4072
J . Org. Chem. 1985, 50, 4072-4080
Highly Selective Nonenzymatic Chiral Induction into 3-Methylglutaric Acid and cis -4-Cyclohexen-l,2-ylenebis(aceticacid) Utilizing a Functional Five-Membered Heterocycle 4(R)-MCTT’ Yoshimitsu Nagao,2a Takao Ikeda,2aTakehisa Inoue,2a Masahiro Yagi,2aMotoo Shiro,2band Eiichi Fujita*2a Institute for Chemical Research, Kyoto University, Uji, Kyoto 611, Japan, and Shionogi & Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, Osaka 553, Japan
Received April 8, 1985
Diamide 8, prepared by treatment of 3-methylglutaric acid (1)with 4(R)-MCTT (5) in the presence of DCC in pyridine, was subjected to aminolysis with 1 equiv of piperidine in CH2C12at -30 “C to give a mixture of diastereomers 9a and 10a in a 88:12 ratio. Compound 9a,separated by silica gel column chromatography, was treated with various nucleophiles to give optically pure bifunctional synthons lla-k in high yields. Highly selective acid) (4) was also performed. Aminolysis of 19 with chiral induction into cis-4-cyclohexen-1,2-ylenebis(acetic 1mol equiv of piperidine gave a mixture of 20 and 21 with 94% selectivity of the former. Similar chiral induction into cis-cyclohexan-1,2-ylenebis(aceticacid) (23) was tried. Aminolysis of its 4(R)-MCTT diamide (24) with piperidine gave 25 and 26 in a 89:ll ratio; the opposite selectivity was obtained with 19. The conformations of 19 and 24 in a solvent, the relationship between the susceptibility of their conformations and environmental temperature, and the diastereoselectivity of the reaction are discussed on the basis of the 400-MHz ‘H NMR spectra. Optically active simple compounds are increasingly being used3 as efficient chiral building blocks for the construction of optically active key intermediates in the total synthesis of biologically active natural products, such as macrolides; m a c r o l a ~ t a m s polyethers,6 ,~ P-lactams,’ peptides: amino sugars: and nucleotidelO antibiotics and/or anticancer agents, prostaglandins,l’ and leukotrienes.12 Therefore, (1) This paper forms Part 7 of the series “Utilization of Sulfur-containing Leaving Group”. Part 6: Nagao, Y.; Miyasaka, T.; Seno, K.; Perkin Trans. 1,1984,2439. Fujita, E.; Shibata, D.; Doi, E. J. Chem. SOC., (2) (a) Institute for Chemical Research, Kyoto University, (b) The Shionogi Research Laboratories, Shionogi & Co. LTd. (3) ,(a) Morrison J. D., Ed. “Asymmetric Synthesis: Vol. 3 Stereodifferentiating Addition Reactions Part B”; Academic Press: New York, 1984 and references cited therein. (b) Bartlett, P. A. Tetrahedron 1980, 36, 3 and references cited therein. (4) (a) Masamune, S.; Hirama, M.; Mori, S.; Ali, Sk. A.; Garbey, D. S. J . Am. Chem. Soc. 1981,103, 1568. (b) Meyers, A. I.; Amos, R. A. Ibid. 1980,102,870. (c) Tatauta, K.; Nakagawa, A.; Maniwa, S.; Kinoshita, M. Tetrahedron Lett. 1980,21, 1479. (d) Seuring, B., Seebach, D. Liebigs Ann. Chem. 1978, 2044. (e) Hanessian, S.; Rancourt, G.; Guindon, Y. Can. J . Chem. 1978,56, 1843. (5) Corey, E. J.; Weigel, L. 0.;Chamberlin, A. R.; Lipshultz, B. J . Am. Chem. SOC.1980, 102, 1439. (6) (a) Collum, D. B.; McDonald, J. H.; 111;Still, W. C. J. Am. Chem. SOC. 1980, 102, 2120. (b) Ireland, R. E.; Thaisrivongs, S.; Wilcox, C. S. Ibid. 1980, 102, 1155. (c) Evans, D. A,; Sacks, C. E.; Kleschick, W. A.; Taber, T. R. Ibid. 1979, 101, 6789. (d) Fukuyama, T.; Akasaka, K.; Karanewsky, D. S.; Wang, C.