5, carbene reaction) produces catio n ^ which transforms into intermediate _3& via cyclopropyl ring

cleavage. No other mechanisms are immediately apparent although __ the three hypothetical cations presented above all contain elements of strain and instability. Without proper deuterium labelling experiments any proposed mechanism remains in doubt.

When effected in an aprotic medium (Lsoamyl nitrite in diglyme plus one equivalent of acetic acid), the deamination failed to produce any alcohols although both acetates and 3,4-benzofluorene (10) were obtained. The intermediacy of diazoalkanes formed by deprotonation tlon of diazonium ions in aprotic solvents has been suspected In this type of reaction; roprotonation of these diazoalkanes with acetic acid is thought to produce compounds such as 30 and 33. 16

34 35

3 8

In conclusion* the dibenzosemibullvalene nucleus has provided some interesting and unprecedented5 rearrangements. . The cation ; 2 5 8 and carbene studies of the 1- and 5-substituted derivates ’ * have introduced a framework for deciphering the expectedly more interesting chemistry of substituted semibullvalcnes. Investigations of semibullvalene chemistry may be complicated by-its'fapid Cope rearrangement, but the mechanistic'results described'above will hopefully facilitate an understanding of the reactivity of the parent system.

Experimental

Melting points were determined with a Thomas-Hoover melting point apparatus and are corrected. Pmr spectra were determined on a Varlan

A-60A sp ectro m eter.

* ~ *•* anibullyalene (1-Carboraethoxydibenzotri- 2,8 cyclo [3.3.0.0 ’ ] octadiene) (15).

A solution of 10.0 g of 14^ in 500 ml of

acetone was irradiated for 4.5 hr under

nitrogen using a 450 W Hanovla mercury arc

and Pyrex filter. The solvent was evaporated

in vacuo and the resulting solid was recrys

tallized from ethanol to give 7.05g (70%) of

15, mp 163.5-165.5° ( lit . 9 mp 169.5-170.5°)

Dibenzosemibullvalenyl-l-carboxylic acid (16).

A solution of 2.00 g (7.6 mmol) of 15 in 50

mi of 40% aqueous sodium hydroxide and sufficient

methanol to cause dissolution was refluxed over-

night. The solution was cooled in an ice bath 15

w hile 20% sulfuric acid was added dropwise with stirring to effect

neutralization. The resulting white precipitate was separated by

filtration, washed with water, and dried to yield 1.5 g (79%) of the

acid. Recrystallization from isopropyl alcohol afforded white

needles: mp 229-231°; pmr (CDC13) $ 10.57(s,l, C00H), 6.9-7.5(m,8,

aromatic H), 4.97(s,l, H-5), and 3.86(s,2, H-2, H- 8).

Anal. Calcd for ° 2 : 82.24; H, 4.87. Found: C, 82.06;

H, 4 .8 8 .

l-p ib en z o 8_emibullyalenylcarboxamlde (17).

To a suspension of 5.15 g (20.8 mmol) of 16

O in 60 ml of dry benzene was added 4.84 g(41 »J .... mmol) of freshly distilled thionyl chloride

and 1.65 g (20 mmol) of dry pyridine. This

mixture was refluxed for 1.5 hr. The solvent

and excess thionyl chloride were removed in I vacuo and the residual oil was treated with '-'*200 ml of ether satur

ated with ammonia. After standing for 30 min, the ether solution was washed with an equal volume of water and the water layer was reextracted with methylene chloride. The combined organic phases were dried,

filtered, and evaporated to give 4.94 g (96%) of 17 as fine white n ee d le s: mp 208-209° from hexane-benzene; pmr (CDCl^) ^ 6.9 -7 .5 (m,

8, aromatic H), 5.71 (br, 2, NH2), 4.75 (s,l, H-5), 3.75 (s,2, H-2, H- 8).

Anal. Calcd for C^H^NO: C, 82.57; H, 5.30: N, 5.66. Found:

C, 82.60; H, 5 .1 8 , N, 5.55. 16

l-Aroinomethyldibenzosemibullvalene (18). - , .

To 40 ml of dlborane in tetrahydrofuran (<~~1 M,

40.0 mmol) was added dropwise under nitrogen

a s o lu tio n of 1.66 g (6 .7 3 mmol) o f 17 in 60 ml

of anhydrous tetrahydrofuran. The solution o o was refluxed for 8 hr, stirred at room tempera ture overnight, treated with 6 N hydrochloric a c id (*"'10 ml) until gas evolution wob complete, and freed of tetrahydro furan in vacuo. The aqueous emulsion so produced was saturated with sodium hydroxide pellets and extracted with six portions of methylene chloride. The usual workup furnished 1.41 g (90.4%) of 18 as a fluffy white powder: mp 180.5-182.5° dec from isopropyl alcohol; pmr (CDCl^)

£ 6 .8 -7 .5 (m, 8 , aromatic H), 4.42 (s,l, H-5), 3.11 (s,2, H-9), 3.00

(s,2, H-2, H-8), and 1.09(s,2, -NHg).

Anal. Calcd for C^H^N: C, 87.51; H, 6.48. Found: C, 87.74, H, 6.63.

Protic Deamination of_18.

To a solution of 1.5 g (6.44 mmol) of 18 in

50 ml of glacial acetic acid was added 3.54 g

(51.3 mmol) of sodium n itrite in small portions.

After the solid dissolved and evolution of

nitrogen ceased, the orange solution was poured

into a mixture of 75 ml of benzene and 75 ml of water. The water layer was extracted with benzene (8 X 50 ml) and the combined benzene layers were washed with saturated sodium bicarbonate solution (5 X 50 ml), dried, and evaporated. Chromatography on silica 17

served to separate the mixture of acetates from 3,4-benzofluorene (10, «*—“s 42.2 mg), white plates, mp 124-125° (lit."* mp 125.5-126.5°). The

composition of the acetate-alcohol mixture was determined by careful

Integration of the pmr spectrum. Preparative thick layer chromato

graphic separation of the mixture led to the isolation of the following

components: 20j-QAc (171.4 mg)', 19-0Ac (111.7 mg), 20j-QH (239.6 mg),

and^1!M)H ( 68.6 mg). The total recovery of products based on starting

m aterial was 39%.

Aprptic Deamination of 18.

C>HiX To a solution of 102 mg (0.44 mmol) of ^18^

in 20 ml of anhydrous diglyme (distilled from

sodium) was added under nitrogen 26.2 mg(25/^1,

0.44 mmol) of anhydrous acetic acid and 62.8 mg

( 72yxl, 0.545 mmol) of freshly distilled

isoamyl n itrite and the mixture was heated

rapidly to 130° by immersing the flask in a preheated oil bath. After

15 min, the orange solution was cooled, poured into 50 ml of water, and

extracted with ether (2 X 50 ml). The ether was washed with saturated

sodium bicarbonate solution (50 ml) and water (100 ml), dried, and

evaporated. Analysis was by pmr. Preparative thin layer chromatography

on silica gel (elution with 20% ether in hexane) gave 8.9 mg(15.7%) of

.JO, 37.1 mg (51.4%) of 20-0Ac, and 23.8 mg (32.9%) of WjCAc. The

overall recovery of products was 59%. 18

1-Acetoxymethyldibenzosemibullvalene (19-0Ac). 5 T reatm ent o f 170 mg (0.726 mmol) o f 19-0H Oflc ^ C.U vith acetic anhydride In pyridine In the JU usual fashion gave j.9-0Ac, rop 141.5-142.5°,

after recrystalllzatlon from lsopropyl alcohol:

pmr (CDCl^) £6.8-7.4 (m, 8, aro m atic H ), 4 .4 4

(s,3, H-2, 11-5, H-8), 3.10(s,2, Ciy)), and

1.92(s,3,C H ,C O ); pmr (C,D ) , th e $ 4.44 singlet divides into <£4.32 3 6 6 (a,l, H-5) and ^4.22(8,2, H-2, H- 8).

Anal. Calcd for C^H^gOg: C, 82.58; H, 5.84. Found: C, 82.36; H, 5.84.

Acid-Catalyzed rearrangement of 19-0Ac.

A 50 mg (0.18 mmol) sample of 19-0Ac was dis

solved in 10 ml of 0.027 M perchloric acid In

acetic acid and this solution was stirred with

exclusion of moisture for 9 hr at room tempera

ture. The contents were poured into 10 ml of

water and extracted with ether (2 X 25 ml). The customary workup gave an orange o il, the pmr spectrum of which was superimposable upon that of authentic 22-0Ac; pmr (CDCl^) £7.0-7.5

(m ,8, aromatic H), 5.43(m,l, H-7) and 5.22(d,l, H-9, J“ 2.0 Hz), 4.93

(d,l, H-9, J- 1.8 Hz), 4.69(8,1, H-4), 4.57(d,l, H-l, J- 3.5 Hz), and

1.95 (s,3, CH3C0). Part II: Equilibrium Displacements Resulting from Substitution of the

Semlbullvalene Nucleus. “ i i — ~ | -I,,, ^ Introduction Semlbullvalene (1) was first prepared in 25-40% yield by Zimmer man and Grunewald who utilized the acetone—sensitized photochemical 18 rearrangement of borrelene (39) in isopentane solution. The only other product found in this light-induced reaction was the isomeric hydrocarbon, cyclooctatetraene (40, 1—2%). When this reaction is

-> "1“

39 1

carried out in the absence of a sensitizer, only cyclooctatetraene (40) is obtained. The mechanism of thebarrelene photorearrangement was subsequently proven to be an example of the well-known di—tT—methane 19 rearrangement by the use of deuterium labeled barrelene. The pmr

spectrum of semlbullvalene ( 1) in carbon tetrachloride solution is

seen to exhibit three m ultipletts centered at*T5.08, 4.X7, and 2.97.

The sim ilarity of this spectrum with those reported for barbaralone(41) 21 and dihydrobullvalene (42) leaves no doubt that semlbullvalene

undergoes a doubly degenerate valence isomerization. The pmr spectrum

19 20 of 1 exhibits no change from 4*117° to -110°; consequently, the

I e

Hi Hi

degenerate isomerization of semlbullvalene ( 1) is more rapid than any previously reported example of a Cope rearrangement. Thus hydrogens

2 , A, 6, and 8 become equivalent, as do A and 8 while 3 and 7 remain unchanged but equivalent. The rapidity of the valence tautomerism of Initially suggested the possibility that semlbullvalene exists 18 19 a s a 6'trelectron, delocalized, symmetrical species A3. *

M 3

However, the ultraviolet spectrum of 1 [ A 225-235 sh nm (£ 2400)] - * max and the obvious absence of a ring current as evidenced by pmr rule t out this exciting structure from consideration.

The difficulties involved in preparing large quantities of 22 barrelene (39) preclude its use as a serviceable precursor to semibullvalene. Preparative irradiation of cyclooctatetraene to give small amounts of J^ a t low temperatures was carried out by Zimmerman 23 and Iwamura in isopentane solution containing acetone as sensitizer.

The problems Involved in performing a low temperature photochemical experiment along with the difficulties associated with the separation of from the large quantities of unaltered cyclooctatetraene make this method an impractical route to semlbullvalene.

A more utilitarian route to semlbullvalene was described simul- 24 25 taneously by Meinwald and Zimmerman in 1969. Fhotochlorlnation

KO-tBu > 1 DMSO

4S Mb

j 6 of tricyclo[3.3.0.0. * ]octane (44) in benzene followed by double dehydrochlorination of dichloride 4£ results in isolation of semibull- 2 6 valene rather than the expected tricyclo[3.3.0.0 * ]octa-3,7-diene (46).

In apparent analogy to the known thermal rearrangement of tricyclo-

[3.3.0.Q^*^]oct-3-ene (47) to dihydrosemibullvalene(48)^ dlene ,46 rearranges to semlbullvalene under the dehydrohalogenation reaction conditions. In fact, diene 46, isolated by carefully controlling the 22 reaction and workup conditions in the dehydrohalogenation step, re 27 arranges rapidly at room temperature to semlbullvalene ( 1).

*f 8

Unfortunately, the overall yields in this sequence are only 5-8% and a better preparation of^w as needed. 28 29 In 1970, Paquette and Askanl independently reported an

1) KOH, H»o, H0CHa.CHa.0H

efficient route to semlbullvalene which made possible gram quantities of this previously elusive hydrocarbon. Acetone-sensitized 23 cyclization of the N-phenylurazole adduct of cy.clooqtatetraene (49) produces the bishomodiazacubane J >0 which undergoes skeletal isomeriza- 30 tlon in the presence of Ag+ ion (80-90% yield). The diazasnoutane 31 (51) so obtained can be saponified and air oxidized to give semibullvalene via intermediate dlazasnoutene 52 in 65-70% yield. Certain improvements in the original synthetic scheme are detailed in the

Experimental Section.

Most recently a new approach was taken toward the synthesis of 32 semlbullvalene by Malherbe. His scheme begins with the intramolecular

I) a e

1) KOtBu HO DMF 55

33 reaction of diazoketone in acetic acid to give acetatein

70-80% yield. Reduction with lithium aluminum hydride converts Jib, to d io l 55 having mixed stereochemistry. Finally, conversion o£^55 to a dimesylate followed by double elimination in dimethylformamide 24 giveB semlbullvalene In modest yield.

A number of polysubstituted derivatives of semlbullvalene are presently known. Octamethylcydooctatetraene ^56) Is converted

S 8

thermally to octamethylsemlbullvalene (57) in IX ethanolic sodium ethoxlde solution at 240°.^* Likewise, the syn and anti tricyclic isom ers 58 and £9 undergo conversion to 5J under sim ilar conditions. 35 The octacarbomethoxy derivative has also been prepared.

\1 I I

60 25

1,3,5,7-Tetramethylcyclooctatetraene £60) Is involved in a similar but less efficient thermal isomerization to give semibullvalene derivative

61 in ca 2% y ie ld . 36

A variety of other tetrasubstituted semibullvalenes have been pre- 37 pared by a novel route starting with diketone 62. Askani reported

0=< 4 CH; % 61 63

CH CH CH.

6 5 a 67 the pmr spectra of derivatives of type ,67 to be temperature independent down to -60°. The semibullvalenes synthesized include a ll combinations of and Rj equal to H, CH^, and CgH^.

Trisubstituted semlbullvalene 70 was prepared by brominatlon of 37 1 , 5 -dimethylseraibullvalene ( 68) followed by treatment of the resultant 38 dibromide (69) with base.' ,39 In 1969, Liu and Krespan reported'" the synthesis and isolation of three bistrifluoromethylsemibullvalenes (72, 73, and 74) formed via 4t L £ L

ZL \L

HD oswq

8 ?

Tj9

9Z 27 a photosensitized rearrangement of the corresponding barrelene ^71.

This conversion accords with the earlier isomerization of barrelene (39) 18 to semlbullvalene ( 1).

The pmr observed for compound Th indicates the dynamic equilibrium between the two valence isomers to favor the cyclopropylsubstituted

semlbullvalene : the presence of three oleflnlc proton absorptions being diagnostic of this preference. Compound 7^ may be the only example of a 2-substitutcd semlbullvalene having an equilibrium im balance in the direction favoring cydopropyl substitution (see

Results and Discussion).

1,3-Diraethylsemibullvalene (76) has been prepared^ by the

CH CH.

7 6

37 method of Askanl starting with diketone ^75. The pmr spectrum of

76^ w ill be discussed later.

Lastly* the effects of annelation on semlbullvalene equilibria 28 41 have been studied and reported by Paquette and co-workers; the perturbatlonal effects of such bridging have been analyzed In terms of

"bracketing" strain. The general route to annulated semibullvalenes starts with propellatrlenes of type which undergo cydoaddition

7 7 7 6

; chxch=ch-chi

•>

- 7 9 H o 80

with N-phenyltrlazolinedione exclusively from the endo face to give adduct 78 in high yield. Photocyclization of 78 followed by Ag+ catalyzed skeletal rearrangement produces the diazasnoutanes JJO.

Subsequent hydrolysis and oxidation of the urazole ring gives rise to the rannelated semibullvalenes JS1.

The Cope rearrangement is characterized as a symmetry-allowed

[3,3] sigmatropic shift or a ^ +cr^ +TT^ cycl°addition.^*^ T*ie ^c“ generate rearrangement operating in the case of hexa-l,5-diene (82)

8 1 81

83 84 is recognized to be greatly facilitated in the nondegenerate rearrange- 44 ment of cis - 1. 2-divlnvlcyclopropane (83) to cyclohepta-l,4-diene (84).

In a further extrapolation of this trend, homotropilidene (85) is seen A3 to undergo a degenerate Cope rearrangement which becomes quite 45 46 rapid when bridging is introduced as in bullvalene ( 86) . ’ The activation barrier to this rearrangement can be decreased still further by diminishing the size of the bridge. This occurs in the examples: 30

85 86 H 2 .

.21 20 dihydrobullvalene (42) barbacalone (41)? barbaralane (87)? ,«7 and

semlbullvalene (I),* Table I shows some o£ the measured free energies

of activation for the Cope rearrangement.

ifl 87 1

These symmetry allowed rearrangements proceed with finite activa

tion energies (Table I) which vary in a predictable manner. Winstein and coworkers have reported a detailed study of the degenerate Cope rearrangement of 1,3,5,7-tetramethylhomotropllidene ( 88) in which -j- 48 the quite high AG term was rationalized. The diene 88 may e x is t

in either a cisoid or transoid conformation. The pmr spectra of 88

8 8 31

Table I. Ac for Cope Rearrnngements

Compound kcal/m ole Temp,°C Ref

1,5-Hexadiene-1,1 1-d _ 35.5 250-350 a cis-Dlvinylcyclopropane ca. 20 5-20 b Homotropilidene 13.7 -35 c B ullvalene 12.8 100 d Dihydrobullvalene 9.5 -40 21 Barbaralane 7.8 -77 46 Barbaralone 9.6 -55 20 Octamethylsemibullvalene 6.4 -141 e Semlbullvalene 5.5 -143 47

(a) V. Toscano and W. von E. Doering, unpublished work cited In reference 46. (b) J.M.Brown, B.T.Golding and J.J.Stofks, J.Chem. Soc.. Chem. Comrnun.. 319 (1973). (c) H.Ctlnther, J.B.Fawllczek, J. Ulmenand W. Grimme, Ang. Chem. Int. Ed. EnRl.. 11, 517 (1972). (d) A.Allerhand and H. Gutowsky, J.Amer. Chem. Soc., 87, 4092(1965). (e) F.A.L.Anet and G. Schenk, Tetrahedron L ett.. 4237w?1970).

Indicates that the transold structure Is the more stable while the

Cope rearrangement necessarily must proceed through the cisold con formation. The conclusion was drawn that the observed free energy of activation Is the sum of the free energy difference between the clsoid and transold conformations and the free energy of activation of the Cope reaction from the clsoid conformation. The bridged homotropllidenes isomerize rapidly because they are locked into the clsoid conformation.

As mentioned above, the activation energy for the degenerate rearrangement of semlbullvalene £1^ is the lowest on record. After several elaborate calculations had been made indicating an energy AQn AQK barrier of 2.8 or 3.6 kcal/molej Anet actually measured this barrier using a superconducting nmr spectrometer operating in the frequency range of 251 MHz . 1 The free energy of activation was thus

4 32 measured to be 5.5 kcal/mole at ->143°. A detailed structure, (electron diffraction analysis^) and orbital sequence^ have also been reported for semibullvalene. The mesovalent structure 43 is clearly only a transition state in its Cope rearrangement. A lower activation energy

can be achieved, however, by destabilizing the reactant or product, or by stabilizing the transition state, or by some combination of both. One might expect suitable substitution of the semibullvalene nucleus to achieve just such a circumstance. Substituent Influences on the stability of cyclopropyl rings are used in rationalizing the remarkable sensitivity of the norcaradiene-cycloheptatriene equil- 52 ibrium to substitution at the 7-position. The Walsh orbitals of the cyclopropane have been shown to interact in a 'tfinanner with acceptors so as to strengthen the 1-6 bond in and with tTdonors

v R

so as to weaken the same bond* V acceptors thus shift the equilibrium 33

to the norcoradiene side, TT donors to the cycloheptatriene side.

The same argument was made In a theoretical analysis of sub- 53 stituent effects on the semibullvalene molecule. Further, certain

substituent patterns were predicted to provide examples of bishomo-

benzene-like ground states. Hoffmann and Stohrer, in fact, proposed

that electron releasing substituents at positions 1,5 favor position

5 (in accordance with the general rule for norcaradlene-cyclohepta-

triene presented above) while electron acceptors favor position 1 .

This effect is due to weakening of the 2,8 bond by donors and

strengthening by acceptors (in position 1); a substituent in position

5 has little or no effect on the 2,8 bond in the cyclopropyl ring

(g l^ S S D *53 Calculations also show that ‘rf donors in positions 2,4,6,8 should favor substitution at carbons 2,8 while withdrawers should favor carbons 4,6.' A second important hypothesis developd from Hoffmann and

StohrerTs extended HUckel calculations deals with the lowering of

the energy barrier to rearrangement. Any substituent which strengthens

th e 2,8 bond stabilizes the ground states and the transition state;

the transition state, however, is not stabilized to the same degree.

Consequently, the Cope energy barrier is greater than in semibullvalene. Likewise, a destabilizing substituent lowers the energy barr.ier.

Simply stated, electron releasing substituents at positions 1,5 or

electron withdrawing substituents at 2,4 ,6,8 should decrease the

activation energy. The above rules do not apply to substituents 39 which are not classified as Tfdonors or acceptors (e.g., CF^ ).

In order to investigate the effects of monosubstitution on the valence tautomerism in semlbullvalene, an assortment of substituted

semibullvalenes has been prepared. The method selected for the pre

paration of these compounds utilizes functionallzed cyclooctatetraenes 28 29 in the manner used by Paquette and Askani for the preparation of

the parent hydrocarbon. A simple pmr analysis of the resultant

substituted semibullvalenes and a comparison with other derivatives

prepared both in this group and elsewhere are presented in the next

sections. No conclusions can be drawn as to the effect of mono

substitution on the energy barrier to Cope rearrangement because none was observed (no "freezing-out" on the nmr time scale); however,

significantly weighted ground state substituent effects were observed

and are explained in terms of stabilization/destabilization of the

classical structures.

Results and Discussion

Our synthesis of substituted semibullvalenes begins with the addition of a triazolinedione (93) to an appropriately substituted

cyclooctatetraene (94). Diels-Alder cycloadditlon of such dienophiles

to a given COT is herein termed direct addition, while reaction with a

dibrominated COT followed by debromination is referred to as indirect 35 a d d itio n .

P / ~ \ r tJ-R

N: 9 3 94

R= CHj , c4hs

Direct Addition. The cyclooctatetraene ring (94} has been 54 shown to exist in a boat conformation which effectively deters the attainment of a properly aligned diene unit for Involvement in a

Diels-Alder reaction. On the other hand, dlsrotatory ring closure to bicyclo[ 4 . 2 . 0 ]octatriene (95) provides a planar conjugated diene moiety capable of rapid capture by a dienophile. Although the energy 55 barrier for this lnterconverslon is high (20 kcal/mole) and the triene (95) is thermodynamically less stable, the reaction between

£5 and dienophile frequently occurs more rapidly than^,4s + cycloaddition to the monocyclic isomer.

The highly reactive trlazolinediones, however, are known to be less selective than most dlenophlles in their addition to cyclooctate-

5 9 —61 traenes. As a consequence, 1,4-cycloaddition to the monocyclic system often predominates. Such behavior is attributed not only to the high.reactivity of these azo compounds but also to their ability to enter into dipolar reactions. 4-Phenyl-l,2,4-triazoline-3,5-dione

(93-CgH^) combines with cyclooctatetraene (94-H) to give not only the 36

4 5 .

"normal" adduct (49)^ but also the direct 1,4-adduct (97).*^ At higher reaction temperatures, more of the tetracyclic adduct Is formed at the expense of 97^ The reactivity of exceeds that 62 of tetracyanoethylene not only as a dienophile but also as an electrophile. Hulsgen concluded that the cycloaddition of 93-C^.H,.

to COT (94-H) proceeds via the homotropyllum zwitterion 96.^^ f

/ =

q 5 - H

9 3 - q H ,

9 7

63 Ample analogy exists to support this conclusion. For our purposes, capture of PTAD (93^-C^H^) by the monocyclic valence tautomer is un- 64 desirable. In this connection, Gastelger and Huisgen have shown that the mode of reaction is appreciably influenced by the electronic nature of the ring substituents which does play a significant role in directing the cycloaddition chemistry of the substituted COT (vide i n f r a ) .

The cycloaddition of PTAD to a substituted cyclooctatetraene is complicated by the presence of four structurally different 38 bicyclo[4.2.0]octatrlenes (95a-95d). The difficulty in interpreting these reactions is sometimes compounded by the fact that the precise mechanism of COT cycloaddition is dependent upon both the dienophile

(electrophllicity) and the substituent. The ratio of isomeric cycloaddition products (98) has been shown to be greatly dependent on the substituent R. In those cases where R is methyl! ethyl, or phenyl, valence Isomerization is in actuality rate determining (i.e. k ) assuming the use of an extremely reactive dienophile such as PTAD.**^k»60»®5 a re su i t> 95 is removed by reaction with dienophile

h.t >

95 98 as f a s t sb it can be produced. Thus the predominant isomer in the product mixture (98) arises from kinetically controlled factors in the pre-isomerization. Most frequently, formation of the 7-substituted bicydo[4.2.0]octatriene is favored.**** In contrast, electron with drawing substituents such as halo, cyano, and carbomethoxy give rise to a range of isomeric products, indicating that equilibration of the bicyclic Isomers (95) is competing with cycloaddition (i.e. kg^sk^, k j). Also observed is the much reduced participation of homotropylium type intermediates.

