Eastern Illinois University The Keep
Masters Theses Student Theses & Publications
1995 The yS nthesis of N-Chlorosulfonyl β-Lactams and Their Rearrangements Lihua Zhang Eastern Illinois University This research is a product of the graduate program in Chemistry at Eastern Illinois University. Find out more about the program.
Recommended Citation Zhang, Lihua, "The yS nthesis of N-Chlorosulfonyl β-Lactams and Their Rearrangements" (1995). Masters Theses. 1967. https://thekeep.eiu.edu/theses/1967
This is brought to you for free and open access by the Student Theses & Publications at The Keep. It has been accepted for inclusion in Masters Theses by an authorized administrator of The Keep. For more information, please contact [email protected]. THESIS REPRODUCTION CERTIFICATE
TO: Graduate Degree Candidates (who have written formal theses) SUBJECT: Permission to Reproduce Theses
The University Library is rece1v1ng a number of requests from other institutions asking permission to reproduce dissertations for inclusion in their library holdings. Although no copyright laws are involved, we feel that professional courtesy demands that permission be obtained from the author before we allow theses to be copied. PLEASE SIGN ONE OF THE FOLLOWING STATEMENTS: Booth Library of Eastern Illinois University has my permission to lend my thesis to a reputable college or university for the purpose of copying it for inclusion in that instit ion's library or res·earch holdings.
Date
I respectfully request Booth Library of Eastern Illinois University not allow my thesis to be reproduced because:
Author Date The Synthesis of N-Chlorosulfonyl ~-Lactams and Their Rearrangements
(TITLE)
BY
Lihua Zhang
THESIS
. - SUBMITIED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN CHEMISTRY
IN THE GRADUATE SCHOOL, EASTERN ILLINOIS UNIVERSITY CHARLESTON, ILLINOIS
1995
YEAR
I HEREBY RECOMMEND THIS THESIS BE ACCEPTED AS FULFILLING THIS PART OF THE GRADUATE DEGREE CITED ABOVE
I
r - f DAT~
V( I """"'"' • v DATE DEPARTMENT HEAD THE SYNTHESIS OF N-CHLOROSULFONYL p-LACTAMS
AND THEIR REARRANGEMENTS
THESIS APPROVED BY
' {)ate Dr. T. Howard Black, fhesis Advisor
Dr. Ellen A. Keiter, Department Head
uate Dr. Daniel J. Sheeran
Date D(/ Jonathan fl. Blitz
L_ The Syntheses of N-Chlorosulfonyl-g-Lactams
and Their Rearrangements
L To: Xiaoping, Tina
and my parents TABLE OF CONTENTS
ABSTRACT ------i
ACKNOWLEDGEMENT ------ii
LIST OF TABLES------iii
LIST OF FIGURES------iv
INTRODUCTION ------1
RESULTS AND DISCUSSION ------16
CONCLUSION ------47
EXPERIMENTALSECTION------49
REFERENCES ------58
FIGURES ------64 ABSTRACT
The synthesis of several N-chlorosulfonyl-g-lactams and
their rearrangements have been carried out via CSI
(chlorosulfonylisocyanate) reaction. The mechanism of g_
lactam synthesis as well as its rearrangements were also
studied. The characterization of g-lactams was performed with
IR, 1H and 13C NMR, and HRMS. g-lactams 2-chlorosulfonyl-l
methyl-2-azabicyclo[4.2.0]octan-3-one (71), l-chlorosulfonyl-
4-methyl-4- (phenylmethyl)azetidin-2-one (74) and l
chlorosulfonyl-4,4-(diphenylmethyl)azetidin-2-one (75) were
synthesized for the first time. g-lactam 4-chlorosulfonyl-
3, 9, 9-trimethyl-4-azatricyclo [6. 1. O. 03 ' 6 ] nonan-5-one ( 73) was
obtained as crystalline solid instead of liquid.
Different effects, such as temperature, sol vents and
catalysts, on the rearrangement of the g-lactam 74 have been
studied. There was no expected rearrangement to r-lactam
observed, and usually the unsaturated amide resulted.
The rearrangement products of a g-lactam can be r-lactam,
a,g- or g,r-unsaturated amide, and alkene, depending on the
conformation of the g-lactam and reaction conditions.
-i-
I_ ACKNOWLEDGEMENT
I am very grateful to my advisor, Dr. T. Howard Black, for his continuous guidance and academic help during this study. I also thank those in our research group for their
assistance and cooperation, especially Mr. J. T. Olson and Mr. D. C. Abt for their previous studies. I appreciate the opportunity the Chemistry Department provided to me for studying here with financial aid, and the help from all faculty and staff, especially Dr. Ellen. A. Keiter for her help in the NMR spectra analysis.
-ii-
L LIST OF TABLES
Table 1: Synthesis of alkenes from ketones
Table 2: Synthesis of :IS-Lactams by CSI with alkenes
Table 3 : High-Resolution MS Data of :IS-Lac tam 73
Table 4: High-Resolution MS Data of :IS-Lactam 74
Table 5: High-Resolution MS Data of :IS-Lac tam 75
Table 6: High-Resolution MS Data of :IS-Lactam 71
Table 7: High-Resolution MS Data of Alkene 63
Table 8: High-Resolution MS Data of Alkene 65
Table 9: High-Resolution MS Data of Alkene 67
-iii-
L LIST OF FIGURES
Figure 1: 1 H NMR Spectrum of B-Lactam 73
Figure 2: COSY Spectrum of B-Lactam 73
Figure 3: 13C NMR Spectrum of B-Lactam 73
Figure 4: DEPT Spectrum of B-Lactam 73
Figure 5: HETCOR Spectrum of B-Lactam 73
Figure 6: MS Spectrum of B-Lactam 73
Figure 7: IR Spectrum of B-Lactam 73
Figure 8: 1 H NMR Spectrum of B-Lactam 71
Figure 9: 13C & DEPT NMR Spectrum of B-Lactam 71
Figure 10: IR Spectrum of B-Lactam 71
Figure 11: 1 H NMR Spectrum of Unsaturated Amide 83
Figure 12: COSY Spectrum of Unsaturated Amide 83
Figure 13: 13C & DEPT NMR Spectrum of Unsaturated Amide 83
Figure 14: HETCOR Spectrum of Unsaturated Amide 83
Figure 15: 1 H NMR Spectrum of r-Lactam 49
Figure 16: 13 C & DEPT NMR Spectrum of r-Lactam 49
Figure 17: IR Spectrum of r-Lactam 49
Figure 18: 1 H NMR Spectrum of Alkene 61
Figure 19: 13C NMR Spectrum of Alkene 61
Figure 20: MS Spectrum of Alkene 61
-iv- Figure 21: IR Spectrum of Alkene 61
Figure 22: 1 H NMR Spectrum of B-Lactam 74
Figure 23: 13c NMR & DEPT Spectrum of B-Lactam 74
Figure 24: MS Spectrum of B-Lactam 74
Figure 25: IR Spectrum of B-Lactam 74
Figure 26: 1 H NMR Spectrum of Alkene 97
Figure 27: i3c & DEPT NMR Spectrum of Alkene 97
Figure 28: IR Spectrum of Alkene 97
Figure 29: 1 H NMR Spectrum of Alkene 63
Figure 30: 13c NMR Spectrum of Alkene 63
Figure 31: IR Spectrum of Alkene 63
Figure 32: 1 H NMR Spectrum of B-Lactam 75
Figure 33: 13c & DEPT NMR Spectrum of B-Lactam 75
Figure 34: MS Spectrum of B-Lactam 75
Figure 35: IR Spectrum of B-Lactam 75
Figure 36: 1 H NMR Spectrum of Alkene 65
Figure 37: 13c NMR Spectrum of Alkene 65
Figure 38: IR Spectrum of alkene 65
Figure 39: 1 H NMR Spectrum of alkene 67
Figure 40: 13c NMR Spectrum of Alkene 67
Figure 41: IR Spectrum of alkene 67
-v-
L INTRODUCTION
Dr. T. Howard Black's research group has been engaged for a long time in the chemistry of B-lactones. These useful synthetic intermediates can be converted into butyrolactones, 1
B, r-unsaturated carboxylic acids2 and a-halo3 or alkyl 4 butenolides. The ring expansion of B-lactones to r-lactones was the main focus in the early studies and was very successful, 5 as shown in Scheme I. Some analogous chemistry of B-lactams is also under active study, which includes the rearrangement of B-lactams to r-lactams by ring expansion.
Previous students have shown6 that some B-lactams readily undergo thermal rearrangements to r-lactams through ring expansion, as shown in Scheme II, and we herein report the results of our further studies.
B-Lactams and their syntheses are always one of the most interesting areas in the studies of antibiotics. 7 Staudinger et al. 8 synthesized the first B-lactam, N, 3, 3, 4, 4-penta phenylazetidinone (23) by the cycloaddition of diphenylketene with benzophenone anil. After Fleming's unexpected discovery of penicillin9 (24) and the antibiotic activity of the B lactam moiety was recognized, 10 many methods11 were developed
-1- Scheme I
R=HorMe ;/
R
4 rroH MgBr2 ~··~ MgBr2 or R3 TiCI 4 R1 R2 8 fo AgN03 R2 R1 10 -2- Scheme II H a, b )lo c • ct>=o - . Me ' S02CI 11 12 13 0 a,b c • Ph~O )lo --j'-N(S0 CI Ph~ 2 14 16 15 0 )\ ,,,so2c1 a,b - N Ph IH\/ 17 19 18 0 c Et~ a, b )lo Ph~ )lo PhANJ=O 'so2c1 20 21 22 -3- Ph Ph "'-N Ph ~.I.____,___ Ph 0 Ph 23 24 Scheme III Cl02S Cl02S I I R~(R2 N- RI cw + c R3 R4 II ~<~r:: 0 0 R 26 3 25 27 2 2 CI0 S "'- - 4 R CI0 s,~N-4 R2 1Nit + 2 I I > 3 > ~2 R4 /2 3 R4 0 R3 R3 28 29 -4- for synthesizing B-lactams, which is the center ring of the penicillins and other antibiotics. Other applications of B lactams are also found, for example, in making fibers by the polymerizations of some B-lactams. 12 Our approach to B-lactams is by way of the cycloaddition of chlorosulfonylisocyanate (CSI) to alkenes, which was discovered by Graf in 1956, 13 ' 14 as shown in Scheme III. The mechanism of the [2+2] cycloaddition is not completely understood, but the general explanation15 ' 16' 17' 18 , 19 is as follows (Scheme III): First the C=C double bond of alkene (26) attacks the carbon of CSI (25) to form a n-complex18 (27) , an allyl-type stabilized carbonium ion. Then-complex 27 then rearranges to the 1,4-dipole (28) which finally forms the B-lactam (29). It is noted14c that the formation of the carbocation in 28 follows the Markovnikov rule, i.e., the carbocation in 28 should be the more stable one. For example, R3 and/or R4 could be hydrogen atoms and R1 and R2 are usually alkyl or aryl groups. The cycloaddition reaction to form 29 is stereospecific, 20 ' 21 being dependent only on the trans or cis structures in 26. Therefore when the intermediate 27 is formed the conformation of the resulting B-lactam 29 is no -5- longer changed. In the case of cyclic compounds containing C=C on the ring, according to Moriconi et al., 1 8 ' 2 ° CSI attacks the double bonds at the exo-position to produce cis g-lactams. A competitive pathway14c. 15 to the g-lactam forming reaction is the formation of the unsaturated N chlorosulfonylamides 30 or 31, as shown in Scheme IV. The ratio of lactam and unsaturated N-chlorosulfonylamide is determined by the differently substituted structures of alkenes and usually the lactam is the predominant compound. Since our main concern was the cycloaddition, the products of the side reaction in our studies were not collected. The CSI reaction provides a simple way to obtain g-lactam moieties since the N-chlorosulfonyl group can be removed reducti vely by several methods. 22 • 23 ' 24 For example, in a solution with ether as solvent, the N-chlorosulfonyl group is removed by adding 25% aqueous sodium sulphite solution. 23 Our goal was to study the synthesis of N-chlorosulfonyl r-lactams through the ring expansion of N-chlorosulfonyl g-lactams. Therefore, the reduction of the N-chlorosulfonyl groups was not performed in our studies. Some r-lactams25 ' 26 have also been found to possess antibiotic properties. This is of interest since some bacteria -6- Scheme IV RI Cl02S Cl~inCR4--- "' N+- R4 Rs o~~' " R6 Rs R6 0 26b 28b 25 R4 =H~ RI 0 0 11 g6 R1 - Cl02 SHN Cl02 SHN Rs• R3 31 Scheme V CSI a ~CHCONHS02 Cl > ·~ 32 33 34 b ~ 35 36 -7- have shown resistance to antibiotic 8-lactams. It is also possible for some r-lactams to undergo polymerizations27 for making fibers. These promise the synthesis of r-lactams to have great application in both biochemical and chemical industries. Although studies on r-lactams are not as common as those on 8-lactams, there are many different ways11a to synthesize r- lactams such as ring-closure, 25 ' 28 cycloaddition, 29 rearrangement, 30 oxidation, 31 and others. 32 The synthesis of N-chlorosulfonyl r-lactams is usually executed by way of the CSI reaction. Graf and Biener33 ' 14 c synthesized the first N-chlorosulfonyl r-lactam (36) from camphene (32) using CSI (Scheme V). Paquette et al. derived several r-lactams (with the N-chlorosulfonyl group removed after the cycloaddtions) from alkenes34 ' 35 as well as bicyclic hydrocarbons36 using CSI (Scheme VI) . Furst and co workers37 obtained the r-lactam (49) from a-pinene (47) (Scheme VII) . Sasaki and colleagues38 also synthesized the r-lactam (36) from camphene (Scheme V) I r-lactam (49) from Q! pinene, and r-lactam (53) from 8-pinene (SO) (Scheme VII) . The rearrangement from N-chlorosulfonyl 8-lactams to r lactams has been studied by several investigators. 33 ' 37 ' 38 The rearrangement of the 8-lactam 48 to r-lactam 49 is a thermal -8- Scheme VI CSI 37 38 CSI 40 39 0 CSI 41 42 A CSI ij 43 44 CSI ~ ~oH 45 46 -9- Scheme VII c10is ~o \ CSI ~ .,,J ~ ~ WO)!