-L. J.; Schmidt, G.; Kishi, Y. Ibid. 1979,101, 262. (7) (a) Iimori, T.; Takahashi, Y.; Izawa, T.; Kobayashi, S.; Ohno, M. J . Am. Chem. SOC. 1983, 105, 1659. (b) Baldwin, J. E.; Au. A.; Christie, M.; Haber, S. B.; Hesson, D. Ibid. 1975,97,5957. ( c ) Woodward, R. B.; Heusler, K.; Gosteli, J.; Naegeli, P.; Oppolzer, W.; Ramage, R.; Ranganathan, S.; Vorbrogen, H. Ibid. 1966,88, 852. (8) (a) Takita, T.; Umezawa, Y.; Saito, S.; Morishima, H.; Naganawa, H.; Umezawa, H.; Tsuchiya, T.; Miyake, T.; Kageyama, S.; Umezawa, S.; Muraoka, Y.; Suzuki, M.; Othuka, M.; Narita, M.; Kobayashi, S.; Ohno, M. Tetrahedron Lett. 1982,23,521. (b) Aoyagi, Y.; Katano, K.; Suguna, H.; Primeau, J.; Chang, L.-H.; Hecht, S. M. J. Am. Chem. SOC.1982,104, 5537. (c) Mauger, A. B. In “Topics in Antibiotic Chemistry”; Sammers, P. G., Ed.; John Wiley & Sons: New York, 1980; Vol. 5, pp 249-254. (9) (a) Rinhart, K. L., Jr., Suami, T., Eds. ‘Aminocyclitol Antibiotics”; American Chemical Society: Washington, D. C., 1979 and references cited therein. (b) Cox, D. A.; Richardson, K.; Ross, B. C. In ’Topics in Antibiotic Chemistry“; Sammers, P. G., Ed.; John Wiley & Sons: New York, 1977; Vol. 1, pp 70-80. (10) (a) Buchanan, J. G.; Wightman, R. H. In “Topics in Antibiotic Chemistry”; Sammers, P. G., Ed.; John wiley & Sons: New York, 1982; Vol. 6, pp 228-323. (b) Ito, Y.; Shibata, T.; Arita, M.; Sawai, H.; Ohno, M.; J . Am. Chem. SOC.1981, 103,6739. (11) (a) Suzuki, M.; Kawagishi, T.; Suzuki, T.; Noyori, R. Tetrahedron Lett. 1982,23, 5563. (b) Stork, G.; Takahashi, T.; Kawamoto, I.; Suzuki, T. J . Am. Chem. SOC.1978, 100, 8272. (c) Paul, K. G.; Johnson, F.; Favara, D. Ibid. 1976, 98, 1285. (d) Ogura, K.; Yamashita, M.; Tsuchihashi, G. Tetrahedron Lett. 1976, 759.
0022-3263/85/1950-4072$01.50/0
Scheme I 8-
A
s-
S-
extensive studies are being conducted on chiral induction utilizing chemical,3J3enzymati~,’@’~’~ and microbiological methods14“J5and chemical degradation of readily available natural products.4b,c,e,5,6a,b,7b,c,8,llb-d,16 While most modern chemical chiral syntheses utilize metal chelation for molecule regulation, we tried to develop a new chiral design based on the symmetry of the organic molecules without using metal chelation. Highly enantioselective differentiations between two identical ligands in prochiral cr-symmetric dicarboxylic acid esters have been done with m i c r o o r g a n i ~ m s ~or~ ~enJ~~ zymes like c u - c h y m ~ t r y p s i n ’and ~ ~ ~pig ~ liver Enzymatic discrimination between conformational enantiomers of cis- 1,2-bis(hydroxymethyl)cyclohexane and the related diols has also been reported.la Some nonenzymatic methods for distinguishing the prochiral ligands of 3(12) (a) Corey, E. J.; Clark, D. A.; Goto, G.; Marfat, A.; Mioskowski, C.; Samuelsson, B.; Hammarstram, S. J. Am. Chem. SOC.1980,102, 1436, 3663. (b) Corey, E. J.; Marfat, A.; Goto, G.; Brion, F. Ibid. 1980,102,7984. (13) (a) Meyers, A. I., Guest Ed. “Synthesis of Chiral Nonracemic Compounds”. Tetrahedron 1984, 40, 1213. (b) A book in Japanese entitled ‘Progree of Asymmetric Synthesis and Optical Resolution”; Ohtsuka, S., Mukaiyama, T., Eds.; Kagakudojin; Kyoto, 1982 and references cited therein. (c) Solladie, G. Synthesis, 1981, 185. (d) Brown, H. C.; Jadhav, P. K.; Mandal, A. K. Tetrahedron 1981, 37, 3547. (e) ApSimon, J. W.; Seguin, R. P. Tetrahedron 1979, 35, 2797. (14) (a) Gais, H.-J.; Lukas, K. L. Angew. Chem. 1984, 96, 140. (b) Schneider, M.; Engel, N.; Honicke, P.; Heinemann, G.; GGrisch, H. Angew. Chem., Int. Ed. Engl. 1984, 23, 67. (c) A review in Japanese entitled ‘Syntheses of Optically Active Substances from the Meso Compounds and the Compounds Having a Prochiral Carbon atom”. Nagao, Y.; Fujita, E.; J . Synth. Org. Chem. Jpn. 1984,42,622and references cited therein. (d) Jakovac, I. J.; Goodbrand, H. B.; Lok, K. P.; Jones, J. B. J. Am. Chem. SOC.1982, 104, 4659. (e) Ohno, M.; Kobayashi, S.; Iimori, T.; Wang, Y. F.; Izawa T. Ibid. 1981,103,2405. (f) Irwin, A. J.; Jones, J. B. Ibid. 1977, 99, 556. (9) Huang, F.