Interestingly, Huisgen reported that the presence of electron donating substituents (methoxy and phenoxy) results in exclusive 39 fi formation of tricyclic products ( 100) upon reaction with tetracyano-

ethylene.A pparently a shift to electron withdrawing substituents

on ■>

OQ I l 100

produces less stable zwitterions (96), thereby reducing the relative

quantities of 1,4-adducts (97) formed. This effect is accompanied by

a gradual change In mechanism as explained above.

It remained to determine what substitution patterns would be

observed upon direct exposure of various substituted COT's to a

triazolinedlone. To this end, phenylCOT (jA-C^H^) was allowed to

react with N-methyl-1,2,4-triazoline-3,5-dione (93r-~CH^) (the N-methyl

urazole was used in this instance to enhance the solubility of the

high molecular weight adducts) in boiling ethyl acetate; by far the

predominant product found was adduct lOl-Cgll^, isolated in 84% yield

by column chromatography. The ultraviolet maxima (in ethanol) of

248 (€ 20,000) and 282 nm (450) are in accord with the presence of a 66 sty ren e chromophore. Comparison of i t s pmr spectrum (CDCl^) w ith

that of the corresponding maleic anhydride adduct*’*’ indeed showed

the phenyl group to be on the cydobutene double bond. Protons and

H_ exhibit differential shielding (£*3.62 and 3.28, see Experimental

Section) and the lone cydobutene proton (H^) appears as a singlet

a t S 6.10 (£6.20 for the maleic anhydride adduct). The mother ~ f R, T \ ^ " - R 102

104 I OS

liquors obtained from the recrystallization (2-*propanol) of 101-C^H,. yielded a minor isomeric adduct (< 1% yield) characterized as 103-CgH^ after separation from lOl-C^H^ on a preparative silica gel plate. The structure of this minor component was evident from the presence of only three methine protons and a single bridgehead absorption in its pmr spectrum (CDCl^). The bridgehead absorptions in the two adducts come well downfield from the normal tertiary position and are con vincingly indicative of adduct formation (see Experimental Section).

Methylcyclooctatetraene (j^CH^) undergoes cycloaddition with

PTAD under comparable conditions to give adduct lOl^CH^ in only 11% yield. A mixture of two isomeric tricyclic adducts 105-CH^ was also 41 obtained in 11% combined yield. Isolation of adduct 101-CH^ was achieved by column chromatography but the mixture of tricyclics could not be conveniently separated into its components. Enrichment of one

Isomer was observed upon repeated fractional recrystallization. The pmr spectrum (CDCl^) o f th e combined ad d u cts ^10^-CH^ c o n ta in s f iv e olefinic protons between£*5.63-6.27* a m ultiplet at 4.33-5.18 for the two bridgehead protons» and two broad singlets at 2.18 (30% of 3H) and 1.93 (70% of 3!i) corresponding to two Isomeric methyl groups.

Adduct 101-CH^ was easily identified by the presence in its pmr spectrum of three olefinic absorptions* one of which was a broadened singlet indicating the single cydobutene proton adjacent to methyl.

This compares well with the pmr of the corresponding maleic anhydride adduct of MeCOT.^ The overall low yield is seemingly explicable in terms of the ene reactivity of PTAD and the obvious possible suscep tib ility of MeCOT to such a process.

Phenyl- and methylCOT's react with triazolinedione in a manner go comparable to acetoxymethylCOT. Birnberg permitted AcOCII^COT to react with PTAD and found not only the expected lOl-CÔAc (32%), but also a mixture of three tricyclic adducts (105-ClI^QAc) in a combined yield on 10%. Treatment of AcOCH^COT with maleic anhydride 6 7 K gives* in contrast* exclusively the adduct corresponding to lOl-GHÔAc. 68 On the other hand* methoxymethylCOT (also prepared by Birnberg) upon reaction with PTAD afforded not only lOl^-CHÔCH^ (42%)* but also

102-CH^QCH^ (14%), 103-CH20CH3 ( 8%), and a mixture of two tricyclics,

Ig^-CHgOCH^ (17%). Why two new t e tr a c y c lic ad d u cts a re o b ta in e d in th is case is not clearly understood. Such an abrupt changeover in product distribution Is also observed with strong electron withdrawing sub stituents however (see below). Zn summary, phenyl-, methyl-, and acefcoxymethylCOT's behave sim ilarly toward PTAD while methoxymethylCOT differs somewhat in its reactivity pattern.

Halocyclooctatetraenes exhibit a range of differing reactivities and propensities for valence isomerization when allowed to react with

PTAD. These findings may be an indication that the relative rates at which the respective monocyclic and bicyclic forms react with PTAD are dependent on the halogen electronegativity and/or their cation stabilizing ability. Thus fluoroCOT is converted exclusively to ^02-F in 95% yield.On the other hand, chloroCOT undergoes reaction with

PTAD to give 101-C1 (27%) and 102-C1 (30%).60 Note that neither fluoro- nor chloroCOT leads to production of tricyclic adducts. A definite change is observed when bromoCOT is the substrate employed. In addition to adducts 101-Br (12%) and 102-Br (25%), a tricyclic adduct 60 (105-Br as the 9-bromo isomer) is formed in direct competition.

Likewise, iodoCOT was found*** to give 13% of 101-1 together with

2-iodo 105 (5.0%) upon reaction with PTAD in boiling ethyl acetate.

If indeed the tricyclic products are formed in a two step sequence via the zwitterion 106, then the electronegativity differences of the halogens may be the cauBe of the product differences witnessed above.

It would scfcm reasonable to assume that the zwltterlon formed by attack of haloCOT by PTAD contains the halogen at since the only two

Isomers observed upon cyclization ore 108 and 109*

io s

The conjugatlvely electron withdrawing cyano group affects the valence Isomerization of cydooctatetraene In such a way that a mixture of all four possible tetracyclic adducts is obtained from reaction with PTAD. These are 101-CN (26%), 102-CN (24%), 102,-CN (31%), and

104-CN (2-4%). The individual isomers are easily Identified by their pmr spectra as detailed in the Experimental Section. Apparently, the electron withdrawing ability of cyano precludes intervention of a 44

zwitterionic Intermediate since no tricyclic product waB d e te c te d . Of

i n te r e s t i s th e f a c t th a t ^104-CN, only a m inor product h e re , i s th e m ajor

product of indirect addition (vide infra). 68 Similarly, treatment of carbomethoxyCOT with PTAD (Bivubefg) af

forded a mixture of adducts which was separated by column chromatography

to g iv e 101-CO0CH 3 (8%) and th e iBom eric adducts 103rC00CH3 (272),

104-Cope^ (2%), and 10£~CO0CH 3 (82). The fact that a tricyclic adduct was found in the case of the COOMe substituent and none isolated in the

cyanoCOT example i s n o t r e a d ily e x p lic a b le . In lin e w ith th e prev io u s

assumption that conjugative and inductive interactions between a sub

stituent and the hypothetical zwltterion 106 determine the extent of

t r i c y c li c adduct fo rm atio n , methoxyCOT a ffo rd s in 60% y ie ld two t r i

cyclic adducts of type JOg and 102. but no tetracyclic products. The s u s c e p tib ility o f methoxyCOT f o r d ir e c t 1 ,4 -a d d itio n to e le c tr o p h ilic reagents has previously been demonstrated.^a*^

Indirect Addition. Huisgen and his coworkers have shown that cydooctatetraene resides chiefly (99.992) in its monocyclic form even when heated to 100°. However, the high ratio of monocyclic to bicyclic isomer is markedly reversed upon chlorination or bromination.

The cis- and trans-7,8-dihalo-l,3,5-cyclooctatetrienes j.10 so pro- 70 duced, being predominantly bicyclic, provide useful substrates for cycloaddition with PTAD. Subsequent dehalogenatlon of adducts 111 reintroduces the cydobutene double bond thus providing a route to tetracyclic adducts ( 101, etc.) which bypasses completely the 71 sometimes troublesome problem of tricyclic compound (105) formation.

Mechanistically, COT has been noted to add halogens in stereospecific 45

cis fashion to yield isomers of the type 112 in both polar and non- 72 polar solvents. Actually the initially formed species is believed 63b c 7? 73 to be an endo- 8-halohomotropyllum ion such as .l^v t s (perhaps 63a preceded by a transient tub-shaped classical cation) which is transformed to cis-dihalide 112 by exclusive endo attack of the

6 3 b counterion at C^. Dihalide 112 is capable of tautomerlzation to give bicyclic isomer 11£ and isomerization to trans dihalide 114, the latter process arising presumably by ring inversion in 116 prior to

6 3 7 3 covalent bond formation. * Ultimately, the trans-dihalobicyclo-

[4.2.0]octadienes 115 result and the two bicyclic dienes present in the mixture (113 and 115) are responsible for the efficient adduct forming reactions previously noted.^

The presence of a substituent on the COT nucleus w ill unquestion ably control the energetics of in itial bromine attack. However, the level of this influence is unclear. The four possible substituted homotropylium ions 118 might exhibit as well a divergence of behavior in their collapse to dihalides by gegenion capture. Some information is available to predict the outcome of competitive halide Ion h y capture at and C^. Should methylCOT, for example, add bromine to give endo-bromo zwltterion 119 having methyl at as in the 46

i a (13 A

s *

. / ' " X

im 115

116 117

63a electrophilic addition of chlorosulfonyl isocyanate, subsequent collapse of the ion pair via paths a and b would provide 120 and 121.

Cycloaddition with PTAD and debromination with zinc-copper couple would then eventuate in the formation of adducts 101-CH^ and ^102^CH^.

When the above sequence was carried out, 102-CH^ <30% yield) was isolated as the sole product. The synthetic importance of this sequence Is now obvious, since the only adduct obtained is one not formed in the direct cycloaddition reaction.

-By r ^ Y — CH Br CH, q jj-c H , 110 1 1 CH.

N ^ W -C ^

I0|-CH3 °

Consequently, the judicious use of both direct and Indirect cycloaddition techniques can provide variously substituted adducts suitable for subsequent conversion to semlbullvalenes. The product data for most of the attempted cydoadditions, both direct and

Indirect, are provided in Table II. The utility of this pair of 48

Table II. Results of Direct and Indirect Addition of PTAD to Various Monosubstituted Cyclooctatetraones

Mode of A dducts, % R A d d itio n ,101 102 103 105^

D ire c t 84 1 D 3 I n d ir e c t — 6 — 9 -CH, D ire c t 11 — — — 11° i — 30 — — I n d ir e c t - c -CH.0AC D ire c t . 32 — — — 10 i — I n d ir e c t 10 35 10 __ n - c h 9och« Direct , 42 14 7.5 — 17 i J — I n d ir e c t — 23 32 d -C00CH- Direct . 8 — 27 2 10° J I n d ir e c t — 31 —— -CN D ire c t 26 24 31 2-4 — I n d ir e c t — 12 9 49 ■— -F D ire c t — 95 —— — I n d ir e c t a*** 90 MM — — -C l D ire c te 27 30 . --- “ j -B r D ire c t 12 25 --- MM 10d — I n d ir e c t — --- 28 . „a -I D ire c t 13 8.5 aTwo Isomers present. ^Performed by G.H. BlrnbergCsee reference 68) . cThree Isomers formed. dA single Isomer detected. eSee reference 60. ^See reference 61. cycloadditions Is likewise evidenced In the case of phenylCOT. The products of direct cycloaddition are lOl-C^H^ and a trace of 103-CgH,., whereas the bromlnation-debromlnatlon sequence provides access to the two remaining tetracyclic isomers 102-CgH,. and 104-CgH^. The resultB obtained In other cases are also impressive. As already pointed out, methylCOT is converted to 101-CHj as the only tetracyclic product of direct addition, but 102-CH^ is obtained by the Indirect method.

Likewise, cyanoCOT provides a good example of the dichotomy of responses to these two synthetic routes. The bromo derivative behaves 49

similarly in that 104-Br (28%) is the consequence o£ Indirect cyclo addition of PTAD, whereas none of this isomer is obtained upon direct

a d d itio n .

Unfortunately, fluoroCOT proved to be an exception to the trends previously discussed because both methods led only to 102-F. A reasonable structure for the endo-bromo zwitterion of fluoroCOT con tains fluorine on as in 1,22. Electronegative substituents such as fluorine should seek positions of high electron density such as.C^ and

Cg. Ultimately, regiospeciflc capture of bromide ion leads to compound 123 having fluorine Isolated from the conjugated diene unit such that it has little effect on the ensuing cycloaddition step.

The results are summarized in Table II.

The Photocyclization^ Reaction. The intramolecular photochemical

(2+2) closure across suitably located olefinlc units has proved particularly useful in constructing polycyclic hydrocarbons from much 75 simpler molecules. Expecially interesting is the sensitized cycll- 2,62 6 a3»9 3 Q n5,8 5 8 76 zation of dicyclopentadiene to pentacyclo[5.3.0.0 * .0 * .0 * ]decane; this conversion is similar to the closure of the presently discussed adducts to substituted 9,10-diazabasketanes. In fact, Farnuro and

Snyder had previously reported the acetone-sensitized photocyclization 2 6 of parent adduct 49 to give 4-phenyl-2,4,6-trlazahexacydo[5.4.2.0 * . 08 ,lli09,13>010,X2jtrldecane_3(5-dlone ( 124_h) In 84% yield . 71(1,77

The characterization of 124-H la founded on its pmr spectrum which consists of a raultlplet (5H) centered at£7.45» a septet (2H) at 5.08, and quintets at 3.78 (4H) and 3.20(2H). The lack of information regarding substituent effects in such cyclizations (important to our synthesis of semlbullvalenes) required that we make a thorough inves tigation of the excited state chemistry leading to the above adducts.

Four decidedly different tetracyclic adducts (101-C^H^ , 101-Br, lOl-CH^, and 101-CN) were sim ilarly irradiated through Vycor or Corex 78 in acetone and with but one exception closure to the corresponding

9,10-diazabasketane .124 occurred. The products of photoclosure are in general easily isolated and purified by column chromatography, and good yields (ca. 80%) are usually had. The only known exception to this generalization occurred with bromo adduct 101-Br; sensitized irradiation of this compound led to rapid decomposition with the production of an amorphous black m aterial. This behavior was also noted for 102-Br and ,104^-Br (vide infra). Bromides have low bond 79 dissociation energies as witnessed by the relatively rapid conversion y i i of bromocyclooctatetraene to trans-fi-bromostyrene. In this regard

Huisgen and coworkers have shown the ionization of the carbon-bromlne bond to be rate determining in that conversion. A rapid C-Br dis sociation induced by light or sensitizer could explain the photochemical decompositions observed with the bromo adducts. The results of these cyclizations are presented in Table III along with the results for fiR several adducts prepared by G.H.Birnberg. 51 Table 111. Results of Photochemical Cyclizations

S ta rtin g Solvent(ml) Filter Time,hr. 9,10-Diaza- Yield,% material (g) basketane

Acetone Corex 37 30 i 2 i r c6H5 a * r c6H5 (5.73) (450) m - w 5 Acetone Corex 22 125-C6h5 42 (0.090) (10)

Acetone Corex 41 21 ^ T C6H5 S - C6H5 (0.10) (10) m r CH3 Acetone Vycor 32 124-CH. 72 (0.27) (50)

102^-CH3 Acetone Vycor 24 125-CH, 93 (0.33) (50)

101-CII20Ac A cetone- Corex 6 124-CH2OAc 82 (0.50) benzene,l:l (350)

,102-CH2OAc:“ A cetone- Corex 3 ^25-CH2OAc 72 104-CH2OAc benzene, 1:1 (1 :1 ,0 .5 0 ) (300)

103-CH2OAca A cetone- Corex 7 126-CH2OAc 70 (1.17) benzene,l:l (350) i o i - ch2och3* Acetone Vycor 24 124-CH2OCH3 24 (1 .11) (500) a 102-CH„OCH, Acetone Vycor 125-CH2OCH3 34 (0.71) (350)

103-CH-0CH * Acetone Vycor 12 126-CH2OCH3 64 ~ " < o : 9 0 ) (300)

103HC00CH3a Acetone Vycor 48 126-COOCH, 35 (1.00) (300) 52 Table 111. (continued)

101-CN Acetone Vycor 9 124-CN 92 (0.30) (350)

102-CN Acetone Vycor 4 125-CN 80 (0.30) (400)

103-ON Acetone Vycor 113 126-CN 50 (0.30) (450)

102-F Acetone Vycor 34 125-F 56 (1.45) (275) a Performed by G.H. Birnberg; see reference 68.

Similar treatment of various 2-substituted adducts of type j.02, except for bromo, provided (Table 111) the basketaneB 125 in modest yield. Unlike the more unstable bromo adduct, 102-F cyclized cleanly in 56% yield. Interestingly, adducts of the type 104, having a

U4 115 116 substituent on C^, also cyclize to give basketanes 125. From symmetry considerations, two dienes can serve as precursors to diazabasketanes

125. 53

Irradiation of ^103-CN proceeded as usual to give the bridgehead substituted basketane J.26-CN in 50% yield. The results of this reaction, as well os the Cyclizations of lO^-CHgOAc, IO 3.-CH2OCH2 , and

103^-C00CH^ for comparison (G.H. Birnberg), are presented in Table III.

As re g a rd s th e c h a r a c te r iz a tio n o f cu b y l p ro d u cts 12A.-J-26, pmr techniques are particularly helpful. The parent basketane 124-H possesses three sets of protons, the twot<-lmido protons, the four proximal cubyl protons, and the two distal ones. The pmr absorptions of these three groups of protons are sufficiently different such that monosubstitution at any site is quickly recognized by simple integra tion of these regions*

One final point: byproducts in these cyclizations were generally not seen. However, 101-CgH^ upon irradiation not only provided 12^-CgH^ but also a small quantity of phenanthrene (0.6%) as well as several other uncharacterized products. The observed production of phenan threne is interesting but lacking further chemical evidence it remains simply a curiosity at present.

Sj.lver (I)-Catalyzed Rearrangements. The discovery that Ag+ ion 80 does catalyze the skeletal rearrangement of cubyl systems with 81 formation of snoutane derivatives has generated a variety of

Q A - A A mechanistic interpretations of this interesting phenomenon. * The effects of substitution on the rate of rearrangement have been partially studied with the result that electronic effects seem to 83 exert the major Influence.

Our proposed synthesis of substituted semibullvalenes required a ready conversion of the 9,10-diazabaslcetanes to the corresponding 54

diazasnoutancs. Therefore, the Ag+ ion-catalyzed rearrangements of

124-126 were Investigated with emphasis on the effect of substituents

on the rate of reaction. In certain instances, new methodology had.

to be developed to obtain successful conversions. The in itial pro

cedure for Isomerization of 12^-H to 9,10-diazasnoutane 127-H

utilized dilute chloroform solutions of the basketane and silver

fluoroborate heated at reflux over a period of 5-7 days. By this 80 method high yields of 12j[-H were consistently realized. The pmr

spectrum of the parent polycycllc showed resonances a t $ 1 . 20-7.70 (m,5),

4.90-5.25 (m,2), and 1.73-2.22 (m,6) in agreement with the anticipated

upfield shift of the b I x newly formed cydopropyl protons.

The reaction times were unduly long using AgBF^/chloroform and

alternative methods were sought. The low solubility of AgBF^ in

chloroform seemed responsible for the slow conversions orignally + 83 witnessed. Silver ion catalysis is known to be first order in Ag , meaning that rate increases should be observed in solvents capable of

dissolving more substantial quantities of silver salts. Three different sets of silver salt-solvent systems have since been inves

tigated and found to be successful within certain lim its. Silver nitrate in aqueous methanol has proven to be the most general re arrangement medium for the basketane to snoutane conversions. Some other systems employed were silver perchlorate in benzene or toluene and silver nitrate in acetonitrile.

A comparison of the rearrangements of several isomeric basketanes provides some insight into the dependence of the reaction upon the electronic character of the substituent and its framework position. For example, 124-CH^, 125-CH^, 124-C^H,., and 12§.-CgHj were sim ilarly treated with silver nitrate In aqueous methanol at reflux in the absence of light. The times required for completion of the rearrangements as followed by tic were: 60 hr, 72 hr, 20 hr, and 19 days, respectively.

Clearly, the position of the methyl group does not affect the rearrange ment nearly as much as does that of the phenyl. The respective products,

128-CH^, 127-CgH,., and^128-CgH^ were obtained in high yields

(see Table VII).

1X7 \X 2 u s

Those diazabasketane isomers containing electron withdrawing groups rearrange rather slowly in the presence of silver nitrate in aqueous methanol. For that reason, silver perchlorate dissolved in a higher boiling solvent such as benzene or toluene seemed preferable for these conversions (also, the acetoxymethyl derivative hydrolyzed 68 in aqueous methanol). Apparently, electron withdrawers attached to the cubyl system retard the (T^coraplexation of Ag ion with the diazabasketane skeleton and thereby lower the rate of rearrangement. 83 56

Treatment of 125-CN with excess silver nitrate in refluxing aqueous

methanol led Unexpectedly to the rearranged carboxamido derivative

12fl~CONH2 in 29% yield. Substitution of the aprotlc solvent aceto-

n itrlle for aqueous methanol permitted the successful rearrangement

of 125-CN to th e snoutane 128-CN in 75% y ie ld over a 6.3-day p erio d .

Unfortunatelyf the related isomer 124-CN refused to rearrange under

the same conditions after 11 days; the starting material was returned

in good yield. Attempts to convert 124-CN to i t s snoutane were made with silver nitrate in refluxing aqueous methanol and iv-butyl alcohol with no success; starting material was recovered (no carboxamido- basketane was found with these protic solvents). Neither silver

fluoroborate in chloroform nor silver perchlorate in benzene or toluene

could effect the desired transformation. In fact, the latter conditions brought about the gradual decomposition of starting material. Likewise,

th e bridgehead n i t r i l e 126-CN fa ile d to rearran g e when heated in acetonitrile containing silver nitrate.

The difficulties encountered not only with the cyano derivatives but also with other powerful electron withdrawing groups support the

theory that electron withdrawal from the strained tr~ bond(s) involved in initial complexatlon deters the relocation of these

Coordination of Ag+ to the electron rich C ° N bond may also help

to explain the limited success in that series. FluorobaBketane ,125^, on the other hand, undergoes a smooth conversion to its corresponding snoutane isomer 128-F in the presence of silver perchlorate in refluxing toluene. The results of these interesting reactions are summarized

in Table IV. 4

Table IV. Results of Ag -Catalyzed Rearrangements

9,10-Diaza- Catalyst Solvent Diaza basketane (mmol) (mmol) systems(ml) Time,days snoutane Yield,%

124-11 AgBFb CHC13 127-H 81 (3A) (17) (100)

42**c6H5 AgNO CH-OH--h2° 0.85 127-C6H5 96 (5.1) (75) (* 7 i. 200)

AgN03 CH30H-H2O 19 128-C-H, 72 i2 5 r C6H5 6 5 (1.2) (18) (A:l» 60)

12^-CH3 AgN03 CH-OH--h2o 2.5 127-CH. 97 (0.68) (10) (A :l, 15)

125-ch3 AgN03 CHjOH--h2o 128-CH. 7A (A.5) (66) (A :l, 100)

12A-CH20Aca AgC10A 7 127-CH2OAc 95 C6H6 (A.0) (30) (150)

125-CH20Aca AgC10A 7 128-CH20Ac 75 C6H6 (0.65) (5) (25)

126-CH2OAca AgC10A 8 129-CH2OA c 91 C6H6 (2 .3 ) (10) (50)

12A-CH20CH3a AgNO- ch3oh- 7 127-CH2OCH3 AO ■h2° (l.A ) (59) (A :l, 75)

125-CH20CH3a AgN03 CH30H--h2o 8 ^28-CH20CH3 82 (2.0) (88) (A :l, 75)

126-CH2OCH3a AgN03 ch3oh-•H-0 10 129-CH20CH3 67 (1.8) (70) (A:l» 50) 58 Tabic IV. (continued)

126-C00CH3a AgClO^ 8 129-COOCH3 88 (3.7) (20) (100)

125-CN AgN03 CH30H-H20 2 128-CONH2 27 (0.33) (5) (4:1, 10)

125-CN AgN03 CH3CN 6.3 128-CN 75 (0.32) (5) (10)

125-F AgClO^ Toluene 4 128-F 93 (4.7) (48) (100) '

0 ^ Performed by G.H.Blrnberg; see reference 68. Added In Incremental amounts; see Experimental.

Hydrolysis Experiments. Preparation of semibullvalene (1)

and its substituted congeners requires vigorous hydrolysis of the

urazole ring in their 9,10-diazasnoutane precursors. The conditions used for the hydrolysis must of course not be so forcing as to cause destruction of the newly generated hydrocarbons. The precursor (127-H) 28 29 to semibullvalene was saponified originally * with excess potassium hydroxide in aqueous ethylene glycol at ca. 100° under oxygen-free conditions. In this way, the ethylene glycol could be partially removed by distillation without causing the oxidation of the liberated hydrazo. intermediate 1JJ0 and thermal destruction of Careful extraction of the resultant cooled solution with ether and methylene chloride sufficed to effect air oxidation of the intermediate hydrazo compound (130). Workup of the organic layer gave semibullvalene (1) in 78% yield; no evidence was obtained at that time for the suspected intermediacy of 9,10-diazasnoutane (52). The infrared and pmr spectra (multlplets at 2.97, 4.17, and 5*08 in the ratio of 2:4:2) of this

Base ia7-H ■> ■> 1

13)0 s “a

19 pungent, colorless liquid were Identical to published data.

Additionally, the noise resonance decoupled cmr spectrum of (in CDCl^) recorded at ambient temperature revealed a three-line array of QA signals at 50.0, 86.5, and 120.4 ppm downfleld from IMS, which is fully reconcilable with the presence of a time-averaged degenerate pair of isomers.