---- 47 48 49 CSI 50 51 NHS02 CI 52 53 -10- process in which the conversion37 • 38 occurs spontaneously at room temperature (Scheme VII; see also Scheme XVIII for detail) . In the case of rearrangement from the B-lactam (51) to the r-lactam (53) , 38 however, the a,B-unsaturated amide (52) also resulted. A similar result, 33 compound 34, is shown in Scheme V. Further studies of the rearrangements from N chlorosulfonyl B-lactams to r-lactams have evidently not been carried out. Our studies were, therefore, undertaken with the aim of making this conversion possible in a simple manner for the synthesis of r-lactams. Postulations on the mechanism of the rearrangement from an N-chlorosulfonyl B-lactam (29b) to a r-lactam (56) have not been reported in the literature; it is here suggested, as shown in Scheme VIII, to be analogous to the B- to r-lactone ring expansion. 1a, 5 Due to its strained four-membered ring, the B-lactam ring tends to cleave under appropriate conditions. 39 The polar chlorosulfonyl group here plays a very important role6 • 40 due to its strong electron-withdrawing force, increasing the polarity of the N1 -C4 bond and thus increasing the ease with which it undergoes heterolysis. Previous studies41 showed that normal B-lactams (without the N-chlorosulfonyl group) would not undergo rearrangement to r lactams, even in the presence of Lewis acid catalysts such as -11- Scheme VIII R1 / / , , Rs Rs R2 R4 R3 R3 29b 54 R5 =H ! 0 Cl0 I/ 0 R4 2s, N R3=H ~8R6 Cl02SHN R2 Rs R6 R4 R2 R3 30b 55 ! 0 0 ClO s II N ,, I I 11 R6 II R2 Cl02SHN 0 2R1 1 ' - Rs R i1 - I : R1 R = R4 2 R 3 31b 56 -12- MgBr2 , ZnC1 2 , TiC14 , BF3 or A1Cl 3 • The formation of the more stable carbocation 55 than 54 is also a very important feature in the rearrangement. 6 Therefore we needed to select alkenes which could provide more stable carbocations adjacent to the C4 atom, such as R3 C+ and ArCH/, for the ring expansion of B-lactams to occur. Since the rearrangement from an N-chlorosulfonyl B-lactam to a r-lactam is a thermal process, 37 ' 38 it would be expected that the rearrangement takes place more readily when the temperature is adequately increased. 38 Usually room temperature has been adequate for the rearrangement to occur. 6, 37, 38 From the studies1 a on the rearrangement of B-lactones to r-lactones, in many cases, the two migrating bonds (e.g., bonds N1 -C4 and C5 -R3 in Scheme VIII) must be antiperiplanar to each other for the migration to occur. Also analogous to the studies on the B- to r-lactone rearrangement, 2 and from other studies, 33 ' 37 ' 38 the possible by products might be CJ., B- or B, r-unsaturated amides (Scheme VIII) . The alkenes used in this study were either obtained commercially or synthesized from ketones via the Takai protocol, 42 • 43 as shown in Scheme IX. -13- L It is possible to use substituted diiodomethanes or dibromomethanes43 to make alkenes of more versatile structures and then B-lactams with C2 substituents. Because the main interest of this study was the ring expansion of N chlorosulfonyl B-lactams to r-lactams through rupture of the N1 -C4 bond and formation of the N1 -C5 bond (Scheme V) , we needed only alkenes 59 for the convenience of getting the 4, 4- disubstituted-N-chlorosulfonyl B-lactams (R 3 = R4 = H in Scheme III [pg 4]) . Further detailed discussion on the synthesis of N chlorosulfonyl B-lactams and their rearrangements including conclusions and experiments will be presented in the following sections. -14- Scheme IX 57 58 59 Scheme X 0 I Ph__Jl 58 Ph~l2 4 60 61 0 I Ph__JLPh 58 Ph~2LPh 62 63 0 I PhJL-__ 58 Phj2~ PhI PhI s 64 65 0 I PhJLo 58 PhJ,L(>, 6 66 67 -15- RESULTS AND DISCUSSION Synthesis of Alkenes. Several alkenes were synthesized ~o act as substrates in chlorosulfonylisocyanate (CSI) reactions (Scheme X) . Table 1 summarizes the alkene products synthesized from ketones by the Takai reaction, 42 ' 43 which is an alternative of the Wittig reaction. 44 It is worth pointing out that the amount of diiodomethane could be decreased to almost half of the recommended amount42 (from 5 eq. to 3 eq.) with no yield decrease. The amount of zinc dust was also decreased to nearly half of the recommended amount (from 9 eq. to 5 eq.). 42 All alkenes were characterized by IR, NMR, and 63, 65 and 67 also by HRMS spectroscopy. Synthesis of N-Chlorosulfonyl-S-lactams. This is a one step reaction, as shown in Scheme XI, starting with adding one equivalent of alkene 26 to 40 mL of anhydrous ethyl ether with stirring under nitrogen, followed by two equivalents of CSI, dropwise. After being stirred at room temperature for 24 hours, the mixture was worked up with water to yield the crude product (yellow oil), which was then purified through a silica -16- Table 1. Synthesis of alkenes from ketones entry ketones products yield(%) 1 60 61 85.4 2 62 63 75.8 3 64 65 62.0 4 66 67 67.3 gel column with dichloromethane as the eluent. The final products were either colorless oils or white crystals. The predominant spectral characteristics of N- chlorosulfonyl :IS-lactams are a strong carbonyl strech at 1810- 1800 cm- 1 and two sulfonyl stretches at 1410-1380 cm- 1 and 1200-1170 cm- 1 , which are consistent with literature values. 37 ' 38, 45, 46, 47 1 H and 13C NMR spectra were also in agreement37 ' 38 with the N-chlorosulfonyl :IS-lactams assigned. High- resolution GC/MS analysis48 of the samples (73, 74 and 75) also confirmed our assignments. The characterization of the :IS-lactams will be discussed in detail later. Our initial efforts involved attempts to synthesize the :IS-lactam (69) from allylbenzene (68) with CSI (Eqn. 1) since -17- Scheme XI CI02S R c102 s I 2 ';N~~ R2 N R)(R Et 2 0 l 3 II + ~1 R4 c r.t., 24 hr 0 R3 R4 II R3 0 26 29 25 Ph~ + CSI X> Eqn.1 68 69 -18- allylbenzene is commercially available and can theoretically form a relatively stable benzylic carbocation upon rearrangement of the cation from the 8-lactam ionization. But no 8-lactam resulted, even though the amount of CSI was doubled or reaction time was considerably extended (48-72 hours) . Since the CSI reactions to make 8-lactams are usually carried out at temperatures lower than O °C (often down to -78 oc) , 38 • 45 ' 46 ' 47 the reaction temperature was then decreased to -10 °C and lower, but the result was the same. It turned out 68 was not consumed completely, and up to about 40% of 68 (confirmed by TLC, IR and NMR spectra) could be recovered after work-up. This unexpected result is in conflict with the previous studies6 (third eqn. in Scheme II [pg 3]). The comparison of the two studies is not possible, since the previous researcher left with lab notebooks and spectra. Previous studies14c, 49 have shown that mono-substituted alkenes react with CSI most slowly, and tri- (and tetra-) substituted alkenes react with CSI most rapidly. Therefore the commercially available 1-methyl-1-cyclohexene (70), 3- carene (72) and a-pinene (47) were chosen, and they were expected to undergo the same type of reaction. (Scheme XII). The reaction of 70 with CSI (Eqn. 2) afforded adduct 71 -19- Scheme XII -9 CSI ruS0/ 2 CI 2 Eqn. 2 4 CY - 3~ 0 70 H 71 - IO CSI II KY Eqn. 3 72 73 0 c10is CIOi s, ~ 5 \ 4N CSI 6 > 2 > tlfo'• ,, j. Eqn.4 ~ 10 ~ 12 47 48 II 49 Scheme XIII CSI Ph___JL Eqn. 5 61 CSI Ph___JLPh Eqn. 6 63 75 -20- in 72. 6% yield. The structure of 71 was determined as 2- chlorosulfonyl-1-methyl-2-azabicyclo [4. 2. O] octan-3-one by IR ( 181 O , 13 9 6 and 116 5 cm-1 ) , 1H and 13 C NMR . But 71 was not stable and rearranged (this will be discussed later) . The addition of 72 to CSI (Eqn. 3) afforded 73 in 56.7% yield which was assigned as 4-chlorosulfonyl-3, 9, 9-trimethyl- 4-azatricyclo [6 .1. O. 03· 6 ] nonan-5-one by IR (1806, 1395 and 1178 cm-1) , 1H, 13 C NMR and high resolution GC/MS, 48 which were in agreement with the literature38 except that we obtained crystals (m.p. 61-62 °C) instead of a liquid. The reaction of 47 with CSI (Eqn. 4) afforded directly the r-lactam (49) in 54.6% yield. The structure of 49 was characterized as 3-chlorosulfonyl-1,8,8-trimethyl-3- azatricyclo[4.2.l.03'7]nonan-4-one by IR (1766, 1402 and 1172 cm-1), 1H and 13 C NMR, and was consistent with the literature values, 37 ' 38 except that the melting points in two literature sources are 75-76 °C37 and 85-87 °C, 38 but ours is 66-67 °C. TLC showed there were no starting alkenes remaining at the end of these three reactions. The studies on the reactions of 2 - (phenyl methyl) -1- propene (61) and 3-phenyl-2-(phenylmethyl)-l-propene (63) with CSI were also carried out, because they both are disubstituted alkenes and have benzylic carbon atoms (Scheme XIII) . There -21- were no r-lactams resulted as expected, 6 and only crystalline s-lactams 74 (in 26.7% yield) (Eqn. 5), and 75 (in 51.3% yield) (Eqn. 6), respectively, were obtained. The structure of 74 was determined as 1-chlorosulfonyl-4-methyl-4- (phenylmethyl) azetidin-2-one by IR (1802, 1395 and 1170 cm- 1 ), 1H, 13C NMR and high resolution GC/MS. 48 The structure of 75 was assigned as 1-chlorosulfonyl-4, 4- (diphenylmethyl) azetidin- 2-one by IR (1805, 1395 and 1170 cm- 1 ), 1 H, 13C NMR and high resolution GC/MS. 48 TLC showed a small amount of starting alkenes at the end of the two reactions. Two other alkenes were also treated with CSI: 2, 3- diphenyl-1-pentene (65) and 1-cyclobutyl-1-phenylethene (67) (Scheme XIV). However, no lactams were obtained in the CSI reactions. These results were also in conflict with the previous studies6 (second eqn. in Scheme II [pg 3]), but analogous to those of other studies on the synthesis of B lactones, in which trimethylsilylketenes were reacted with aldehydes or ketones to yield a,B-unsaturated acids (Scheme XV) . so When a conjugated aldehyde was used, there was no reaction observed (second eqn. in Scheme XV) . 51 Some starting alkenes were also observed with TLC at the end of both reactions. -22- Scheme XIV 0 )\ ,,so2c1 Ph_JL-_ CSI -:. N PhI x )lo Ph~ 65 Ph 76 0 CSI )\ ,,so20 -:. N Ph_Jlo x )lllo 67 Ph~ 77 Scheme XV 80 79 81 -23- The above studies showed that the trisubstituted alkenes such as 70, 72 and 47 can be consumed completely in the CSI reactions, while disusti tuted alkenes (two subs ti tuents bonded to the same vinyl carbon) 61 and 63 were recovered in small amount, and monosubstituted alkenes such as 68 were recovered in much greater amount (e.g., 40% for 68). Table 2 summarizes the synthesis of :fS-lactams. The yields are good except for 74, for which efforts will be needed to increase the yield. Characterization of N-Chlorosulfonyl-S-lactams by FT-NMR and GC/MS Spectroscopy. The structure assignments of compounds 71, 73, 49, 74 and 75 were based mainly on IR (for recognition of carbonyl and sulfone, as stated before), NMR evidence and high-resolution GC-MS data48 (for 73, 74 and 75). Compound 73 is here taken as example to illustrate the characterization process. Compound 73 is a white crystalline solid, m.p. 61-62 °C. Its NMR spectra (o in ppm) are shown as Figures 1 (1H), 2 (COSY) , 3 (13C), 4 (DEPT) and 5 (HETCOR) . 52 The numbers of carbons and hydrogens are determined from Figure 3 [11 lines (11 carbons) except three lines for CDC1 3 ] and Figure 4 (16 hydrogens): three quaternary carbons (o -24- Table 2. Synthesis of 8-Lactams by CSI with alkenes Entry Alkenes Products Yield(%) Note 1 70 71 72. 6a 2 72 73 56. 7b 3 47 49 54. 6b r-lactam 4 61 74 26. 7b 5 63 75 51. 3b a: Calcd after column chromatography. b: Calcd after column chromatography, with subsequent recrystallizatiion from hexane/ethanol (5:1). 164.64, Cs, C=O; 68.87, C3 ; 18.37, Cg); three CH carbons (6 55. 91, c6; 17.42 I cl or 8; 16. 83 I Ca or 1) ; two CH2 carbons ( 6 2 6 . 7 3 I C2 or 7; 1 7 . 0 3 I C7 or 2) ; three CH3 carbons ( 6 2 8 . 0 6 I 2 3 . 9 3 I 14. 96) . Cs, C3, Cg and C 6 are assigned above simply with common NMR knowledge (more or less deshielding) .s2 Figure 1 confirms H6 (6 3.07, most deshielding since C6 is a to the carbonyl) with one unit of integration. Figure 5 confirms the relation of C6 and H6 • The difference between C2 and C7 can be deduced from Figure 2 and 5. In Figure 2, because H6 couples only with the -25- II "'- ... . I .~ L'---""'-' 0 pp1.,1 4 3 2 Figure 1: 1H NMR Spectrum of S-ldctam 73 • • 11 • CJ1 .... • I :I D II Cl • e 'I N " . I ..fl ------·· +.. j 1 I ' II II --···-- • • ..l • • ¥. o~ "1J "1J 5: 8 7 6 5 4 3 2 0 PPM Figure 2: COSY Spectrum of B-Lactam 73 ALL PE"K llSTI~G t HT PPM =Kl S02CI 1 J 5 14 Q6 : / 2 44 16 83 II J 19 1? OJ ><(ti 4 J~ 11. 