-C.; Lee, L. F. H.; Mittal, R. S. D.; Ravikumar, P. R.; Chan, J. A.; Sih, C. J.; Caspi, E.; Eck, C. R. Ibid. 1975,97, 4144. (h) Cohen, S. G.; Khedouri, E. Ibid. 1961,83,4228. (15) (a) Chen, C.-S.; Fujimoto, Y.; Sih, C. J. J. Am. Chem. SOC.1981, 103,3580. (b) Fuganti, C.; Grasselli, P. J. Chem. SOC.,Chem. Commun. 1979,995. (c) Leuenberger, H. G. W.; Boguth, W.; Barner, R.; Schmid, M.; Zell, R. Helv. Chim. Acta 1979, 62,455. (d) Schmid, M.; Barner, R. Ibid. 1979, 62, 464. (e) Zell, R. Ibid. 1979, 62, 474. (16) Hanessian, S. “Total Synthesis of Natural Products: The ‘Chiron’ Approach”; Pergamon Press: New York, 1983.
0 1985 American Chemical Society
J. Org. Chem., Vol. 50, No. 21, 1985
Selective Nonenzymatic Chiral Induction phenylglutaric anhydride have been reported, but they were unsatisfactory from the viewpoint of enantioselectivity.17 In a recent preliminary report, we described a highly regioselective differentiation between two identical groups in 3-methylglutaric acid (l).l* We developed this method for meso compounds, enabling highly selective chiral induction into meso-2,4-dimethylglutaric acid (2)19vz0and meso-5-norbornene-2,3-endo,endo-diacetic acid (3).
4073
Me
I
O=/
Figure 1. Perspective view of the crystallographic structure of compound 8. Scheme I1 pro - R
1
Here, we report the complete details of the design and chemical chiral induction to 3-methylglutaric acid (1) together with recent findings on highly diastereoselective chiral induction into cis-6cyclohexen-l,Bylenebis(acetic acid) (4). Basic S t r a t e g y for t h e C h i r a l Design. We chose the prochiral a-symmetric molecule 1 for the new chiral design because we wanted to (1) perform the enzymimic chiral recognition through a simple chemical procedure, (2) establish a new concept for chiral induction into the prochiral a-symmetric molecule by using a chiral auxiliary, and (3) obtain the optically active product from 1 for further enantioconvergent reactions by suitable exchange of the functional groups because of its latent To regulate the free rotatory molecule in the transition state of chiral induction, we utilized the dipole-dipole repulsion between the carbonyl and the thiocarbonyl groups. The basic regulation system is illustrated in Scheme I. The thiocarbonyl group conjugating with the electron-donating atoms or groups, e.g., nitrogen atom, oxygen atom, the aromatic ring, and olefinic a-bond system, exhibits higher enhancement of the dipole moment than the corresponding carbonyl group.z1 Thus, 4(R)(methoxycarbonyl)-l,3-thiazolidine-2-thione [4(R)-MCTI'] (5) was selected as a chiral auxiliary. This five-membered heterocycle 5 is easily prepared in large quantities from the commercially available L-cysteine methyl ester hydrochloride and offers five merits for the chiral synthesis: (1)The fairly planar l,&thiazolidine-Zthione moiety can clearly differentiate the asymmetric environment of 4(R)-MCTT (5). (2) Because of its excellent leaving property,2zmild and smooth reaction of its 3-acyl derivatives can be expeded at low temperature. (3) Since 4(R)-MC?T (5) and its 3-acyl derivative 6 show UV absorption [compound 5 279 nm (t = 1.40 X lo4, CHCIJ; compound 6 (17) (a) Schwartz, P.;Carter, H. E. R o c . Natl. Acad. Sci., USA 1954, 40,499. (b)Altahul, R.;Bernstein, P.; Cohen, S. G. J. Am. Chem. Soc. 1956, 78, 