Moriarty and coworkers recently reported trapping the diazasnoutene

.52 as a cuprous chloride complex (131) by oxidizing 130. with cupric 85 chloride. Subsequently, Paquette and Birnberg showed that the brick- red complex 131, upon decomposition in aqueous ammonium hydroxide,

86 gave semibullvalene (1) as the only product. The intervention of diazasnoutenes (e.g., 52) in the synthesis of semlbullvalenes from their snoutane precursors is therefore established. 60

The rather rapid loss of nitrogen from 52 (not isolated) is not

unexpected although a number of polycyclic azo compounds are relatively 87 88 89 stable. * Cheletropic ejection of gaseous fragments (CO, SOg*

etc.) with formation of stable hydrocarbon products has been investigated 90 extensively in the past decade. Azo compound 132 readily loses at

> 35

-78° to give 1,3-cyclohexadiene^ and the endo cyclopropyl homolog 133. 17 92 undergoes cheletropic fission 10 times faster than its parent (134).

However, derivatives of the exo cyclopropyl isomer(135)require temper- o 87 88 atures of 160-190 to extrude nitrogen. ' The reason for the large

rate enhancement in N 2 expulsion from JL33 seems to be the rather

favorable alignment of the three <7~bonds partaking in the concerted

0 —2^ +0-2s +q-2q bond reorganization; nitrogen leaves syn to the

fragmenting £T~bond of the cyclopropyl ring and little geometrical 61 change Is necessary to align the newly forming 'Tforbitals. In contrast, the relatively stable Isomer 135 possesses severe geometrical constraints to developing orbital overlap and probably decomposes via a radical mechanism. Consequently, 9,10-diazasnoutcne (52) contains what Is believed to be an almost Ideal geometry and adequate strain for rapid, 93 concerted expulsion. AIb o , the conversion of^52 to semibullvalene is Independent of which edge cyclopropyl bond experiences fission.

The isolation of most semibullvalenes required care to minimize thermal isomerization to cyclooctatetraenes. In general, vpc methods s u ffic e d for the purification of moBt semibullvalenes if the lowest feasible oven temperature was employed. Semibullvalene J^l), for example, can be gas chromatographed on a standard 6 ft. aluminum column packed with a "boiling point" stationary phase such as 5% SF-96 on Chromosorb

G at an oven temperature of 65°. The thermal rearrangement ot cyclooctatetraene amounts to a few percent (unfortunately, under these conditions, semibullvalene and COT have the same retention time, i.e. 94 12 rain.) Further reductions in oven temperature and column length have lowered the degree of isomerization to an insignificant level

(vide infra).

The strenuous hydrolysis conditions used initially for the 28 29 preparation of semibullvalene * proved to be inappropriate for 41b the liberation of certain other semibullvalene systems. A milder procedure was discovered for the hydrolysis of the urazole ring which involves initial alkaline hydrolysis to give a semi- 95 carbazide followed by oxidation (and spontaneous loss of Ng) with activated manganese dioxide. The oxidation step is derived from 62 analogous oxidations of phenylhydrazides and hydrazobenzenes with

MnOg* Significantly, MnO^ and its reduced forms do not complex meaningfully with azoalkanes and do not prevent cheletropic loss of

Ng. Details of the procedure for removal of the urazole ring are presented in the Experimental Section.

A variety of other techniques have been tried at various times to accomplish the liberation of the semibullvalene skeleton from its diazasnoutane precursor. For example, D.H.R. Barton, et. al. have used PTAD for the protection of steroidal dienes; the retro Diels-

Alder reaction was achieved in almost quantitative yield by treat- 98 ment of the adduct with lithium aluminum hydride. Treatment of the diazasnoutane 3^27-CgH^ (R* “ CH^) with LiAlH^ as prescribed, followed by a typical workup, produced a small quantity of semicarbazide 136 as the only product. Failure at this poin't discouraged us from

CC0CH,CC|,

N— COOCH.CCI

further investigation of this procedure. Several attempts were made to utilize the readily removable dienophile bis-2,2,2-trichloroethylazodi- 99 carboxylate (137) instead of PTAD. Treatment with zinc in methanol sufflees to liberate the protected diene but, unfortunately, this reagent (137) is not reactive enough to cycloadd to COT's. In fact,

137 failed to add to any COT, either directly or indirectly (through the dibromide).

1(5)-Substituted Semibullvalenes. The synthesis of l(5)-methyl- semlbullvalcnc (91-CH^~L92-CH^) was effected in 49% isolated yield by hydrolysis of 127-CH^ in refluxing alkaline isopropyl alcohol followed by oxidation (MnO^)* The hydrocarbon was isolated as a pungent, colorless liquid after separation from aniline (from urazole decomposition) by preparative vpc on a 2 ft OV-ll column operating at

45°. This CgH^Q hydrocarbon appeared to be both thermal and air

sensitive and had to be stored in a freezer under an inert atmosphere.

Identification of JSJI-CH^ was based on its pmr spectral characteristics its molecular ion of m/e 118.0781, and its great similarity to semi bullvalene. The pmr spectrum at -<-36° in carbon disulfide solution consists of a doublet of doublets (J^ Jg ^-4.0 Hzj J ^ g“2,0Hz) centered at 8 5.06 assignable to the permanently olefinic protons and H ,. The two rem aining s e ts of p aired protons H„,H_ (3.42,m) and / * o H^,Hg (4.78,dd) proved distinguishable by double resonance techniques

(quite helpful with all the l(5)-substituted semibullvalenes) which revealed only the latter hydrogens (olefinic region) to be spin

* coupled to (2.68,t,J^ 6"3.0 Hz)* Also, l°w temperature pmr analysis (see Figure 1) indicated that the lowest field absorptions 64 are not temperature dependent. However, the olefinic signal at $ 4.78 moves downfield as the temperature is lowered (temperature dependent equilibrium constant). This finding bears out the above assignments.

The appearance of g at substantially lower field that g demands that be the predominant isomer in this nondegenerate equilibrium m ixture.

A variable temperature pmr analysis of 1(5)-methylsemibullvalene over the temperature range of -85° to +132° was carried out at 60 MHz.

As revealed dramatically in Figure 1, variations in chemical shift and line shape were observed (see data tabulation in Experimental Section).

More specifically, a lowering in temperature caused the multiplet due to Hg g to move upfleld and the resonance due to ^ to move downfield where it finally overlapped the y signal. Consequently, the concentration gradient favoring 91-CHj over J92-CH^ increases as the temperature decreases. As is apparent from Figure 1, no coalescence point was reached in the low temperature study and l(5)-methylsemibullvalene wsb never "frozen" into its Individual Isomers on the nmr time scale. In fact, none of the semibullvalene isomerizations presented here were slowed to the point that the two tautomers could be observed

Independently. Only three semibullvalene cases have been reported to date to have been observed under slow exchange conditions: they are octamethylsemlbullvalene (57),*^ an annelated system t:81-(CHg)|J , ^ a and the parent, semibullvalene (1). * Various methods are available for the computation of thermodynamic parameters associated with variable temperature phenomena. One such technique first employed by Wood, F ic k e tt, and Kirkwood*®*- i s to c a lc u la te K fo r an eq u ilib riu m Figure 1. Selected variable-temperature pmr Spectra of l(5)-nothylseraibullvalene (60 MHz, CS2 solution). 66

by plotting chemical shifts vs. temperature. Unfortunately, in our

case, the observed chemical shift changes were rather small (less

than one ppm over a 150° temperature range) and the peaks were too

broad to permit precise assignments and so the 2-3 significant

figures in S and T were less than adequate for such computations.

Another approach considered for obtaining a quantitative estimate

of the ground state energy differences at play Involved the use of

the following equations. The observed chemical shift at a temperature

m of a proton undergoing rapid exchange is denoted by .f m; 5^ and are

the chemical shifts, respectively, of the vinyl and cyclopropyl protons

in the absence of rapid chemical exchange, and £ is the mole fraction 102 103 of one of the isomers. * Clearly, all that is needed to make

- l &v + a - i ) S c £. * ( $ m-S c ) / (<5V- S c) (Equation 1)

Km - £/ (1- £)

equation 1 work is a static model system from whence values of ^.and

£ can be chosen. Perhaps the best available model is semibullvalene which can be "frozen-out" on the nmr time scale. ^ Anet and coworkers

have measured values for the pure cyclopropyl and vinyl protons in 1

at -160° to be 2.79 and 5.59 ppm, respectively (in CCl^F^; relative to

TMS). Accordingly, the chemical shift data (see Experimental Section)*^

at +36° for l(5)-methylsemibullvalene suggest the mole fraction for

91^01^ to be ca.0;71%,with the consequence that K+.jgo ** 2.4(AG° -

533 cal/mole). The validity of this approach must be tempered with

the realization that the presence of a substituent on the semibullvalene

nucleus, particularly a strongly interactive one, changes the environment 67 of the protons used in these calculations and their chemical shifts can become less precisely indicative of the quantitative direction of equilibrium present in 91^92. Solvent-induced chemical shift changes should also not be ignored.

The preferred equilibrium displacement of l(5)-methylseraibullvalene can be compared to the similar imbalance present in 40 1,3-dlmethylsemlbullvalcne (76) mentioned in the Introduction.

Analysis of the 100 MHz pmr spectrum of 76 revealed^ the same

76 positional preference as the monomethyl case discussed above. Again double resonance techniques were helpful In determining this pre fe re n ce .

Hydrolysis of 12J-CgHg gave j)l-CgH^=?92-CgH,. in 76% yield as a colorless oil which solidifies below 0°. Purification was accomplished on a 1 ft. OV-11 column at 100°. The 100 MHz pmr spectrum of l(5)-phenylsemibullvalene at +33° in CD^Cl^ consists of an aromatic multiplet a t£7.10 corresponding to the 5 phenyl protons, three multlplcts of area 2 at 5.43(H^ and Hg), 5.21 (H^ and Hy)» and 3.43

(H2 and Hg), and a triplet at 3.31 (J^ 2.5Hz) associated with

Hg (see Figure 2). Saturation of the 5.43 ppm multiplet caused the

Hg triplet to collapse to a singlet. Since the signal at 5.43 is 68 temperature dependent, it must correspond to H^,Hg . On the other hand, the resonance at 5.21 is temperature independent and is assigned toH j and H^. The remaining set of peaks at 3.43 pprfi must be due to llgfHg and the isomerization equilibrium is seen to favor 91-CgH,.. The variable temperature pmr spectra of l(5)-phenylsemlbullvalene (see

Experimental Section for numerical data) mimic the spectra observed for its methyl counterpart with the g signal shifting to higher field and the g multlplet to lower field with decreasing temperature.

The earlier reservations concerning the general applicability of equation 1 are manifested in these experiments since the chemical shift of H. , at -126° is at lower field than the "standard" chemical 4 ,6 shift obtained from "frozen-out" semlbullvalene, viz. ,<5*5.69 v s .

5.59 ppm(vlde supra). The equilibrium is obviously heavily weighted toward cyclopropyl substitution but the precise degree to which this operates is unknown.

l(5)-Methoxymethylsemibullvalene (91-CHÔCHjSKl-CÔCH^) was likewise prepared by hydrolysis and oxidation of its precursor l^-CHÔCH^ in 39% isolated yield. Pmr analysis of this fluxional compound was performed as above and showed beyond doubt th a tp i-CHÔCHj predominates in the equilibrium to the extent of 80-90% (experiments 86 carried out by G.H.Birnberg in this group).

Likewise, hydrolysis-oxidation (necessarily 0^; MnO^ promoted pro duct decomposition) of 127-CH2OA.C furnished alcohol ^l-CHgOAc^^^-CH^OAc

(54%) which because of its thermal sensitivity was purified by prep arative thick layer chromatography on silica gel. The molecular ion and pmr spectrum were consistent with l(5)-semibullvalenyl carbinol + 3 3

- 5 8 '

-97

7.0 6.0 5.0 4.0 3.0 Figure 2. Selected variable-temperature pmr spectra of l(5)-phenylsemibullvalene [100 MHz, CD^Cl^-Freon 11 solution (1:1)1*

4 70 and the equilibrium distribution of isomers appeared very similar to the 86 other cases (experiments carried out by G.H.Birnberg).

Finally, l(5)-cyanosemibullvalene has been prepared in this group by an interesting sequence of reactions based on the work of Moriconl*®^ and VorbrUggen.Treatm ent of barrelene (39) with chlorosulfonyl isocyanate (CSI) followed by prolonged heating of the product mixture 108 in dlmethylformamide resulted in the production of chloronitrile 138.

HSSC ft CSI

MO k r

CN KOtSi DhSO

Bicyclo[3.2.1]octadiene 138 was readily converted to l(5)-cyano- 109 semibullvalene in good yield using potassium J>butoxide in DMSO.

This interesting derivative was purified by preparative vpc to give a crystalline solid which was characterized by the sim ilarity of its pmr spectra to those already presented. A 100 MHz pmr spectrum of

91-CN^92-CN in carbon disulfide solution at +33° showed a low field 71 multiplet at ^5.64 assignable to H.»H, * a multiplet of two protons 6 a t 5.14 (H^fH )» a t r i p l e t o f one p ro to n a t 3.40 (H,.)., and a m u ltip le t

Integrating to two protons centered at 3.37. Double irradiation studies served to establish that £1-CN is the predominant tautomer in the mixture. This molecule is of considerable synthetic importance since the cyano function can in principle be readily converted into a host of other functionalities.

2,4-Substituted Semibullvalenes. In contrast to the 1(5) substi tuted systems just discussed with their plane of symmetry, 2(4)- substituted semibullvalenes lack any symmetry element. More signifi cantly, the intrinsic differences in the number of olefinlc protons which each valence structure possesses (139 has three, 140 has four olefinlc positions) permit facile qualitative determination of equili brium weighting by standard pmr integration. Simply stated, if 139

a e

predominates in the equilibrium, there w ill be only three olefinlc resonances in the time-averaged pmr spectrum, while if 140 predominates four olefinlc signals will be seen.

When 128-CH^ was hydrolyzed/oxidized by the conventional method, 72

139-CH^^£ 140-CH^ was obtained In 52% y ie ld . S elected 60 MHz pmr spectra recorded at several temperatures ranging from +99° to -101° are shown In Figure 3. The ambient (+42°) spectrum contains a series of overlapped multlplets and no fine structure Is visible. Integra tion indicates the presence of three olefinlc protons. Consequently,

139-CHg Is the major component in the mixturb. The assignments made at 42° are as follows: the narrow multiplet a t£2.93 corresponds to

Hgi Hg, H^, and H^; Hg and Hy overlap a t 5.19, and which is proximal to the methyl group is seen at 4.84. Upon reduction of the temperature to -101°, the protons or pairs of protons become individually visible.

Double resonance experiments aided in the necessary assignment (see

Experimental Section). Clearly, the equilibrium is heavily weighted in favor of olefinlc substitution and becomes even more so as the temperature is reduced. However, a precise quantitative estimate of this effect is not possible because of previously discussed factors.

In analogous fashion, 2(4)-fluorosemibullvalene (1 3 9 -F 140-F) was prepared from its snoutane precursor 128-F in 72% yield. Again purification was by preparative vpc and the identification of this pungent, colorless compound was by its characteristic molecular ion at m£ 122.0530 and the definitive pmr spectrum at +35°. The spectral features at this temperature in CSg solution consist of a broad multiplet centered a t^2.82 assignable to the three pseudocyclopropyl protons, a second multiplet due to at 3.17, and two sets of olefinlc signals at 4.62 (m,l,Hg) and 5.41 (m,2,Hg and Hy), A lowering in temperature separated the signals for Hg and Hy since the Hg resonance moves downfield, but the rest of the spectrum gains no I I I o ai N -4 W $ P “s <

Figure 3. Selected variuble-temperature pmr spectra of 2(4)*-methylseraibullvalene (60 MHz; C2C1^ solution at 80° and 99°; CS2 solution at 42 and below).

•*4 -4 4

-91

6.0 50 40 30

Fifjurc A. Selected vnrJal>Ie-tcmperaturc* pmr spectra of 2(A)-fluoroseroI- huLlvnlcne (60 Mlh'., CS,, .so lv.tlou). 7* additional readily interpretable features (see Figure 4). The olefinlc fluoro isomer dominates the equilibrium as usual.

G.H.Birnberg converted his 9,10-dlazasnoutane l^-CH^OCHg successfully to 2(4)-methoxymethylsemibullvalene (I 39-CH2OCH3 86 lAO-CHgOCH^) whose pmr spectrum clearly establishes lM-C^OCH^ as the major structure. At 30° in CDCl^ solution, three well separated olefinlc protons appear as multiplets centered ati'5.28, 5.12, and

4*73. The cyclopropyl protons and Hg are found at 3.72 and 3.78, respectively, while and H,. appear at 3.07 and 3.13. Substitution at again predominates in the mixture.

U n fo rtu n ately , a l l attem p ts to co n v ert 128-CgH,. and 128-CN to their corresponding semibullvalenes have met with failure. Insoluble orange colored polymers were Invariably obtained. The n itrile group was originally expected to cause difficulty especially at the alkaline hydrolysis step. However, no reasonable explanation can be offered for the failure to realize the preparation of 2(4)-phenylsemibullvalene.

Of interest in this section are the reported syntheses of 38 2-bromo-l,5-dimethylsemibullvalene (70) and 2,3-his-trifluoromethyl- 39 semlbullvalene (74). Whereas the bromide 70 complements the previous observations in that the vinylic bromide predominates in the valence isom er m ix tu re, compound 74 e x is ts m ainly as a cyclopropyl s u b s titu te d semlbullvalene. No other unsymmetrical 2-substituted case is known where this preference for cyclopropyl substitution holds. Perhaps steric hindrance or dipole-dipole repulsions between the two CF^ groups are smaller in the 2,3-positions than in the 3,4-positions where these groups would have a dihedral angle relationship of 0° . 3-Substituted Semibullvalenes. The only semibullvalenes derivatized at that have been prepared in this study are the methoxymethyl and carbinol cases synthesized by Dr. G.H.Birnberg.

These systems are of lesser Importance with regard to equilibrium measurements because their Isomerization is degenerate. Consequently no ground state energy differences exist.

\n \

However, for the record, 129-CH^OCH^ was converted to JMI-C^OCH in 45% yield. The temperature Independent pmr spectrum consists of a single olefin absorption at5”4.93 (H^, t, J**3.5 Hz), four time- averaged protons at 3.92 and Hg,m), and two protons at

2.85 (m) corresponding to H^ and H,.. This sequence of ring protons is reminiscent of the time-averaged semlbullvalene spectrum. 77

Comparable hydrolysis of lW-CHgOAc followed by air oxidation

gave 3-semibullvalenylcarbinol in 57% yield as one of the few crystal

line semibullvalenes known. The Infrared spectrum (KBr) shows an

hydroxyl stretching mode at 3320 cm**^. The pmr spectrum of this

Interesting compound again contains a single olefinlc resonance as

a triplet at

a multiplet at 3.01 associated with and H,..

A ttem pts to co n v e rt IW-COOCH^ to 3 -se m ib u llv a le n y lc a rb o x y lic

acid (141-C00H) met with failure. Apparently^ functionalities such as

cyano or carbomethoxy are too sensitive to the hydrolytic conditions

and reaction at these sites causes destruction of the entire ring

system in some unknown manner.

Discussion, of Semlbullvalene.

Extensive discussion relating to substituted semibullvalenes has been presented in the introduction to Fart II. A few summarizing

comments are in order however. The valence orbitals of semlbullvalene contain the Walsh orbitals of cyclopropane or a set of comparable 53 symmetry. According to Hoffmann and Stohrer, TT-electron donors

should therefore shift the equilibria of l(5)-substituted semibull valenes markedly toward 92^ and 2(4)-substituted derivatives toward

140, while 'TT-electron acceptors should cause weighting in the opposite directions (toward 91 and 139 respectively). Further explanation appears in the Introduction as it relates to varied substitution 52 110 on the norcaradiene-cycloheptatriene equilibrium. * Only a few other relevant ground state equilibrium displacements have been studied. 78

Cases Involving blcyclo[4.2.0]octadiene-cycloocCatrlene^^ pairs lack

Ideality since they contain a ground state preference for one isomer

even In the absence of substituents. But bullvalene equilibria have 112 also been examined. A general trend has been observed in this

system for aliphatic > olefinlc > cyclopropyl substitution. A two

fold degenerate system seems best suited for a substituent effect

study. In this connection, Schleyer has recently examined several

substituted barbaralones and has observed that a deuterium atom

exhibits a preference for bonding to aliphatic ^ cyclopropyl^ olefinlc

carbon, whereas methyl preference is in the order olefinic > cyclo- 113 propyl > aliphatic.

The methylsemibullvalenes presented in this study exhibit comparable

preferences and it would seem that the same influences are at work.

Theoretically, the methyl subBtituent is donor dominant (as Libit and 114 Hoffmann have termed it) either by electron donation or by polar

ization. A resultant conjugative effect with the cyclopropane ring

or olefin bond of semlbullvalene is expected to result. On the other

hand, recent studies have shown that a methyl group behaves like a

TT-acceptor in that it weakens the adjacent ring bonds and strengthens 115 the remote bond. The behavior of l(5)*methylsemibullvalene certainly

conforms to this analysis, but it is doubtful that these factors are

the only ones causing such a preference since all substituents placed

to this time at have preferred cyclopropyl substitution. What

is needed here is a very strong ‘ff'electron donator positioned at

to see if the equilibrium is shifted towards 92. Unfortunately, 79 electron donators, it w ill be remembered, prevent synthesis of suitable adducts to COT because they force the cycloaddition to proceed through the monocyclic form. Ground state preference for methyl attachment to olefinlc carbon in 139. 140 again agrees with the principles stated above. However, it is impossible at this point to determine how much of that influence is due.to usual strong preference of methyl 2 112 116 for attachment to sp -hybridized carbon. * 53 Hoffmann and Stohrer have predicted that a phenyl group attached to a cyclopropyl ring w ill strengthen the opposite C-C link if the phenyl ring is in a bisected conformation. Thus is predicted to be more stable than its tautomer. Indeed, 91-C^1L is found to heavily predominate in the equilibrium mixture.

The only other molecule of interest to this discussion 1 b 2 (4 )- fluorosemibullvalene. The somewhat sim ilar compound fluorobullvalene was found to exist ca. 80-85% as isomer 142 where fluorine is bonded to 49a the lone aliphatic position. The remainder of the tautomeric mixture contains the olefinlc fluorides 143 and 144. No cyclopropyl attachment was evidenced. The conjugatively donating fluorine, therefore, is seen to prefer aliphatic> olefinlc >■ cyclopropyl positions. 80

In the case of 2(4)-fluorosemibuHvalene, one would predict that the electron donating fluorine would prefer cyclopropyl substitution 53 over olefinlc. In fact, Hoffmann's theoretical analysis of 2,8-di- fluorosemlbullvalene (145^.146) views 145 as the predominant Isomer.

1 4 5 w

117 Also 1,1-dlfluorocyclopropanes have been shown to exhibit stabilization of the ring for the reasons explained above. Why fluorine prefers olefin attachment in our semlbullvalene is unknown. Some additional substituent effects as yet unrecognized must be partially directing the observed equilibria. As concerns monosubstituted semibullvalenes,

It may be stated that without exception 1(5) substituents prefer bond ing to Cp while the majority of 2(4) substituents enjoy attachment to 114 C^. Other factors such as polarization must be important and a comprehensive theoretical analysis of all possible effects would be enlightening.

Experimental Section

Melting points are corrected and boiling points are uncorrected.

Proton magnetic resonance spectra were obtained on Varian A60-A,

Varian HA-100, and Jeolco MH-100 spectrometers; apparent splittings 81 are given in all cases. Infrared spectra were determined on Perkin-

Eltner model 137 and 467 instruments. Mass spectra were recorded on a

AEI-MS9 spectrometer at aA ionization potential of 70 eV. Elemental analyses were performed by the Scandinavian Microanalytical Laboratory,

Herlev, Denmark. Microanalyses were not acquired for the various semi bullvalenes due to their air sensitivity and thermal Instability at room temperature.

Direct Addition of N-Methy 1 trlazolinedione to Phenylcydooctatetraene.

Generalized Procedure. A solution of 8.25 g (45.8 mmol) of phenylcyclo-

octatetraene^ in 400 ml of ethyl

acetate was heated to reflux with

stirring while a solution of 5.18 g

(45.8 mmol) of freshly sublimed N- 118 methyl-1,3,4-triazoline- 2, 5-dione o in 400 ml of the same solvent was added dropwise during 1 hr. Discharge of the red color of the dieno- phlle was almost immediate and a pale yellow color persisted, the solvent was removed in vacuo to leave a yellow-orange oil which was chromato graphed on neutral activity III alumina. Ether elution returned 2.15 g of phenylcydooctatetraene and also yielded 8.34 g (84%) of white crystalline adduct. Recrystallization from 2-propanol furnished pure

101-CfiH5, mp 192-194° d e c ; ^ C2H5OH 248 (G 20,000) and 282 nm (450). ’ max When the mother liquors were subjected to preparative thick layer chromatography (silica gel, ether-hexane ( 1 :1) elution), small amounts of 103-0,^, mp 175.5-176.5° (from 2-propanol), could also be isolated. /■—•* o J 82 2 5 3-Methyl-7 > 8-diazatricyclo[4.2.2.0 * ]deca-3,9-diene-7, 8-dicarboxylie

Acid Phenylimide (lOl-CH^). Treatment of a solution containing 1.0 g 119 (8.49 mmol) of methylcyclooctatetraene

dissolved in ethyl acetate (40 ml)

w ith 1 .5 g (8 .5 7 mmol) o f f r e s h ly

sublimed N-phenyl-1,3,4-triazoline-

2,5-dione,^®*^^ followed by heating

at reflux under nitrogen for 24 hr and chromatography on silica gel (200 g, methylene chloride elution), gave in the in itial fractions 274 mg (11%) of JLOl-CH^. Recrystallization from benzene-hexane gave the pure tetracyclic adduct as colorless crystals, mp 189.5-190°.