42 5 1 l 18 JI 6 40 23 qJ I 43 2$ 13 12 H '""o 8 43 28 06 q 41 55. q I 1 0 13 68 81 11 51 !6 61 12 53 17 I 0 13 ~2 17 52 14 8 164. 64 ALL PF'M Figure 3: 13 C NMR Spectrum of 15-lactarn 7 3 CH PEAi< dSilNG ?~Al< L!Si!NG HT ""M • HT <>PM • H !)P~ 2b 16 cJ 23 I 7. C3 2 14 or 11 17 42 30 26 73 2: C? 2~ ~5 91 2: '."'O 11 CH Figure 4: DEPT Spectrum of B-Lactam 73 ' ·~I J j _IO j tt ~s~o- en-i 6 .. 12 - ~ 0 ' H ..; . ' : ""i ' ~ ( ~ ' II I II I 0 "'O "'O l': ·~ ~1 !I ~ i I I ;J j I - I I :60 14.Q I 20 :oo 80 60 J.0 20 0 Figure 5: HETCOR Spectrum of 8-lactam 73 two protons on C7 , o 2.27 (one unit of integration) and o 1.15 2 are assigned as H7 e (equatorial) and H7 a (axial), 5 respectively. Therefore, from Figure 5, C7 absorbs at o 17. 03, and then C2 appears at o 26. 73; from the C2 -H2 relation, the o 2. 60 and o 1. 03 are assigned as H2 e (equatorial) and H2 a (axial), respectively (also from Figure 1) . Next we can assign H1 , Ha, C1 and Ca. Because H2 only couples to H1 , from Figure 2, H1 's chemical shift must be o 0.81. Similarly, Ha's chemical shift is also o 0.81 (overlapped, same in Figure 5) . By checking Figure 2 carefully, one can conclude that o (H 1 ) is a little larger than o (Ha), which leads us to assign the o 17.42 to C1 and o 16.83 to Ca, respectively, from Figure 5. The two units of integration at o 0.81 in Figure 1 confirms the assignment. Finally, the three methyl groups can be assigned in the following way: due to the similar chemical environment, the methyl groups attached to the same Cg atom should have almost the same chemical shift, which gives rise to the methyl group (C 10H3 ) attached to C3 with o 1. 68 (Figure 1) . Further considering the equatorial and axial positions on Cg, we can assign the equatorial methyl group (C 11H3 ) with o 1. 07 and the axial methyl group ( C12H3 ) with o O. 98. Consequently, from Figure 5, C10 atom (attached to C3 ) has o 23. 93, the equatorial -31- C11 has b 28.06 and the axial C12 has b 14.96. Comparison of the chemical shift values (as well as IR values) with those in the literature38 supported our assignment. GC-MS spectrum48 (Figure 6) and high-resolution MS data48 (Table 3) also confirmed our assignment. The major peaks in Figure 6 are characterized as follows: m/z 277 (M+), m/z 278 (M+l, the ion in which a proton is attached to the sulfone of the parent molecule, which is the reason why there were 17 hydrogen atoms in Table 3, since methanol was used as solvent), m/z 279 (M+2, chlorine, sulfur), m/z 178 (M S02 Cl), m/z 135 (M - CONS0 2 Cl); m/z 93 (loss of cyclopropane ring and CONS0 2 Cl) Table 3 shows the most compatible formula is C11H17ClN03 S, but, as stated above, the additional proton came from methanol (solvent) . Therefore the molecular formula of B-lactam 73 is C11H16ClN03 S. 48 Anal. (HRMS ) Calcd for C11H16 ClN03 S: 277.053943; found: 278.061600. Rearrangement of N-Chlorosulfonyl-S-lactams to r-Lactams. In previous studies, 6 the N-chlorosulfonyl-B-lactams (Scheme I I [pg 3] ) were reported to undergo a spontaneous ring -32- I F1le:CZ1152 Ident:S-Mer Def 0.25 Acq:28-APR-1995 15:27:12 +0:42 Ca1:CAL71J 70SE EI+ Magnet BpM:93 BpV:l.4V TIC:31236442 Flags:HALL File Text:HOWARD BLACK CZ-II-52 100~ 9~.l 3.6E6 95 _3.SE6 90 3.3E6 85 3.1E6 80 _I() 2.9E6 75 II 2. 7E6 70 2.6E6 65 135 .1 H 2.4E6 60 2.2E6 55 2.0E6 50 1.8E6 45 1.6E6 178.1 40 1.5E6 35 l.3E6 30 121.1 1.1E6 25_ 278 .1. 9.lES 81.1 20 107.1 7.3ES 15 162.1,, 5.SE5 10 150.1 241.1 3.6ES 222.0 5 I.BES O.OEO 320.. '3fo' . ml z Figure 6: MS Spectrum of B-Lactam 73 Table 3: High-Resolution MS Data of B-Lactam 73 Elemental Composition Date : 28-APR-1995 File:CZ1152HR Ident:l5 SMO(l,3) PKD(3,3,3,0.00%,0.0,50.00%,F,F) 70SE Cl+ Voltage BpV:ll5.5mV TIC:5791787 Flags:NORM File Text:HOWARD BLACK CZ-II-52 Heteroatom Max: 20 Ion: Both Even and Odd Limits: -0.5 0 0 0 2 0 0 '278.061600 10.0 20.0 30 50 1 4 1 1 Ma£.s mDa PPM Cale. Mass DB~ c H N 0 s Cl 278.061600 0.2 0.6 278.061768 3.5 11 17 1 3 1 -0.3 -1. 1 278.061281 8.0 1 4 14 4 1 -3.2 -11 . 5 278.058396 8.5 14 13 1 3 1 -3.7 -13. 3 278.057909 13. 0 17 10 4 9.4 33. 7 278.070972 8.0 15 15 3 1 expansion to the related r-lactams under the conditions6 of ether, room temperature and 24 hours, while the present results showed there were no such expansion rearrangements observed except for compound 49 under identical conditions. The :15-lactam 71 was unstable and spontaneously rearranged to the :IS, r-unsaturated N-chlorosulfonylamide 83 instead of the r-lactam 85 (Scheme XVI) after several days (1H NMR o 10. 72: N-H; o 5. 24: HC=C) . The reason why no r-lactam resulted is likely that the process 82 -> 84 is a 2° -> 3° shift, and the two migrating protons are not antiperiplanar. The unsaturated amide 83 is also thermodynamically more stable. 50 The unsaturated amide 83 is characterized as N chlorosulfonyl- (2-methyl) 2-cyclohexenamide by 1H and 13C NMR spectroscopy. There was also no rearrangement from the :15-lactam 73 to the r-lactam 88 observed in the CSI reaction (Scheme XVII) . The reason is similar to the case of 71, but 73 is stable. The fact that 73 did not undergo rearrangement during the CSI reaction is compatible with another report. 38 :15-Lactam 48 (Scheme XVIII) existed as intermediate53 and rearranged to r-lactam 49 afterwards. 37 ' 38 The reason why 48 underwent ring expansion to 49 should be due to the two highly -35- Scheme XVI 0 ,Vo d~sopI a > s NH L Ne S02CI ~3 7 71 83 ?f 82 0 Cl~ s, f > H 85 84 Scheme XVII 73 86 H 87 88 -36- strained rings (rings A and B are both four-membered rings) in 48, and that A tends to undergo ring cleavage followed by the rearrangement of the carbocation (89) to (90) (even though it was a 3° -> 2° shift38 ) together with another ring cleavage (ring B) . As a result the more stable r-lactam 49 was formed with two less strained rings (C) and (D) (both are five membered rings) . In fact, from the point of view of the expansion of ring B, it resembles a Wagner-Meewein rearrangement . 54 Other workers37 ' 38 and our studies6 show that when a carbonyl stretch at 1780-1760 cm- 1 in IR is observed, together with two sulfone stretches at about 1400 and 1200 cm- 1 , it is reasonable to conclude that a N-chlorosulfonyl r-lactam (such as 49) has resulted; the lower IR absorption frequency is due to the loss of the strain in a four-membered ring. :l.S-Lactams 74 and 75 also did not undergo rearrangement to r-lactams (93) during the CSI reactions, though this process was anticipated to be quite facile since both compounds can form a benzylic cation at the C5 position for the migration of the carbocation 91 to 92 (Scheme XIX) . Therefore ArCH/ is evidently not electrophilic enough for the migration to occur. The result is in conflict with the previous studies, 6 especially with the fourth equation in Scheme II. -37- Scheme XVIII 0 Cl~ S" ~ N 49 48 89 90 Scheme XIX 0 R )~ _,.S02 CI - N >< ,.. Ph:x:>==O Ph~ 'so2 c1 R 93 74: R=Me 75: R=Bn \ I 0 S02Cl S02Cl '\N "'N 8 ,.. 8 Ph R H 92 91 -3~- There were also no :IS- to r-lactam rearrangements observed when these two :IS-lactams were refluxed in ether for 24 hours. The :IS-lactams were recovered unchanged in 90.3% and 93.5% yields, respectively. Because we were able to obtain pure N-chlorosulfonyl :IS lactams (especially 74 and 75) instead of r-lactams under the conditions6 (ether, room temperature, 24 hours) of the CSI reaction, it is reasonable to conclude that these conditions are too mild for the N-chlorosulfonyl :IS-lactams to rearrange to their r-lactam analogs. With several grams of :IS-lactam 74 in hand, therefore, different conditions were tried with 74 to elicit the :IS- to r lactam conversion. (1) Effect of temperature. Compound 74 was melted at 80 °C (m.p.) under nitrogen and kept at this temperature for six hours. Its color turned to black-brown. TLC showed 74 was consumed. The IR spectrum showed that the peak at 1802 cm- 1 had moved to 1670 cm- 1 and that an absorption at 3300 cm- 1 had appeared, probably corresponding to an N-H stretch. These data indicated that an unsaturated N-chlorosulfonylamide had probably resulted. The same experiment was conducted at 70, 60 and 50 °C, with identical results. -39- I_ - (2) Effect of Solvents. The :IS-lactam 74 was dissolved in dimethylsulfoxide (DMSO) and also in dimethylformamide (DMF), but they both caused immediate decomposition to the unsaturated N-chlorosulfonylamide based on the IR spectra. And, absolute ethanol also made 74 decompose to the unsaturated N-chlorosulfonylamide in six hours at 40 °C, though it was used in recrystallizing 74 (ethanol:hexane = 1:5) but in short time. When tetrahydrofuran was employed as the solvent for 74, part of the :IS-lactam decomposed after the mixture was refluxed overnight and l-phenyl-2-methyl-1-propene (97) was obtained (in 19.5% yield), which was confirmed by IR and NMR spectroscopy. Scheme XX shows the possible pathway for 74 to decompose to 97. The :IS-lactam 74 was also recovered in 70.3% yield. (3) Effect of Catalysts (i) Magnesium bromide (MgBr2 ). This catalyst was used under the same conditions (ether, room temperature, six hours) in which the ring expansion of :IS- to r-lactones occurs readily. 1 a However, no evidence for r-lactam formation was obtained, and the unsaturated N-chlorosulfonylamide was the apparent product based on the IR spectrum of the crude product. -40- L Scheme XX 4 THF, Reflux, 24 hr Ph~ 3 74 97 t H+ e > JH2 Ph Ph ~ 96 H 95 94 Scheme XXI y-Lactam a, ~-Unsaturated Amide ~, y-U nsaturated Amide / N-Chlorosulfonyl-~-lactam / Alkene N.R. -41- (ii) Titanium tetrachloride (TiC14 ) was also tried as a catalyst. No r-lactam was obtained, and again, the unsaturated N-chlorosulfonylamide apparently resulted (same IR spectrum) . (iii) Silver trifluoromethanesulfonate (CF 3 S03Ag) . This potent source of silver(I) caused consumption of 74 within 30 minutes when it was added to a solution of 74 and acetonitrile (solvent) , and an IR spectrum showed that the unsaturated N chlorosulfonylamide had resulted. (iv) Silver tetrafluoroborate (AgBF4 ). This reagent also caused 74 to convert to the unsaturated N-chlorosulfonylamide, but much more slowly (24 hours) than silver triflate. A similar IR spectrum to that in (iii) was obtained. (v) Zinc chloride (ZnC1 2 ). Zinc (II) behaved similarly to AgBF4 , using dichloromethane as solvent. The reason why a B-lactam such as 74 failed to rearrange to r-lactam could be due to its ease of rearranging to the unsaturated N-chlorosulfonylamide (originally a by-product of the CSI reaction), and sensitivity to catalytic conditions. The possible rearrangement products of a N-chlorosulfonyl B-lactams are summarized in Scheme XXI. From the above discussions, including the successful rearrangement of B-lactam 48 to r-lactam 49, and by checking -42- the conditions for Wagner-Meerwein rearrangement, 54 we deduce a likely important condition for the rearrangement of N chlorosulfonyl :IS-lactam to N-chlorosulfonyl r-lactam, i.e., a strained ring (three-, four- or five-membered ring) at C5 position next to the :IS-lactam ring is necessary for the :IS- to r-conversion to occur. Several suggested candidate reagents are shown in Scheme XXII to test this hypothesis. The first and third equations show, in addition to the :IS- to r-lactam ring expansion, a 3- to 4-membered ring expansion, while the second and fourth equations show a 4- to 5-membered ring expansion, and a 5- to 6-membered ring expansion (also with a 7- to 6-membered ring contraction spontaneously in the fourth eqn. ) , re spec tively. It would be worthwhile to study other reactions similar to the first eqn. in Scheme II (pg 3), as shown in Scheme XXIII. In the future, it would also be educational to take advantage of the fourth and fifth reactions in Scheme I (pg 2) to realize the rearrangement from :IS- to r-lactams. Some possible reactions are proposed in Scheme XXIV. -43- Scheme XXII 98 101 104 105 CI02S \ N CSI \ 106 107 108 0 0 CI02S \ 6 CSI N 109 110 111 112 -44- Scheme XXIII .