5091. (18) Nagao, Y.; Ikeda, T.; Yagi, M.; Fujita, E.; Shiro, M. J. Am. Chem. SOC.1982,104, 2079. (19)Nagao, Y.;Inoue, T.; Fujita, E.; Terada, S.; Shiro, M. J. Org. Chem. 1983,48, 132. (20) Nagao, Y.; Inoue, T.; Fujita, E.; Terada, S.;Shiro, M. Tetrahedron 1984,40, 1215. (21) (a) Fukuyama, M.; Ohno, A. Kagaku no Ryoiki (in Japanese) 1968, 22, 977. (b) Lumbroso, H.; Schijl, P. J. W. CR Acad. Sci., Paris., Paris, Ser. C. 1967, 264, 925. (22) (a) Nagao, Y.; Miyasaka, T.; Hagiwara, Y.; Fujita, E. J. Chem. Soc., Perkin Trans I 1984, 183. (b) Nagao, Y.;Fujita, E. Heterocycles 1982, 17, 537 and references cited therein. (c) Nagao, Y. Yakugaku Zasshi (in Japanese) 1982, 102, 401 and references cited therein. (d) Fujita, E. Pure Appl. Chem. 1981, 53, 1141. (e) Nagao, Y.; Yagi, M.; Ikeda, T.; Fujita, E. Tetrahedron Lett. 1982,23, 201, 205. (23) Nagao, Y. Farumashia (in Japanese) 1983,19, 179.
5 "
NU& J iJ t.
"
yellow
'
N"'
Nu'","Nu2"= nucleophile
265-276 nm (e = 1.32-1.50 X lo4, CHC13), 304-316 nm ( 6 = 0.57-1.15 X lo4, CHCld], analysis of the chiral induction process should be easy by high performance liquid chromatography (HPLC) together with a UV detector. (4) Because 3-acyl derivatives 6 of 4(R)-MCTT (5) are yellow, their reactions with nucleophiles can be monitored by the color disappearance.zz (5) The enantiomeric purity of 5 can be readily checked by HPLC and NMR (lH and 19F) analyses of its MTPA [a(S)-a-methoxy-a-(trifluoromethy1)phenylacetic acid] amide 7.23 Chiral Induction into 3-Methylglutaric Acid. First, we tried to attain highly regioselective differentiation between two identical groups in 3-methylglutaric acid (1). The sequential reaction process is illustrated in Scheme
11. The important key compound 8,3-methylglutaric acid (1) diamide with 4(R)-MCTT (5), was designed as follows. In the molecule 8, the fairly strong dipole-dipole repulsion between the thiocarbonyl and the carbonyl groupsz1 and the repulsion between the pro-S group and the pro-R group may regulate the stereochemistry of the compound to stabilize a favorable W-shape or a slightly twisted W-shape conformation especially at low temperature. In the hypothetical W-shaped structure 8, the a-face of the carbonyl group in the pro-S ligand should be the least hindered when compared with the other three faces; the @-faceof the carbonyl group in the pro-S ligand is the most hindered by the /3-methoxycarbonyl and @-methylgroups; the @-face of the carbonyl group in the pro-R ligand is hindered by the P-methyl group; the a-face of the carbonyl group in the pro-R ligand is hindered by the a-methoxycarbonyl group, but the said face is not hindered by either group, both of which are @-oriented. Therefore, a suitable nucleophile can predominantly attack the amide carbonyl group in the pro-S ligand from the least hindered a-face in the transition state. The key diamide 8 was prepared and subjected to X-ray analysisz4and its crystallographic structure was shown to have a slightly twisted W-shape conformation, supporting in principle our working hypothesis (Figure 1).
4074
J. Org. Chem., Vol. 50, No. 21, 1985
Nagao et al. Scheme IV"
Table I. Search for a Useful Amine Nucleophile ("Nu'")" ratio of diastereomersb entry "Nul" at room temp at -30 "C le
Hfi-~HZa
2d
H " 3
3d
H
N
S
4d
H
N
a
5e
6'
..D M
(1 min)f 48.5:51.5
(1 h)' 50.5:49.5
(1 min) 66.9:33.1
(0.5 h) 78.4:21.6
(1 min) 72227.8
(2 h) 86.9:13.1
(1 min) 71.528.5
(3.5 h) 84.7:15.3
(1 min) 74.495.6
(13 h) 85.9:14.1
a a, p-Bromobenzenethiol, NaH, THF; b, NaBH,, aqueous THF; c, 6 N HCl, refluxing; d, benzene, azeotropic refluxing; e, CH,CI,, room temperature.