Later fractions consisted of 273 mg (11%) of a mixture of two CDC1 tricyclic adducts in the form of a white solid; <5 .^g 7.42 (m,5,aryl),

5.63-6.27 (br m, 5, olefinlc), 4.83-5.18 (m,2,bridgehead), 2.18 (br s,

30% of 3H, methyl), and 1.93 (br s, 70% of 311, methyl).

2 5 2-Fluoro-7, 8-diazatricyclo[4.2.2.0 * ]deca-3,9-diene-7, 8-dicarboxylic

Acid Phenylimide (102-F). After heating a solution containing 1.60 g

(1 3 .1 mmol) o f f lu o r o c y c lo o c ta te tr a e n e ^

and 2 .3 g (13.1 mmol) of PTAD in

40 ml of ethyl acetate at reflux for

2.5 hr, there was isolated after sol

vent evaporation and alumina chroma

tography (neutral, methylene chloride elution) 2.93 g (75%) of ^102-F as a white flocculent solid, mp 204-205° /Q _ (lit mp 204-205 ), after recrystallization from chloroform-ethanol. 83

Direct Addition of PTAD to Cyanocyclooctatetraene.

^ f t

101'CN

c* o J04-CW

121 Reaction of 4.0 g (31 mmol) of cyanocyclooctatetraene with 5.42 g

(31 mmol) of PTAD in 400 ml of ethyl acetate (reflux, 12 hr), followed by solvent removal in vacuo, gave an orange oil which was triturated with a small quantity of ethyl acetate. The crystalline white solid so obtained (2.06 g, 26%) was identified as ^101-CN, mp 250° dec (from ncetonitrile).

The remaining material (6.83 g) was chromatographed on silica gel

(500 g). The collected fractions gave in order of elution 40 mg of recovered cyanoCOT, 2.37 g (31%) o f 103-CN, mp 180-182° dec (from

2-propanol-acetonltrile), and 1.84 g (24%) of 102-CN, mp 214-218° dec (from 2-propanol-acetonitrile). nC 9H,0U For 101-CN: A * 3 215 (£ 3 0 ,0 0 0 ) and 260 nm (4250), For 103-CN; t— - max *— 84 iC J I .O H A J 260 nm (£ 2000) . max 2 5 7,8-Diazatricyclo[4.2.2.0 * ldeca-3,9-diene-7,8-dicarboxylic Acid

Phenylimide (101-H). General Procedure for Indirect Addition.

A 30.0 g (0.288 mol) sample of

cydooctatetraene was dissolved in

300 ml of methylene chloride* and

this solution was treated dropwise

with bromine (46.1 g, 0.288 mol) at

-78° during 30 min. The resultant

solution was stirred for 15 min and 50.4 g (0.288 mol) of freshly

sublimed PTAD in 100 ml of the same solvent was added slowly. Stirring

was maintained for 4 hr while the red solution was allowed to warm to

room temperature. Evaporation of the solvent and recrystallization of

the residue from ethyl acetate gave 110 g (87%) of white crystalline

dibromide, mp 253.5-257.5°. 122 Solid dibromide (110 g, 0.25 mol) was added to zinc-copper couple

(20.0 g, 0.31 mol) stirred magnetically in refluxing dimethylformamide

(800 ml). Refluxing was continued for 9 hr, then the mixture was

filtered hot. The light brown filtrate was concentrated in vacuo to

give a wet crystalline mass. This was washed with 3N sulfuric acid

and water to yield 69.5 g (99%) of 101-H as a sparkling white solid.

Recrystallization from carbon tetrachloride produced glistening plates,

mp 216-217° (lit 77 mp 216-217°).

Indirect Addition to Methylcyclooctatetraene.

Treatment of 1.0 g (8.46 mmol) of methylCOT sequentially with 1.39 g

(8.70 mmol) of bromine and 1.5 g (8.48 mmol) of PTAD gave a crimson o il 85

which was dissolved In 50 ml of

absolute ethanol and heated at reflux

w ith 5 .3 g (81 mmol) o f z in c -c o p p e r

couple for 12 hr. Chromatography of

{5 the pale orange residue on silica gel

(methylene chloride elution) afforded

691 mg (30%) of ^lO^CH^ as white prisms, mp 184-185° (from 2-propanol).

Indirect Addition to Phenylcydooctatetraene.

\ ^ w- c6hs o o KKl-CtHs

Bromine (8.70g, 54.3 mmol) was added to 9.78 g (54.3 mmol) of phenylCOT at -78° in methylene chloride solution, followed by 9.50 g

(54.3 mmol) of PTAD. The resulting orange oil was taken up in 550 ml of absolute ethanol and heated at reflux with 16.3 g (0.25 mmol) of zinc-copper couple (12 hr). Chromatography on silica gel (ether- hexane elution) gave 1.74 g (9.1%) of ^104rCgH^, mp 174.5-175° (from

2-propanol-acetonltrlle) and 1.13 g (5.9%) of mp 222.5-223° dec (identical solvent mixture).

Indirect Addition to Cyanocyclooctatetraene.

When 1 .0 g (7 .7 4 mmol) of cyanoCOT was brom inated (1 .2 4 g Br^) at -78° in methylene chloride and subsequently treated with PTAD

(1.35 g) and zinc-copper couple (2.29 g), there was obtained an orange 86

oil. Chromatography on silica gel (300 g) and elution with ether- hexane gave three products; the in itial fractions returned 580 mg of the COT, followed by 489 mg (49%) of J^-CN, mp 212-213° dec (from

2-propanol-acetonitrile), 86 mg (9%) of IO 37CN, and lastly 120 mg (12%) of 102-CN.

Indirect Addition to Fluorocyclooctatetraene.

Reaction of 1.0 g (8.19 mmol) of

fluoroCOT with 1.31 g of bromine

and 1.43 g of PTAD afforded 3.39 g

(91%) of a white powdery dibromide.

A 3.39 g sample of this solid was

debrominated with zinc—copper couple in absolute ethanol (100 ml, reflux 12 hr) to give 1.39 g (90%) of 102r F.

Indirect Addition to Bromocyclooctatctraene.

From 1.00 g (5.46 mmol) of bromoCOT,

0.88 g of bromine, and 0.96 g of PTAD

with subsequent debromination and

chromatography on silica gel (elution

with methylene chloride), there was 2 5 Table V. Physical Data for the 7,8-Diazatricyclo[4.2.2.0 * ]deca-3,9-diene-7,8-dicarboxamides

Anal d a ta Compound Pmr ( £ , CDCl^, 60 o r 100 MHz) Calcd Found

1 0 l-n Hr 7.33 (s,5, phenyl), 6.21 (s,l,H4), 5.86-6.36 For C17H15N302 : C, 69.36; H, 5.29; D J (m,2,H^ and A.87-5.36 (br m,2,H^ and Hg), C, 69.61; H, N, 14.48. 3.62 (t,J=4Hz,l,H2), 3.28 (t,J=4Hz,l,Hg), and 5.15; N, 14.33. 3.04 (s,3,methyl).a

102-C 6h5 7.19-7,60 (m,10,phenyl), 5.99-6.63 (br m,4,ole For C, 74.26; H, 4.98 finlc), 4.86-5.33 (br m,2,H^ and Hg), and 3.57 C, 74.35; H, N, 11.89 (d,J~4.5Hz,l,H5) .a 4.82; N, 11.82.

JD3-CgH5 7.32-7.64 (m,5,phenyl), 6.64 (d,J=8Hz,l,Hg), For C, 69.29, H, 5.35; 6.20 (dd,J=6 and 8H z,l,olefinlc), 6.02 (d,J=* C, 69.61; H, N, 14.12. 3Hz,1,olefinlc), 5.82 (d,J=3Hz,l,olefinlc), 5 .1 5 ; N, 14.33. 5.04 (dd,J=4 and 6Hz,l,Hg), 3.32-3.48 (m,2,H2 and Hg), and 2.90 (s,3,methyl) .b

104-c 6H5 7.36 (m,10,phenyl), 6.28 (dd,J=2 and 6 Hz ,H^q), For C22H17N3°2: C, 74.27; H, 5.17j 5.98 (d,J=3Hz,l,H3or H^), 5.86 (d,J=3Hz,l,H3 or C, 74.35; H, N, 11,91. H4), 5.36-5.46 (1,1,^), 5.08 (dd,J=4 and 6 Hz, 4.82; N, 11.82.

l,Hg), and 3.26-3.50 (m,2,H2 and Hg).b 00 s Table V. (continued)

101-ch3 7.AO (br s,5,phenyl), 6.05-6.30 (m,2,Hg and H^g), C, 69.30; H, 5.12; F0r C17H15N3°2! 5.60-5.75 (m,l,H^), A.98 (pent,J=4Hz,2,H^ and Hg), C, 69.61; H, N, 1A.2A. 2.98-3.25 (m,2,H2 and H,.), and 1.57 (s,3,methyl) .a 5.15; N, 1A.33.

102-ch3 7.42 (s,5,phenyl), 5.85-6.50 (m,4,olefinlc), For C yiyi^s C, 69.44; H, 4 .9 4 ; 4.66 and 5.05 (m,lH each,^ and Hg), 2.88 (d,J= C, 69.61; H, N, 14.48. AHz,l,H^), and 1.50 (s,3,methyl).a 5.15; N, 14.33.

101-CH20Ac 7.42 (m,5,phenyl), 6.02-6.32 (m,2,Hg and H^q), 5.83 (br s,l,H ^), 4.70-5.25 (m,2,H^ and Hg), 4.41 See reference 68. (s , 2,-0CH2-), 3.05-3.45 (m,2,H2 and H5), and 2.02 (s,3,methyl)

102-CH^QAcS 7.31 (s,5,phenyl), 5.80-6.28 (m), 5.88 (s,H3 and 104-CH2OAc j H^), 4.78-5.10 (m), 4.30-4.65 (m), 3.20-3.40 (ra), See reference 68. 2.90-3.05 (d with fine splitting), 2.07 and 2.03 (s,methyls).

103-CH20Ac 7.43 (s,5,phenyl), 6.1-6.3 (m,2,H^ and H^q)» (s , 2,H3 and H^), 4.80-5.20 (m,l,Hg), 4.91 (s,2, - See reference 68. -0CH2-), 3.20-3.52 (m,2,H2 and H5) , and 2.10 (s, 3, -CH3) . a Table V.(continued) i o i - ch2och3 7.40 (m,5,phenyl), 6.08-6.20 (m,2,Hg and H^g), 5.82 (br s,l,H ^), 4.86-5.14 (m,2,H^ and Hg), 3.76 (in,2, See reference 68. -0CH2~), 3.27 (s,3,methoxyl), and 3.06-3.40 (m,2, H2 and H5) .b

102-CH2OCH3 7.48 (a,5,phenyl), 5.95-6.42 (m,4,olefinlc), 4.92 -5.20 (m,2,H^ and Hg), 3.75 (center of AB,J^=9Hz, See reference 68. 2,-OCH2-), 3.43 (s,3,methoxyl), and 2.95 (d,J=5Hz,

i , h5) . ‘

103-CH2OCH3 7.42 (m,5,phenyl), 5.85-6.20 (m,4,olefinic), 4.95 -5.20 (m,l,Hg), 4.18 (center of AB,J^B“llHz,2, See reference 68. -0CH^-),3.45 (s,3,methoxyl), and 3.33 (d,J=2.5Hz, 2,H2 and H g).3

102-F 7.20 (br s,5,phenyl), 5.75-6.35 (m,4,olefinlc), 4.80-5.10 (m,2,H, and H,), and 3.32 (dd,J=4 and See reference 69. a 1 6 5H z,l,H 5) .

101-CN 7.34 (s,5,phenyl), 6.73 (s,l,H^), 6.28 (t,J=4Hz, For C ^ N ^ : C, 67.01; H, 3.97; 2,Hg and H1()), 5.00-5.24 (0 ,2 ,^ and Hg), 3.64 C, 67.09; H, N, 18.66.

3.98; N, 18.41. 00 (t,J=4Hz,l,H2 and Hg), and 3.45 (t,J=4Hz,l,H2 vO or H g).b Table V.(continued)

7.36 (s,5,phenyl), 6.00-6.28 (m,4,olefinlc), 5.02 For C^H ^N ^: C, 66.78; H, 4.14; -5.24 (mf2yH^ and Eg), and 3.68 (d with fine coup C, 67.09; H, N, 18.61. lin g , J=5 Hz , 1,H5) . a 3.98; N, 18.41.

7.44 (s,5,phenyl), 6.36 and 6.30 (two s,lH each, For C^H^N^: C, 67.22; H, 4.09; Hg and H ^), 6.13 (s,2,H3 and H4), 5.12 (q with C, 67.09; H, N, 18.52. fine coupling,J=4Hz,1,H,), and 3.40-3.73 (n,2,H„ 3.98; N, 18.41. a 6 2 and Hg).

7.34 (s,5,phenyl), 6.82 (dd,Ja2 and 6Hz,l,H^), For C17H12N402: C, 67.03; H, 4.12; 5.98 (AB q,J=4Hz,2,H3 and H^), 5.10 (m .2,^ and C, 67.09; H, N, 18.56. Hg), and 3.38 (m,2,H2 and Hg).^ 3.98; N, 18.41.

7.40 (s,5,phenyl), 6.63 (s,l,H4), 6.10-6.30 (m, 2,Hg and H ^), 4.90-5.40 ( 111, 2,^ and Hg), 3.72 See reference 68. (s,3,methyl), and 3.20-3.65 (m,2,H2 and Hg).a

7.40 (s,5,phenyl), 6.62-6.85 (m,l,Hg and H ^), 5.88-6.30 (m,3,olefinlc), 4.95-5.20 (m,l,Hg), See reference 68. a 3.92 (s,3,methyl), and 3.36-3.75 (m,2,H2 and Hg),

VO o Table V.(continued)

104-C00CH3 7.40 (m, 5,phenyl), 7.06 (d d ,J“ 2 and 6H z ,H^q ), 6.00 ( s ,2 yH3 and H^), 5.18 and 5.58 (mt l each, See reference 68. H. and H,), 3.76 (s,3,methyl), and 3.27-3.58 (m, 1 b a 2,H2 and H5) .

104-Br 7.43 (s,5,phenyl), 5.95-6.18 (m,l,H10), 5.99 (s, For C^H ^B rN ^: Found m/e 357.0119. 2,H3 and H4), 4.88-5.23 (m ^,^ and Hfi), and 3.15 calcd m/e 3.45 (my2,H2 and Hs) . a 357.0113. a60 MHz spectrum. b100 MHz spectrum.

VO 92 o Isolated 540 mg (287.) of 104-Br, rap 197-204 dec (from ethanol), as

the only characterlzable product.

4-Phenyl-2,4,6-triazahexacyclo |j.4.2.0.2_*6.08 ^ trl" decane-3,5-dlone (124-H). General Photocycllzation Procedure.

A solution of 10.0 g (35.8 mmol)

of 101-U in 1000 nil o f acetone

was purged with nitrogen and

irradiated through Vycor with a

V — Hanovia 200 W lamp source w ith

magnetic stirring. After 29 hr,

the solvent was removed in vacuo and the residual solid was washed with absolute ethanol and dried to give 8.4 g (847.) of 124-H, mp 77 0 193-194° (lit mp 193-194 ).

As concerns the irr a d ia tio n of lQ l-C^Hg, 102"CgH,j, and 104,-CgH,.,

orange-red oils were obtained in each instance and chromatography on

« silica gel (thick layer or column) was required in each instance.

Under milder conditions ifil-CgH^ generally gave some tricyclic product

a ls o . The is o la tio n of I 24-CH3 was sim ila rly e ffe c te d , but 125-CH^ was crystallized directly. The> efficient photocyclizatlon of 101-CN

lent itself to direct isolation of 124-CN by crystallization; however,

the purification of 125-CN and 126-CN required chromatography on

silica gel (elution with 107. ethyl acetate in ether) and Florisil

(same elution solvent mixture), respectively. Finally, the isolation

of 125-F was achieved by chromatography on activity 1 neutral alumina using 307. ether in methylene chloride as the eluent. 93

jTable VI.Physical Data for the 9,10-Diazabasketanes

Compound Mp,° Pmr(

124-C,H_ 146 dec® 6.95-7.46 (m,5), 4.88-5.30 Calcd for C17H15N302: ------6 5 (m,2), 3.33-3.83 (in, 5), C, 69.61;H, 5.15;N, and 3.02 (s,3).e 14.33. Found:C, 69.44; H, 5 .2 2 ; N, 14.46.

125j-CgH3 G lassy 7.08-7.64 (m,5), 5.00- Calcd for C22H17N3°2! 5.24 (m,2), 3.64-3.80 m/je 355.1321. Found: (m,3),3.40-3.56 (tn,l), 355.1323. and 3.16-3.32 (m ,l).b

124-CH3 219.5-220.5b 7.20-7.72 (m,5), 4.86- Calcd for C^H^NjO,,: 5.19 (t,J»6Hz,2), 2.82- C, 69.61; H, 5.15; N, 3.77 (m,5), and 1.21 14.33. Found:C, 69.46; ( s , 3 ) . e H, 5.25; N, 14.32.

125-CH3 182-184b 7.30-7.72 (in,5), 4.6-5.3 Calcd for ci7Hi5N302: (m,2), 2.85-3.90 (m,5), C, 69.61; H, 5.15; N, and 1.39 (s,3).e 14.33. Found:C, 69.56; H, 5.05; N, 14.06.

124-CH2OAc 159-160° 7.25-7.70 (m,5), 4.9-5.2

125-CH20Ac 94-95° 7.2-7.68 (m,5), 4.76-5.12 (in,2), 4.23 (AB,Jab=12Hz , See reference 68. 2), 3.23-3.7 (in,3), 2.95- e 3.18 (m,2), and 2.00 (s,3). 94 Table VI. (continued)

126-CH20Ac 170-171° 7.2-7.75 (m,5), 4.90-5.25 (m,l), 4.75 (br 8.2), 3.40 See reference 68. -3.90 (m,4), 3.0-3.4 (tn,2), and 2.10 (s,3).e

124-CH20CH3 156-156.5° 7.2-7.75 (m,5), 4.85-5.25 (tn,2), 3.4-3.8 (m,4), 3.42 See reference 68. (s,2), 3.32 (s,3), and 3.0 -3.35 (tn,2).e

125-CH20CH3 7 6 .5 -7 7 .5 ° 7.25-7.70 (m,5), 4.88-5.25 (m,2), 3.4-3.85 (m,3), See reference 68. 3.54 (s,2), 3.37 (s,3), and 3.07-3.28 (tn,2).e

126-CH20CH3 145-146° 7.25-7.70 (m,5), 4.9-5.25 (m,l), 4.04 ( 8 ,2 ) , 3.5- See reference 68. 3.80 (m,4), 3.47 (s,3), and 2.03-2.4 (m,2).e

126-C00CH3 202.5-203.5b 7.2-7.6 (m,5),4.9-5.18 (m ,l), 3.89 ( b , 3), 3.5- See reference 68. 4.15 (m,4), and 3.05-3.42 (m,2).e

124-CN 236-238 decd 7.28 (s,5), 5.18 (t,J-5Hz Calcd for C^H^N^O,,: 1), 4.96 (t,J“5Hz,l), and C, 67.09; H, 3.98; N, 3.40-4.05 (m,5).f 18.41. Found: C, 66.78; J , 4 .0 8 ; N, 1 8 .7 1 . 95 Table VI.(continued)

JL25-CN 211-217 dec 7.64,1*,£), 4,93-5.40 Calcd for C^H^N^O,,: (m,2), and 3.12-3.93 C, 67.09; H, 3.98, N, (in,5) . f 18.41. Found:C,66.78; H, 4 .1 4 ; N, 18.46.

126-CN 224-228 dec 7.18-7.54 (m ,5), 4.93 Calcd fo r C^-tU^2N^02 : (t with fine splitting, C, 67.09; H, 3.98, N, Ja5Hz,l), and 3.04-4.05 18.41. Found:C,66.90 (m,6).e H, 4 .1 8 ; N, 18.55.

125-F 167.5-168° 7.25-7.73 (m,5), 4.90- Calcd for C16H12FN302: 5.32 (m,2), and 2.91- C, 64.64; 11, 4.07; N, 4.09 (m,5).e 14.14. Found:C,64.36; H, 4 .1 6 ; N, 14.15. a. The following recrystallization-solvents were employed: 2-propanol; ^benzene-hexane; Cethanol; d-propanol-acetonitrile. determined at 60 MHz. ^100 MHz spectrum.

Silver (I) - Catalyzed Rearrangement of 124-H.

A solution of 9.50 g (0.034 mol)

of 124-H in 100 ml of chloroform

was treated with 250 mg of anhydrous

silver fluoroborate and the mixture

was heated at reflux in the dark

with magnetic stirring for 7 days.

At approximately 12 hr intervals, additional 250 mg quantities of the

silver salt were added to the reaction mixture. The cooled solution

was passed through a silica gel column (elution with methylene chloride)

and the resulting solid (7.73 g, 81.2%) was recrystallized from ethanol

I 96 to give JL27.-H as colorless blades, mp 183-184°.

Silvery(1) -^Catalyzed Rearrangement of 125-C^H^. General Pro- cedure for Silver Nitrate - Aqueous Methanol Reactions.

A solution of 431 mg (1.21imnol)

o f 125^-CgH,. and 3.06 g (18 mmol)

of silver nitrate in 60 ml of

methanol-water (4:1) was heated

at reflux in the dark for 19 days. o The cooled solution was treated with 100 ml of water and extracted with an equal volume of methylene chloride. The organic phase was washed with water (3 X 100 ml), dried, and evaporated. The resulting orange residue was chromatographed on activity 1X1 neutral alumina (chloroform elution) to give 310 mg

(72%) of 128-C6H5, mp 166.5-167.5°.

Silver (I) - Catalyzed Rearrangement of 125-F. General Pro-

cedure for Silver Perchlorate-Toluene (Benzene) Reactions.

A mixture of 1.40 g (4.72 mmol)

of 125-F and 10.0 g (48.2 mmol) of

silver perchlorate in 100 ml of

toluene was heated under reflux

for four days. The resultant

orange suspension was cooled and

filtered to remove precipitated silver and silver salts. The toluene

solution was washed with water and two portions of saturated sodium

chloride solution.

Evaporation of solvent gave an orange solid which was chromatographed 97

Table VII,Physical Data for the tiiazasnoutanes •

Compound Mp,°C Pmr(jt,CDCl3,60 or 100MHz) Anal Data

127-H 183-184 7.20-7.70(m,5), 4.90-5.25 (m,2), and 1.73-2.22(m, See reference 68. 6).8

127-C6H5 166.5-167.5C 7.0-7.34(m,5), 4.97- Calcd for C^^H^N^O^iC, 5.22(m,2), 3.04(8,3), 69.61;I1, 5.15;N, 14.33. and 1.95-2.47(m,5).8 Found:C, 69.47;N, 5.29. N, 14 .4 3 .

128-C-H. 166-167C 7.02-7.66(m,10), 5.14- w -* 6 5 Calcd f o r C22Hj j N302 :C» 5.47(m,2)» and 1.96- 74.35;H, 4.82;N, 11.82. 2.60 (m,5).8 Found:C,74.06;H,5.03; N, 11.68.

127-CH3 165.5-166.5d 7.15-7.65(m,5), 4.98- Calcd f o r C^yH^3N302:C , 5.20(m,2), 1.60-2.12 69.61;H, 5.15;N, 14.33. (m,5), and 1.28(s,3).8 Found:C,69.63;H,5.13; N, 14.35

128-CH3 146.5-147.5° 7.25-7.75(m,5) , 4.80- Calcd for C^H^N^tC, 5.29(in,2) , 1.70-2.15 69.61;H 5.15; N, 14.33. (m,5), and 1.23(s,3).8 Found:C,69.86;H,5.11; N, 1 4 .7 5 .

127-CH2OAc 147-148b 7.20-7.60(m,5), 4.90-5.20 (m,2), 4.16(s,2), 2.02 See reference 68. (s,3), and 1.87-2.15(m,5).8

I Table VII. (continued) l^CHgOAc Oil 7.25-7.70(m,5), 4.90-5.30 (m,2), 4.03(AB,J^JJ*>12.5 See reference 68. Hz,2) 1.95(s,3), and 1.85- 2.30(tn,5).8 lg^-Cl^OAc 153-154b 7.20-7.65(m,5), 5.00-5.30 (m,l), 4,88(s,2), 2.11 See reference 68. (s,3), and 1.80-2.30(n,6).8

127-CH2OCH3 112-113b 7.17-7.67(m,5), 4.90-5.25 (m,2), 3.49(s,2), 3.32 See reference 68. (s,3), and 1.85-2.25(in,5).8

128-CH2OCH3 O il 7.20-7.70(m,5),4.80-5.25 (m,2), 3.34 (AB,Jab- 10.5 See reference 68. Hz,2), 3.25(8,3), and 1.80 -2.25(m,5).8

129-CH2OCH3 97-98b 7.14-7.60(m,5), 4.90-5.20 (m,l), 4.16(8,2), 3.48 See reference 68. (s,3), and 1.80-2.20(ra,6).8

129-C00CH3 158-159d 7.27-7.68(m,5), 5.03-5.26 (m,l), 3.91(8,3), and See reference 68. 1.83-2.60(in,6).8

128-C0NH2 242-242.5® Insoluble Calcd for C^H^N^, Qj :C, 63.35; H,4.38; N.17.38. Found:C,62.99;H,4.41; N, 17.61. 99 Table VII.(continued)

128-CN 225-236 dec£ 7.28-7.68(m,5) , 5.16- Calcd for Cj^Hj 2N4° 2 :C* 5.36(m,2), and 1.96- 6 7 .0 9 ;1l, 3 .98; N, 18.41. 2.84(m,5).h Found:C,66.68;H,4.03; M, 18.40.

128-F 177.5-178.5° 7.0-7.58(m,5), 5.00- Calcd fo r 5.55(m,2), and 1 .7 0 - 64.64;H, 4.07;M 14.14. 2.75(ra,5).B Found:C,64.47;H,4.16; N, 14.56. N, 14.56.