··''~o ti C(o- ___. ct)=o C(-- CN'so,c1 - N - ...... Me Me S02Cl 113 114 115 116 117 118 119 120 Me 121 122 123 124 -45- L Scheme XXIV H Br 2 CSI C10 s/[ MgBr2 > > j( y Br 125 126 129 i I 2 CI0 S![ c102s/[ > Br a~ IfJ H 128 127 CI02S/[ CSI AgN0 3 Br__)l > rH > 130 Br~ Al 132 131 -46- CONCLUSIONS 1. Several N-chlorosulfonyl :15-lactams have been synthesized in pure form (Table 2) by the cycloaddition of alkenes to chlorosulfonylisocyanate (CSI) . Some of them were synthesized for the first time such as 71, 74 and 75; 73 was obtained as pure crystals instead of liquid. 2. The mechanism of the rearrangement of N-chlorosulfonyl :15-lactams has been studied. The products of rearrangements depend mainly on the electrophilicity and stability of the carbocations after the four-membered rings of :15-lactams are cleaved. The most stable carbocations lead to the predominant products, which could be r-lactams, a,:15- or :15,r-unsaturated amides and even some alkenes (Scheme XXI) . It might be necessary for a :15-lactam to have strained carbocyclic ring(s) next to the C4 atom to undergo rearrangement to r-lactam (Scheme XXI I) . 3. The N-chlorosulfonyl :15-lactams all have higher wave numbers for the stretching bands of their carboxyl groups at 1800-1810 cm- 1 in IR spectra than the N-chlorosulfonyl r lactams at 1780-1760 cm- 1 , respectively, which provides a simple way of identifying N-chlorosulfonyl r-lactams from :IS- -47- lactams. 4. In the CSI reactions, trisubstituted alkenes are consumed completely, while the less substituted alkenes are left more at the end of the reactions. 5. Our studies show that some analogy between lactams and lactones does occur, not only in their synthesis, but also in their rearrangements. 6. Further studies should include: (1) checking more in detail on the effects of solvents, catalysts, and temperature, as well as combinations of these variables. (2) choosing alkenes with strained rings next to the more substituted vinyl carbons (Scheme XXII) ; (3) carrying out the reactions shown in Scheme XXIII to synthesize the r-lactams similar to that in the first eqn. of Scheme II (pg 3); (4) providing some functional groups, such as halogens attached to the C5 atom (B to N1 atom) or C3 atom, as shown in Scheme XXIV, to make the rearrangement of B- to r-lactams more facile and predominant. -48- EXPERIMENTAL SECTION Materials and General Methods. All reagents were purchased from Aldrich Chemical Company, Inc. except 24, which was obtained from Sigma Chemical Company, Inc. All reactions and distillations were performed under nitrogen, and glassware, including syringes, was dried in an oven at 120 °C for at least four hours before use. Tetrahydrofuran (THF) was distilled from potassium and benzophenone, diethyl ether from sodium and benzophenone, and dichloromethane from calcium hydride. Alkenes and liquid ketones were distilled before use whenever necessary. Thin layer chromatography (TLC) was performed on Analtech silica gel G (250 um) plates using specified solvents as eluents. Gravity chromatography was done on Aldrich silica gel (70-230 mesh). Solvents were removed with a rotary evaporator and under high vacuum when necessary. Infrared spectra were obtained on a Perkin-Elmer 1319 IR spectrophotometer. 1 H and 13C spectra were acquired on a GE QE-300 FT-NMR spectrometer. Mass spectra were run on Hewlett Packard 5890 Series II Gas Chromatography/5971 Series Mass Selective Detector. Melting points were measured on a MEL-TEMP II. High-resolution GC-MS spectra were obtained from -49- the Mass Spectrometry Laboratory, University of Illinois at Urbana-Champaign. General Method42 ' 43 for Synthesis of Alkenes from Ketones. A three-neck, round-bottom flask was set up with a nitrogen bubbler, magnetic stirrer, and reflux condenser. The flask was charged with tetrahydrofuran (120 mL), followed by freshly activated zinc dust (5 eq.) and lead (II) chloride43 (5% in mol of zinc) . The mixture was stirred for 20 minutes, then diiodomethane ( 3 eq.) was added dropwise. The resulting mixture was stirred at room temperature with a water bath until an exotherm was observed (and the color of the mixture turned to dark-gray from light-gray) . After the mixture had cooled down to room temperature, 1 M tetrachlorotitanium dichloromethane solution (1.2 eq. in TiC14 ) was added dropwise. After 30 minutes the ketone (1 eq.) in tetrahydrofuran (5 mL) was added dropwise and the mixture was stirred for half an hour. Ether (60 mL) was added to dilute the mixture which was then poured into 1 M hydrochloric acid (100 mL) . The ether layer was washed with brine (100 mL) and dried with magnesium sulfate. The solvents were then removed and the crude product was purified by column chromatography with hexane as the eluent to give a pure colorless oil. -50- L 2- {Phenylmethyl) -1-propene (61) from phenylacetone (60): a colorless oil was obtained in 85.4% yield (2.525g, 19.10 mmol); IR (neat) 3065, 3020, 1640, 1595, 1490, 1440, 890, 730, 690 cm-1 . 1H NMR (CDC13) 6 7. 35-7. 20 (m, SH, Ar H), 4. 80 (d, 2H, C1H), 3.36 (s, 2H, C3H), 1.72 (s, 3H, C4H); 13 C NMR (CDClJ 6 145.50 (C2 ), 139.98, 129.07, 128.44 and 128.23 (Ar carbons), 112. 07 (C1) , 44. 83 (C4), 22 .19 (CJ ; MS m/z 132 (M+) , m/z 117 (M - CH3), m/z 91 [M - C (CH3) =CH2 ]; TLC (hexane) Rf 0. 37. Lit.ss: IR (neat) 3070, 3030, 1645, 1590, 1500, 1450, 890, 7 4 0 I 6 9 5 i 1H NMR ( CD cl 3 ) 6 7 . 2 0 I 4 . 7 3 I 3 . 3 3 I 1 . 7 2 . 3-Phenyl-2-{phenylmethyl)-1-propene (63) from 1,3- diphenylacetone (62): a colorless oil was obtained in 75.8% yield (2.635g, 12.65 mmol); IR (neat) 3080, 3020, 1635, 1596, 14 9 O , 14 4 5 , 1O7 O , 1O3 5 , 8 9 O , 7 4 O , 6 9 O cm-1 . 1H NMR (CDC 1 3 ) 6 7 . 5 O - 7 . 2 5 ( m , 1 OH , Ar H) , 4 . 9 5 ( s , 2 H , C 1H) , 3 . 4 O ( s , 4 H , 13 C3,4H); C NMR (CDClJ 6 148. 54 (C2 ), 139. 70, 129. 33, 128. 54 and 126. 36 (Ar carbons), 113. 62 (C1), 42. 41 (C3,4) ; TLC (hexane) Rf 0.21. 48 Anal. (HRMS ) Calcd for C16H16 : 208.125203; found: 208.125164. 2,3-Diphenyl-1-pentene (65) from 1,2-diphenyl-1-butanone -51- (64): a colorless oil was obtained in 62.0% yield (2.403g, 10.81 mmol); IR (neat) 3080, 3020, 1620, 1590, 1490, 1445, 1020, 900, 770, 695 cm-1; 1H NMR (CDC13) O 7.32-7.18 (m, lOH, Ar H), 5.42 (s, lH, C1H), 5.22 (s, lH, C1H), 3.70 (t, lH, C3H) ,1.99-1.84 (m, 2H, C4H), 0.94 (t, 3H, C5 H); 13C NMR (CDC13) 0 15 2 . 0 7 ( C2) I 14 3 . 6 7 I 14 3 . 0 0 I 12 8 . 51 , 12 8 . 4 4 I 12 8 . 2 8 I 12 7 . 3 2 I 127. 04 and 126 .40 (Ar carbons), 113. 32 (C1), 52. 70 (C3), 28. 35 (C4), 12.97 (C4); TLC (hexane) Rf 0.20. 48 Anal. (HRMS ) Calcd for C17H18 : 222 .140851; found: 222.140765. l-Cyclobutyl-1-phenylethene (67) from cyclobutyl phenyl ketone ( 6 6) : a colorless oil was obtained in 6 7. 3 % yield (2.526g, 15.96 mmol); IR (neat) 3080, 3020, 1620, 1595, 1490, 14 4 O , 8 9 O , 7 7 O , 7 0 0 cm-1 ; 1H NMR (CDC 1 3 ) o7 . 5 0 - 7 . 2 5 ( m, 5 H, Ar H), 5.25 (d, 2H, C1H), 3.55 (5, lH, C3H), 2.30 and 2.10 (m, 4H, C4, 6 H), 2. 20-1. 80 (m, 2H, C5 H); 13 C NMR (CDC13) o 152. 08 (C2), 140.80, 128.26, 127.31 and 126.17 (6C, Ar C), 109.83 (C1), 39. 65 (C3), 28. 51 (C4, 6 ), 17. 89 (C5 ) ; TLC (hexane) Rf O. 57. Anal. (HRMS 48 ) Calcd for C12H14 : 158 .109552; found: 158.109562. General Method6 ' 37 ' 38 for Synthesis of N-Chlorosulfonyl :B- -52- or r-Lactams from Alkenes and Chlorosulfonylisocyanate (CSI) : Freshly distilled diethyl ether (30-50 mL) was added to a three-neck, round-bottom flask with a nitrogen bubbler, magnetic stirrer, and septa followed by an alkene (1 eq.). Chlorosulfonylisocyanate (2 eq.) was then added dropwise at room temperature. The mixture was stirred for 24 hours at room temperature and then 30 mL of ether was added to dilute the mixture which was poured onto 40-60 g of cracked ice. The organic phase was washed twice with water (30 mL). The solvent was then removed and the resulting crude product was purified through column chromatography with dichloromethane to yield colorless oil, which was then put under high vacuum to induce crystallization. Pure white crystals were obtained after recrystallization with a 1: 5 solution of absolute ethanol and hexane. 2-Chlorosulfonyl-1-methyl-2-azacyclo[4.2.0]nonan-3-one (71) from 1-methyl-1-cyclohexene (70) : a colorless oil was obtained in 72.6% yield (1.794 g, 7.547 mmol); IR (neat) 1800 1 1 (C=O) , 1396 and 1165 (802 ) cm- ; H NMR (CDC1 3 ) o 3 .16 (d of d, lH, C4 H), 2. 24 (m, lH, C5He), 1. 90 (m, lH, C8 He), 1. 77 (m, 2H, 13 CsHa, and CaHJ I 1.70 (s, 3H, CgH) I 1.70-1.50 (m, 4H, c6,7H); C NMR (CDC1 3 ) o 165.29 (C3 , carbonyl C), 69.80 (C1 ), 55.76 (C4 ), -53- L 29.70 (C5), 24.87 (C9 ), 19.30 (Ca), 17.Sl (C617 ), 17.0S (C716 ); TLC (CH2Cl2) Rf 0. S9. Anal. (HRMS 4 a) Calcd for CaH12 ClN03S: 237.022621; found: 2 3 8 . 0 3 0176 . (cf . pg 3 2 ) N-Chlorosulfonyl-2-methyl-2-cyclohexenecarboxamide (83) : viscous oil; 1H NMR (CDC13) o 10.24 (m, N-H), S.72 (t, lH, C3 H) , 3. 06 (t, lH, C1H) , 2. OS (m, 2H, C4 H) , 1. 9S (m, 2H, C6H) , 1.70 (s, 3H, C7H), 1.S8 (m, 2H, C5H); 13 C NMR (CDCl3) 0 173.00 (lC, carbonyl C), 128. 09 (C3), 47. S9 (C1), 26. 72 (C6), 24. 73 ( C4 ) , 2 2 . 3 S ( C7) , 19 . 19 ( C5) . 4-Chlorosulfonyl-3,9,9-trimethyl-4- azattricyclo[6.1.0.03'6]nonan-5-one (73) from 3-carene (72): a white crystalline solid was obtained in S6.7% yield (2.312 g, 8.323 mmol); m.p. 61-62 °C; IR (CH2Cl2) 1806 (C=O), 139S and 1178 (802) cm-1; NMR (CDC13) : 1H o 3. 07 (d of d, lH, C6H), 2. 60 (d of d, lH, C2He) I 2.27 (m, lH, C7He) I 1.68 (s, 3H, C10H) I 1.lS (m, lH, C7Ha), 1.03 (m, lH, C2Ha), 1.07 (s, 3H, C11H), 0.98 (s, 3H, C12H), 0.81 (m, 2H, C1,aH); 13C o 164.64 (C5), 68.87 (C3), SS. 91 (C6), 28. 06 (C11 ), 26. 73 (C2), 23. 93 (C10 ) , 18. 37 (C9 ), 17.42 (C1), 17.03 (C7), 16.83 (Ca), 14.96 (C12 ); m/z 277 (M+), m/z 278 (M+l, sulfone, M+H), m/z 279 (M+2, chlorine, sulfur), -54- m/z 178 (M - S02Cl), m/z 135 (M - CONS02Cl); m/z 93 (loss of cyclopropane ring and CONS02Cl) ; TLC ( CH2ClJ Rf 0. 64. Li t 38 : IR (neat) 1807, 1403, 1165 cm-1; NMR (CDC13) 6 3.07 (d of d, lH, C6H), 2.75-1.85 (broad m, 2H, C2He and C7 He), 1.71 (s, 3H, c10H), 1.00 and 1.09 (s, each 3H, CllH and C12H), 1.35-0.60 (m, 4H, other ring protons) . 48 Anal. (HRMS ) Calcd for CllH16ClN03S: 277.053943; found: 278.061600. 3 - Ch 1orosu1fony1 - 1, 8, 8 - trim et hy 1 - 3 - azatricyclo[4.2.l.03 ' 7 ]nonan-4-one (49) from a-pinene (47): a white crystalline solid was obtained in 54.6% yield (1.113 g, 4. 007 mmol); mp 66-67 °C; IR (CH2Cl2) 1766 (C=O), 1402 and 1172 (802) cm-1; 1H NMR (CDC1 3 ) 6 4 .19 (d, lH, C3 H), 2. 45 (d, lH, C6H), 2.38-2.20 (m, 2H, c2,9He) I 2.00 (t, lH, C1H) I 1.75 (d, lH, C2Ha) I 1. 62 (d, lH, C9HJ, 1.13 (s, 3H, c 10H) , o. 94 (d, 6H, cll, 12H) ; 13 C NMR (CDCl3) 0 174. 86 (C5) I 68. 88 (CJ I 56. 08 (C9) I 49. 44 (C6) I 47. 91 (C7) I 46. 20 (Cl) I 34. 40 (C2) I 33. 20 (Cg) I 19. 52 (Cll) I 18.85 (C10 ), 11.52 (C12 ); TLC (CH2Cl2) Rf 0.49. Lit38 : IR (KBr) 1768, 1406, 1167 cm-1; NMR (CDC1 3 ) o 4. 20 (d, lH, C3 H) , 2. 53- 1. 44 (m, 6H, methine and methylene protons), 1.15 (s, 3H, c10H) , o. 97 ( s, 6H, ell, 12H) . -55- l-Chlorosulfonyl-4-methyl-4-(phenylmethyl)azetidin-2-one (74) from 2-(phenylmethyl)propene (61): a white crystalline solid was obtained in 26.7% yield (2.41S g, 8.822 mmol); mp 1 1 79-80 °C; IR (CH2Cl2) 1802 (C=O) I 1398 and ll 7S (S02) cm- i H NMR (CDC13) 0 7. 36-7. 20 (m, SH, Ar H), 3. 36 (d, lH, C3H6 ), 3. 23 (t, 2H, C5H), 2.83 (d, lH, C3HJ, 1.84 (s, 3H, C6H); 13 C NMR (CDC13) o 161.04 (C2), 134.40, 130.19, 128.99, and 127.81 (6C, 48 Ar C), 69. 43 (C4 ), 47. 93 (C5), 43. 71 (C3 ), 23. 37 (C6); MS m/z 273 (M+), m/z 274 (M + 1, N and 802), m/z 27S (M + 2, Cl and S), m/z 182 (M - PhCHJ , m/z 132 (M - 0=C=N-S02Cl), m/z 118 (PhCH2C'CH3), m/z 91 (PhCH/); TLC (CH2Cl2) Rf O. 60. 48 Anal. (HRMS ) Calcd for C11H12 ClN03S: 273. 022642; found: 273.02280S. 1-Phenyl-2-methyl-1-propene (97): colorless oil; IR (neat) 3080, 3020, 16SO, 1S9S, 1490, 1440, 890, 770, 700 cm- 1 ; 1 H NMR (CDC13) o 7.40-7.20 (m, SH, Ar H), 6.30 (s, lH, C1 H), 1. 90 (d, 6H, two CHJ; 13C NMR (CDClJ o 139. oo (C2), 13S. 80, 128.77, 128.07 and 12S.81 (6C, Ar C), 12S.14 (C1 ), 26.9S (C3), 19. 4S (C4 ) ; TLC (CH2Cl2) Rf 0. 82. l-Chlorosulfonyl-4,4-(diphenylmethyl)azetidin-2-one (75) from 3-phenyl-2-(phenylmethyl)propene (63): a white -56- crystalline solid was obtained in 51.3% yield (1.829 g, 5.228 mmol); mp 99-100 C; IR (CH2 Cl2 ) 1805 (C=O), 1395 and 1170 (802 ) cm-1; 1H NMR (CDCl3) 0 7.42-7.20 (m, 10 H, Ar H)' 3.53 (d, 2H, C5 ; 6H), 3.33 (d, 2H, C6 ; 5H), 3.08 (s, 2H, C3H); 13 CNMR (CDC13) O 160.85 (1 C, carbonyl C), 134.13, 130.50, 129.07 and 127.92 48 (12C, Ar C), 72. 