The following recrystallization solvents were employed: ^ethanol; c2-propanol; *H»enzene-cyclohexane; eacetonitrile; £2-propanol-aceto- o h nitrile. “Spectrum obtained at 60 MHz. At 100 MHz. on activity I neutral alumina (elution with chloroform) to give 1.30 g (93%) of a white solid; recrystallization from Isopropanol gave fine needles, mp 177.5-178.5°, Identified by pmr analysis as 128-F.

Silver (I) - Catalyzed Rearrangement of 125-CN. A. Aqueous Methanol. — 1 ■ - — A solution of 100 mg (0.33 mmol) of CONH. 125- CM and 850 mg (5 mmol) of s ilv e r

nitrate in 10 ml of methanol-water

, u (4:1) was heated at reflux in the

dark for 48 hr and processed as

above to give 100 mg of a white solid. Preparative thick-layer chromatography on silica gel (develop ment with ether) gave a low component amounting to 29 mg (27%) of

128-C0NH2* This product was recrystallized from acetonitrile to give colorless bladeB, mp 242-242.5°;^ 3400, 3300, 3170, 3080, 1760, IQQX 1685, 1620, 1500, 1410, 1280, 1150, 1130, 1000, and 880 cm**1. 100

B. Acetonitrile Solution.

A solution of 100 mg (0.33 mmol) of

125-CN and 850 mg (5 mmol) of

silver nitrate in 10 ml of aceto-

nitrile was heated at reflux in the U dark for 152 hr. The solvent was

evaporated and the resultant oil was triturated with methylene chloride and filtered to remove the precipi tated silver salts. The filtrate was washed with water (2 X 50 ml), dried, and evaporated to leave a light orange oil which was chromato graphed on a thick layer silica gel plate (development with 10% ethyl acetate in ether). Two major bands were obtained; these were extracted separately to give 34 mg of recovered 12j>^CN and 49 mg of 12JB-CN (75%) mp 225-236° decjU j^ 3070, 3000, 2235, 1760, 1685, 1600, 1495, 1405, waX 1295, 1180, 1120, and 765 cm”1.

Semlbullvalene: Manganese Dioxide Oxidation of Semicarbazide

Intermediate.

A 100 ml three-necked round bottom

flask equipped with condenser

serum cap, magnetic stirrer, and

stopper was charged with 500 mg

(1.79 mmol) o f 127-H and 1.0 g

(17.8 mmol) of potassium hydroxide.

The flask was flushed with nitrogen and 20 ml of isopropyl alcohol was

Introduced through the serum cap. The mixture was brought to reflux with stirring and held at this temperature for 45 min before cooling in 101

Ice. Hydrochloric acid (3JN) was added until pH 2 and the mixture was

stirred for 3 tnin. Ammonium hyrdoxide (3N) was added dropwise to give

pH 8, at which point 6 ml of pentane and 1.56 g of manganese dioxide

were introduced sequentially in single portions. The resulting black

suspension was s ti r r e d fo r 1 h r a t 0° and 30 min a t room tem perature

Decantatlon of the solution and rinsing of the remaining sticky solids

with small amounts of pentane was followed by washing of the combined

organic layers with water (2 X 50 ml) and brine (50 ml). The aqueous

layers were reextracted with pentane and the pentane layers were

dried. Filtration gave a clear solution which when distilled as above

gave a residue which was isolated by preparative vpc on a 6 ft X 0.25

in SF-96 on Chromosorb G column at 65°. There was isolated 85 mg (46%)

of semlbullvalene.

1(5)-Methylsemibullvalene (91-CH^^jL 92-CH^).

A mixture of 250 mg (0.85 mmol) of

potassium hydroxide, and 13 ml of

isopropyl alcohol was refluxed

under nitrogen with magnetic

stirring at a bath temperature of

90° for 45 min. This solution was cooled in ice, acidified with 3N hydrochloric acid, basified with 3JN ammonium hydroxide, treated with

pentane (6 ml) and manganese dioxide (750 mg) as described above. The

analogous workup furnished an intensely odorous orange oil which was

purified by preparative vpc on a 2 ft X 0.25 in OV-11 column at 45°

to give 49.8 mg (49%) of 91-08^92^0^. Calcd for C9H10 ra/e 118.0782; 102

found 118.0781.

T ab le V III. V a ria b le Tem perature Pmr S h if t D ata f o r ^91^-CHy^i 9 2 ^ 0 ^

(S, 60 MHz, TMS).

Temp, °C Solv Methyl H^H, 8 H3*H7 V H6 »5

+36 CS2 1.10, s 3•42, m 5.06, dda 4.78, ddc 2.68, c d -19 CS2 1.10, s 3.36, m 5.07, dda 4.87, ddc 2 .7 2 , t -2 6 CS2 1 .1 0 , s 3 .3 4 , m 5.07, dda 4.87, ddc 2 .7 2 , t -40 1 .1 0 , s 3.32, m 5.07, dda 4.88, ddC 2 .7 2 , t «! -4 6 cs9 1.10, s 3.31, m 5.07, dda 4.90, ddC 2 .7 3 , t b -5 5 cs, 1 .1 1 , s 3.28, m 5.05, rab 4.91, m 2 .7 2 , t b -6 5 cs 1.11, s 3.27, m 5.07, mb 4.95, m 2 .7 4 , t -7 4 CS2 1 .1 2 , s 3 • 24, m 5.01, br m 2.74,t -80 cs2 1.12, s 3.22, m 5.02, br m 2 .7 5 , t -8 5 1 .1 2 , s 3 .1 9 , m 5.04, br m 2 .7 5 , t CS2

a ~ .0 Hz; 2.0 Hz. ^Partial overlapping of peaks. J3q ,4 / 1"J6,7‘ 4 J 2 ,3 " J 7 ,8 “ c * .0 Hz; 3 .0 Hz. J, , “JC 3.0 Hz. All apparent 3*4 ■J6,7“ 4 J 4 ,5 " J 5 ,6 " 4 ,5 5 ,6

.1 (5)-Phenylsemibullvalene (91^C^H^^di 92^0^^).

A s o lu tio n o f 500 mg (1 .7 1 mmol) o f

127-C^H^ and 1 .0 g (1 7 .8 mmol) o f

potassium hydroxide in 25 ml of

2-propanol was heated under reflux

in the absence of oxygen for 30 min,

cooled in ice, and treated with 3!N hydrochloric acid to render the mixture acidic. After stirring for 5 min at 0°, the mixture was basified with 3N. ammonium hydroxide solution,

10 ml of pentane and 1.50 g of manganese dioxide was added, and stirring 103

continued for 30 rain at room temperature (cessation of nitrogen evolution).

The black suspension was vacuum filtered, the filtrate added to 100 ml of water, and the aqueous mixture extracted with pentane (2 X 100 ml). The dried organic layers were concentrated to small volume and the concen

trate was subjected to preparative vpc separation on a 1 ft X 0.25 in

OV-11 column at 100°. There was obtained 232 mg (76%) of 91-C^.H,.

--—'92-C,H_ 6 5 as a colorless oil;V>neat ’ max 3030, » 2950, 1610,* » 1575, 745,» and » 697 cm-1. Calcd for ro/©, 180.0939; found 180.0943.

Table IX. Variable Temperature Pmr Shift Data for 91-C^Hyi* 92-C^H,.

( i f , 100 MHz, TMS) .

Temp ,°C Solv Phenyl k2 , h8 h3 , h7 H4’H6 «5

+33 CD-C1. 7.10,m 3.43,m 5.21,m 5.43,m 3 .3 1 ,tc -58 CD-Cl, 7.12,m 3 .3 4 ,m 5 .2 0 ,d d a 5.55,ddb 3.34,m —68 CD„Cl„-Freon 11(1 1) 7.10,m 3 .3 1 ,b r s 5 ,2 1 ,d d a 5 .58,ddb 3 .3 8 ,tC -97 CD„C1_-Freon 11(1 1) 7.10,m 3 .2 7 ,b r s 5.20,dda 5.60,ddb 3 ,3 9 ,t c -113 CD,C1,-Freon 11(1 1) 7.10,m 3.25,br s 5.20,dda 5.64,ddb 3.42,tC -116 CD2Cl2-Freon 11(1 1) 7.10,m 3.24,br s 5.2 1 ,d d a 5.64,ddb 3.43,t° -126 CD2Cl2-Freon 11(1 1) 7.10,m 3.22,br s 5.21,dda 5 .6 9 ,ddb 3 .4 5 ,b r s aJ_ .-J, ,-5.0 Hz; J, ,-J, a»1.0 Hz. °J, .-J, ,-5.0 Hz; J, ,«J, ,-2.5 Hz. 3,4 6,7 ’ 2,3 7,8 3,4 6,7 4,5 5,6 CJ^ ga2.5 Hz. All apparent splittings are rounded to the nearest h a lf Hz.

2(4)-Methylsemlbullvalene (139-CH^^j 3^0-CH^).

H y d ro ly sis-o x id atio n o f 128^CH^ (250

mg, 0.85 mmol) following exactly the

procedure d escrib ed fo r 12£-CH3 CH afforded after preparative vpc under 104

comparable conditions 53 mg (52%) of 139-CI1^^140-CH^ as a colorless

liquid. Calcd for C^H^ m/e 118.0782; found 118.0781.

Table X. Variable Temperature Pmr Shift Data for 139-CHy^-140-CH^

( S t 60 MHz, TMS) .

Temp, °C Solv M ethyl H1 H2’U8 H5 H6 H7 H3

+42 1 .7 8 ,da 2.93,m 5.19,m 4.84,m CS? -2 1 CS 1 .8 2 ,da 2.87,m 5.28,m 4.84,m -39 cs2 1 .8 1 ,da 2.83,m 2,77,m 3.03,m 5 .3 2 ,d d C 5 .2 6 ,d d d 4 .8 3 ,m -57 cs0 1 .8 2 ,d a 2.84,m 2.72,m 3.03,ddb 5.37,ddC 5 .2 5 ,d d d 4.82,m -7 6 1 .8 2 ,d a 2.84,ro 2.68,m 3.04,ddb 5.42,ddc 5 .2 6 ,d d d . 4.82,m CS2 -101 c s 22 1 .8 3 ,d a 2.83,m 2.61,m 3.06,ddb 5.48,ddc 5 .2 5 ,d d d 4.82,m

J-1.5 Hz. J. 6.0 Hz; Jc -«2.0Hz. CJ£ ,»5.0 Hz; Jc ,-2.0Hz. JyO D |/ j |0 y“5.0 Hz; Jy q“ 1*5 H z . All apparent splittings are rounded to the nearest half Hz.

2(4)-Fluorosemibullvalene (139-F^> 140-F).

A mixture of 250 mg (0.84 mmol) of

128-F and 473 mg (8 .4 3 mmol) o f

potassium hydroxide In 13 ml of

2-propanol was heated at reflux

under nitrogen with'magnetic stir

ring for 45 min. Subsequent acidi

fication, basiflcation, and manganese dioxide (750 mg) oxidation in the prescribed manner gave a colorless solution which was concentrated to a volume of 2 ml by careful removal of the pentane by distillation

through a 6 in Vigreux column. Vpc fractionation of the residual 105 liquid on the 2 ft OV-11 column at 45° afforded 73.4 mg (71.5%) of pure 139-F£* 140-F. Calcd for CgHyF m/e 122.0532; found 122.0530.

Table XI. Variable Temperature Pmr Shift Data for 139-F^ 140-F

( S* 60 MHz, TMS) .

Temp,°C Solv H1 ’«2»H8 H5 H3 ,l6 H7

+35 2 .8 4 ,b r m 3.17,m 4.62,m 5. 41 ,m CS2 +13 2 .8 3 ,b r m 3.18,m 4.62,m ,m CS2 5. 43 -8 2 .7 9 ,b r m 3 .1 8 ,d d a 4 .5 9 ,ddb 5. 45 ,m CS2 -3 1 2 .7 5 ,b r m 3.18,dda 4.59,ddb 5 .5 3 ,d d c 5. 43,ddd CS2 -5 3 2 .7 2 ,b r m 3 .1 9 ,dda 4 .5 8 ,d d b 5 .5 8 ,d d c 5. 4 2 ,ddd CS2 -6 4 c s 2 2 .6 8 ,b r m 3 .1 8 ,d d a 4 .5 7 ,d d b 5 .5 9 ,d d c 5. 42,ddd

-7 0 c s 2 2 .6 8 ,b r m 3.19,dda 4.58,ddb 5 .6 1 ,d d c 5. 43,ddd

-8 0 c s 2 2 .6 7 ,b r m 3 .1 8 ,d d a 4.57,ddb 5.63,ddc 5. 41,ddd

-9 1 c s 2 2 .6 6 tb r m 3 .1 8 ,d d a 4 .5 7 ,d d b 5 * 65 5. 43,ddd

.0 Hz; Jc 2.0 Hz. a? ,5 Hz; J2^3-1.5 Hz. CJ, 5.01 Hz; 5 ,0 3,F L' 6, T

3 Hz. dJ , _“ 5 .0 Hz; Hz. All apparent splittings a re J 5 ,6 - 2 -' 0 ,7 J 7 ,8 " 2 *5 rounded to the nearest h a l f Hz. Part III; Synthesis and Chemistry of Hypostrophene

Introduction

The chemistry of (CH)n hydrocarbons has attracted considerable 123 attention in recent years. Particularly interesting are those 124 molecules which have unusual reactivity. The thermal and photo

chemical rearrangements of such compounds have frequently been the 123 subject of intensive study. Those (CH)^ systems capable of under

going degenerate Cope rearrangement comprise a rather small but

exciting list of molecules in that category.

The activation energy for the Cope rearrangement can be lowered

substantially by weakening the 3-4 bond in the diallylic moiety.

This has been accomplished most notably in semibullvalene (1), where this bond is part of a strained ring (see Part II for a discussion

of the Cope rearrangement in ^1). Although the preferred chair-like / *1 transition state cannot be attained, the degenerate rearrangement of

8emlbullvalene is more facile than any other example. Anet * has

recently determined that the Cope transition state for 1 is only

5.5 kcal/mole higher in energy than the localized forms.

The classic example of fluxional behavior, the hydrocarbon, bullvalene (86), ’ exists as an equilibrium mixture of 1.2 million

isomers since all ten carbon atoms can interconvert by repeated valence

isomerization. Due to these facile rearrangements, the pmr spectrum of bullvalene exhibits, as predicted, a single sharp proton signal at

106 107

100°, indicating that at this temperature all the hydrogen atoms have the same average magnetic environment.

Another (CH)^q hydrocarbon which undergoes an endless sequence of degenerate Cope rearrangements resulting in complete time-averaged 2 6 equivalence of its atoms is the laterally fused tetracydo[5.3.0.0 * . 3 10 0 * ]deca-4,8-diene (147), given the trivial name hypostrophene by 125 Pettit and coworkers who first synthesized it. In this case, the

3-4 bond of the diallyl moiety is incorporated into a strained cyclobutane ring. The degenerate cis-divinylcyclobutane rearrangement is filow on the nmr time scale and cannot be demonstrated by observing absorption coalescence at higher temperatures. The reported pmr spectrum fo r 147 c o n sists of two s in g le t ab so rp tio n s a t ^ 6 .1 (4H) and

3.2 (6H) up to 80°. At about 80° an irreversible and nondegenerate bond reorganization sets in producing the isomeric (CH)^q 142.* the 108

etc. etc.

IH7

125 product of formal (1*3) sigmatropic migration. Since the latter

change Is a symmetry disallowed process, a nonconcerted mechanism 125 Involving the postulated diradlcal intermediate 148 has been proposed.

IH7 ms

Despite the inability to observe degenerate Cope rearrangement

in hypostrophene by the nmr coalescence technique, P ettit and coworkers

did successfully prove the fluxional character of the title compound by specific deuterium labeling experiments. Dideuteriohypostrophene

(150), generated at low temperature, was studied by pmr as the temp

erature was gradually raised. At -50° the olefinic to saturated proton

ratio was 1:3, the expected ratio in the absence of rearrangement. At

0° the olefin/aliphatic ratio began to Increase until at +35° the

ratio was observed to be 1:1.5 and showed no further change. This

ratio Indicates complete deuterium scrambling and thus confirms the

proposed fluxionality of hypostrophene. Obviously the rearrangement 109 of JA 7 proceeds slowly at 0° (I.e., t^ ^ on t*ie order of minutes) and fairly rapidly at 35°.

ISO

Although the two nonconjugated double bonds in hypostrophene bear a close face-to-face relationship, photocycllzation to penta- 125b prismane (151) has not been successful. Pentaprismane belongs ,,126 to a class of compounds whose molecular outlines are "regular prisms.

® *“ - ® IHJ 151;

126 Schultz calculated the expected molecular dimensions of several members of the prismane family, assuming that the molecular dimensions would conform to the shape of a solid prism. His results indicate that

151 has the least amount of strain of all the prismanes. The non photoreactivity of hypostrophene has been attributed to the presence of an exceptionally high lying cyclobutane

oriented for effective through-bond coupling, the consequence of which

is to transform the customarily allowed (h^s Photochemical 127 closure to a symmetry-forbidden process. In this regard, the im

portance of substituted hypostrophenes makes its appearance since 127 Schmidt and Wilkins have proposed that appropriate substituents

could reduce the through-bond coupling of the two ’Tf’levels without 128 affecting their through-space interaction significantly. There

fore, if through-bond coupling is indeed the factor preventing ring

closure of hypostrophene to 151, the possibility exists that certain

substituted hypostrophenes could be cycllzed photochemically to the

as y e t unknown pentaprism ane system .

These findings suggest that 147 and closely related molecules

hold promise as possible sources of new theoretical and mechanistic

understanding. Alas, the chemistry of hypostrophene has remained

unexplored. This is chiefly because the preparation of substantial

quantities of this exciting molecule has not heretofore been possible.

P ettit's original elegant synthetic route to 14? furnishes the 125 hydrocarbon in only 3.4% yield from cyclobutadleneiron tricarbonyl, 129 or, more realistically, in 0.7% yield from cyclooctatetraene.

The Pettit synthesis is outlined on the next page.

For the purpose of studying the chemistry of hypostrophene and

also utilizing this hydrocarbon as a starting material for other

interesting systems (vide infra), a more efficient and less expensive

route to 147 was investigated. We chose to examine the synthesis of bishomocubane derivatives as possible precursors to hypostrophene

(cf. P ettit's synthesis) since the available chemical literature Ill

IV Ce CD -» Q=<1 l> =o

Fe(CO\

HO 1 UAIHh 1 0 7 C8r4

H H

Na s r U

1 5 2 m i

130 contains many reports dealing with the construction of such systems.

The final step in the original synthesis of hypostrophene (147) Involves a 1,4-dehalogenation of dibromide 152. The question then arose: could the same process be induced in a related dihaloblshomocubane which

Itself could be readily synthesized? The 1,3-bishomocubane system 131 153 seemed the obvious choice for our synthetic needs because of its 112

sim ilar structural nature and Its more ready synthesis £rom available 130 cydopentadlene dimers. Most Important, however, Is the fact that

both 153 and the blshomocubane system used by P ettit contain the same

153

1,3-brldge relationship meaning that 1,4-debromination of dibromide

153. (R^R^Br) should indeed produce the title compound (147).

Results and Discussion 132 The first step of our initial synthesis of 147 (Scheme III) involved the preparation of dicyclopentadienone dloxime (154). This was accom plished w ith e a se in 77% y ie ld by n ltr o s a tio n (NaOC^H^,

CgHi-ONO) of cydopentadlene according to the directions of Doering 133 and DePuy. Conversion of this rather stable dioxime into cyclo- 134 pentadienone dimer 155 was effected by sequential transoximation 135 with levulinic acid (78%). The resultant white solid is readily recrystallized from ether or sublimed to give colorless crystals which are identical by infrared and pmr spectra to the reported diketone.

No other reagents seem to work as well as levulinic acid in this step.

The endo-cyclopentadienone dimer 155 is an interesting molecule

In its own right and several preparations are available. One method commonly used for its generation consists in the dehydrobromination

i 113

I5H IS5

cC b

156 157 #58

i 5 a i X =oH c q

Jb X sOSO^CHj & X=I

136 of A-bromo-2-cyclopentcnone (160). The resultant cyclopentadienone rapidly diraerlzes via a Diels-Alder reaction to give 155. This route 114

-> IS 5

160

was avoided by us because o£ the lengthy preparation of the bromoketone

160. A second synthesis of the required diketone 155 that was con

sidered involved acid hydrolysis of the monomeric cyclopentadienone 137 N,N-dimethylhydrazone (161). However, this conversion met with

failure in our hands.

155

The photochemical conversion of endo-cyclopentadienone dimer 138 (155) to l,3-bi8homocubanedione (158) is known. However, this process is sensitive to the conditions of irradiation and usually gives

a mixture of isomeric products which must be separated by careful

column chromatography. He therefore chose to selectively ketalize

155 with ethylene glycol in refluxing benzene containing g-toluene- 139 sulfonic acid. Purification of monoketal 156 was achieved by

column chromatography on neutral activity I alumina (benzene elution)

in 81% yield. The infrared spectrum of 156 contains both a ketal 115

stretching band at 1297 cm”* and a carbonyl stretching mode at

1698 cm”*.-in agreement with literature reports. Note that the bisketal

is not readily produced under these reaction conditions because of the lowered reactivity of the enone moiety.

The photochemical ring closure of molecules such as 155 and 156 to generate bishomocubane derivatives**®**^® has become an indispensable tool for the synthesis of polycydics. Upon irradiation of ether solu

tions of keto ketal 156 under nitrogen through quartz with a Hanovia

200 W lamp, photocyclization to the structurally related caged keto 139 ketal was realized in 95% yield. The residue obtained after evapora tion of solvent could be used directly without further purification or could he crystallized by dissolution of the oily residue in ether and cooling to -60°. Characterization of this low melting solid was based on its unique infrared spectrum which exhibits a carbonyl absorption at 1767 cm"* and a shoulder at 1718 cm *,**■* The pmr spectrum lacked olefin signals and contained absorptions at 8 2.6

(m,4), 3.12 (m,4) and 3.89 (m,ketal) in agreement with the bishomocubane formulation. Later we discovered that the photochemical conversion of keto ketal 156 to 157 was much cleaner and the workup greatly facilitated if a solution of 15£ in dry benzene was irradiated through Pyrex with a 450 W Hanovia lamp. Under these conditions large quantities of diene can be cyclized in a fairly short time (12-20 hrs) with high yield (94%) formation of 157 as a colorless oil after simple filtration of the benzene solution through Florlsil. Generally, the oily product was carried on to the next step without attempting the tedious low temperature crystallization. Removal of the ketal function requires severe hydrolysis condi tions, apparently because of the strain added to the bridge In going 3 2 from sp - to sp -hybridized carbonyl carbon. The ease with which 142 bishomocubanones form hydrates would tend to support this hypothesis.

Stirring a solution of the ketal in a mixture of 10% sulfuric acid and 143 tetrahydrofuran at room temperature led to little hydrolysis.

Reaction of 157, with concentrated sulfuric acid in methylene chloride gave less than 50% of dlketone 158, while treatment with £-toluene- 144 sulfonic acid in acetone led to still less conversion. When the h y d ro ly sis was attem pted by the method of Chapman and c o w o rk e rs^ ^ 1

(concentrated sulfuric acid at room temperature), complete decomposition was observed. Even under the best conditions found, deketalization of

157 proved to be capricious. Exposure to a mixture of 10% sulfuric acid and tetrahydrofuran at 80-90° for three hours gave usually (but not always) the diketone in isolated 76% yield after suitable workup and purification. The spectral properties of the resultant white crystalline material were consistent with those reported for bishomo- cubanedione 130b,138,145 pro

(shielding of«=< protons in these systems is discussed in reference 130b) and at 3.32 (br m,4).

On standing open to the air, this diketone gradually forms a 142 hydrate which appears as a white powder or coating on the glass surface of the container. This hydrate is relatively insoluble in most solvents and only upon heating can some dissolution be observed. Although no effective method was found for reconversion of this hydrate to the ketone, Its presence does not seem to hinder the next step In our synthetic sequence. However, the dlketone can be purified by sublimation at 80° and 0.05 mm.

Lithium aluminum hydride reduction of 158 produced In 90% yield the cage dlol 159a, whose epimeric composition was revealed clearly by its pmr spectrum (In CDCl^): S 2.10 (br s,2,-0H), 2.68 (m,4),

2.88 (m,4), and three broadened singlets of differing Intensity centered at 3.98, 4.20, and 4.36 (total 2H, ^CHOH). The three methlne absorptions gave integrated areas of 5:16:4, respectively, close to predicted values. The LIAIH^ reduction of 1,3-bishomocubanone (162) has been shown to be subject to an unusually high degree of stereoselective 146 control. The product mixture contains the two epimeric alcohols

163 syn and 163 anti in a ratio of 4:1. The chemical shift of the

Syh Bhtl ! Q J Q o^-methine proton (anti) in the syn isomer is £*4.04 while the methlne proton (syn) on the carbon bearing the anti OH appears at 4.28. The bridge methlne in ^63syn. Is seen at higher field presumably because of i anisotropic shielding by the bent bond of the cyclobutane ring beneath it. Using the data on the reduction of monoketone JL62, Dilling was able to calculate fairly accurately both the ratios and chemical shifts 118 of the various bridge niethlne protons In the three possible isomeric dlols. His predictions indicate that the high field methine resonance at £>3*98 in our reduction mixture corresponds to the syn proton in

the syn, anti isomer (two protons contribute to the area under this signal because the anti, syn isomer produced in the reduction is equivalent to the syn, anti isomer). The major signal at 4.20 is due

to both the syn, syn (major product) and the anti, anti (minor component) isomers. The remaining low field absorption (4.36) corresponds to anti protons in the syn, anti and anti, syn isomers. The mixture of eplmeric alcohols could be recrystallized from benzene to give color less crystals whose pmr spectrum indicated an enrichment in the syn, syn isomer (major product) at SU,20. The alcohols, however, could not be satisfactorily separated by chromatography.