99 (C4 ), 44. 28 (C3), 41. 50 (C5 , 6 ) ; MS m/z 349 (M+), m/z 350 (M + 1, N and 802 ), m/z 351 (M + 2, Cl and S), m/z 251 (M - S02 Cl + H) , m/z 233 (M - S02 Cl - OH) , m/z 208 (M - O=C=N-S02 Cl), m/z 118 (PhCH2 C"=CH2 ), m/z 91 (PhCH2 +); TLC ( CH2 C1 2 ) Rf 0 . 6 6 . 48 Anal. (HRMS ) Calcd for C17H16ClN03S: 349.053943; found: 349.054043. -57- REFERENCES 1. (a) Black, T. H.; DuBay, W. J.; Tully, P. S. J. Org. Chem. 1988, 53, 5922. (b) Black, T. H.; Hall, J. A.; Sheu, R. G. J. Org. Chem. 1988, 53, 2371. 2. (a) Black, T. H.; Eisenbeis, S. A.; McDermott, T. S.; Maluleka, S. L. Tetrahedron. 1990, 46, 2307. (b) Black, T. H.; Maluleka, S. L. Tetrahedron Lett. 1989, 30, 531. 3. Black, T. H.; McDermott, T.S. J. Chem. Soc., Chem. Commun. 1991, 184. 4. Black, T. H.; McDermott, T. S.; Brown, G. A. Tetrahedron Lett. 1991, 32, 5601. 5. Black, T. H. in "Trends in Heterocyclic Chemistry," Trivandrum, India, 1993, 3, 275. 6. Black, T. H.; Olson, J. T.; Abt, D. C. Syn. Commun. 1992, 22 (18) I 2729. 7. (a) Morin, R. B. "Chemistry and Biology of B-Lactam Antibiotics," Gorman, M. Ed., Academic Press, New York, 1982, Vol. 1-3. (b) Greenwood, D. "Antibiotics of the Beta-Lactam Group," Gruneberg, R. N., Ed., John Wiley & Sons, New York, 1982. 8. Staudinger, H. Liebigs Ann. Chem. 1907, 51, 356. 9. Fleming, A. British Journal of Experimental Pathology 1929, 10, 226. 10. Clarke, H. T.; Johnson, J. R.; Robinson, R. "The Chemistry of Penicillins," Princeton University Press, 1949. 11. For a review of the synthesis of B-lactams, see (a) Ogliaruso, M. A.; Wolfe, J. F. "Synthesis of Lactones and Lactams," John Wiley & Sons, New York, 1993. (b) Georg, G. L.; Ravikumar, V. T. "The Organic Chemistry of B Lactams," Georg, G. L. Ed., Verlag Chemie, New York, 1993. (c) Isaacs, N. S. Chem. Soc. Rev. 1976, 5, 181. (d) Mukerjee, A.K.; Srivastava, R. C. Synthesis, 1972, 327. (e) Manhas, M. S.; Bose, A. K. "Beta-Lactams: Natural and Synthetic," John Wiley & Sons, New York, 1971, Part 1. 12. Graf, R.; Lohaus, G.; Borner, K.; Schmidt, E.; Bestian, H. Angew. Chem., Internat. Ed. Engl. 1962, 1 (9), 481. 13. Graf, R. Ber. 1956, 89, 1071. 14. For a review of the synthesis of B-lactams from the cycloaddition of chlorosulfonyl isocyanate (CSI) to alkenes, see (a) Szabo, W. A. Aldrichimica Acta. 1977, 10 (2), 23. (b) Rasmussen, J. K.; Hassner, A. Chem. Rev. 1976, 76, 389. (c) Graf, R. Angew. Chem., Internat. Ed. Engl. 1968, 7, 172; Graf, R. Angew. Chem. 1968, 80, 179. 15. Rasmussen, J. K.; Hassner, A. Chem. Rev. 1976, 76 (3), 389. 16. Bestian, H. "Cycloadditions with Sulfonyl-isocyanates," Pure Appl. Chem. 1971, 27, 611. 11. Moriconi, E. J. "Mechanisms of Sulfur Compounds," Intra Science Research Foundation, Santa Monica, Calif., 1968, Vol. 3, 131. 18. Moriconi, E. J.; Crawford, W. C. J. Org. Chem. 1968, 33 (1) I 310. 19. Graf, R. Justus Liebigs Ann. Chem. 1963, 661, 111. 20. Moriconi, E. J.; Kelly, J. F. Tetrahedron Lett. 1968, 12, 1435. 21. Brady, W. T.; Gu, Y. J. Org. Chem. 1989, 54, 2838. 22. Dust, T.; O'Sullivan, M. J. J. Org. Chem. 1970, 35, 2043. 23. Hoechst, F. A.G., Franch Patent, 1970, 2016990; Chem. Abstr. 1971, 75, 63164a. 24. Graf, R. Org. Synth. 1973, Coll. Vol. V, 673. 25. Baldwin, J.E.; Lowe, C.; Schonfield, C. J.; Lee, E. Tetrahedron Lett. 1986, 27, 3461. 26. U. S. Pat., 1984, 4,428,960; Chem. Abstr. 1984, (23), 191655. 27. (a) Bonetskaya, A. K. Polyamidy 1975. Sb. Prednasek, 97. Chem. Abstr. 1976, 84, 31512g. (b) General Anilin & Film Corp., U.S.-Pat. 1953, 2809958. (c) Arnold, Hoffmann & Co., U.S.-Pat. 1951, 2638463. 28. (a) Baldwin, J. E.; Adlington, R. M.; Jones, R. H.; Schofield, C. J.; Zarocostas, C.; Greegrass, C. W. Tetrahedron 1986, 42, 4879. (b) Steliou, K.; Poupart, M. A. J. Amer. Chem. Soc. 1983, 105, 7130. 29. (a) Mkhairi, A.; Hamelin, J. Tetrahedron Lett. 1986, 27, 4435. (b) Brambilla, R.; Friary, R.; Ganguly, A.; Puar, M. S.; Sunday, B. R.; Wright, J. J.; Onan, K. D.; McPhail, R. T. Tetrahedron 1981, 37, 3365. 30. (a) Wassermen, H. H.; Han, W. T.; Schaus, J.M.; Faller, J. W. Tetrahedron Lett. 1984, 25, 3111. (b) Alcaide, B.; Dominguez, G.; Martin-Domenech, A.; Plumet, J.; Monge, A.; Perez-Garcia, V. Heterocycles 1987, 26, 1461. 31. (a) Murata, S.; Miura, M.; Nomura, M. J. Chem. Soc. Perkin Trans. 1 1987, 1259. (b) Pavlik, J. W.; Tantayanon, S. J. Amer. Chem. Soc. 1981, 103, 6755. 32. (a) Boyd, D. B.; Elzey, T. K.; Hatfield, L. D.; Kinnick, M. D.; Morin, Jr., J.M. Tetrahedron Lett. 1986, 27, 3453. (b) Mori, M.; Washioka, Y.; Urayama, T.; Yoshiura, K.; Chiba, K.; Ban, Y. J. Org. Chem. 1983, 48, 4058. 33. Graf, R.; Biener, H. Angew. Chem. 1963, 75, 857. Graf, R.; Biener, H. Angew. Chem., Internat. Ed. Engl. 1963, 2 (9), 546. 34. (a) Paquette, L. A. Tetrahedron Lett. 1968, 17, 2133. (b) Paquette, L.A.; Krow, G. R. J. Amer. Chem. Soc. 1969, 91, 6107. 35. Paquette, L.A.; Kirschner, S.; Malpass, J. R. J. Amer. Chem. Soc. 1969, 91, 3970. 36. Paquette, L. A.; Allen, Jr., G. R.; Broadhurst, M. J. J. A. Chem. Soc. 1971, 93, 4503. 37. Furst, G. T.; Wachsman, J.P.; Pieroni, J.; White, J. G.; Moriconi, E. J. Tetrahedron 1973, 29, 1675. 38. Sasaki, T.; Eguchi, S.; Yamada, H. J. Org. Chem. 1973, 38 (4) f 679. 39. Barbaro, G.; Battaglia, A.; Giorgianni, P. J. Org. Chem. 1995, 60, 1020. 40. Moriconi, E. J.; Meyer, W. C. J. Org. Chem. 1971, 36 (19), 2841. 41. Black, T. H.; Olson, J. T., unpublished result. 42. Hibino, J.; Okazoe, T.; Takai, K.; Nozaki, H. Tetrahedron Lett. 19 8 5, 2 6 ( 4 5) , 5 5 7 9 . 43. Takai, K. ; Kakiuchi, T. ; Kataoka, Y. ; Utimoto, K. J. Org. Chem. 1994, 59, 2668. 44. (a) Maccker, A. Org. React. 1965, 14, 270. (b) Johnson, A. W. "Ylid Chemistry," Academic Press, New York, 1966. 45. Sassaki, T.; Eguchi, S.; Hirako, Y. Tetrahedron 1976, 32, 437. 46. Moriconi, E. J.; Meyer, W. C. J. Org. Chem. 1971, 36, 2841. 47. Durst, T.; O'Sullivan, M. J. J. Org. Chem. 1970, 35 (6), 2043. 48. The Mass Spectrometry Laboratory, University of Illinois at Urbana-Champaign. 49. Graf, R. Liebigs Ann. Chem. 1963, 661, 111. 50. (a) Huang, J. Masters Thesis, 1992. (b) Zhang, Y. Masters Thesis, 1994. 51. Zhang, Y.; personal communication. 52. (a) Derome, A. E. "Modern NMR Techniques for Chemistry Research," Pergamon Press, New York, 1990. (b) Silverstein, R. M.; Bassler, G. C.; Morrill, T. c. "Spectrometric Identification of Organic Compounds," John Wiley & Sons, 1991. 53. At lower temperature the :15-lactam 48 can be obtained. See ref. 3 7, 38. 54. Gutsche, C. D.; Redmore, D. "Carbocyclic Ring Expansion Reactions," Academic Press, New York, 1968. 55. (a) "The Aldrich Library of Infrared Spectra," 2nd Ed. Aldrich Chemical Company, Inc., USA, 1975. (b) "The Aldrich Library of NMR Spectra, " Aldrich Chemical Company, Inc. , USA, 1974. .,_ ..J I~ 'VI I..,. .,I-- - .,j---- I - i- I__, ..... i\ol'L ~ _,, ._ -..- \Wi -- ..--- - . 1'10. PR 199-1042 '.l.5 3 MICROMETER: Figure 7: IR 73 '} 10 l'L 1-i 16 w ll(~() I '_I I - · j :. . I ! 'I I: ! I ,' I, I !....,., ' I I' !- _-- I ' I I- -: I:jj I I : I I I GO•· .-i --J ·r I ' 'ii I I I I ; : ! I I I '' I I- . ' - t' 'i- i '! i - 1- 1:1.. ·' - I' - ' - ! : I * 60 11 ! g I I , I - 1 :-- -' H - __,_J . __. _. :,; I ; (..:; I i 7 ,, "'11" ,',l'i'"' ' ' : II -I -- _:; ' ' I'I ' I I: : I ' i ': : I ' I I ,.., I I Ill I j I I '•' ,l ! . ' I. I : '''. ' • I I I 1 ' I 1 1 ' I I ' - ' I I I ~ - '0 1 •• ,j l) ' ' ' ' ' · I I - ' ! - l (} ' I - ,q 'I + 11 It 1' I ' I ! • l I ' I•' 11'1 I ' I I' I ,. I I I ' ' I :. I 'I I I ,1 ' ' I I I : I I - I ! I' I '1'1 I : I ,1111 ! '::! ' I ' ( ! + : I ' I ' " I l II- I.' ' ' I I' I ' ' I I I I I 1' ;II I:, 1:1'1' 11 l ' ' : II ' i : - -1'1 _ ' . 1' i·:: • I I I 'l1 t ' I l I I -_,._I I ' I ' ' I I' 11,I I ' ' ' ' I ' ' : ' 11- ·I I I ' - i ,... . ' -1 ,- t·_-·· . 'I .11' .•i"I l·I" Ill - ' I I ' I '' ' I ' ' 1·· ,-,··---_ I. - I I I l --- -·--· 11 1 11 I 11 1'11 1 '"II I I 1 I I Ij 'II , . I '1 ' ' I ! I . ' I ' ;jl' ···, 11 I- ' I ! : L \J -- I ' I . I I - ' -' 1 · I ' ' - I ' ., I " /II -- : ; I :! I .' ' ! 111: I 111''1 ', I ! I +:,: ' ' 11 '. I . J ' I ' I I ..·'. ': • l 1 1 1 1 . _I' I -' 11 ,, "1 I ·'1,1 111· • " '1il1'ij ' ' ' I" -_- I" 1' I 1-·-' '_' I ' -_I· II ,_ .. '·-'. I 'j I 'I 1 "I, I'1 ''I 11"Ii 111' ' I I 1''' ' I:,' .I lfl'., ' I I i I ' " ' -·'' ' I I ' :; ,, :: ' I: ,:, '1 I ·:·I ''I Ii I 11 11: 11,./ ' ',i ' ' ' I ' ·I::. '' ,: I : !'' I I 1 ~ • " I . I l I j I ! I I i ' I I I I 11 I I ' I I I I ' . j ' : ~ ; I ' . ' I I I . : : -··-i-,··1 · ·\· · · 111 • 111-ll !1 1jl J1 /Ji I 1- · "1 '·r ·j -- 1 -· , .. I ,,.1. 1: ,j -· "-- ,J1, --· ---- 1 I ' I I '11 I j ' i l · I I ' I I I I""' ' I I I I I I.:. ' ' I '1 ' ' 1111 1'11 !•1 l,11 I ·11 : ' ' ' I,- i I I I' I 1 : '' ' ' 'I : I I I l '~ I 11:: l·I ' ' 1;' ' '' 1'l ' I_' ' : :1 ' !-.1 . I 11 jl 1:1, l'i j '111111 :'I ' 'i' I i !I ':I,, ! I"! ; ! I :!·;"I· I· ' -_I 'I I I I '' 'II' 11'' 1111111 ,,, I II •I I 'I - ' I.,: '• I I 'I ' : i ' ' - - ' fl I I II I'II I I I ' I' ' 'I• ' ' I i' ' ' 0 I1IIiI111 I ,_.r I I UJ lilllililLLU.Llll.lllLU IJJ2JJJ 11 .LLIL1 1 iil cul i_;I J J 1 :/. . i I -I 1~_. t J J I ,. _, I - J ' I I_ J ' I J. 4000 J500 3000 (0-1'. ') 7500 2' Hit 1 H:oo 1600 1 no 1 '• i!l 1000 (CM') oon 60n ~ 0 ' s i :::1 ! >-i I Ii +.Jo ' l Q) ~ i, .j JI:L L~ !,- j I : l ~ I :1 !- '[_ -:0 .L lj IL I.... L All CH Cl-~2 c~~J ------· ··------· -----··--·--·-· ----·------ ?EAK LISTING nAK us:;:1;c PE~.K L !STING PEAK L rsrrtrG # HT PPM # HT PP"4 # HT 1'P~ HT PPM I 5'. 17.07 .. '. 7. 07 I 28 !7.06 2' 4 •I 2 17. 07 2 I 17.27 '7.53 z 28 1 7. s:: 2 -s '7. so 3 53 i1. 52 3 3 i9. 31 3 35 '9. 30 4 3 3 -5 '9.29 4 2 '9. IS 24.88 4 7 24.88 4 38 24.87 s 55 '9. 30 5 4 29. 72 5 35 29. 7' -J. I 6 35 5 29. 69 6 2 23.92 ! SS. 77 6 -2 SS. 78 7 2 24. 74 ·j =' 8 49 24. 87 so a/ 9 so 29. 72 10 2 34.39 11 I 48. 77 12 52 5S. 77 CH3 13 13 69. 79 dt2' 14 6 76. 83 ~ :s 8 77.25 - 0 18 6 11. ea H 17 a !85.25 CY 2 f, f I : ~ I u i i Ol ~00 150 100 50 0 PPf\1 Figure 9: 13C & DEPT NMR Spectrum of B-Lactarn 71 I - Table 6: High-Resolution MS Data of 8-Lactam 71 Elemental Composition Date : 2-AUG-1995 Heteroatom Max: 20 Ion: Both Even and Odd Limits: -0.5 0 0 0 0 0 0 238.030176 10.0 20.0 50 100 3 6 2 2 Mase mDa PPM Cale. Mase DBE c H N 0 s Cl 238.030176 -0.2 -0.8 238.029981 7.0 11 10 4 1 0.3 1. 2 238.030468 2.5 8 13 1 3 1 1 -0.4 -1. 7 238.029776 12.0 14 7 2 1 -0.9 -3.7 238. 029289 16.5 17 4 1 1 1. 4 6.0 238.031606 7.0 13 12 2 -1. 5 -6.5 238.028638 7.5 9 8 3 3 1 1. 8 7.7 238.032010 2.5 6 12 3 3 2 2.5 10.4 238.032661 11. 5 14 8 1 1 1 -2.6 -10.9 238.027583 3.0 8 12 2 2 2 3.0 12.5 238.033148 7.0 11 11 2 1 1 -3.1 -12.9 238.027096 7.5 11 9 1 3 1 3.2 13.3 238.033353 2.0 8 14 4 2 -3.6 -15.0 238.026609 12.0 14 6 4 -4.2 -17.7 238.025958 3.0 6 10 2 6 1 4.8 20.2 238.034978 2.0 10 16 1 2 -4.9 -20.5 238.025287 2.0 9 15 1 2 1 -4.9 -20.6 238.025266 12.5 12 4 3 3 5.0 20.9 238.035162 7.5 10 8 1 6 5.5 23.0 238.035649 3.0 7 11 2 5 1 -5.8 -24.2 238.024416 3.0 8 11 6 1 5.9 24.6 238.036033 6.5 11 12 1 1 2 -6.2 -26.2 238.023944 2.5 7 13 3 2 1 6.3 26.7 238.036520 2.0 8 15 2 2 1 -6.7 -28.2 238.023457 7.0 10 10 2 1 2 -7.1 -29.8 238.023073 3.5 6 9 3 5 1 -7.6 -31. 9 238.022586 8.0 9 6 2 6 7.7 32.2 238.037842 12.0 13 6 2 3 -7.8 -32.7 238.022402 2.5 9 14 1 1 2 8.2 34. 3 238.038329 7.5 10 9 3 2 1 -8.3 -34.7 238. 021915 7.0 12 11 1 1 1 8.4 35.1 238.038534 2.5 7 12 1 6 1 -9.4 -39.5 238.020777 2.5 7 12 1 4 2 9.5 39.9 238.039672 7.0 12 11 3 1 -9.6 -40.3 238.020572 7.5 10 9 3 1 1 10.0 41. 9 238.040159 2.5 9 14 1 2 2 I . ,.. I : .. I. \ '·I ... , ... \ l . I \ " I I.'/ i I/' I ; i ··;--i I I I 1 1 · , , I. I .. ;· . '" " ! ::;! . ·,'.:y \" r :'.: ..:· ·::~ ·.·· ··.r \ : I. ' . I I' ' .. I . ! I '. I I ' I: . I. . .. ' ,. I: , .. , I : · ; ... j :.: 1.;:! ' .. 1: I! . I. I 1 . . ,! •:,; " : I' : '1 :. " . I j I l I J. I . • I i . I .j 00 I· ... ,, .... ·--· 1 • .,.,_, •• .. .!. .. p·l. ····;·-··I ... ·! ...... I. I l'H\ • .· ... - J .. J1;;i1 .:.~ '.:_:_; ::.1~ ~:.:: ::::JI, ;no: i:· ii :: ..,._ I. I : • : I . I : . : . I I" .:' I . : : • ' I ' ~ f . I I I ~ I ! I: . l j I : ' ' : .. . t 1 1 ::.·1. ~· i,: 1 I;:;!' ~ :!:11" ' . ·: ·I Figure 10 IR Spectrum of B-Lactam 71 j.:i: ::'· ::: i:. :::: !;: : · .:. · : 1· ' i • • .L. • i ... f I I. . I !! 1 I •• ~ • 1 t J... ! ••• I! ... 1 .. 1 1 .•• ' 11 \ I 11 t I '.,\ 1111 I •• l' .,, I • ;l;:. :.:. ;iJ; q:: :1:: iil'. :.i;·F--· :.:.. .:. . ! ... ) " 1' " I ' ·I ' I • ' . " I I. ' ! I I . : : I f " ' ' ! . I . '- I : . : : I 11 ! : : . i ! i I i I . "'; I. '' ' I •11 ·'•' ifl· " • . . ' . I:.. • . I. 1· . I . ·1l• .. 1 t 1 11" .. , 1, 1. ,. , I ..I 1:, ·I· i 1::"1:!: !!iJl;i: ::;· :::! i.1'. '.'i; :j i:i! 1:: .:::1·:: . '': .. ,.,.,_1J ... .l. ., .... '"I 1.. l.J., ·1·1 :... ··-tr;. J._ ...... 1 ... 1. I . I. ,. I I k i I •• . ~ ·:,I" ·:-. :1~l;:.I ;·!: '.;": :·· i .. I :;1il;': I':.: 'I 1111 .. , iii 1:. ::: I ·1 " . :1: ::· .• II ; i : I I . ·: ... , ... ,:'''.1;::: F"' . : ... :, . . ,, "·I '" 1··1111· I'·; I. I ' . ·;.ti .I I I ·1 . I : .::(::.:::· II .. :. ·i·:' , 1 · ... t;: ,,: tJ• ... ·:· 1· ...... ! : . I 1 1 r:.11:, ·:;": ····· ·1 1 ' I ! ' : Ii!: !'.t. :ll! :·· ' ! I ; ,,, • ·• I ,..__,.·...... ,,. I ., ··:1· ·:·;;". I 1'·., I .. ·. I I . ! . ', ... ' j·· ' ,. ·, .d .. .•:·1;.".:!'I-_ ' I I 1 I I:~ ' 'J 1 j' , .'' .. : '.:,:;· I, , ': i 'I I :. / 60 1... -· ·r --·!--·· :...: ...... ··+- .J ...... ' ... . •. 1 1.. I . . _· r I 1 : . · 1 :: . r • . ~ ; ; ~ >: · : . 1 . ; 1 ' • ol 1, ' II . I. I ... (.p-, .. : : ... i .l .... ~ .. 1 ..... (.(l· ·,--- , .. I I '!· .; ;· i.. \ .. , :j :;:i::::rl!: :·:I:.: .. : I '::;;:ii 1: !... 1· .. : .. :.!:": :<1:' I· ::(.I! . '. ....· I •. ! I .' . I 'l·'. J,. ,I! Ii· "'I: ·I i I ·:·' I. . ·l '.' '·J' ··I ,. I I ';",I ··::·· i·::·i··;--,: ~,·::'.:: .. I:";;.:;: . i::· --·:· ' : I.. .I . : l ' ; . . ' : . I i ; ~ : ! ' 1 · ! I ·l ::,.: ,.f ;I ' '·1·) !: ' .: .. :: ; .:. 1' ... I :. , .. ·I·;;· I:: :lL I!' :. i ' I:.. ·.. i. .., ... , .. I. I . : "I• I ! ..... "' !. \ i · ·· ' · : .. , ·j : . I l I . . . ':: I I . ! ; I ' '::1 i . ! . i . I i . : I 40 l·· .. 1···" .. ··- .... .l. ... i. ... l .... t ... ,.... " I -.-Af\ .• ' .. I I I ' I. , . I. I · 1 · ·1· I I • I. . ,. I j .... 1,,~ HJ : Vj 1 1 , i \ . , '· • i :: .. :'!! :,, : . I : : -9 "'·:I. . I : :. ... I : · l". !'. >: I i . I i : = s 02 Cl I · I · · · 1· I I . I. I 1. ·I· . I 1J I . i ' I I l: I. : .. , " I ; I . • '1· I . . eq:=N / .. t .. , . . .. , .. i . I" . . " .. ' .. , . . . 7 I 2 i :. I . I .. 'i"I' . ".. ". I · 1·; I I. ! ! 'I ... ! i . . I "I 1-:l• ... ' .. : I; ' ·'1 I . " 4 I .. 1·,_ I .. ,.. 1 :.,_·l:'.i.l_J,. ::; .:.::: '1': = 3~ I 1. ... , I ; . '! l I.' .. f .. 1. ,,,_,.. '. I - 0 I ! . I . ' . l ...... ' .. ·1 ... . I ' I I . ; I I. . I I ...... : .... I ! H I · , ! : i I "'O I· ...:i..:...... ·!· I . I I L ')n, 1, ' ' . 'it'l I I --1· .... . • ... 1 · . I I : .. i.. I I' : I . ' . 11• I 1' . ''I·" 111 11 I I . I I . I ' I I ; I I , '. . I I I u· I ·::_: .... ! .. I .. ,. I I .. I· ... I , . " ' I I I . I I . ! I 1' .· 1' I I : l ..• l I ...... ,if I ' I ' .. I I . ~ i. I ' i I I I' . . ; . ! ' I I : ·' .. ' II • I " I I : I I I . I I I .•.;It.:.. .• ..: .. ),...... " .." ""I..4.1 .... ] .. ··'I ..... ' ,.. "'I.J...... 1. .. ' i I I I ' I ~- !"'" .. 1 1 ::: ::.i .. : I i'.i I" .. I •. .,1 ::· :;: • ,, I : 1 :·: · 1 •· 1 ·:·1::·, ·1 ·: 1 .... i ,. 11, l \ I l .. 1, 'I•' .. 1 •• :., I , .. r ·... i· I : · 1.... : !' ;. i j 1 1 ; ~ ;: t~ :: i: ; : ;' I ; : : ; : : ' : • ' '. : J I l : ' I : ; ' ' ; i: •• " ; l I ' i I I I • t .,,1 ... , 'I; I" .. '1•! 1• 'li· "I' "I I .. I j' j · j .I !ll. 1 ,, ll,I1. J 'fl ",1,l. • I I Ii. ' l:: " I " ' : I 1.. : ; ' . " I .. " I .. I . "'.U. " I ' ' ' " I 1I " ' J ... 1.. I I I t. 0 .:.i...... _._...... I ! ___ l. . -~ tt. .il._. I-·· .. __ - -4·-··· "'-·--··- - . . i .J. J .: ...I .!~J.... J ...!. i____ :. l..J-~. --~: ...... L. 1...... !.._ -~·l~ 4000 3500 3000 (CM') 2500 7C'OU 1fl()Q IMhJ 1400 l)fH) 1000 (CM 1) 800 600 ..Q @ :! ... .. GE NMR QE-300 J\.__ I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I -T---1 CZ48 501 14.5 14 0 13.5 13 0 12 5 12.0 11.5 11.0 10.5 10.0 9.5 9.0 PPM 23MAR95 ~ctl-41' ;"'!fi•_ "J•'"' /w'"'J...•I OPHAlOll. C'Z ONE: 'Ul..5£ S[QULNCI: 'ULll G:OJH • I U Ul£C 21 DiGAf[I ~.- ACQ. flMl • I 11 l[C . llECYCLE flt& • J 11 UC .; ;; Q NO Of 4CQI. • u .D ... DATA SIU • :U1H . Q Q LINC IAOAONG • 00 llZ ------l'IN llAfl' • u "" QISUl/l l'R[QUENCY • HO. UHSS *Z. SPCC llGDTH- 1114" HZ G41H • d •I HIGH rOWE:lt OM HIGH PO"i:I ClUTPUJ • II OI ( PLOJ SCA&.£ ti. II Hl/CN UU PPM/CM FROM 6.H : TO - II PPM 0 : ~ 1S0 2Cl NH 5d. / 2 1 3 _: ,/J / . :! = : Q ----_/ D Q PPM Figure 11: 1 H NMR Spectrum of Unsaturated Amide 83 ~ a.. a.. 0 , .. --;--~-- -~- ---- • - - f ___ o}r-• -~~-~ N ) ,, ~ • .. ) • . - ... .· r- f1 . '41 I: t · f l f'riJ . /:~ J)l_,,,___,J) "~.I I I ' I 7 8 I 6 5 4 3 2 1 0 PPM Figure 12: COSY Spectrum of Unsaturated Amide 83 o .. '0 ...... ·r: N O>N•~~--~-~-~-MMO•M•MNR•OGN• MmoG• ··-~R-G••Rm•G•~•-N N••-mmmW•GNm <.~ ~~ t~~~-~-~~~~~~~ ... ~-~~~~~~-~~~-~~~~~ :- -• -NNNNNNNNNNNNNNNNNNR•~-----~~~ 3 ! NR~---a•o-NR~---GO>O•NR•~-~GO>O•N u, • • · - • _.. •• -- • • ·NNNC'.: NNNNC'.INMC?t"' 0 f""LJ VI 13 ,. • A I 14 •b. ,, • .. .1.1..,~.~- f ...... ,.' j i , I ,,i' ,,. , ------....-...._....Uit______ Cr.'I ...... •--1 t i 11 I j I 11 I I , •I ...... , ...... i.- ...... 1,...... "I :• ~ I ~~ ~.,.,,,.~;.,, u .. .. • .). .i, ... ,J L. ,1,;~ ,, ·-----;- ISC I 00 :c c Figure 13 & DEPT NMR Spectrum of Unsaturated Amide 83 .;~·;.>.r~~·:r~~ '\.I "J,.' ... I/ ~ j ~-"' I I CE_ :):'I. ; n~ - '"] o o 11 Ic.:· 2 '3 :.:. . , l I ') 9 r-.rr-"' Qt: I 1 C!-il· ;1· I l l ICJCc 3 I i I O?~~ ~ roft c;: m-1 ' =''iAS£ SEfriS!T ! \ [ CSCM HYP:.!lCOM,t" ~X/:!'~I I ri 1 • J 4 •o usr c 0 , P2 'I 20 JSEC 1 :)3 a SS '-'Sf:C l• ~ 2 20 ~·s•c !35 =- 00 S£C 01 =- '.2 00 L..S!'C ' ' ')~;50FI I )7 • •4 00 USEC :ll ~ 1 00 l.iS~C I NH I :1 • ·1~ oo csrc I ~co. :!~l< • ·u. I" \!SEC a RECVC!..! THE •. Oi s:c ~-, I 3 7 t10. Of .~CQS. .. I '.l~'" s:z~ • 2!)1 .1 '..:~IE BO•.D.~G • S 00 tt! I S?:~. il'TE .. '-2 ~~s 08SUVE. - I r· rREQ ~ is oos1u ;2 F~EQ • 300. iSl715 1'1[~- I f: •.!Dir< • · 2500 ~2 ',.'JD .. H • :7·7 11 F: Ofti.C SJ!:: • •091 I ;2 OR4C SJ:?f: ,,. -"I ,,, F; f lttl... SIZE ~ 20•1 :"'..l'II ~-----~---·-2. ! FZ fJt,.:J. SIZ~ • :21 ., _.e·------,,· ~ ~ I G~!~! ... iO •: I' I ~f COJPLC:R. 51 •.'.0MO· •• '<00'.fcA 'lC Ji r rtiat;E:tcY • '· 'I& p,:ik •o.,R • 2fH I "!CH PO•t"~ 00 '"'~C~ ~0~£.R o:.:T~'j'" • 60 :la l' I 0 LOl SC>t i. 1 JS 98 '1~ c.. : 11 ~5:9 .:1Prt c~ I : ao;.1 a 1 c -1 ... 0 . 2~ ~.:. ... ------· ------______....__. ______ ~ : j I .'? j _('. ' . I ' I , I i , ' · I I t I ' i i I 13 . ,, ..~. l l., ------·-- -· - ·-··-·--·- - - -·- --·-- --·------~. ----- I ;:. .t- 0 1 2 () . 0 C E 0 6 C 4 0 ;-i 0 C P :-> ~· i Figure 14: HETCOR Spectrum of Unsaturated Amide 83 ~ 0> N '.:! ~ Q "' Q ~ 1 - ~· I'' 11 I I· I I Ii 1111 I 9 0 8. 5 8. 0 7.5 7.0 6. 5 6. 0 5.5 5.0 4. 5 l m 0 m N m fs 2 .------( II __/~ ;---- .~ - 0 ~ /~ Q Q ~ \. JI ~ Q 4 0 3 5 3.0 2 5 2 0 1 5 1 . 0 05 00 PPM Figure 15 : 1 H NMR Spectrum of r-Lactam 49 t. I . L... . - ('-l ---·--- I... :-'.2 CH 3 ------··------. - --·----- ..... ·-·------~~AK. L:s~:'111o riT ,>p14 P~~.K '• .LS,.!PiG ,>E..:K ~.:sr.~:r.iG ?{;;!( ~ :~TZ:NC s ' 1. 1 ' 2 SI 11. 51 t'' ?PM ~ ~r .•?:.1 '1T .l~:,,. 3 2 14. 81 J J3.20 1 -4 5· 4 4 I II '1 44 IS. 84 2 3 34. 40 2 8 1s s· 2' 38 • '. 52 5 48 19. 51 3 31 48.20 3 38 33.20 J J5 '8. 85 6 1 19. 59 4 ZS 49. 4 .. 4 3! 34. 40 4 26 : 9. 52 1 s 20. IH 2 5 38 aa. 88 s 5 '9. so 8 54 33.20 s 4 20.07 9 5 34. 32 10 49 34.40 II 2 35. 82 12 3 45.98 13 48 41. 2 1 ,, !3 47. 9f c~3 15 47 49. 44 !6 11 58. oa 17 47 sa. 88 11 '8 !9 78. 13 :9 19 77, •S 20 17 77.Sa 2· a !7 4. 86 I 1: ·I I, , ii L II I I Ii l I I I ; I c: ~ - j Figure 16 13C & DEPT NMR Spectrum of r-Lactam 49 ,o ------c .cf-'-- - '-0 .J 1 i -..,,, -r:--~ - - 1 ::; 0 ·t<>------~----- 0 - -- .. o •O N -~ - --,--i -f~--- - _ __;___;__--: l ~ .. 'u 0 t: __ ---~ ~- -~- f:':-~-~ 0- ~ -_-_-- __-_ - -f -t--·---: .... :· , ~---, -- ...... ____ _.... __ .''- c ------·c. -----~ -- -~ -- - ' -.: -- __ . . - _j ------.._, •. ~ : · --- -: 8 -: ---- = -- ---~,.-- : __ -_ N ------ IT •·· . -- _· -- P-'~ -~- -~- 1 : - ~ -:- l. - .-.-__------·:·: .. ------:-:-- . . ~ _:_::_ - - . ;.. · .--- . --- ·----=- :_:::__ __:_ -~i~-=- ·: . j. - --~-· ---- 0 0 ,, c;; L. 0 Q) ~ Q) ~ ,..-1 ~ 4-l 0 s::s )..I J.J u ~ Q) 0... CJ) : -· 0::: z~ ....~ L er ) ') ~- Ll ~ I l CJ I l 0 ("J , l""4 \0 Q) l '' i:: ..,. Q) I ~ I M< ~ I 0 i C• s <.C ::s i lo-I .j.J ... u Q) __JN Pl C/l l .-, ..._,0 ~ °'r-i Q) lo-I ::s tn ·r-1 ..._, i:i. I ( J I -· L' •..J· I c.; - . undance Scan 575 (7.042 min): CZ4.D 80000 117 70000 60000 Ph~i---, 50000 132 40000 91 30000 20000 10000 65 39 l ' 51 - I 7 7 l G.~ 4 0 I I I I I I I ?1 t'o--r-r-.{1+1-t-,-',--r~Jl--hT'-J-qJJ~j-~- ~~-1-41.--.-r V ,1-iJj /Z--> 30 ~l.~P" 40 50 60 70 80 90 100 110 120 130 140 Figure 20: MS Spectrum of Alkene 61 --··· ...... --~~ I ' I 1 I. I !·:: !· ... 1 r j.. ! : j'. ! ; :p .._ :" ... , __ i ._, 7,,._[ Figure 21: IR Spectrum of Alkene 61 ·1-. 1 I'.! ' I. :,·11 :: ii.' ' :'··\· ! .. , i I i I I . .. : ·1 : i ' ,. • ,:;: '.iii :·_ j:: ! i . ·: !_. :1·: . I I ! ' ! ; ' 1' I. . (' ' . I . ' . 1 ' !. L : I : : : I I : : : l j I . ' ~ :: I I • l : : I ' I j u0 ! r· ·' -·I .... ,. I--··,'; '·-1: ' .. 80 ·1· ... 'I ' i . ! . . . ' ' I . ' ' I ' ' .i'c .. ' 1 J : • : '·I ·1· ' I· I ' ! 1 l . . J:· j, I : ' I I,. ' "I j_ . ! ' ·. . 'j • ', II"!. 1·. · 1• ' ' 1 .. : . I. 1 ! , ·. i j." ' '. I . ' I. I :11 I., 1;11 : I :· ,1 i· I I.• I .;,.' I I'" ':: " 1:' '1 I I l . i : ' : ! ' ,' ! i !' ! . ' : I . ' J : • I I .. ' J ~ i ! : t : ' 1 ' I I j I I ·:1 i ; '·. _.,,., 'Iii'"' 11' "'l!I.. • ' ' '_'!• ; I I j I . ; ' 1 . I : . I I,'. :Ll I':;11: 1:.1 ... : :I ;·,: ;T: '.;'.! j; :: ! J '' ' '·. '. j l 1 I +1" ; 'I'' . ' '·.:. j i !. ! !' - • •. " ' :.• 'I ' I I ., ' . 11 1·1· ' ' ···1 ' ' ' ' " ' ' .. •. I' ' I I ': Ii" 111' ''I 11: '· .,, ' :·'I ' : ' ' :I-: ·i I , ' · :'!' :1i! :!,! •;; 1:;i'. . 'j .. · ::; . : ': ! , , ! i . : , · II 11111 1 1 U l'!"i i I ! I I 1·1 'I 1t:!i '~I : . I ~ 6') 1 :f!:;:1:·.-:'~:;_· ~+~~- ;_p: fl!J'iti;- · .·-. ·1:~:·.·--6~._,.~----·: · ~ .. :-· i · -l · i 1 i : : _; ~ii ·il iG\..; {-: l: ;.. ; ·• · · -·~-1~~.;i·::·1:~ ·ii.+_· (;o : ; ' I i I : : I ; : : ! : ' ; : I I: Ii I l I ! i Ii ,: j 111· 1' ' ' i ' 1' ' I .. I1 I· j ' I I '' ' I :: ! ' ' ' ' ~.-· 1 ll~ l!:'. p:: ;;.~ l~!: ~ !! ihl 11, ,. .... f: ,; ,' ... :· ;. I , .. , . , • • ... , • ~ -· •. 5 1 l 111 ,::1 ·_.· ':1:::: 1_:' ifi 11_1; _11: ' : ···.[·'. I' ··1_11 ' ,, i ·~ ~· l 'I II ' '1' ·_._'I :_:J:' I I 11!• •!I ''"' ' : ! ' ." •: I ' 1I I I ' ' ·'" i;: /)" ',i :1 '1 .•'I· ,1·1 11'" .. q.:II'·'1 11,,.+r '!jl1.,:i, ~L I' i' I::.,· I ••• 1,_ ... ,_·''['"''' '1_.' .1_ ••_ jr1t 'r':. "jl' . ·_"_" ..... '-,·-_·· .. ,. .. . . i ·, ! , 1 - t ·•·!··: ,J. .:1. ,;,, :i.il'...... ,_~ I I ' ·. '111: ::.; ,11 'iii: ,'1 ,' ' :··:1·' l'' .. I' ' : I I ' 1· ' " l : " I ,., : ':. :' ' 11,I :11 !1[! I':· ·11 ' ' '1· , ! 1': ': ' ' Pl I I ' i I '. :·. ' T I. I . '-1'.·i·jt 1!ii 11111;:1 i_I ! .,. ;'.:I I 1_ .• : ; :;: :_. 1 3 2 4 I ' !, ·1" . I ! ' " I·... :_.' ... :. :_' '· 1 1 1 ~ l: '1!t1; :;111ll'l j'~ I ~l;i :11 :1 ,:'., _;_,:;'·j.:i 1: ;'.~II j:i I I II .', f .j 1•i : : :: .;!11· I :&:. ' i i •,,._ ';• 11 l 1·1 i'I 'I '.•" 1:1: ' ' ·: ' 'ljl 1·.! i I ' I' I'" ' I I : i I ' ' ,'_:_ : 1' .. ' '' I ' l{ ! ' . " J 1 ,j I j I ' I ' ~ ' I '' ' . ·, ' I I j ! ! I I ' ' AO '~ . ! - ••. :'''_ ·''_, ... '_ti_: ; 1_ ·~ .. I'. ,1_ ·_···_.:_ •• • •. ·.I··'·_·· 4. o__ ' ._·_· . - ·1·· Ml i· . i. . . 11J '"·j· •_· .. : !I '11 i; I j ; I ' ' ! j l: : !! 1' : II i:' I : i :: : ! ' ';I!; ii ' :; :: ' I ! i 1, I ': ' I I ! '1 I ' ' : ' I " I I ~ . I ' ' I I I " l l lj I I I! -. ' . . ' I I . I I ' ' • I I . ! I I I ' ! 1 I I l ' I I' ·1' ' : I i ' ' i ·. ! : : ; I ~ii ! )11 ' ! '1 · i q :I : ' I : : : JI i ' :I : : :: : '. ; I I I I ' ' I I ' ' I I I l , ' .,. ':! :, I I i ' :1: i :l:l: •1'J :, :i 'I :: :"I' : .' ''.' I I I i I I ! I I '1 ' i ' I' ' I Uj ll 1 1 I' '" 1 • 1 [ I!, ti I' : 'I '" ' . ' I ' I ' ' ' I I I ' I I I ' ·11 " . ' ' ' :. I!' l.! :" : 'I • .. ' . . ! • " ·. . " .. , .. ; ' . ' ' I : . ' ' ' ' ·. . I I . 1· - ' · 1- I ·. I ii I " ti I ' :·· • I' I ' • I I. •Ii ' ii" ' i ! I ' ! l ! ' ! ' ', ' ' ! I : ! ' ·,: I J. I I I I ' ' I ' 'I '1 'I I I i ' I I . . I i : . ! I i I" 1··.}U ' ' ,, ' I I! ' ;l: I :? I 'I I I ·i I I ' ' ' ' I ; ', :. I 'II ' ,. ' 'I'· .. ::· '::: ' ' :, ' ·I ':i·1·_,,._.. ' I I ' ! :, • ' I I ' I I I ' ! j : I ' ' I I I i ! ~ ' 1 I ' J. 