Treatment of 159a with sulfene (roethanesulfonylchloride + tri- ethylamine) according to the method of Crossland and Servis^® gave dimesylate 159b directly as a white crystalline solid (85X). Infrared analysis confirmed the presence of the sulfonate ester groups by the strong absorptions at 1170 and 1350 cnT^. The pmr spectrum (in CDCl^) showed no alcohol absorptions, although it exhibited the same general patterns as the spectrum of starting material: a multiplet for 4H at

$ 2.8 (skeletal protons), the methyl singlet (6H) at 3.02, the re- 3 maining four sp -bound protons at 3.2. and three broadened singlets of unequal area at 4.74, 4.90, and 5.04 (2, ^CHO-).

Unsuccessful attempts were made to convert dialcohol 159a and dimesylate 15£b^directly to hypostrophene (147). Recent successes with homo-1,4-reductive eliminations of diols have been reported using 119 the novel reagent ^ * 4 *n cac^on disulfide solution containing 149 pyridine. However, treatment of the epimeric mixture of alcohols

159a with ^ 2^4 under the reported conditions led to isolation of only starting material. Similarly, when dimesylate 159b was treated either with sodiura-phenanthrene or Na-K alloy, unreacted starting material was singularly recovered.

S^2 displacement of the methane-sulfonate groups in 159b by iodide ion to produce 159c was acheived most conveniently by reaction with dry sodium iodide in freshly distilled anhydrous hexamethylphos- phoramlde at 130-140° for 1-2 days under a nitrogen atmosphere. Due to the unsolvated nature of the iodide ion in this medium,its effective steric bulk is reduced and its nudeophilicity is enhanced such that displacement of the mesylate groups operates at a reasonable rate and without obvious side reactions. The dark mixture obtained upon cooling of the above reaction mixture was simply diluted with water and extracted with ether. The ether solution containing the dilodlde was washed consecutively with acid and base to give the nicely crystal line dilodlde in 90% yield. Purification was achieved by column chromatography on silica gel (pentane elution) followed by recrystal liz a tio n from petroleum e th e r. A nalysis of th e product by pmr (CDCl^) was again indicative of an epimeric mixture: jjP 2.44-3.60 (br in,8),

3.76, 3.88, and 4.02 (br s,total 211, ^CHI). Several alternative methods for conversion of the dimesylate to 159c failed to provide any reaction at all. Prominently, treatment of 159b with potassium 151 iodide in refluxing acetonltrile in the presence of 18-crown-6-ether led to the return of starting material with high recovery. 120

The preferred procedure for dehalogenation of 159c consists in

exposure of the dilodlde to sodium-potassium alloy In anhydrous tetra-

hydrofuran at room temperature. After 75 minutes, filtration and par

titioning of the filtrate between water and pentane provides a

pentane solution of 147 which Is free of contaminants. Other methods

such as those Involving sodium naphthallde or sodlum-phenanthrene

suffer from the problem of ultimate separation of 147 from aromatic

byproducts and are accordingly less desirable. Hypostrophene so

produced can be isolated by sublimation or preparative gas chroma

tography in 54% yield as pungent white plates exhibiting the character

i s t i c p a ir of pmr s in g le ts (in CDCl^) a t $ 3.20 (6H) and 6.12 (4 H ).^* ’

The overall yield of 147 beginning with cyclopentadiene is 12% (compare

0.7% via P ettit's synthesis from cydooctatetraene).

The major difficulty associated with the previously discussed 132 synthesis is the economical and technical problems of using large

quantities of levullnic acid for the conversion of dioxime 154 to dlcydopentadienone (155). Accordingly, a new synthetic entry was sought. Chapman and coworkers^^ have reported the synthesis of dlcydopentadienone ethylene ketal (168) in high yield starting from relatively inexpensive cyclopentanone (164). Ketalization of 164 in 152 the usual fashion provided ketal 165 in 87% yield after distillation.

A solution of 165 in dioxane was dibrominated^^ using molecular bromine as th e reag en t o f choice. Workup im m ediately upon com pletion of the bromine addition furnished

Br Br »

X66

-> 156

167

possible and any unnecessary heating (e.g., for removal of solvent) should be avoided to prevent decompositon of 166. The dibrotnide appears to liberate HBr when heated or left at room temperature for any length of time with the result that the material turns black.

The double dehydrobromination of 166 giving cydopentadienone ethylene ketal (167) and ultimately its dimer (168) was achieved by treating the dlbromlde with either sodium methoxide in refluxing methanol for 12 hrs (Chapman's method) or potassium tert-butoxide in tert-butyl alcohol at elevated temperature for the same length of time. Removal 122 of most of the solvent by vacuum distillation and dilution with water followed by continuous ether extraction of the dark mixture furnished bisketal 168. in 86% yield'. This material is readily purified by re- crystalllzation from ether and is identical to the substance described by Chapman. 139 Vogel and Wyes reported the partial hydrolysis of 168. to conjugated ketone 156 in high yield by stirring with hydrochloric acid in tetrahydrofuran solution for one hour at room temperature. In our hands, the hydrolysis gave 156^ in 95% yield after a two-hour reaction period. If the reaction time was extended to 4-5 hrs, the product yield was consistently and drastically reduced, Keto ketal

156 1b an intermediate in the previously discussed synthesis of hypostrophene. The latter sequence (Scheme IV) has definite advantages over that Involving deoximation of 154 since it can be carried out on a large scale and is more economical. Furthermore, the overall yield of

147^ from cyclopentanone is 18% compared to 12% from dicydopent'adlene.

Synthesis of Alcohols

A recent theoretical study by Hoffmann and Heilbronner of the

7-norbornyl cation (169) has unveiled the possibility that the low solvolytic reactivity of this system with its structurally rigid boat six-membered ring is due to an unfavorable interaction between the 153 Cy 2p orbital and the high-lying cyclohexane o~ orbitals. Introduction of a double bond to arrive at the anti-7-norbornenyl system (170) leads to a pronounced rate enhancement for solvolysis on the order of

10^.^**^ Significantly, interaction of a orbital with the vacant orbital at now permits two-electron delocalization over three

centers (cf. 170) and partially offsets some of the positive charge

density at this reaction site.^*^ Conversely, the symmetry rules

established by Goldstein and Hoffmann for laticyclic interactions of

two or more "ribbons" predict that a stabilizing interaction should

exist between a cation center and a double bond in close proximity.

This bishomocyclopropenyl cation interaction leads to approximately

15 kcal/mole of stabilization energy at 2 5 ° . There is ample evidence

that a cyclopropane ring in the 2,3 position (cf. 171) stabilizes

Positive charge at Cy to a larger extent than a double bond at the 158 same position, presumably because the vacant orbital is capable of greater homoconjugative interaction with the symmetric e Walsh “S orbital of the cyclopropane moiety than with the TP orbital of the 1 A 159 double bond at the same site.

A less obvious factor is the ability of most molecular frameworks

to adjust their geometry so as to maximize stabilizing interactions.

The 7-norbornadienyl cation (172) is now known to possess a distorted

geometry*^® in which the cationic center leans toward one of the double bonds with a resultant increase in homoaromatic orbital overlap, the two-ribbon laticyclic interaction producing stabilization 124

171 of ca 4.1 kcal/mol over the norbornenyl cation ( 1 7 0 ) . It may be asked how powerful this laticyclic Interaction can become given a more suitable geometry. Overlap falls off rapidly with distance and with 156 it the magnitude of through-space stabilization. In partial com pensation, typical ribbon interactions are of the more efficient O kind rather than the less efficient 'tf One system which may be regarded as having a favorable geometry for strong orbital inter actions is the tetracyclic cation 173. Framework molecular models show

'TTbond; strongCT"type interactions would certainly be expected.

The proposed cation 173 is quite similar in its skeletal frame work to hypostrophene (147). He recall that Pettit and coworkers 125b failed to achieve a photochemical cyclization of 147 to pentaprismane. \

125 127 This was tentatively explained by Schmidt and Wilkens as being due

to a 'ff'level reversal In the ground state of 147 because of strong

through bond Interactions, If, In fact, the strained edge bonds of the

[2.2.0]blcyclohexane moiety in 173 do cause a Tflevel reversal In the

interacting olefin, what effect would this have on the proposed stabili

zation of cation 173? Hypothetically, a'nf'reversal could lead to

1 7 7

destabilization (or nonstabilization) of the cation center as reflected

in the solvolytic reactivity of the system.

An additional factor to be considered is the possibility of 162 cydobutane ring interactions with the cation center. Such inter

actions have been found to be quite important in the case of homocubyl 131 163 and bishomocubyl derivatives. * Particularly in structure 175.

where there is no o^ifin or cyclopropyl interaction could cydobutane 126 ring anchimcric assistance make Itself known.

Should double bond participation be Important, cyclopropyl participation (the e 111 0 Walsh orbital is directed toward the cation center) could be even more Intense than that found in the 170/171 pair.^®'^*^ A comparison of the proposed cation systems 173, 174, and 175 with the lower (177) and higher (176) homologs could likewise prove Interesting. Whereas the more rigid cation 177 contains an empty p orbital which impinges directly into the center of electron density of the transannular I f bond such that better overlap than in th e case of 173. can be expected, a l l y l i c c a tio n 176. should s u ff e r a destabilizing Interaction with the proximal double bond according to

Goldstein and Hoffmann's topological rules.Consequently, the synthesis and solvolytic study of precursors to cations 17j» 174, and

175 was deemed worthwhile in preparation for a study of all the

Systems mentioned above.

Synthesis of the six alcohols in Figure 5 was therefore undertaken using the now readily available hypostrophene (147) as starting material. Originally, it was anticipated that epoxide 184. could be reduced to provide exo alcohol 178. Accordingly, 184. was prepared by a typical peracid oxidation of hypostrophene in 73% yield together with a lesser quantity (15%) of bisepoxide 185.

The pmr spectrum of 184. showed a singlet of area 2 at ^6.14

(olefin), a broad multiplet between 2.84-3.44 corresponding to 5 cydobutane protons, a sharp singlet at 3.36 for the 2 oxirane protons, and a multiplet of area 1 centered at 2.72 (H^). These features are in agreement with those spin-spin interactions expected from molecular 127

Ftg. 5

A = 7\ . k l H HO ho^ ''"I ' h \iQ 178 180

2 \ . k l > oh H OH 181 182. 183 models of the exo isomer which show a 90 dihedral angle between and

Hg. On this basis, the sharp singlet signal for the epoxide protons confirms the exo stereochemistry of 184.

147 MCPRA + k

I8H 185

Likewise, the bisepoxide was characterized by analytical and pmr methods. The lack of olefinic signals and the sharp singlet at

<£3,51 integrating to 411 ( ^CH-0-) support the structural assignment to 185 (see Experimental Section). 128

Several attempts were made to cleave the oxlrane ring in 184*

Reductive ring opening^®** with lithium metal in a variety of amine solvents was first tried; however, only inseparable mixtures of * several products were obtained. Perhaps olefin participation interferes with these dissolving metal reductions. In any case, the total absence of 178.was determined post facto by pmr spectral comparisons. 166 Attempts to reduce the monoepoxide with Brown's "Super-Hydride"

(lithium triethylborohydride) and also lithium aluminum hydride were next made. Analysis by vpc indicated the presence of several products in both reaction mixtures. However, these mixtures again proved inseparable by common techniques. Apparently, a relatively small amount of exo alcohol is formed via this route (post facto pmr analysis) but not enough to make separation of the products worthwhile.

The exo alcohol was made available in large quantities and in relatively pure form by the hydroboration of hypostrophene with the hindered reagent 9-borabicyclononane (9-BBN).^*^ Addition of 9-BBN to 147 according to Brown**^ and subsequent alkaline oxidation of the borane intermediate with 30% hydrogen peroxide gave 178 in 73% yield.

A 10

k l *) "OH, H A. . k l HO 147 1 7 8

The general structure of 178 was confirmed by comparison of its pmr spectrum to that of hypostrophene epoxide (184). In particular, the 129 narrow m ultiplet at £>6.31 (2H) indicates the loss of one double bond while the signal at 4.20 (dd,l) signals the presence of the alcohol methine proton. The doublet-of-doublets character of this proton is consistent with the exo stereochemistry of the 011 moiety. Framework molecular models show a 90° dihedral angle to exist between this endo methine hydrogen and the adjacent cydobutane ring proton. Spin-spin interaction with the two different methylene protons (H^) provides the dd character observed. For the same reasons, the doublet-of- doublets nature of the endo methylene proton (H,.) at & 2.15 is rationalizable. Both endo protons are canted into the shielding region of the transannular double bond as evidenced by a downfield shift of and H,. (endo) in saturated alcohol 179 (vide infra).

Oxidation of exo alcohol 178 with chromium trioxide-pyridine 168 complex as described by Ratcliffe and Rodehorst furnished ketone 186 which was immediately reduced with lithium aluminum hydride to endo alcohol 181 in good yield. The close face-to-face j'uxtapositioning

178 ■> kl I OH

186 i s i of the cyclopentane rings in this tetracyclic system prevent endo approach by the reducing agent. Consequently, stereospecific exo attack occurs with exclusive formation of endo alcohol. Analysis of

181 by pmr indicates several significant changes upon epimerization. 130 \ The exo methine proton (^CHOH) Is now seen as a m ultiplet at fr 4.34

because of additional coupling to the adjacent cydobutane ring proton.

The downfield shift, of this signal (4.34 vs. 4.20 for 178) Is explainable

in terms of anisotropic shielding by the double bond in #178, (vide supra).

The olefinlc protons, because of the influence of the neighboring OH,

exhibit an appreciable chemical shift difference, the proximal proton being shifted downfield to

a t 6 .2 3 . 169 Reduction of both 178 (exo) and 181 (endo) alcohols with diimide

178 HKINU u HO> 179

A 181 HNMH

H't>H

1 8 1

readily provided the saturated alcohols 179, and 182. In the case of 179, the endo methine proton ( ^CHOH) possesses a chemical shift of S 4.50, and therefore is downfield shifted from the analogous shielded proton in 178 ( $ 4.20). Expectedly, the prar spectra of these two compounds (see Experimental Section) lack ole£inic resonances and contain additional methylene signals between 1.2-2.2 ppm due to the ethano bridges.

Otherwise, these compounds retain the general pmr absorptions charac teristic of the tetracyclic skeleton.

Construction of the two homoalcohols 180 and 183 was viewed to be most feasible by a hydroboration-epimerization sequence on homohypostrophene (187). Accordingly, the exo cydopropyl hydrocarbon 187. was

Ox A = A A A L *)( ok] A I a) |Re] V"'OH H HO 107 180 IBS prepared by two separate routes. Dlbromocarbene addition to hypostrophene generated a mixture of monoadduct 188 and bisadduct 189. The monoadduct,

!C B ra IH7 Br k Br IBB

H O tBu

187 obtained in 77% yield, was identified by its characteristic pmr spectrum, sharp singlets at S 6.23 corresponding to 2 olefin protons and at 2.03

a 132

(211) foe the cyclopropyl protons being consistent with the exo assignment.

Blscarbene adduct 189, on the other hand, lacks olefinlc signals but exhibits a sharp singlet at £ 2.35 for the four cyclopropyl protons. 170 Dibromlde 188 was reductively dehalogenated with lithium in

tetrahydrofuran containing tcrt-butyl alcohol as the proton source.

In this manner, 187 was obtained in 76% yield as a pungent, colorless oil after purification by gas chromatography. In addition to the

typical skeletal proton signals, the pmr spectrum of 187 contains nicely split cyclopropyl signals at ^-0.24, 0.25, and 1.19.

The more direct Simmons-Smith route^* to hydrocarbon 187 has proven useful but has the distinct disadvantage of forming a relatively large quantity of bishomohypostrophene (190) as well. In the presence

IB 190

of zinc-silver couple, 147 reacted with diiodomethane during 88 hr to give a mixture o f'187, and 19Q.. Separation by gas chromatography fur nished homohypostrophene (17%) and bishomohypostrophene (14%) as colorless oils. The bishoroohydrocarbon 190 was identified by its characteristic pmr spectrum which contains the typical cyclopropyl proton signals a t & -0.33, 0.36, and 1.42.

1 6 7 Hydroboration of homohypostrophene (187) and subsequent oxidation gave exo alcohol 180. Purification by gas chromatography furnished a

i 133 colorless oil which was characterized by the sim ilarity of its pmr spectrum to those of the earlier alcohols* A doublet-of-doublets at

2)4.69 for the methine proton ( ^CHOII) indicates the exo stereochemistry of the alcohol moiety, while cyclopropyl signals appear at S -0.25 and

0 .3 0 .

An oxidation-reductlon sequence (CrO^’Pyrj, NaBH^) performed on

180 furnished endo alcohol 183. This alcohol was obtained in 39% yield and was likewise characterized by pmr methods. The multiplet of area 1 at f>4.40 waB consistent with endo stereochemistry for the methine proton ( ^ CHOH); the differing environments of the two methine cyclopropyl protons are Indicated by the large shift difference {8 1.81 and 1.29) for their signals.

Synthesis of the series of six alcohols as presented above provides the basis for a solvolysis study designed to unveil the various effects discussed in the Introduction. Those experiments seem destined to provide a better understanding of some of the nuances of anchimerlc assistance.

Experimental

Melting points are corrected. Infrared spectra were recorded with a Ferkin-Elmer Model 467 spectrometer. The pmr spectra were ob tained with Varian A-60A and Jeolco MU-100 instruments and apparent splittings have been cited where applicable. Mass spectra were measured with an AEI MS-9 mass spectrometer at an ionizing energy of 70 eV.

Microanalyses were performed by the Scandinavian Microanalytical

Laboratories, Herlev, Denmark. 134

endo-Tricyclo[5.2.1.0^***]deca-4,8-dien-3,10-dione Blsoxime (154) .

A substantial quantity of dicyclo-

pcntadicnonc bisoxime (154) was

prepared in 77% yield by the method 133 of Doerlng and DePuy. The

crude solid obtained by Soxhlet

extraction of the reaction mixture was used without further purification. The infrared spectrum was identical to that reported by Doering and DePuy.

Dlcydopentadienone (155).

A m ix tu re o f 20 g (105 mmol) o f

bisoxime 154 in 480 ml of freshly

distilled levulinlc acid (Aldrich

Chem. C o.) and 54 ml o f IN hydro

chloric acid was stirred for 3 hr

during which time the solids dis solved. The orange solution was heated on a steam bath for 3 hr, cooled, diluted with 1000 ml of water, and extracted with four portions of methylene chloride totalling 2000 ml. The combined organic layers were carefully neutralized with saturated sodium bicarbonate solution, fol lowed by washing with 100 ml of 20% sodium hydroxide solution and finally with water until color was no longer extracted. The dried

(MgSO^) solution was filtered and the solvent was removed under re duced pressure to leave a yellow solid. Purification by column chroma tography on activity I neutral alumina (elution with benzene) produced

13.13 g (78%) of off-white crystals. The spectral properties of the 135 CDC1. product were Identical to those reported in the literature; o ao TMS *y (pseudo t, 1), 3.24 (m,l), 3.48 (m,2), 6.28 (m,2, olefins), 6.39 (dd,l»

'c-CH-A-0,J -1.5 Hz,J2=5.5 Hz) , and 7.44 (dd,l,-CH»CH-C=0, J3“2.5 Hz,

J_*5.5 Hz); V (neat) 1590, 1720, and 1800 cm"1. Z IU3X 139 endo-Dicydopentadienone 8-Ethylene Ketal (156).

A solution o£ 5.10 g (31.8 mmol)

of diketone 155, 3.95 g (63.7 mmol)

of ethylene glycol, and 100 mg of

j)-toluenesulfonic acid in 50 ml of

benzene was heated under reflux

while water was removed in a Dean-

Starlc trap. After 22 hr the mixture was cooled, extracted with equal volumes of saturated sodium bicarbonate solution and water, and dried

(MgSO^), F iltr a tio n through 10 g o f n e u tra l alum ina and ev ap o ratio n of solvent gave 5.15 g (81%) of 156 as a white solid. This material could be recrystallized from carbon tetrachloride, mp 94-95° (lit139 94-95°), CDCl, or used without further purification; 2.89 (m,3), 3.56 (m,l), TMS N , 3.89 (t,ketal), 5.92 (m,2,olefin), 6.07 (dd, XC=CH-O0, ^-1.5 Hz,J2=5.5 I Hz), and 7.38 (dd^CjWJH-C-O.J^.S Hz,J,»5.5 Hz); O (CH.ClJ 1297, ™ J Z UWJ3C Z Z 1579, and 1698 cm"1 .

Pentacyclo[5.3.0.02 *5.03»9.0* *8]deca-6,10-dione 6-Ethylene Ketal s a - r ------

A solution of 28.6 g (0.14 mol) of 156 in 1500 ml of dry benzene was placed in a large Pyrex vessel and Irradiated with a 450 W Hanovia

lamp for 36 hr. Filtration of the resultant yellow solution through 136

10 g of Florlsil removed colored

impurities and led to the Isolation

of 27.0 g (94%) of a c o lo rle s s o i l .

Crystallization could be achieved

II at -60° from diethyl ether; ^CDC*3 ° TMS 2.60 (m,4), 3.12 (m,4), and 3.89

(m,4,ketal); D (neat) 1325, 1720 (weak, unknown origin), and 1760 cm ■**. IQaX

Pentacyclo[5.3.0.0.2,5.03,9.0*’8]deca-6,10-dione (158).

A heterogenous mixture of 2.39 g

(11.7 mmol) of 157 and 110 ml

of 10% aqueous sulfuric acid together

with 20 ml of tetrahydrofuran was

heated at 80-90° for 3 hr. After

cooling, the mixture was poured onto

100 g of ice and carefully neutralized with solid sodium bicarbonate.

The contents of the flask were diluted to 700 ml with water and extracted continuously with methylene chloride. Evaporation of the organic phase gave 1.71 g of orange oil. Cage diketone 158 was isolated as white crystals (1.42 g, 76%) from silica gel (4:1 benzene/ethyl acetate). 138 r ^ ^ 3 Spectral properties were consistent with literature reports; 2.76 XHb (br m,4) and 3.32 (br m,4);\3 (neat) 1130, 1250, and 1760 cm max

The diketone, on standing open to the air, gradually forms a hydrate which appears as a white powder.

4 2,5 _3,9 n4,8 Pentacyclo[5.3.0.0 .0 .0 * ldeca-6,10-diol (159a).

To a stirred suspension of 9.9 g

.OH (0.26 tool) of lithium aluminum

hydride in 300 ml of dry tetrahydro-

furan under nitrogen was added drop-

wise a solution of 20.7 g (0.13 mol) OH of 158 in 400 ml of dry tetrahydrofuran. The resultant mixture was heated under reflux for 24 hr, cooled, and treated carefully with 10 ml of water, 10 ml of 15% sodium hydroxide solution, and 30 ml of water. The mixture was suction filtered and the solids were leached repeatedly with diethyl ether. The combined organic f i l t r a t e s w ere ev ap o rated under reduced p re s s u re to g iv e 19 g (90%) of a pale yellow oil. Recrystallization from benzene gave 6.84 g of color- p C D C l. less crystals, mp 185-197° (mixture of epimers); Ojjjg 2.10 (br s,2,0H),

2.68 (m,4), 2.88 (m,4), and singlets at 3.98, 4.20, and 4.36 (total 2H,

^CH-011); the three methine signals were in the ratio 5:16:4;O (neat) / — max 3320 (OH) cm"1. N 6,10-Bis(methanesulfonyl)pentacyclo[5.3.0.0 * .0 * .0 * Jdecane (159b)

To a s o lu tio n o f 1.61 g (9 .8 mmol)

of 159a in 200 ml of methylene chloride OSQ j CHj a t 0° was added 2.52 g (22 mmol) o f

triethylamlne under nitrogen. Me- 148 , thanesulfonylchloride (3.0g, 29.7 OSC^CHj mmol) was added dropw ise o v er 30 min at 0° and the resultant clear solution was maintained at 0° for 20 min and poured into 200 ml of ice water. The aqueous phase was extracted 138 w ith 100 ml of methylene chloride and the combined organic layers were washed consecutively with cold 51) hydrochloric acid (200 ml) and saturated sodium bicarbonate solution, and dried (MgSO^). The mixture was filtered and the solvent removed under vacuum to give 2.68 g (85%) of a white crystalline solid. Recrystalllzatlon from ethyl acetate CDC1_ gave colorless blades, mp 151.5-153 ; 2.8 (m,4), 3.02 (s, 6),

3.2 (m,4), and singlets at 4.74, 4.90, and 5.04 (total 2H, ^CH-0-);

(neat) 1170 and 1350 cm**1. max A n al. Calcd f o r ^ i 2^16^ 6** 2 ! 44.99; H, 5.03; S, 20.02. Found:

C, 44.93; H, 5.06; S, 19.81.

6,10-Diiodopentacyclo [5.3.0^.0^,^.0^*^.0^*^]decane (159c).

A m ix tu re o f 200 mg (0 .6 mmol) o f

dimesylate 159b and 1.88 g (12.5

mmol) of sodium iodide in 4 ml of

d istilled hexamethylphosphoramide

was heated to 130-140° under nitrogen

for 2 days. The resultant black solid mixture was cooled and treated with 50 ml of water. The suspension was extracted with diethyl ether followed by washing of the combined organic phases with 6N^ hydrochloric acid, water, and saturated sodium bicarbonate solution. Drying (MgSO^), filtration, and evaporation gave

230 mg of orange oil which solidified on standing. The diiodide was isolated by column chromatography on silica gel (elution with pentane) to give 216 mg (90%) of colorless crystals. Purification can also be achieved by sublimation at 60° and 0.1 mm pressure. Recrystallization from (30-60°) petroleum ether gave colorless blades, mp 171-173°; 139 r CDCl3 Ujms 2.44-3.60 (br in, 8) and singlets at 3.76, 3.88, 4.02 (total

2H, W ) ; \ > (CHC1J 1150, 1260, and 2960 cm"1 . r lUUn i j A nal. Calcd fo r c 1qh^oI2: C* 31,28» 11» 2*63* Found: C, 31.56; H, 2.77.