'i 1·· : : . , 'l '· .. , 1 ··1, 1 . I :;:j' - ... ' I I : I ' ' ' ' l' ' ' ' I; : : I i i . ' i : I I ' ' I ' I I I ~ I I ' ' I I I I I I ' : ' ' 'i ' \ ' ' ' I ' ' l ' i I ' .I: I ' I I . I Ii, 11 I I ·:1 ' ' I' : : I I: - . l .. '. 1 .'.'~ : ', __ l_;_ ··- __ L J. '--. L.~.I '·' --"-' lJJ 1l 1__ _' . , ' I~~--_, ·-I _L '. j no 1800 1{-()\ 1 AOO 1700 000 (CM') fl()i) 600 ...... N 0 N e1 ....OI )~ ,,so2 • Ph4,3 - NI OI ( ..,...... "' ( l-_l ..,... 't _,,I ~ .___, _.i.. .----.--..----..---.----.-~-.----.--..----r---1------~------.--.------~--.-----~~-~--.-~ 8 6 4 2 0 PPM Figure 22: 1H NMR Spectrum of B-Lactam 74 ALL ------ PEAK LISTING 0 CH CH 2 CH 3 HT PPM \ ------•1 27 23. 37 2 29 43. 71 0 )~ ,,so2 PEAK LISTING PEAK LISTING PEAK LISTING 3 30 47.93 4 5 87. 70 3 - N 89. 43 - I HT PPM HT PP\4 HT f'PM s 8 1 19 127. 81 6 19 78.68 •I 23 43. 11 •1 22 23 17 2' 31 128.99 2 22 47.91 7 19 77. 10 3 38 8 18 77. 53 130. 19 9 30 127. 81 r 10 54 128.H Phs6 11 48 130. 19 12 8 134. 40 CH, 13 3 181. 04 j ' --lb• 't W t 1 ...... t I ,.. 1 • '* • uµJ't tJIJl1 • •••• • ••• 'r m fl ..... 'J ...... JI 11 =· I F if t .. LL I I I I I I I I I I I I I I I I I I I I I I I I l 200 150 100 50 0 PPM Figure 23: 13C NMR & DEPT Spectrum of B-Lactam 74 F-i1.e-:c:::-z1T2B !dent: s · Me-r De 70SE EI+ Magnet BpM:91 BpV:l.9V Flags:HALL File Text:HOWARD BLACK CZ-II-28 100%. 91.1 x3.00------~ 4.9E6 4.7E6 4.4E6 4.2E6 0 3.9E6 3.7E6 )~ /.S02CI 3-:. NI 3.4E6 65 Ph~6 3.2E6 60 3.0E6 55 2.7E6 50 2.5E6 45 2.2E6 40 2.0E6 35 l.7E6 30 1. 5E6 25 1. 2E6 20 9.8E5 7.4E5 273.1 4.9E5 2.5E5 O.OEO 220 240 '3 2o' · '3 4o' m/z Figure 24: MS Spectrum of g-Lactam 74 Table 4: High-Resolution MS Data of B-Lactam 74 Elemental Composition Date 1-MAY-1995 Heteroatom Max: 20 Ion: Both Even and Odd Limits: -0.5 0 0 0 0 0 0 273.022805 10.0 20.0 50 100 4 6 2 2 Mass mDa PPM Cale. Mass DBE c H N 0 s Cl 273.022805 -0.2 -0.6 273.022643 6.0 11 12 1 3 1 1 0.3 1. 2 273 .023130 1. 5 8 15 2 2 1 2 -0.6 -2.4 273.022156 10.5 14 9 4 1 0.7 2.5 273.023493 15.5 15 5 4 1 -0.9 -3.1 273.021951 15.5 17 6 2 1 1. 0 3.6 273.023781 10.5 16 11 2 -1. 3 -4.8 273.021505 1. 5 6 13 2 6 2 -1.3 -4.9 273.021464 20.0 20 3 1 1 1.4 5.1 273.024185 6.0 9 11 3 3 2 -1. 5 -5.5 273.021300 6.5 9 10 4 2 1 1 1. 9 6.8 273.024672 1. 5 6 14 4 2 2 1 -2.0 - 7. 3 273.020813 11.0 12 7 3 3 1 2.0 7.4 273.024836 15.0 17 7 1 1 1 2.5 9.2 273.025323 10.5 14 10 2 1 1 2.7 10. 0 273.025528 5.5 11 13 4 2 -2.8 -10.4 273.019963 1. 5 8 14 6 1 1 -3.0 -11. 2 273.019758 6.5 11 11 2 2 2 3.2 11. 7 273.025994 11. 5 11 5 4 5 3.2 ll. 8 273.026015 1. 0 8 16 1 3 2 1 -3.5 -12.9 273.019271 ll. 0 14 8 1 3 1 -4.0 -14 . 7 273.018784 15.5 17 5 4 4.1 14. 9 273.026865 10.5 12 9 4 2 -4.2 -15.3 273.018620 2.0 6 12 3 5 1 1 4.3 15.9 273 .027153 5.5 13 15 1 2 4.5 16.6 273.027337 11. 0 13 7 l 6 -4.7 -17. 1 273.018133 6.5 9 9 2 6 1 -4.9 -17.8 273.017949 1. 0 9 17 1 2 2 -4.9 -17. 9 273.017928 11. 5 12 6 4 2 1 5.0 18.4 273.027824 6.5 10 10 2 5 1 -5.3 -19.6 273.017462 5. 5 12 14 1 2 1 -5.4 -19.6 273.017441 16.0 15 3 3 3 5.4 19.8 273.028208 10.0 14 11 1 1 2 5. 5 20.2 273.028312 2.0 7 13 3 4 2 -5.7 -21.0 273.017078 2. 0 8 13 1 5 2 5.9 21. 6 273.028695 5.5 11 14 2 2 1 -6.2 -22.8 273.016591 6.5 11 10 6 1 6.6 24.0 273.029366 6.5 8 9 4 5 1 -6.7 -24 . 5 273.016119 6.0 10 12 3 2 1 6.8 25.1 273.029654 1.5 9 15 5 2 - 7. 1 -25.9 273.015735 2.5 6 ll 4 4 2 -7.2 -26.3 273. 015632 10.5 13 9 2 1 2 7.2 26.4 273.030017 15.5 16 5 2 3 -7.6 -27 .7 273.015248 7.0 9 a 3 5 1 7.7 28.2 273. 030504 11. 0 13 a 3 2 1 7.7 28.3 273. 03052 5 0.5 10 19 2 2 7.9 29.0 273. 030709 6.0 10 11 1 6 1 -8.0 -29.5 273.014761 11. 5 12 5 2 6 8.2 30.0 273.030992 6.5 10 11 4 1 2 -,, i, j I ______:::> ------0-...: ------· __ ,_~- . - -- -- ;".- -- -- ~ ...... - - -- :~-=--- - - ... :: - :-=:--__:-. - __ ....:_-_-:---- 4-i ---:----':.....:._:-_---- 0 E ;:::l -~- - -- -~- ~.:..... ------H .w , (.) "-' - QJ -- c:. ~ . - Cl) __ - P:: H -- Lf) N __ _: ~------~- ·:---=-:.- . . ..:_ .::..:::-=-=--:; :..-"':' ______. --- - - ~-- _j '- .: L:.: - ---- ) 6- cr: _!-- ..:::: ~: ----: --· 0.. :::::'-""'-~' -- . -~· ·- ___---~~--- ··--- ~~=-~ _- :::::.:::::§ .;:-- __ ~- ~ __------·~~·2~llli"~~ ) . -- _____ : N -·--·- !'.""" --- ( ':;' ' •J·'-· I ...- ,.''- ','\_,I,'';""'..:_~ '("" ' \ .•-:: .- I_ I --~ [_ L .. _...... ,...... _. - L -_;,,,:.. - .. ---=-=---=-:- -- .:::,- ] I - =:..::-- - -·:.-=---~ __ - -=- -· -- ':"~ l 4-1 l_ 0 E ::l H .j.J f CJ ! aJ P-l U) 0:: :E:z ...::r: .. l.O N I aJ H ::l 01 ·r-i I IJ:. i i I I I 't I- L -- Cr c~ 13 I 1------·- P£AI( I_ LSTH.G 4 PEA~ :.rs~!IJG • ~r pi,:i:.i I '8 '9. lS # ~T n"' 2 28 :s 96 ; -zo !OS.O! ,,\ 3 38 7 6. 56 Ph~ 2 '4 !ZS. 'L ~JO ?C:Al U' I - ,· ( i ~) I . ) 5 1, 0 Figure 2 7: 13C & DEPT NMR Spectrum of Alkene 97 _J ,'") r------ ~ -:::---- :: --- ' --- ' ------ ) J -~r ! -·- -; ·,,,_ N0 ____:· ,..... :-::s------_J - -- ..:I-; - - ---' -______! ~ f : _r---;-----~ J ; - -- .' -·~---- :~ ___;C --' j_: J - -~ J-:-- ---_----l-- 0:: - i H - -- CX> = N - i l _,' 1-_-:- 1 ,- t O ______o ' - --- .... • ---- C',...,_ - '- Tc --,--,---;..JL ------·: I.'-- ~ -.--- -.--- .., i v; ! . : 0:: 1------L:..i I . _, ,_ -1~--- LU.., . ~ _,.:-:------0 ' . -- a:::_-;------:-- --- ~ '. . -·---·-_ ._ ~ ~--.• -_--~--: --~--- !-!·-----:---'----,-- I ' ·-~ -~------T ------i ("') -i ! ~ -- - . : ~ ....__! - ---- L _ ""! ; i ~------· _j • ~ _...... __ - : - - ~-:-- i ) -----~J~. ~-' -1 -- i . . :---- - . ·------______.- --r-- _____:. __ _J c ) r 0 c~ " \ ) In' \ \ /;,_' ~ Q_ Q_ I lo I r r rt'I \D r Q) i:: IN Q) ...!.( r-1 r i::x: 4-l r 0 s I :;j )..j r-~ .w ' u Q) r 0.. r Cl.l ~ i z~ r CD ...::r: .. r O'\ N Q.,-= \. ·rI Q) H -, :;j tn ·r-i _J r'° ti. l" r I Q.,-= r L ALL ------ PEAK LISTING CH CH2 CH t HT PPM 3 I 0 42. 13 ------2 30 42. 41 ------3 2 78.88 I 4 2 11. 21 PEAK LISTING LISTING PEAK LISTING 5 1 11. 10 8 11 113. 62 HT PPM HT PPM 128.31 HT PPM 7 33 •1 I 42. 43 23 42. 41 •1 -1 42. 41 II 0 128.85 2 I 113.12 ")3 Ph~LPh I 13. 62 z ~ I 13. 63 9 0 1211.22 3 20 128. 31 -1 121.37 3 121.54 0 128.35 10 SS 4 31 1211. 54 -l 1211. 5S 4 I 129.54 11 I 1211. 75 5 34 129.33 -2 129.34 5 1 129.33 12 0 1211. 93 13 0 129.09 14 55 129. 33 CH3 15 0 129.H 18 6 131. 70 17 4 1411. 54 1____ r ' CH ALL ·-r·- I ·1 ··-,--- -r- I I .. , - ., . I . ., . ,- I - ,. - I .. T - , .. , - .,- ..,--· -,-···-r. I 200 150 100 50 0 PPM Figure 30: 13C NMR Spectrum of Alkene 63 L Table 7: High-Resolution MS Data of Alkene 63 Elemental Composition Date 2-AUG-1995 Heteroatom Max: 20 Ion: Both Even and Odd Limits: -0.5 0 0 0 0 208.125164 10.0 20.0 50 100 4 6 Mass mDa PPM Cale. Mass DBE c H N 0 208.125164 o.o 0.2 208.125201 9.0 16 16 -4.0 -19.2 208.121178 5.0 11 16 2 2 4.6 21. 9 208.129731 0.5 7 18 3 4 5.9 28.4 208.131074 0.0 9 20 5 -6.7 -32.0 208. 118498 0.5 8 18 1 5 7.2 34.8 208.132411 5.0 10 16 4 1 -8.0 -38.5 208.117155 1. 0 6 16 4 4 8.6 41. 3 208.133754 4.5 12 18 1 2 '-" " " t·. 1·nl."". rv. 11;"7 i n:rr · rro?.,'~MICKUMETERS 4 '.> ,, ! ll ? 10 17 I tl 16 .I • 1.!,L' 11 1 1 1 .;. 11 I 11 1' 'f'' ',lJJll.~ .t .... 1-. • .. '... f .. ' _r_.1 1 1 J,.J.J~•. JQQ f1'.+11m~~11·!_..I ~..._...++++H. ·'H++ ,,4.!.. ":Mtrutt·("·,'··" ' , ' i . I lt'i I ' . ' I I .. " j .. I· ' 1' "' ' · 1· I .. " !1:1 11 1 J 1; l 1 Pl 1: : !1, 1 • i : r··rl . I I i I ' • I ' ' 1 J ! l'.;'. ' !. ; :. : 1 ul: I .J.! i!l'I: !.ii:!'! :1.. Figure 31: IR Spectrum of . 1 .1 : .: .. ,1 Alkene 63 I · ;I i : · 1 1 ... . I ,' '', I ' I . I 11111;111,'1' .1i'IH1·.·:: i1l:!': :t:!1ij::: ::f : : ! I' 'I' ·1 I l ' ' ·11'1. Hll" ''. I I ' • . . I :.: '1':tH"7 .rr.t • II'":• '.il\I . .. ' :· I . 11· .I .. I :.::~:i- ·:: ! : l.:· I .1 ... ,::·:::··': .. ·I· ; .l ..!... ·' 1·, '11.i' I 1j·' ',I. r,i:, : I . : , . ' I l i ' : ' I" I ' ! I 1 · I j i I j . ' I : : I !.: .;i!I•: ·: ,,!.' .! j Ji ,_· 1 :.,: :.. I I I i t: • 1 0 I ; I , ··· : ' ' :: ' :" : . "' . . i lj.o".J...... ,..'f"-+-+----~ I : /,;;.I I ·11·. ·ii·11 I I .;I" : I '' I :j 1 I. !· , 80 fi·:·m'1'' .iL,:J. : t :; ':.· :~~. · .... ·" ·" : • .. 130:. ... ' I . . .. ,. ·1 ... 1 I'"' "I' 'I . I 1:q I 11' 11 I l :I·· <.:Ii,.j' .I, ".. " . ' I I I I 1· ' ' • • : • ; . : .,1 • 1· 1 • f , • r 1 I I I' II . .. ! I I ' i ~ 1 l ;· i : ;I· l :I ! ' ;' l i l : · : ! . I . i 1 I .1' I 1 ! :.1; ;... .': ," 'I '; :... " " I ' I. ! .. I. : ·1{1j: ·: T;\.i ':.Ii ~::·1111: :.i: ::: " • : j' . '1'1 i i i I II ' I I.·. ' ·!.,:. ;· .. ! .. : I '"i I 1.1. I ! ! I ., '.,: I.;··.,:;::. j:.:: '.ii i!. ·, . . ' l i l ' , . i i. :i . I ; . , : :• ;! ">': ! ! ' I : . · , j . I:·~·,:;:'t:~I •f·I' '\l;L:,,F: 7~ . : . : ... . ::··,·::·1···-' I I I .. I i l ... ~.. l ... :., .... j, .... j.... , . ·l' .1 .... I. ·I~· .. I. I .11 1" 'i "it::'. 11:: I '.· I !. :1'.!' I ' I· 1· : ·· 1" 'i .: ':: ,. i : : I,' ' ;·;·;I. I . I I : 1·.'.il',, .: l '11I, ·:.:.T:L.,i(:,i,1;· f.:j·:,,·::1: .: : ' . ~ ' ~· '. i · 1 . I"' ' ' I . 'I .: : i' ' . 1· · 1 I •. I• 1·il1 I • ·'if', '.1•: ' : ''1 ' I" . I I ' .. : . : ' " I I '' ! Ii ! I I I 1 1 i;: " :·1 I I : :; ·. ·: .: I . ' ' ,.. - 60 ,H~tJJj; 1 :~.: llji '.:.; tJJ'. HHl(li 1 • • !J ·•r: f:.J.:61) .j 1 I ... , I . : : . ,! . i . liO 1 J. . 11 .. , , {1U ' ...~ .... 1 ~. l•I :.1 I' ,: i' 111, ' ·Ii 1'.,1 :I !1•·1" ·I '! :;1• ! ' I 1 1 11 I I .,.... : ' ....,.. . I''. 1 .: '11:1 : i ilj' !'!'. '" ' . ' I ''. i :· ' I 1 ·:'.1• I ":· ,,' I / ' '• 11 1 I\.,, ' , ; z ...... I ., .. ,. ·lj· 11...... I.!. ! I . I .. . ' ' 'I 'I ,.. . ,.. '" ... l I ·;·: .. :.;: .. 11 l,,i'1· 'I 0 ' :1111:.1. ,. I ' : I ' ' ' " I : : ' il ~ i : ' '. i . I i ! ' ( J, ".. I 1 1 I -1) I ' ' ' l 'II' ,'" 11' il I"' '.· ... " ' I ... 1.' ' '11 . I ' I' I ' '-'' -·-V•l-··1' .. ;; ;•. ;ul .i!~ P~J L.'l;'. ... i , . · .. :; :;1 , , l t I ·:I .. )1 r !! , .. , l· r I i': I ' ' I • :I ' 1· ! - ·I : •... ; :' l ' I I ' I ' I • I ' I . • ' i . , 1' I ' 1: I ' ~ I I 'I I ! I . I I ' '' t I • I I. 11 • • I ' t ! ! . I I ·":1;r:'J1· :., .. ,.;·.,•:.•:"''"f1! ',·! :;;:,:. '1':,1· j' I , I j I . I ... ' . '' " . I ! I · 1'' i.: l·I I·! I I; t' I: i! i: :! i : Ii I 'I I: I! I; ' I: iI: Ii : I!' i< : ;'I : ' ,. ' l II ; I I '"' '" . I I I I 11 . ·'.··1':··1 ·· ... ·1· ! !+ ::I ':Ii!:,"':':':. '.: I\! ·1''1: •,-:.·, :'.:.·i· I . .. 1· .. . ". . "I . I ' ' I . "1 · "j.. .. . I " ' . ·I 1, '" '! I ' 1 •1 !:I 1111 Ii· "ii i' 1 " '!j ! 1! "'.I ' I I ... ." ". I . ' I" ' : ; "'I I ' 1 1 ·1 ... i !, . . I ',.:i'l' ' I. ''I· )ll1 l'lilt'lii '.:'. : ,: .· ~ !! o.1': !. . ; ' I ·I: .. i.:: JJ._·:;· :i:t:t:: l. .. Lf .. ~ •. L... , _. _.. . . . I ·l: :1 ' I ' . ! I I,,.,, Annn 'l'·00 1nrHi /f-t • '\ ·, · -.. 1 r.11:; I~, I i ~ (li'l •t 1( H II! ' '\ I ' \ ' ' . ~ ,1' I ~ ' \ I ..~ ,-. ( 1 0 ! ) )~_,,sop 3 - N - I Ph~Ph 0 ~ ; .. 0 0 ., ; ~ ( .. ~.. ___./ ) 0 0 . .. 0 .0 ~ . 'l' ... 0 ' .. J .A_ - - 4 5 4. 0 3. 5 3.0 PPM Figure 32: 1 H NMR Spectrum of g-Lactam 75 ALL ------ PEAK LISTING HT PPM 1 0 41. 24 2' 26 41. 50 0 CH CH 2 CH 3 3 12 44. 29 4 6 72. !19 ------5 3 76. 78 6 3 77. 21 ,.,S0 CI PEAK LISTING Pf:AK LI STING 7 3 77. 63 )~ 2 Pf:AK LISTING 8 0 126.23 3 - N HT PPM , - I HT PPM HT PPM 9 28 127. 92 •1 2 41. 52 1 21 41. 50 10 0 128. 16 •1 -2 41. 52 2 21 127. 92 2 11 44.28 I -T 44.28 11 1 128. 4 CHz CH ALL 200 150 100 50 0 PPM Figure 33: 13C & DEPT NMR Spectrum of B-Lactam 75 r .1..1.e :cz..t.L'.:>4 Ident: 3TMer-DeT-0-:25. Acq: 70SE EI+ Magnet BpM:91 BpV:362.5rnV Flags:HALL File Text:HOWARD BLACK CZ-II-54 100~ 91.1 9.6E5 95 9.1E5 90 8.6E5 8.2E5 0 7.7E5 7.2E5 )~ /S02Cl 3 - N - I 6.7E5 Ph~Ph 6. 2E5 5.8E5 5. 3E5 4.8E5 45 l4.3E5 160.l 40 118.l 3.8E5 35 3.4E5 30 2.9E5 25 2.4E5 20 233.1 l.9E5 15 65.0 I 206.1 1.4E5 10 349 .l 9.6E4 5 4.8E4 0 O.OEO 0 m/z Figure 34: MS Spectrum of B-Lactam 75 JI ! Table 5: High-Resolution MS Data of g-Lactam 75 Elemental Composition Date 1-MAY-1995 Heteroatom Max: 20 Ion: Both Even and Odd Limits: -0.5 0 0 0 0 0 0 349.054043 10.0 20.0 50 100 4 6 2 2 Mass mDa PPM Cale. Mass DBE c H N 0 s Cl 349.054043 -0.1 -0.3 349.053943 10.0 17 16 1 3 1 1 0.4 1. 1 349.054430 5.5 14 19 2 2 1 2 -0.6 -1. 7 349.053456 14. 5 20 13 4 1 0.6 1. 7 349.054635 0.5 11 22 6 2 1 -0.8 -2. 1 349.053292 1. 0 9 20 3 5 2 1 0.8 2.2 34'.1.054793 19.5 21 9 4 1 -0.8 -2.3 349.053251 19.5 23 lO 2 1 1. 0 3.0 349.055081 14.5 22 15 2 -1. 2 -3.5 349.052805 5.5 12 17 2 6 2 -1. 4 -4 . 1 349.052600 10.5 15 14 4 2 1 1 , ~ 1. 4 4 . 1 349.055485 10.0 15 • :i 3 3 2 -1. 9 -5.5 349.052113 15.0 18 : 1 3 3 1 1. 9 5. 5 349.055972 5. 