Tetracyclo[5.3.0.0^'^.0^'^]deca-4, 8-diene (Hypostrophene, 147).

A dry 250 ml three-necked, round-

bottomed flask was charged with 2 g

(87 mmol) of sodium and 2 g (51 mmol)

of potassium under nitrogen. The

flaBk was evacuated to 0.1 mm and

the metals were fused by heating with

a Bunsen burner. The flask was permitted to cool and the vacuum was

carefully released under nitrogen. The sodlum-potasslum alloy was

treated with 50 ml of dry tetrahydrofuran followed by the dropwlse addi

tion of 4.95 g (12.9 mmol) of dilodlde 159c in 100 ml of the same solvent.

The resultant grey suspension was Btirred for 12 hr. After settling,

the supernatant solution was removed by syringe and the flask and

contents were washed with 25 ml of pentane which was again removed by

syringe. The combined organic layers were suction filtered through a

pad of Celite to remove inorganic solids and the filtrate was concen

trated under reduced pressure (80 mm) at 10° to 25 ml of dark solution.

This was diluted to 250 ml with water and extracted with three 100-ml

portions of pentane. The combined organic extracts were washed several

tim es w ith w ater and b r in e , and d rie d (MgSO^). A fte r f i l t r a t i o n the volume of solution was reduced to 10 ml as before and the solution was placed in a sublimator where the remainder of the solvent was removed under vacuum. Sublimation of hypostrophene from the resultant orange 140 o i l w aB achieved at 25° and 0.1 run with the use of a Dry Ice-cooled cold finger to give 890 mg of 147 as pungent colorless plates (53% CDC1 yield); J3.20 (s, 6) and 6.12 (s,4); O (CC1.) 3020, 2950, 1580, ina max 1330, 1280, 1225, 988, 937, and 900 cm"1.

152 Cyclopentanone Ethylene Ketal (165). + 1 " "■ "" Prepared according to the method of 152 Eaton and Hudson In 87% yield.

Spectral properties of the product

were Identical to those reported

In the literature.

2,5-Dibromocyclopentanone Ethylene Ketal (166).

Prepared according to the procedure

of Chapman, Key, and Toyne1^** in

96% yield and identified by spectral

Br 0r analysis using the reported data for the ketal. In order to avoid de-

- composition, the reaction had to be worked up immediately after completion of the bromine addition. The product should not be heated above room temperature and should be used as soon as possible.

endo-Dlcyclopentadienone Bisethylene Ketal (168).

To 2000 ml of tert-butyl alcohol

dried over anhydrous potassium car

bonate was added 141 g (3.6 mol) of

potassium metal portionwise under

a nitrogen atmosphere with 141 mechanical stirring over a period of 1 hr. The mixture was gently re

fluxed to achieve reaction of the last amounts of potassium. To the potassium tert-butoxide solution was added 281.28 g (0.98 mol) of di bromide ^166^ dropwlse under nitrogen. The resultant black mixture was heated gently for 12 hr and diluted with 2000 ml of water. The

tert-butyl alcohol was removed under reduced pressure and the black aqueous mixture was diluted to 5000 ml and extracted continuously with diethyl ether to give 104 g (86%) of light yellow crystals. Recrystal lization from ether gave colorless crystals, mp 91-92° (lit.'*'^^92°); r CDC13 O TMg 6.10-6.33 (m ,l,olefinic), 5,5-5.97 (m,3,olefinic), 3.82-4.07 (m,8» ketal), 3.33-3i62 (m,1,aliphatic), and 2.58-3.05 (m,3,aliphatic);\3 max (CHC13) 2985, 2865, 1620, 1573, 1418, 1360, 1290, 1092, 1060, 1025,

1004, 962, 950, and 929 cm"1.

139 endo-Dicyclopentadlenone 8-Ethylene Ketal (156).

A solution of 60.8 g (0.245 mol)

of 168 in a mixture of 96 ml of con

centrated hydrochloric acid and 960

ml of tetrahydrofuran was allowed to

stand at room temperature for 2 hr, and

no longer! (If the reaction is al lowed to continue for longer than 2 hr, the yields are drastically reduced).

One lite r of water was added and the aqueous mixture was neutralized carefully with sodium carbonate. The tetrahydrofuran was removed on a rotary evaporator and the aqueous layer was diluted to 1000 ml, extracted exhaustively with diethyl ether, and dried (MgSO^). Filtration and evapo ration gave 49.36 g of colorless crystals (quantitative yield). 142

Recrystallization £rom ethanol gave 44.5 g (89%) of colorless blades, mp 94-95°.

Hypostrophene Monoepoxide (184).

A s o lu tio n o f 890 tng (6 .8 5 mmol)

of hypostrophene in 25 ml of chloro

form was cooled to 0° under nitrogen A _____ and a solution of 1.18 g (6.85 mmol)

of m-chloroperbenzoic acid in 10 ml

of chloroform was added dropwise over 30 min. The solution was allowed to warm to room temperature and stirred for 12 hr. The tan, cloudy mixture was washed with two equal portions of saturated sodium bicarbonate solution and dried (Na^SO^).

The solvent was removed under reduced pressure and the resultant yel low oil was taken up in pentane and deposited on a Florisil column.

Chromatography (elution with pentane) provided 78 mg of hypostrophene,

667 mg of monoepoxide, and 170 mg of bisepoxide 185^ The yield of monoepoxide based on recovered 147 was 73%, while that of 185.was 15%.

The monoepoxide was recrystallized from pentane to give colorless 0 CD Cl- crystals, mp 170 (dec); 0 6.14 (s,2,olefin), 2.84-3.44 (br m,5, cydobutane), 3.36 (s,2, ^CH-0-), and 2.64-2.80 (m ,!,^) •

Anal. Calcd for c* 82.16; H, 6.90. Found: C, 82.02; H, 6.99.

The bisepoxide was recrystallized from diethyl ether to give color less needles which sublimed slowly above 150° and decomposed above 200°; jfs CDC13 O 3.51 (s,4,oxiranes), 3.08 (m,4,cydobutanes), and 2.56 (m,2,H. ln b i and H2)•

Anal. Calcd for ® 2 0 ® 1 0 ^ 2 6.22. Found: C, 73.80; H, 6.25. 143

9 19-Dlbromopentacyclo[5.4.0.0^*®.0^*^ .0^*^ ]undec-4-ene (188).

A solution of 170 mg (1.31 mmol)

of hypostrophene In 5 ml of pentane

£ 1 / \ was cooled to - -30° and 291 mg (2.6 Br mmol) of potassium tert-butoxide

5r (sublimed) was added In one portion.

The resultant green solution was

treated slowly with 329 mg (1.30 mmol) of bromoform In 2 ml of pentane.

The tan colored suspension was stirred under nitrogen for 12 hr at

room temperature and 25 ml of pentane was added along with 50 ml of water. The layers were separated and the aqueous phase was further ex

tracted with 10 ml of pentane. The combined pentane extracts were washed once with water and dried (NagSO^). Filtration followed by

evaporation of pentane at 60° to a volume of 5 ml through a short VI-

greux column gave a colorless solution which deposited colorless crystals

upon standing in a freezer overnight. The crystalline precipitate was filtered to give 35.5 mg (15%) of biscarbene adduct 189. Recrystal

lization from hexane gave off-white plates which decomposed between

175-205°; <5 3*18 (dd,4,cyclobutanes, J^H z, J2»4Hz), 2.78 (m,2,

and Hg), and 2,35 (s,4,cyclopropyl protons).

Anal. Calcd for C12H1{)Br4: C, 30.41; Ht 2.13. Found: C, 30.52, H,

2 . 2 0 .

The mother liquors were evaporated at reduced pressure to give a yellow o il from which was sublimed 100 mg of hypostrophene (50-60°/20 mm) and finally 126 mg (77%) of the monocarbene adduct (60°/0.05 mm) as white crystals which turn yellow on standing. Recrystallization from CDCl- pentane provided large, colorless crystals, rap 79-80 ; X 6.23 ( b, Trio 2,olefin), 3.10-3.48 (br m,4,cyclobutanes), 3.01 (m,l,H over double bond),

2.76 (m,l,H over cyclopropane), and 2.03*(s,2,cyclopropyl protons).

Anal. Calcd for 43.74; H, 3.34. Found: C, 43.84; H, 3.37.

170 Homohypostrophene (187) A. Reductive Debromination of 188.

A so lu tio n of 50 mg (0.165 mmol)

of 188 in 1 ml of dry tetrahydto-

furan was treated with 50 rag of

lithium wire and 0,5 ml of dry tert-

butyl alcohol portionwise over 30

min. After 1 hr a cloudy precipi tate had formed and the lithium was visibly reacting. After an addi tional 3 hr, the mixture was decanted to remove lithium pieces and the solution was diluted with 25 ml of water. The aqueous mixture was extracted with two 25-ral portions of diethyl ether followed by washing of the combined organic layers with water and drying (Na^SO^). The mixture was filtered and evaporated through a short Vigreux column in a 60° bath to a volume of 1 ml. Preparative gas chromatography on a

2 f t SE-30 column a t 65° gave 18 mg (76%) of a c o lo rle s s o i l whose pmr spectrum was identical to that of the hydrocarbon obtained from Simmons-

Smith cyclopropanation of 147.

B. Slmmons-Smith Reaction of 147.^*

A zinc-silver couple was prepared as follows: a mixture of 2 mg of silver acetate in 1 ml of glacial acetic acid was heated to boiling and

144 mg (2.2 mg-atoms) of 30 mesh zinc granules was added in one portion with stirring under nitrogen. After 30 seconds the acetic acid solution was pipetted from the mixture and the couple was washed with 1 ml of fresh acetic acid followed by five 1-ml portions of anhydrous diethyl ether. Finally, 1.5 ml of dry diethyl ether was added as the reaction so lv e n t.

The ether suspension of the grey-brown couple was treated with

100 mg (0.77 mmol) of hypostrophene. Under nitrogen, a solution of

295 mg (1.1 mmol) of diiodomethane in 1.5 ml of ether was added dropwise over 10 min. The mixture was refluxed while the progress of the reaction was followed by gas chromatography. After 88 hr, the mixture was cooled to 0° and 98 ml of pyridine was added dropwise to precipi tate zinc salts. After suction filtration, the clear filtrates were again treated with pyridine until no more precipitate formed. The mixture was filtered and reduced in volume to 1 ml. Preparative gas chromatography on a 2 ft SE-30 column at 65° gave three components:

10 mg of hypostrophene at 7 min, 17 mg (17% yield) of homohypostrophene

187 at 18 min, and at A3 min, 15 mg (1A%) of the bishomo hydrocarbon 190. - CDC1 Homohypostrophene 187: X 3 „ ^ -0. 2A

(dd, 1,endo-cyclopropyl H^, 2*=4 Hz ,

-THA, Uj * JU<'/ * VUU,A,Ilj| U

"AHz, 3**7*5 Hz), 2.A8-3.A6 (br m

6,aliphatic H), and 6.28 (br s,2, o l e f in ) .

Anal. Calcd for C> 91.08; H, 8.92. Found: C, 91.A8; H, 9.07 146 CDC1, Dishomohypostrophene 190: S TMS -0.33 (dd,2,endo H^, 2=4Hz, ^ 3

■4Hz), 0.36 (dt,2,exo 2"4Hz,

J 2 >3-7.5Hz), 1.42 (dd,4,H3, 3»

4Hz, J 2 3"7.5Hz), 2.36-2.64 (m,2,

aliphatic H), and 2.72-2.94 (m,4,

aliphatic H).

Anal. Calcd for ci 2H14:^* 91.61; 11, 8.39. Found: C, 91.26; H, 8.77.

cxo-Tetracyclo[5.3.0.0^,^.0^*^]dec-4-en-8-ol (178).

A s o lu tio n o f 2 .6 g (20 mmol) o f

hypostrophene (147) in 40 ml of

dry tetrahydrofuran was cooled to 0

under nitrogen and 9-borabicyclo- k j 167 nonane in tetrahydrofuran solu

tion (Aldrich, 0.5 M, 40 ml, 20 mmol) was added dropw ise over 2 h r . The r e s u lta n t m ix tu re was warmed to ambient temperatures during 1.5 hr and then cooled to 0°.

Sodium hydroxide solution (15%, 10 ml) was added, followed by 8 ml of 30% hydrogen peroxide. This mixture was stirred for 8 hr, saturated with potassium carbonate, and the layers separated. The aqueous phase was extracted with 100 ml of diethyl ether and the combined organic phases were dried (Na 2S0^). Filtration and evaporation gave a large quantity of yellow oil which was chromatographed on F lorisil (elution with ligroin-ether). Recovered hypostrophene amounted to 0.72 g while later fractions produced 1.58 g (73%) of exo alcohol 178 as a low-melting, semicrystalline material. Purification could be achieved by gas 147 o C CDC13 chromatography on a 6 ft SE-30 column at 110 ; 0 6.31 (m,2,* inb olefin), 4.20 (dd,l, ^CHOH, *^Syn“7Hz» ^*32 (m,5,cydobutane

H), 2.92 (m,l,cyclobutane 11 adjacent to OH), 2.15 (dd,l,endo methylene H,

JgcjjjdS Hz, Jsyn“7Hz) , 1.89 (s,1,011), and 1.56 (m,l,exo methylene H);

V) (neat) 3340 (Oil), 1043, 986, 800, and 738 cm-*. The molecular ion ra&x la too weak for accurate mass determination.

A 3,5-dlnitrobenzoate was prepared by the customary procedure and recrystallized from diethyl ether to give off-white crystals, mp 136-

137°.

Anal. Calcd for C^H^SjOg* C, 59.65; H, 4.12; N, 8.19. Found: C,

59.76; H, 4 .20; N, 8.03.

exo-Tetracyclo[5.3.0.0^*^.0^*^1 decan-4-ol (179).

To a magnetically stirred solution

of 100 mg (0*675 mmol) of 178 in

25 ml of methanol under nitrogen u was added 2.0 g (10.3 mmol) of .169 HCT dlpotassium azodicarboxylate in one portion. The yellow mixture was cooled in an ice bath and 1.75 ml of glacial acetic acid was added dropwise over a 30-ralnute period. The yellow mixture was stirred until the color discharged (ca. 1 hr) and the solution was poured into 150 ml of water. The aqueous mixture was extracted with three 50-ml portions of diethyl ether and the combined organic layers were washed with sat urated sodium bicarbonate solution and dried (NagSO^). Filtration and evaporation gave 150 mg of oil which was purified by gas chromatography 148 on a 6 ft SE-30 column at 110° (300 cc/mln) to give 42 mg of white solid (t »9.5 min); the yield of product was 41%. This solid was r e t easily identified as 17jj. because of the close sim ilarity of its pmr spectrum to that of 178, (and ultimately to that of hypostrophene CDC1 s ep o x id e); 3 4.50 (dd,l, ^CHOH, JsynB7Hz, ^anti"2Hs), 2.68-3.29

(br m,6,cyclobutane H), 2.47 (dd,l,endo methylene adjacent to OH, Jgem"

15Hz, J “6Hz), and 1.20-2.00 (br m,6,methylene H + OH) . syn ■" Calcd for C--.H...0: m/e 150.1045. Found: 150.1047. 10 14 — — The 3,5-dinitrobenzoate was obtained in quantitative yield as off- white crystals, mp 135.5-136° (from diethyl ether).

A nal. Calcd fo r ci 7Hjl6^2°6: C* ^9.30; H, 4.68; N, 8.14. Found:

C, 59.11; H, 4 .80; N, 7.98.

exo-P entacyclo [5 .4 .0 . 0^ ***. 0^* ^ . 0^* ^ 1 undecan-4-ol (j.80) .

Homohypostrophene (ca. 100 mg) was 167 hydroborated with 9-BBN solution

(Aldrich) as before (cf. 178) to

give alcohol 180 in 60% yield.

Purification of the product was per

formed on a 5 ft SE-30 column at CDC1 105°; d ms 4.69 (dd.l, )cHOH,Jsyn“7Hz,Janti»2Hz), 2.36-3.24 (br ra,

7,cyclobutanes + endo methylene H adjacent to OH), 1.20-1.72 (br m, 4, cyclopropyl methines + exo methylene adjacent to OH + OH), 0.30 (d t,l, anti cyclopropyl methylene, Jgem**4Hz, Jsyn“7.5Hz), and -0.25 (dt,l,syn cyclopropyl methylene, 'Jgem"4Hz, Jfln<.^B4Hz) ; 0 ^ y(neat) 3380 (OH),

1055, 1009, and 900 cm \ The molecular ion is too weak for accurate mass determination. 149

The 3,5-dinltrobenzoate was obtained as off-white clusters, mp

148-149° (from diethyl ether).

Anal. Calcd for C18H16N206: C, 60.67; H, 4.53; N, 7.86. Found:

C, 6 0 .4 3 ; H, 4 .6 4 ; N, 7 .7 9 .

endo-Tetracyclo[5.3.0.0^ * ^.0^ * ^ ]dec-4-en-8-ol (181). " 1 ■ ” 168 Dry chromium trioxide (600

mg, 6 mmol) was added to a magneti

cally stirred solution of 949 mg (12

mmol) of anhydrous pyridine in 15 ml k H of distilled methylene chloride.

The flask was stoppered with a dry ing tube (Drierlte) and the deep burgundy solution was stirred at room temperature for 15 rain. A solution of 149 mg (1 mmol) of 178 in a few ml of dry methylene chloride was added in one portion and a tarry, black residue immediately formed. After 30 min, the solution was decanted into 10 ml of 5% sodium hydroxide solution and the residue was washed with diethyl ether. The combined organic layers were washed with two 10-ml portions of 5% sodium hydroxide solution, two 10-rol portions of 5% aqueous hydrochloric acid, 10 ml of saturated sodium bicarbonate, and 10 ml of brine. Drying of the solution, followed by filtration and evaporation of solvent left 144 mg (97%) of a yellow oil. Infrared analysis Indicated a successful oxidation of the alcohol function;

0 (neat) 1730 (C=0), 1392, 1343, 1259, 1075, 878, 803, and 739 cm"1. IQdX Calcd for C^H^Otm/ti 146.0732. Found: 146.0734.

Ketone 186 was carried to the next step without further purification.

The sample was dissolved in 10 ml of anhydrous diethyl ether and this 150 solution was treated with 38 mg (1 mmol) of lithium aluminum hydride followed by gentle refluxing under nitrogen for 1 hr. The usual work up provided 160 mg of white crystals which were purified by sublimation

(4 5 °/0 .0 3 mm) to g iv e 77 mg (51%) o f c o lo r le s s c r y s t a l s . S p e c tra l c c d c i3 analysis was consistent with an epimer of 178; 6.65 (dd,l, olefin, J^»3Hz, Jg^Hz), 6.23 (dd,l,olefin, J^“3Hz, J 2®6Hz), 4.34 (m,l,

^CHOH), 2.80-3.60 (br m, 6,cyclobutane H), 2.00-2.52 (br m,l,exo methyl ene), 2.02 (br s,l,0]l), and 1.56 (dd,l,endo methylene, Jgetn“15Hz,

6Hz);\) 3370 (011),1345, 1260, 1110, 1054, 1010, 815, 790, 755, and max 733 era

Calcd for m/e 148.0888. Found 148.0891.

The 3,5-dinitrobenzoate was prepared by the customary procedure and isolated as off-white crystals, mp 155-156° (from diethyl ether) in quantitative yield.

Anal. Calcd for C, 59.65; H, 4.12; N, 8.18. Found:

C, 59.68; H, 4.33; N, 8.12.

endo-Tetracyclo[5.3.0.0^*^.0^*^1 decan-4-ol (182).

Unsaturated endo alcohol 181 (31 169 mg) was reduced with diimide as

before (cf, 179. ) to give a white

solid after gas chromatography

(33% y i e l d ) ; £ CDC13 "'OH 4.32 (m ,l, H TMS CH011), 2.48-3.20 (br m,7,cyclobutanes + exo methylene adjacent to OH), and 1.48-2.28 (br m, 6, ethano bridge, endo methylene, and -OH); 3320 (OH), 1110, 1062, 1020, 927, Ul&X -1 908, and 890 cm 151

Calcd for C^H^O: m/e 150.1045. Found: 150.1047

The 3,5-dinitrobenzoato was obtained as off-white plates, mp 148-

149° (from diethyl ether).

Anal. Calcd for C^H^gN^Og: C, 59.30; H, 4.68; N, 8.14. Found:

C, 59.17; H, 4.79; N, 8.27.

endo-Pentacydo[ 5.4.0. 0^ * **. 0^ * . 0** * ^ 1 undecan-4-ol (183) .

The exo alcohol (180, 322 mg) was 168 oxidized with chromium trioxide—

pyridine as before (cf. 183j to

give 78 mg of impure ketone; 0 max

(neat) 1730 (C*0). Reduction with H % sodium borohydrlde (100 mg ) waB carried out in 3 ml of absolute methanol at 0° for 10 min. After stir ring at room temperature for 1 hr, the mixture was processed in the customary fashion to give 57 mg of oil which crystallized on standing.

Preparative gas chromatography on a 6 ft 5% SE-30 column at 110° (300

_ p n p l cc/mln) gave 31 mg (39%) of colorless crystals (t » 16 min); A 3 r IMS 4.40 (m,l, ^CHOH), 2.90 (m,6,cyclobutanes), 2.52 (m,2,exo methylene and

-0H)m 2,20 (m,l,endo methylene), 1.81 (m,l,cyclopropyl methine adjacent to -OH), 1.29 (ra,l,cyclopropyl methine), 0.42 (d t,l, anti cyclopropyl methylene, Jgem-4Hz, JSyn“7.5Hz), and -0.18 (dt,l,syn cyclopropyl m ethylene,J **4Hz,J ,..*,4Hz); (n eat) 3340 (OH), 1447, 1347, 1330, gem a n ti max 1312, 1298, 1110, 1062, 1035, 1010, 910, 827, and 804 cm”1. The molecular ion is too weak for accurate mass determination.

The 3,5-dinitrobenzoate was prepared in the usual manner to give 152 in 93% yield, off-white blades, mp 184.5-185.5° (from diethyl ether).

Anal. Calcd for C^gH^gN^Ogj C, 60.67; 11, 4.53; N, 7.86. Found:

C, 60.46; H, 4 .5 0 ; N, 7 .8 5 . References

^A.K,Cheng, F.A.L.Anet, J.Mloduski, and J.Meinwald, J. Amer. Chem. S o c ., 96, 2887 (1974).

^L,A.Paquette and G.H.Birnberg, ibid., 94, 164 (1972).

^L.Friedman and H.Schechter, ib id .. J31, 5512 (1959).

^W.Kirrase, "Carbene Chemistry," Academic Press, New York, N.Y., 1964, Chapter 3.

'’l.A.Paquette and 6.V.Meehan, J.Amer. Chem. Soc.. 92, 3039 (1970).

^D.J.Cram, F.Willey, H.P.Fisher, H.M.Relies, and D.A.Scott, ib id ., 88, 2759 (1966).

^S.J.Cristol, private communication. Q S.J.C ristol, G.C.Schloemer, D.R.James, and L.A.Paquette, J. Org. Chem., 37, 3852 (1972). q E.Clganck, J . Amer. Chem. S o c ., Jt8, 2882 (1966)} see a lso P.W. Rabideau, J.B.Hamilton, and L.Friedman, ibid. , 9£, 4465 (1968).

10G.Zweifel and H.C.Brown, ib id ., 81, 1512 (1959); H.C.Brown and P.Heim, ibid.. 86, 3566 (1964).

^J.W.Cook, A.Dansi, C.L.liewett, J.Ib all, W.V.Mayneord, and E. Roe, J. Chem. Soc., 1319 (1935); see also reference 5. 12 (a) S.J.C ristol and D.D.Tanner, J. Amer. Chem. Soc., 86, 3122 (1964); (b) S.J.C ristol, F.P.Parungo, D.E.Plorde, and K.Schwarzenbach, ibid., 87, 2879 (1965); (c) S.J.C ristol, R.J.Bopp, and A.E.Johnson, J . Org. Chem., 34^, 3574 (1969). 13 See for example (a) H.Zollinger, "Azo and Diazo Chemistry," W iley-Interscience, New York, N.Y., 1961, pp. 123-136; (b) R.A.M. O 'Ferrall, Advan. Phys. Org. Chem.. 3. 362 (1967); (c) E.H.White and D.J.Woodcock in "The Chemistry of the Amino Group," S. Patai, Ed., W iley-Interscience, New York, N.Y., 1968, pp. 440-483; (d) L.Friedman in "Carbonium Ions," Vol. II, G.A.Olah and P.v.R.Schleyer, Ed., Wiley- Interscience, New York, N.Y., 1970, pp. 655-713; (e) C.J.Collins, Accounts Chem. Res., 4, 315 (1971).

153 14 15A S.J.C ristol! J.R.Mohrig, and G.T.Tiedeman! J. Org. Chem.. 37, 3239 (1972). "

^G.C.Schloeraer, Ph.D. Thesis, University of Colorado. 16 (a) A.Streitwieser, Jr. and W.D.Schaeffer, J. Amer. Chem. Soc., 79, 2893 (1957); (b) L.Friedman and J.H.Bayless, ib id ., 91, 1790 (1969); "(c) J.H.Bayless and L.Friedman, ib id .. 89, 147 (1967).

^W.Vaughan and K.Hilton, ibid., ^74, 5628 (1952). 18 H.E.Zimmerman and G.L.Grunewald, ib id .. £8, 183 (1966). 19 H.E.Zimmerman, R.W.Binkley, R.S.Givens, G.L.Grunewald and M.A. Sherwin, ibid., 91, 3316 (1969). 20 J.B.Lambert. Tetrahedron L ett., 1901 (1963).