5 12 18 4 2, 2 1 2.1 6.0 349.056136 19.0 23 11 l 1 -2.3 -6.6 349.051750 1. 0 11 21 1 5" 1 2 2.6 7.4 349.056623 14.5 20 14 2 1 1 -2.8 -8.0 349.051263 5.5 14 18 6 1 1 2.8 8.0 349.056828 9.5 17 17 4 2 -3.0 -8.5 349.051058 10.5 17 15 2 2 2 3.3 9.3 349.057295 15.5 17 9 4 5 3.3 9.4 349.057315 5.0 14 20 1 3 2 1 -3.5 -9.9 349.050571 15.0 20 12 1 3 1 -3.6 -10.4 349.050408 1.5 9 19 4.., 4 l 2 3.8 10.8 349.057802 0.5 11 23 .. 2 2 2 -4.0 -11. 3 349.050084 19.5 23 9 4 -4.1 -11. 8 349.049920 6.0 12 :6 3 5 1 1 4.1 11.8 349.058165 14. 5 18 13 4 2 4.4 12.6 349.058453 9.5 19 :9 1 2 4.6 13. 2 349.058637 15.0 19 11 1 6 -4.6 -13. 2 349.049433 10.5 15 13 2 6 1 -4.8 -13. 7 349.049249 5.0 15 21 1 2 2 -4.8 -13. 8 349.049228 15.5 18 10 4 2 1 5. 1 14 . 6 349.059125 10.5 16 14 2 5 1 -5.3 -15. 1 349.048762 9.5 18 18 1 2 1 -5.3 -15.2 349.048741 20.0 21 7 3 3 5.5 15.7 349.059508 14.0 20 15 1 1 2 5.6 16.0 349.059612 6.0 1J 17 3 4 2 -5.7 -16.: 349.048378 6.0 14 17 ~ 5 2 6.0 17 . 1 349.059995 9.5 17 18 2 2 1 -6.2 -17.6 349.047891 10.5 17 14 6 1 -6.6 -19.0 349.047419 10.0 16 ,.o - 3 2 1 6. 6 19. 0 349.060667 10.5 14 1J 4 5 1 6.9 19.8 349.060954 5.5 15 19 5 2 -7.0 -20.1 349.047036 6.5 12 15 4 4 2 -7.1 -20.4 349.046932 14.5 19 13 2 1 2 3 7.3 20.3 349.061317 19.5 22 9 2 ..., -7.5 -21.4 349.046569 0.5 12 23 3 ;. 2 -7.5 -21.5 349.046548 11. 0 15 12 3 5 1 :-T~ :~[:; ' T.J.... '· ' .•. J. j '· . ,.L,:j .:. :'I. j .•r .; t-i- ~ . ' - .... 10P j·· .' Figure 35: IR Spectrum of ·~~ ~~·~~~·~ ·~;;, ... r· ...... r·"'T~~1·0·:-''t~'.r1;}(-:-. i ' : ,,,.:;.,! ::: ··I: ·1 I 1J:l· 1 ···: -1-· I I: '. · j I I .•. I" ·1 .. I ' ' I . , ' ' , .. , I . ·I ... l'i.,. ' ' I ' ' I l I I I I ' l I I I I i l I I l•i . i I· I : I I iI "-._,.,_...... ~~I 1: ; I I;.: I I ,_ I ~I I ~1-- -"I -- I I I I ' I I I' ' ' l I I I I i ,--{ I.:. I l ! I I . " ' I I I • ' :. . :1· . I I t·,, I. I I I I : I·· 1": ... :·I:: I 1 I"·. I . I,,·:-.! t I l ; ! 1 I · 1·. 1 • • , ! I I '1 I. I . .I I .: ,I I " .....' I ' I: I . I i I ! , ...... I I. I i I ; i I .I i1 I I' I I I I I 1 .. : I. . : ';fl() : fl'.) I.. ' : . I . :' I . ,, • J . /. . I I I.. I I " I : I ' I '. I ' ' l I I. ! ·1 .. 1: I 'i_. ; i '' ' 1·. i ;... ·\'·. l ! I I • 1· I ' ' I I I '• :' '.1: I ' . ' ' 11 ' : I n . . , . ·1 1 I 1 1 • ·, I ' '1 . ! . 1. 1 • ! , rl i ; : t· ;~ . i ·;;I,:' :;;,11. ·1· '. f." ,. i· 11 111 j' , ·:, I I, 1 . : . I : • ; : 1 . '. ··:r . I I "' I.. ' . I .. : ' ·· ... ' I I' I j:• j·:· :., . ' I ' ~ ' Iµ'I Ii : :II i I I " . ' "•' I I 1 I"•· ...,. ,. .. i . I I I -.. . I' . ' , .. ..: . , • " . 'I . ; , ., . ·1 · . I' , I .. I'' il· . l . I . I "I, 'i' I" 11 I I: • : I: :I ' : ' I I : ·j r I ; . · . · · 1:[;; 1 .•. ' i i I I• I, •I 11•[ , '' " . I ! . .... - I ~ 1 1.. ... ,. ·:· ;;: .. '""60·' '''.) ·I . I · • 1 " l" · · · • <(.(J ;;~ 60 .... ··'····1··· .. ;r 1 :j· , .. I i I ··I 1 I I I Ii i . 1 I -:: I ! ,t ::.·1;:': ·.·1 · I 0 ·::11··. : ; :;· ·1:;!] ::; ;Ii: .. ".: . ., I·"'I ,' ! · . 1 ' • ' • I• I I I ,, ' I V> . . I . I ,l 1!11 ·l· !''I. ..,, 1 I ' I ' I I i I I ' '.: '.: ; '.; . ... :. : .- I I .. . ~ i~.: .. :. ~.,-,.-M-~ , .: I . !. . . .. I ... ' I I ' i· ~ l i 'I !j l ! ... ., I .,. iql !;' " '. 11 ;. I :·! I Ii t ; ! "1. ·111. •I ... I I H. I - I ' ,... . I I • 1 I ! .. '.:,' ! '-: I' I : ' I I : i I I ! I . : . 0 '\ 1· I I' " ' '' " ' , , , I I , I 1 ~ I I' '1 I 1, I ,1j' •' 1 ,_ Ao . ..,1 ·'· . . .. .Lr ..... ,... " ...... j .. .. i· .i n . I ! I ... :. . ... : )o 1 J·. ,, . i I : ' ,. 1! ,,, '!I 1 : I 'I '! . j I I )~ ,,so2c1 ' ; ' :1. ' ' :ii' ! ! 1i:;! ~ !; : 1: .. ;! I I I .. : . 3 - N I' I. I 'I I ', " . I . I - I ! ': ! ! : :: : : i' ' •. : I LI. :: : '.: ',;: i I I i I . ' 7 .. . ! . 1:; ; 1!" !"i' .. , ;·; ·;:': ii'; :. ;'. - 'i ::· .... Ph~Pl1 I' . I..I . ' I I I ·. 1 · \ 1;/.J ii :,.). ;1~: :::: u: :;: c I ! !. I : I I ; ... . ·' 1··: i , j':: ·r" , .. , i-·:. ,. i ', I i I I ' I !1·:1 J '!:I 1' !l_:_ ,!,'. 11:1 !.1, lj!: I I'' ' I I ' ! ! I I,, '1·· . 11 .1 .. •,. 11 ,lj'J''l•J I I .. I 20 l 1 :"j· .. ·'' 1· . : ... .. l, ''· 1 ".'· • • • • • .! • ' 20· . . ' . 'll i . ! ... '. ! ·)() .. •I I ... ',.... I ' ' ' I . , , I. :!Ji J Ii 1111 j I Iii l I I £ I • ! I j' I.. I 'I ; ; ; I ; j ; I: ' ! ' j . : : : i ! : i :i :: : : ~ : :: ! ~ ' '. . ' ' I I I I I .I I· .. I I . I :.1 ,;· '' ::: I '' I'!.! ·:: I 'I I I .:: :. ·:I I 1 1 1 ; ' ; 1 1 ; : i l j j ! : ' ! ~ l ~ 1 l \ , I j j l 1 '". . : j · .. " 'C '.! "t. ',. •71' i. ;. ' i I 1J. . j I I i ··'1<· I i i 1 I I I "' I I . i I . , . i 1 ! • • : . I . . I ,:.:.:.,,:·:!1±.1:!.T'.. l\ ,;! .::1_l 'l:l;1 _:·,:1!·_::::.,::::! ' i j : " ' : .. . ) I I i . ' ' i ! . ' ; . ' : : I ' ~ I ! " ' I \ I 'I. ' I I i . 'I ' ' ' l 0 LiLL:1·[:· :" .,: . ' '·•]'"':'I'". ' . I •... i ..I. .. -· 1. _ .I I I J .. ~ 1...._. . ... I._!__ I 4000 -· - · 3500 3000 - (<~Mr 250·0 ·· · ·· , 7nun 11100 j (,( ~; J J.1(1() 1700 1000 (CM') (H!fl 600 0 "' Nl/1 I '-'a> ...."'""'""' _, O>...... 1 Uc:'N NOC....""' UUOr- I I I I i I L_ I\,_ J-~~0... -y LoJ L l l L c~ .j t-.LL I 150 100 50 0 PPM Figure 37 13 C NMR Spectrum of Alkene 65 Table 8: -lf.igh-Resolution MS Data of Alkene 65 Elemental Composition Date 2-AUG-1995 Heteroatom Max: 20 Ion: Both Even and Odd Limits: -0.5 0 0 0 0 222.140765 10.0 20.0 50 100 4 6 Mase mDa PPM Cale. Mass DBE c H N 0 222.140765 0.1 0.4 222.140851 9.0 17 18 -3.9 -17.7 222.136828 5.0 12 18 2 2 4. 6 20.8 222.145381 0.5 8 20 3 4 6.0 26.8 222.146724 0.0 10 22 5 -6.6 -29.8 222.134148 0.5 9 20 1 5 7.3 32.8 222.148061 5.0 11 18 4 1 -8.0 -35.8 222.132805 1. 0 7 18 4 4 8.6 38.9 222.149404 4.5 13 20 1 2 ~, ~ --.------~. - j i '.'.) ·l ! -· ------+---- ··-·------Nr-.~ -l~· ------i----~ [ ---·1 I - -~ ----~---·- ---1 ------j-----·Jf' . c.'"'" ------·-----·------·------+-'----_J - . ' . ' : : ! . : j: . l an ID -·---~------____· -·-·-----~ -~ ------R------1.5 -I ) 3 ~ _____ : ___ +---:-10 J ) ·-.' ) 1 i. ------·----·------; g Li , I . ·-·-· -l~------__ J~ ri-:· .,, I ~__;_-· __ _:.__ _,______-----,------~--·------~ ' I 1 I J------·-- j c ·------!~ ------·------1! '" ..c ___!______, Q.. : ! ~ - . I - :_ - -'--'------! c 0 !·? -<.:• ------('.;------, ~-~ '('.' ------·-----~------~------:--.-: -- :---·-: >:~. ------~-----. ---~-----:---.------:---- ..... ---·------;-:------·-·----: ' - :-=., ~~~~~~~~~~~~~~~~~,,;,,,;,;;;~------..---- I ----~~---:x; r: ! ~ =------.....__ ------· ---=------·-·.__ :-----····--- ___ :._---,~_.:. ____ ! ' - - __ _,_____ --- --.c..J.:~.:__ - _J i ·--·I ------.---- ,- ·10! _;___. ____ .;_ ___: ___ _: C: ·------. ------·------.: i .! ,~.; ~J-~ ___ ;___ ·-- __ , J I : I . ' ---- ·------· -i I ----L - -· ------...... - ·----_I ' ' ff- -=~~--- .!' i-1---~--- .... i . '.: ; 1..-:' ------·-----'------~------~'$-:' 0 c 0 ~, c: N 2 0..... 0..... 0 I t""' \D ~ Q) I s:: IN Q) ~ ..-l Ii r 11$ 4-1 0 r e ;j H r .w r- -tj- CJ ' ' Q) Oi I Cl) r 0:: ~ r I ::r: I .... r- co I C"1°' r QJ H ;j I II tJl r ·r-i taJ' ~ I Ir I r '--- ALL ------ PEAK LISTING HT PPM •1 2 11. 47 CH CH2 z 4 17.07 CH3 17. 91 3 27 I ------··--·-- --~------4 54 Zl.54 5 4 31. 22 4 32.50 PEAK LIS~ING PE.t.K LISTING •7 Z2 31. 70 PEAK USTitlG I -1 17. 72 HT PPM HT PPPI PhJ,L(), •1 11 HT PP14 9 5 71. 72 39. 70 •1 9 17.92 • 10 5 77. 15 . 27 128.20 2 21 21.54 3 NO PEAKS• 11 4 77. 57 6 J 128. 51 J 19 109.U 0 12 33 101.13 4 14 ;z7.J3 25. 74 13 4 125.H 5 19 121. 27 14 52 121. 20 15 7 121.51 CH 3 ti 21 127.32 17 7 121.01 18 41 121.27 19 2 121.31 zo J 140.15 21 4 152. 13 CH A.LL I I I I I I I I I I I I I I I I I I I I I I I 1 200 150 100 50 0 PPM Figure 40 13C NMR Spectrum of Alkene 67 Table 9: High-Resolution MS Data of Alkene 67 Elemental Composition Date 2-AUG-1995 Heteroatom Max: 20 Ion: Both Even and Odd Limits: -0.5 0 0 0 0 158.109562 10.0 20.0 50 100 4 6 Mass mDa PPM Cale. Mass DBE c H N 0 158.109562 o.o -0.1 158.109551 6.0 12 14 -4.0 -25.5 158.105528 2.0 7 14 2 2 7.2 45.5 158 .116761 2.0 6 14 4 1 8.5 54.0 158. 118104 1. 5 8 16 1 2 r•1t1l'HIC CTT-\1\ • : ' .' I ·< I '/9-- I (142 2 • ( .· ~--~::-:i'.., .).T~T~T~,~~~ 1 "'!'.~T?~-f-' .l,.:; ..4 __ Figure 41: IR Spectrum of 10 17 14 16 20 !(lo I:. l~::'..-t'·r -l,:1::1::1;'"i~.1l~:,1t'::.~ ... ··;: i.I :;·,- l 1_010 .... .0-; ! I i. l.. I : . l I ! !:i''.'!'' !.. ': 1: !ii: I. 1 :.;::! :". ,j ,··,: . !,;;· '.,, 1'::j: ::!'.;'1 ;:, ; i : I ( I I ; . 1'; i :. I : I I . .. ' . . . " ... -. ';. ., .. .. ".L .. ·I ' . ' - ., I . ' ' : I': : I : . .: I·:. I I I' , :: •·: 1' 1 .. 1 ,· I I . . '.I . I I ' 1:: '. I·, I ; ·: i ; . I I ; ,:11 ' .:: ! I ! :; : I I I I : , •• I • ' I ti : jl 1.i' . : I I . ' ' ~--. . -J~-1 :.-:tJ+ ··'·i:-· I I I I I' ... ' ' , . , I I- i I . " . . I I I I I ' . ! 1·" I I ~ . : , ! • ~ : , . : : 1 " , I . ! : j I I ' , : '. l I I I , I :'. 'I· ., 1-- ' I· ' I ·I ' ' I I I I ·. I ' ,.. I ' ' . ;I, '·' I I I ! . : I I ; ! 1· I· '· ! ... 'I I I I I ' ' , I i . \, : . ' I• I I ' " I ' I ; . ,. I I ., 00 I -...... i ·:.. .. •. - +".. (l() -1 ·_· I I .. I 8lj 'j"•'L. ·I"' I' I I I I . I I . 1·· . I I" 1·' . 'I , ' I ' '1· . I I I ' , ,, '·1· I, . I I • · 1 .• I i · . 1 - 'I 1 • ·•. · 1 1 i 1. 1 11 1 'J r1 . .1, ! ! ,, ' I ' . I . ..I . " 11 ' I ! ! ' J .. !' j ' ' I .: I t ' ' .... '.". .. ' I ' I ! : - I I.. ' . I '1 t ~- I.! l "I . I ' . I ' ·1 · . I I ' I I J, . . I .. . ' "' ' i. ' " , 11I1 1 • I ',I! I " ' i " , ' !. ' ""I'I : ". , ; '. I I : ' I I '' "I !l.1 ,1 'I I : ' • ,' I I ' l',, I I I' 1! I;:. I 1 1 I ' • ' ' I I 1\1 J1 11 11:' ' t : I i I : . ·l'· '· I . '!:'' I t I ! • ! - .l. ..• ,.. ·11. .. ··r· .. 1!+rL ... ,H. •• ..I -1-...... r,~·tf-1. :· L . i ...... -Li- ! - - .-- ..... ·- •.... 1. I ·::· j· - ' , ' I ' I' !•i ... , : j I 1· I ,,1 '•I I I ' I \·1., ... , . ' . ' .. . ' I I . I I. . . ' ' I I 1 I I ' 'I! 'I I I ' I 'I " I I ' I .' I I . I . . 1· I . ' I ! ti ' I I i I l I I I I ' I I I . J l I" 1; 1, ·•I . ' l ' ' I •• I' I· I I .1. 11 I ,I 11 ' I 11"1 ' I I I I ' , . " - 1.:1. I·'· ·'· •" " ' "·1'. l·-HI +l! lq 1.l11l;1 ,i1, -·ll ltll ' . I I ... ,. , ' I I I. I I - I 1 · ...... ' 'I.,:--. ·:-- '.t· '. 1-- I I "I 11 I ,1 ' , 1qi I'· I I I , . I ! I" I 1 1;, 1 1 1• • 1 1 !·· , 1 11 1 1,1 I•ti I 1 1 • 1 ,.. I .. 1· '· .. '. '"-Iii!• 1·-- 1 '·ii·..... 1 I j I ' I• " I' l'I' ' I I ,, l!1• I I ' ' . ,: . 11. I•' t. 1• I I I I ' I I• I t l 1!' I ' 1111 ', I I L I ' ! I :. ;, 1 ..... ,., .• 60 l··""lL U- · 1·· ·i--·· .... t .... ,,., "" ··t' .... 60 .. 1 .. ··· - 1 • • · • • ... I-- 1... '.-- ',n. 1 '.'" • - 1.·• 1 , , , ' " I , • ' ! I 11" I I• ' I ' I ' I I ' I I I ' I. ' ,_ '-' I '" 1-- . '.I "1- ·11 : :;; ii ·:, 1111! , : " ,, 1!"111 I· i :.. I ' 1' I' I : ;i' . i ,• . ' I ) !If I I ' I ! I t 1 ·1 ! · ti 11 t1 ' , ... 1 ' I I . I·· "" "" "I' li11 I ' • . •. 'I '!""• ! 1.. I ' I . . .. " ·"1111 ·I· L. I 1 i I ' ,,, ! ' ' I I ' . I '1 I I I ' If I I 11l 11.j.11 'I''J I' l ' ···1 I ' I ' , I 11 I l 11: '' . . I I l I l I '!' I I l ,1 " I I t ' I l I ! I , I " 1 I I ' ' I ' ' . . I ' ' . ··1··--1. ... 1·-··.-· I· .. .l. ., --~ .... "I . " .. i I - 1·· .... ! . .. !. I - .... I ••. -···, ' .... !11, _,\, 1111' ",'ii 11! ! ' 'I I '1 I I 1•1,111·, 1 .. 11, , . , '•' , ' ,:I :1' 1' I I , ":·I, ' I ' , ' , ' I I •I , ' ·'I . ' I _J·L<> :: ,, . I 1 1 l '!1"·1 • '.-j.1 .. t •1· .. , . t ... : .. .. l I I- . I: ·I· I ' . ! ,. I J 'I I " ' 'I , ' , 'I ',, ' ' ;i.~I .i ' I , Ph 2 . ~ I I . ' ' I .. , ,,, I 1'11 I ' I I ' , I I . I .. '. ~ : l I ' ' I • ! I • ; 1 : 1 ' I : I ' I I • '. : I I ' ' " ; j 40 l...: .. ~., 1...... , .... I.. .. . A() ..... J ., ••. . ·I Jlf) 1----i· . _ . r 11 1, '1 -···r·, ..... , , " , " . , ' i ' • I - I , i 6 ! . • , i , ',' ' " I!', .. : f i I I I ' I , I ' i I ' ' ' .: 'I: .1:,' I ·II ' I " I I ! .. I 1 --1· 11 · I; 1 ! · j · · ' 11 : rii : , , ; 1 il · ·: I" : 1 1 , I : ! · I , · · ! . 1 I 'I , I 111111 1. 1" I' 'I " I I I ! '. 'I I I 'I "I I I' d , , •I' , ' I I ' , ' I I' I , 1 " ' ' i I . . ," I ,...... lft :J1 111 .. ,I ' .. , I ·1 I I . - i ·. I ,_ I 1 ' I ' ' I 1 /' 1 1 • I I !' i ! ' I ii'II j 1111' :1 ,, i I I I I ":: I ,. I ,. ;::: : I :11'1· i1' ' ' ' ' ' I . I ' :.: I : I I , '· . ! I.'' 'I•' I I ' I " I1 ,1I l Ij I!I I II I ' 'I I , I 'I I I , I I I I I I I ' ' ' I i"' ' ! 'I ' ! ,, ·: I I I ·I" II 1. ' ' I II I I . I : . I ' I I' ,1+ 11,1 I I I I j ll '11 I I ' i .. I. 20 l .. 1 ..... : .. :/ .... ~·: · ""' ) ! '1, .. :l·r L ... , ... I·· 20 .J · I l . I : · I· 1 · 1 · J