^^R.Merenyi, J.F.M.Oth, and G.SchrHder, Chem. Ber., 97, 3150 (1964). 22 (a) H.E.Zimmerman and R.M.Paufler, J. Amer. Chem. Soc., .82, 1514 (1960); (b) H.E.Zimmerman, G.L.Grunewald, R.M.Paufler, and M.A.Sherwin, ibid., 91, 2330 (1969). 23 H.E.Zimmerman and H.Iwamura, ib id ., JM, 4763 (1968).

2^J.Meinwald and D.Schmidt, ib id ., 91, 5877 (1969).

2^H.E.Zimmerman, J.D.Robbins, and J.Schantl, ib id ., 91, 5878 (1969).

(a) W.R.Roth and W.Peltzer, Annalen, 685, 56 (1965); (b) H.M.Frey and R.G .H opkins, J . Chem. S o c ., (B ), 1410 (1970). 27 J.M einw ald and H .T su ru ta, J . Amer. Chem. S o c ., 5878 (1969).

28L.A.Paquette, ibid., 92, 5765 (1970).

2^R.Askani, Tetrahedron L ett., 3349 (1970). 30 (a) L.A.Paquette and J.C.Stowell, J. Amer. Chem. Soc., 92, 2584 (1970); (b) W.G.Dauben, M.G.Buzzollni, C.H.Schallhorn, D.L.Whalen, and K.J.Palmer, Tetrahedron L ett., 787 (1970), 31 For nomenclature, see L.A.Paquette and J.C.Stowell, J. Amer. Chem. Soc.. 93, 2459 (1971).

82R. Malherbe, Helv. Chim. Acta..56,. 2845 (1973). 33 (a) P.K.Freeman and D.G.Kuper, Chem. Ind., 424 (1965); (b) J. Meinwald and G.H.Wahl, ib id ., 425 (1965). 34 R.Criegee and R.Askani, AnRew. Chem., JJO, 531 (1968); AnRew. Chem. Intern* Ed. Engl.. 7j 537 (1968). 35 J.C.Kauer and H.E.Simmons, J. Org. Chem., 2720 (1968). 36 H.E*Zimmerman and H.Iwamura, J . Amer. Chem. S o c.. 92, 2015 (1970).

^R. Askanl, Tetrahedron L ett.. 447 (1971). 38 R.Askani and H.SBnmez, T etrahedron L e t t . , 1751 (1973).

^R.S.H.Liu and C.G.Krespan, J. OrR. Chem., 34_, 1271 (1969). 40 L.A.Paquette, S.V.Ley, R.H.Meisinger, R.K,Russell, and M.Oku, J . Amer. Chem. S o c .. 9^6, 5806 (1974). 41 (a) R.K.Russell, L.A.Paquette, L.G.Grelfenstein, and J.B.Lambert, Tetrahedron L ett., 2855 (1973); (b) L.A.Paquette, R.E.Wlngord, Jr., and R .K .R ussell, J . Amer. Chem. S o c.. 94, 4739 (1972). 42 W.von E. Doerlng and W.R.Roth, AnRew. Chem. Int. Ed. Engl., 2j 115 (1963) .

^ R.B.Woodward and R. Hoffmann, J.Amer. Chem. Soc.. 87, 2511 (1965); AnRew. Chem.. 81, 797 (1969).

^ E.Vogel, K.H.Ott, and K.Gajek, Justus LlebiRB Ann. Chem., 644, 172 (1961).

^ W.von E.Doerlng and W.R.Roth, Tetrahedron. 19, 715 (1963).

^ G.Schrttdcr, An row. Chem., 75, 722 (1963); Chem. Ber.. 97, 3140 (1964)

^ W.von E.Doerlng, B.M.Ferrier, E.T.Fossel, J.M.Hartenstein, M.Jones, Jr., G.Klump, R.M.Rubin, and M.Saunders, Tetrahedron, 23, 3943 (1967).

^L.Birladeanu, D.L,Harris, and S.Wlnsteln, Ibid., 92^ 6387 (1970).

^ (a) M.J.S.Dewar and W.W.Schoeller, ibid., 93, 1481 (1971); (b) M.J.S.Dewar and D.H.Lo, Ibid. .93. 7201 (1971).

^Y.C.Wang and S.H.Bauer, ibid., 9hj 5651 (1972).

■^R.Askani, R.Gleiter, E.Heilbronner, V.Hornung, and H.Musso, Tetra hedron L ett., 4461 (1971).

52(a) R.Hoffmann, ibid.. 2907 (1970); (b) H.GUnther, ib id ., 5173 (1970). 53 R.Hoffmann and W.D.Stohrer, J. Amer. Chem. Soc., 93, 6941 (1971). 54 156 (a) K .Z iegler and H.Wilms, L iebigs Ann. Chem., J*67, 1 , 26, 28 (1950); (b) I.L.Karle, J. Chem. P hys.,20, 65 (1952).

55R«H, AH »27.4-28.17kcal/m ol;56,57R«CftH,, AH =24.5 kcal/m ol;56 R= C2I15,AH -27.5 kcal/mol; R=Br,A H -23.1 kc8l/mol.

(a) R, Huisgen and F.M ietzsch, Angew. Chem. I n t. Ed. E n g l..^3j 83 (1964); (b) R.Huisgen, F.Mietzsch, G.Boche, and H.Seidl, Chem. Soc.. Spec. Publ.. 19. 3 (1965).

^R.Huisgen, private communication.

CO R.Huisgen and W.E.Konz, J. Amer. Chem. Soc., 92, 4102 (1970). 59 A.B.Evnin, R.D.Miller, and G.R.Evanega, Tetrahedron Lett. 5863 (1968). 60 R.Huisgen, W.E.Konz, and G.E.Gream, J . Amer. Chem. S o c ., 92, 4105 (1970).

^R.Huisgen, W.E.Konz, and v.Schnegg, Angew. Chem.. Int. Ed. Engl., 11, 715 (1972). 62 R.C.Cookson, S.S.H.Gilani, and I.D.R.Stevens, J. Chem. Soc.. C, 1905 (1967). 62 (a) L.A.Paquette, J.R.Malpass, and T.J.Barton, J. Amer. Chem. Soc. 91^ 4714 (1969); (b) R.Huisgen and J .G a ste lg e r, Angew. Chem., I n t. Ed. Engl.. (1972);(c) J.Gastelger and R.Huisgen, J. Amer. Chem. Soc., 94, 6541 (1972). 64 J.Gastelger and R.Huisgen, Angew. Chem., Int. Ed. Engl., 11, 716 (1972). 65 L.A.Paquette, W.E.Heyd, W.Kitching, and R.ll.Meisinger, J. Amer. Chem. Soc., in press.

^A.C.Cope and M.R.Klnter, J. Amer. Chem. Soc., JJ3, 3424 (1951) .

**7(a) A.C.Cope and H.Campbell, ibid. . 74, 179 (1952); (b) for pmr see L.A,Paquette and R.S.Beckley, ibid.'T^in press. 6B L.A.Paquette, D.R.James, and G.H.Birnberg, ibid., in press.

^G.SchrHder, G.Kirsch, J.F.M.Oth, R.Huisgen, W.E.Konz, and U.Schnegg Chem. Ber., 3 ^ , 2405 (1971).

7®A.C.Cope and M.Burg, J . Amer. Chem. S oc., 74, 168 (1952).

71(a)W.Reppe, O.Schlichting, K.Klager, and T.Toepel, Ann.. {>69,1 (1948); (b) M.Avram, E.Sliam , and C.D .N enitzescu, i b i d . , 635, 184 (1960); (c) D.G.Farnum and J.P.^Snyder, Tetrahedron L ett.. 3861 (1965). 72 R.Huisgen, G.Boche, W.Hechtl, and H.Huber, Angew. Chem., Int. Ed. Engl.. 585 (1966). 73 (a) R.Huisgen and J.Gastelger, Tetrahedron Lett. 3661 (1972); (b) J.Gastelger and R.Huisgen, ibid. , 3665 (1972); (c) G.Boche, W.Hechtl, H.Huber, and R. H uisgen, J . Amer. Chem. S o c .. 8JJ, 3344 (1967); (d) R.Huisgen, G.Boche, and H.Huber, ibid., 89, 3345 (1967).

74(a) L.A.Paquette and K.A.Henzel, ibid.. 95, 2726 (1973); (b) W.E.Konz, W.Hechtl, and R.Huisgen, Ib id .. 92, 4104 (1970). 75 For a review, see W.L.Dilllng, Chem. Rev., 66.. 373 (1966). 76 G.O.Schenck and R.Steinmetz, Bull. Soc. Chim. Beiges, 71, 781 (1962); Chem. Ber.. 96, 520 (1963).

77J.P.Snyder, Ph.D. Thesis, Cornell University, Ithaca, N.Y., 1965; Dissert. Abstr., 26, 5728 (1966). 78 G.H.Birnberg discovered that,a Corex filte r and acetone-benzene solvent mixtures were advantageous in the acetoxymethyl series; although no reinvestigation of the other isomers using these two conditions was made, one should keep them in mind when attempting Intramolecular cyclizations such as these. Note also that yields seemed best at low diene concentrations. 79 B.E.Knox and H.B.Palmer, Chem. Rev., 61, 247 (1961). 80 (a) L.A.Paquette and J.C.Stowell, J. Amer. Chem. Soc., 92. 2584 (1970); (b) W.G.Dauben, M.G.Buzzolini, C.H.Schallhorn, D.L.Whalen, and K.J.Palmer, Tetrahedron L ett., 787 (1970). 81 For an explanation of this nomenclature, see L.A.Paquette and J. C.Stowell, J.Amer. Chem. Soc.. 2459 (1971). 82 (a) J.E .B y rd , L .C assar, P .E .E aton, and J.lla lp e rn , Chem. Cotnmun., 40 (1970); (b) K.L.Kaiser, R.F.Childs, and P.M.Maitlls, J. Amer. Chem. Soc.. S>3, 1270 (1971); (c) W.G.Dauben and A.J.Kielbania, Jr., ib id ., 93, 7345 (1971); (d) For a review, see L.A.Paquette, Accounts Chem. Res., 280 (1971). 83 (a) L.Cassar, P.E.Eaton, and J.Halpern, J. Amer. Chem. Soc., 92, 6366 (1970); (b) L.A.Paquette and J.S.Ward, Tetrahedron L ett., 4909 (1972); (c) L.A.Paquette, R.S.Beckley, and W.B.Farnham, J. Amer. Chem. Soc.. in press; (d) L;A.Paquette, J.S.Ward, R.A.Boggs, and W.B.Farnham, ibid., in press; (e) L.A.Paquette, R.A.Boggs, R.S.Beckley, and W.B.Farnham, ibid. , in press;(f) L.A,Paquette and R.S.Beckley, ibid., in p re s s .

®4E.Wenkert, E.W.Hagaman, L.A.Paquette, R.E.Wingard, J r., and R .K .R u ssell, Chem. Commun.. 135 (1973). 85 ajo R.M.Moriarty, C.L.Yeh, and N.Isliibi, J.Amer. Chem. Soc., 93, 3085 (1971). 86 D.R.James, G.H.Blrnberg, and L.A.Paquette, ibid.. in press. 87 L.A.Paquette and M.J.Epstein, ibid., 93, 5936 (1971); 95, 6717 (1973). ~

DO -E.L.Allred and K.J.Voorhces, ib id .. 95, 620 (1973). 89 R.B.Woodward and R.Hoffmann, "The Conservation of O rbital Sym metry," Verlag Chemle GmbH and Academic Press, Inc., 1970, pp. 152 ff. 90 (a) L.A.Paquette, R.F.Elzember, and O.Cox, J. Amer. Chem. Soc.. 90, 5153 (1968); (b) T.R.Darling, J.Pouliquen, and N.J.Turro, ibid.. 96, 1247 (1974); (c) D.M.Lemal and S.D.McGregor, ib id .. 88. 1335 (1966); (d) J .E .Baldwin, Can. J . Ch'em. . 44, 2051 (1966); (e) L.A.Carpino, Chem. Commun.. 494 (1966). ^

9h .Rieber, J.A lberts, J.A.Lipsky, and D.M.Lemal, J. Amer. Chem. Soc.. 91, 5668 (1969). 92 E.L.Allred, J.C.Hinshaw, and A.L.Johnson, ib id .. 91, 3382 (1969); E.L.Allred and J.C.Hinshaw, Chem. Commun.. 1021 (1969). 93 E.L.Allred and A.L.Johnson, J. Amer. Chem. Soc., 93, 1300 (1971). 94 L.A.Paquette, R.K.Russell, and R.E.Wingard, Jr., Tetrahedron L ett., 1713 (1973). 95 M.Heyman, V .T.Bandurco, and J .P .S n y d e r, Chem. Commun.. 297 (1971). 96 R.B .Kelley, J. Org. Chem.. 2§, 453 (1963); R.B.Kelley, G.R.Umbreit, and W.R,Liggett, ibid., 29, 1273 (1964).

99N.Rabjohn, Org. Syn., Coll. Vol. Ill, Wiley, New York, N.Y., 1955, p. 375; D.MacKay, C.W.Pilger, and L.L.Wong, J. Org. Chem.. 3g, 2043 (1973).

*®9F,A.L.Anet and G.E.Schenk, Tetrahedron L ett.. 4237 (1970).

*®*(a)W.W.Wood, W .Fickett, and J.G.Kirkwood, J. Chem. Phys.. 20, 561 (1952); (b) See also H.Joshua, R.Gans, and K.Mislow, J. Amer. Chem. Soc.. 90, 4884 (1968); (c) R.J.Abraham and H.J.Bernstein, Can. J. Chem., 3j>, 39'"?1961); (d) H.S.Gutowsky, G.G.Belford, and P.E.McMahon, J. Chem. Phys.. 3

^**Dr. Masayoshi Oku, unpublished results: ^*2*2 (-41°) 5.13 (dd, J-4.4 and 4.5 Hz, H?), 4.86 (m,H,), 4.53 (m,H,), 3.28 (dd,J» 4.4 and 5.0Hz,Hft), 3.09 (d,J«5.0Hz,Hj,2.72 (t,J-2.5Hz, H_), 1.65 (s, 3-Me), and l.ll°(s, 1-Me). L 3 106 E.Moriconi and C.Jalandoni, J. Org. Chem., J^5, 3796 (1970). 107 H.VorbrUggen, Tetrahedron L ett.. 1631 (1968). 108 W.E.Volz, unpublished results. 109 See S.Cristol and B.Jarvis, J. Amer. Chem. Soc.. ^89^ 401 (1967).

^■^(a) H.J.Reich, E.Ciganek, and J.D.Roberts, Tetrahedron L ett., 92, 5166 (1970); (b) G.H.Hall and J.D.Roberts, ibid., 93, 2203 (1971); 'tc) E.Ciganek, ibid.. 93, 2207 (1971). 111 R.Huisgen, G.Boche, A.Dahmen, and W.Hechtl, ib id ., 5215 (1968); L.A.Paquette, T.Kakihana, and J.F.Kelly, J. Org. Chem., 36. 435 (1971). 112 (a) G.SchrOder and J.F.M.Oth, Angew. Chem. Inter., Ed. Engl., 6. 414 (1967); (b) H.P.LBffler and G.SchrOder, ibid., .7, 736 (1968); (c) J.F.M.Oth, R.Merenyi, H.RUttele, and G.Schrtider, Tetrahedron L ett., 3941 (1968); (d) J.F.M.Oth, E.Machens, H.RUttele, and G.SchrBder, Ann., 745, 112 (1971). 113 J.C.Barborak, S.Chari, and P.von R.Schleyer, J. Amer. Chem. Soc., 93, 5275 (1971). 114 L.Libit and R.Hoffmann, ibid.. 96, 1370 (1974). 115 (a) R.Bianchi, A.Mugnoli, and M.Simonetta, Chem. Commun., 1073 (1972); (b) H.GUnther, H.Schmickier, W.Bremser, F.A.Straube, and E. V ogel, Angew. Chem., 85, 585 (1973); Angew. Chem. I n te r n . Ed. E n g l., 12, 570 (1973). 116 L.A.Paquette, J.R.Malpass, G.R.Krow, and T.J.Barton, J. Amer. Chem. S o c .. 91. 5296 (1969). 117 V.Rautenstrauch, J.J.Scholl, and G.Vogel, AnRew. Chem., 80, 278 (1969); AnRew. Chem. Intern. Ed. Engl., ^7, 288 (1968)• 118 J.C.Stickler and W.H.Pirkle, J. Org. Chem.. 31, 3444 (1966). 119 Prepared by halogen-metal exchange of BrCOT with methylllthium, followed by methylotion with methyl iodide. For the original character ization, see: A.C.Cope and H.Campbell, J. Amer. Chem. Soc., 74, 179 (1952). 120 R.C.Cookson, S.S.H.Giloni, and l.D.R.Stevens, Tetrahedron L ett., No. 14, 615 (1962).

^^T.A.Antkowiak, D.C.Sanders, G.B.Trlmitsis, J.B.Press, and H. Schechter, J. Amer. Chem. Soc., J>4, 5366 (1972). 122 R.D.Smith and H.E.Simmons, Org. Svn.. 41, 72 (1961). 123 Review: L.T.Scott and M.Jones, Jr., Chem. Rev., 72, 181 (1972).

*^See (a) R.J.Roth and T.J.Katz, J. Amer. Chem. Soc.. jM, 4770 (1972); (b) P.G.Gassman, Accounts Chem. Res., 4^ 129 (1971). 125 J.S.McKennls, L.Brener, J.S.Ward, and R .Pettit, J. Amer. Chem. Soc., jQ, 4957 (1971); (b) L.Brener, Ph.D. Thesis, The University of Texas, 1972.

P.Schultz, J. Org. Chem., 30, 1361 (1965). 127 W.Schmidt and B.T.Wilkins, Tetrahedron. 28. 5649 (1972). 128 C.R.Brundle, M.B.Robin, N.A.Kuebler, and H.Bosch, J. Amer. Chem. Soc., 94, 1451 (1972); C.R.Brundle, M.B.Robin, and N.A.Kuebler, ibid.. 94, 1466 (1972).

^^R .Pettit and J.Henery, Org. Synth., 50, 21, 36 (1970). 130 (a) See reference 75; (b) N.B.Chapman, J.M.Key, and K.J.Toyne, J.Org. Chem., 35, 3860 (1970); (c) P.E.Eaton and T.W.Cole, J. Amer. Chem. Soc., 3157 (1964); (d) G.W.Griffin and A.K.Price, J. Org. Chem., 29, 3192 (1964); and many others. 131 For the bishomocubane system of nomenclature see W .L.Dilling, C.E.Reineke, and R.A.Plepys, J. Org. Chem., 34, 2605 (1969); 37, 3753 (1972). 132 L.A.Paquette, R.F.Davis, and D.R.James, Tetrahedron L ett.. 1615 (1974); much of the preliminary work was carried out by Dr, R.F.Davis. 133 W.von E.Doerlng and C.H.DePuy, J. Amer. Chem. Soc.. 75, 5955 (1953). 134 For a review of cyclopcntadlenone chemistry sec M.A.Ogliaruso, M.G.Romanelll, and E.I.Becker, Chem. Rev.. 261 (1965). 135 C.H.DePuy and B.W.Ponder, J. Amer. Chem. Soc., 81, 4629 (1959). 136 C.H.DePuy. M.Isaks, K.L.Ellers, and G.F.Morris, J. Org. Chem.. 29, 3503 (1964). 137 K.Hafner and K.Wagner, Angew.Chem., Int. Ed. Engl., 2, 740 (1963). 138 E.Baggiollni, E.G.Herzog, S.Iwasaki, R.Schorta, and K.Schaffner, Helv. Chlm. Acta. 50, 297 (1967). 139 E.Vogel and E.G.Wyes, Chem. Ber.t j)8, 3680 (1965).

*^(a) G.O.Schenk and R. Stelnmetz, Ibid., 96f 520 (1963); (b) See reference 75 for a review. 141 Complex absorptions in the carbonyl region are observed (ver- schiedentlich) in the case of ketones with a cage structure; e.g. P.E. Eaton and T.W .Cole,Jr., J. Amer. Chem. Soc.. 86, 3157 (1964); R.Howe and S.Winstein, ibid.. 87, 915 (1965); T.Fukanaga, ibid.. 87, 916 (1965).

^^See P.Isaac, Ph.D. Thesis, Carnegie-Mellon Institute, 1973.

1/1 E.J.Corey, et. a l.. J. Amer. Chem. Soc.. 90, 3245 (1968). 144 G.Rosenkranz, J.Patakl, and C.Djerassi, J. Org. Chem.. 17, 290 (1952); J.A m er. Chem. S o c .. 74, 3634 (1952). ' 145 R.C.Cookson, E.Crundwell, R.R.Hill, and J.lludec, J. Chem. Soc.. 3062 (1964). 146 W.L.Dilling and C.E.Relneke, Tetrahedron L ett.. 2547 (1967). 147 W.L.Dilling, private communication.

^®R.K.Crossland and K.L.Servis, J. Org. Chem., 35, 3195 (1970). 149 (a) T.Hanafusa, S.Iraai, K.Ohkata, H.Suzuki, and Y.Suzuki, Chem. Comm. 73 (1974); (b) H.Kessler and W.Ott, Tetrahedron L ett.. 1383(1974); (c) See also R.Kuhn and A.Winterstein, Helv. Chim. Acta, 11, 106 (1928); H.H.Inhoffen, K.Radscheit, U.Stache, and V.Koppe, Liebigs Ann. Chem.. 684, 24 (1963).

*’’®(a) 11.Normant, Bull. Soc. Chem. France. 791 (1968), a review of HMPT chemistry, idem., Angew. Chem.. Int. Ed. Engl., jr, 1046 (1967); (b) for mesylate displacement by iodide in HMPT see L.A.Paquette and J.C. Philips, Tetrahedron L ett.. 4645 (1967). C.J.Pedersen. J. Amer. Chem. Soc., 89, 7017 (1967). 1 59 P.G.Eaton and R,A.Hudson, ibid., 87, 2769 (1965).

1 5 3 R.Hoffmann, P.D.Mollere, and E.Heilbronner, Ibid.. 95, 4860 (1973).

154(a) H.TanIda and T.Tsushima, Ibid.. £2, 3397 (1970); (b) S. Wins tain and M.Shatavsky, Ibid. , 78.. 592 (1956); (c) S.Winsteln, A.L. Lewin, and K.C.Pande, Ibid.. 85, 2324 (1963).

1 5 5 R.Hoffmann, Accounts” 1 Chem. 11 Res., 1 4, 1 (1970). ^**Sl.J. Goldstein and R.Hoffmann, J. Amer. Chem. Soc., 93, 6193 (1971).

^ 7S.Winstein, Chem. Soc.. Spec. Pub. No. 21, 5 (1967). 158 (a) H.Tanida, T.Tsujl, and T.Irie, J. Amer. Chem. Soc., ,$9, 1953 (1967); (b) M.A.Battiste, C.L.Deyrup, R.E.Flncock, and J.Haywood- Farmer, ibid., 89. 1954 (1967); (c) R.Hoffmann, Tetrahedron L ett., 3819 (1965); (dT~P.G.Gassman and A.F.Fentiman, J r., J. Amer. Chem. Soc., 92, 2551 (1970).

■^E.Heilbronner and H.D.Martin, Helv. Chim. Acta. 55, 1490 (1972).

(a) P.R.Story and M.Saunders, J. Amer. Chem. Soc., 82, 6199 (1960); 84, 4876 (1962); (b) P.R.Story, L.C.Snyder, D.C.Douglass, E.W. Anderson, and R.L.Kornegay, Ibid. , 8§_, 3630 (1963) ;(c) R.K.Lustgarten, M.Brookhart, and S.Winsteln, ib id ., 89, 6350 (1967); (d) M.Brookhart, R.K.Lustgarten, and S.Winsteln, ibid. , 89, 6352, 6354 (1967); (e) R.K. Lustgarten, M.Brookhart, and S.Winsteln, ibid., 90, 7364 (1968).

■^E.Heilbronner and H.Bock, "Das HMO-Modell und seine Anwendung," Vol. 3, Verlag Chemie, Welnheim/Bergstr., Germany, 1970, p. 247.

1 6 2For a recent survey, see R.Hoffmann and R.B.Davidson, J. Amer. Chem. S o c ., 93, 5699 (1971). 163 (a) P.v. R.Schleyer, J.J.Harper, G.L.Dunn, V.J.DiPasquo, and J.R.E.Hoover, ibid.. 89, 689 (1967); (b) W.G.Dauben and D.L,Whalen, ibid. , 93, 7244 (1971); (c) W.L.Dilling, R.A.Plepys, and R.D.Kroening, ib id .. J94, 8133 (1972).

*^4J .Haywood-Farmer, Chem. Rev., J74, 315 (1974) .

1 6 5 H.C.Brown, S.Ikcgami, and J.H.Kawakami, J. Org. Chem., 35, 3243 (1970).

^^S.Krishnmnurthy , R.Schubert, and H.C.Brown, J. Amer. Chem. Soc., 95, 8486 (1973).

167E.F.Knights and H.C.Brown, ib id .. 90, 5281 (1968). 163 168 R.Ratcliffe and R.Rodehorst, J* Org. Chem., 35, 4000 (1970). 169 (a) E.J.Corey, W.L.Mock, and D.J.Fasto, Tetrahedron L ett., 347 (1961); (b) E.E. van Tamelen, R.S.Dewey, and R.J.Timmons, J. Amer. Chem. S o c .. 83, 3725 (1961).

^■^(a) L.L.Fieser and D.H.Sachs, J. Org. Chem., 29, 1 1 1 3 (1964); (b) M.Z.Nazer, ibid.. 30, 1737 (1965). ^

Denis, C.Girard, and J.M.Conla, Synthesis. 549 (1972).