(4 h) 70.0:30.0
HNw
"For the reaction conditions, see text. "he ratio was determined by HPLC analysis of the reaction mixture. Detection: UV (305 nm); column JASCOSIL SS-05-250(silica gel type); solvent benzene-AcOEt (5:1),C(21): or (l:l).e 'Reaction time. Scheme HIa C02Me
93
L s
7 2%1,"
a, 4(R)-MCTT ( 5 ) ( 2 mol equiv), DCC, pyridine; b, piperidine (1mol equiv), CH,Cl,, -30 'C; c, silica gel column, hexane-Et,O-EtOAc ( 2 : 2 : 1 ) .
a
According to our hypothesis, the nucleophile ("Nu'") may attack selectively from the a-side of the carbonyl group in the p r o 3 ligand to give compound 9 as a major product (see Scheme 11). Separation of a mixture of diastereoisomers 9 and 10 should be easy, which is one of the merits of this diastereomeric-differentiating method over the corresponding enantiomeric-differentiating reactions (e.g., enzymatic chiral hydrolysis). The second attack of the other nucleophile ("Nu2") may produce compound 11 from the major product 9 and compound 12 from the minor product 1 0 11 and 12 are enantiomers. Thus, highly regioselective differentiation between two identical groups (CH2COOH) in 3-methylglutaric acid (1) should be achieved. The key compound 8 was prepared as yellow needles (mp 113-114 "C)in 69.9% yield by treatment of 3methylglutaric acid (1) with 2 mol equiv of 4(R)-MCTT (5) in the presence of DCC in pyridine. As a preliminary experiment, aminolysis of 8 was tried in CH2C12with 1mol equiv of various amines a t room temperature or a t -30 "C in order to find the best nucleophile "Nul" (Table 1). As expected, the ratio of the two diastereomers, checked by H P L C analysis, showed excellent regioselecitivity (78-87%) of cyclic secondary amines (entries 2-5 in Table I) especially at -30 "C. The best result was obtained with piperidine (entry 3), which was adopted as "NU'". Compound 8 was subjected to aminolysis with 1 mol equiv of piperidine in CH2C12a t -30 "C. The mixture obtained was chromatographed on a silica gel column with hexane-Et20-EtOAc (2:2:1) to separate a pure major product 9a as yellow needles (mp 95.5-96 "C) and a pure minor product as a yellow oil in a ratio of 88:12 (Scheme
111)* To check the structure and absolute configuration of the major product, 9a was allowed to react with p-bromo-
Figure 2. Perspective view of the crystallographic structure of compound 1IC.
benzenethiol in the presence of NaH, and the thio ester l l a (96.9% yield) obtained was reduced with NaBH, in aqueous THF, giving alcohol 13 in 83.6% yield. Acidic hydiolysis of this followed by lactonization gave compound 14 (65% yield), which proved to be identical with (-)-3(S)-methylvalerolactone (14) (Scheme IV).14f Furthermore, aminolysis of 9a with (-)-(S)-a-methylbenzylamine gave diamide l l c in high yield (Scheme IV). The structure and stereochemistry of l l c were established by X-ray analysis (Figure 2).24 Thus, the structure and absolute configuration of the major product were confirmed to be 9a, and our working hypothesis was proved to be correct. The structure and absolute configuration of the minor product 10a were established by transforming it into di, aminoamide 12c, the enantiomer of compound l l ~via lysis with (+)-(R)-a-methylbenzylamine (Scheme IV). The major product 9a was subjected to "monitored reactions" with several nucleophiles "Nu2". As can be seen from Table 11, thio ester preparation (entries 1 and 2), aminolysis (entries 3-6), esterification (entries 7 and 8 ) , C-C bond formation (entries 9 and lo), and hydrolysis (entry 11)proceeded smoothly to afford the corresponding optically pure compounds 1la-k in high yields. Some of these optically pure products may be useful as bifunctional synthons for the total synthesis of biologically active natural products. 1 3
U
t i ~ ? - S o B r
M',
1 3
NL'=-O-ICH~)Z
-0
Y
a,
(24) Crystallographic details, tables of atomic positional, and thermal parameters are availabe as supplementary material of our preliminary communication.18
Selective Nonenzymatic Chiral Induction
J. Org. Chem., Vol. 50, No. 21, 1985 4075
Scheme Va
L d Y90:MP
9
H
;-?
2'
a a, LiAlH,, THF; b, TsC1, pyridine; c, NaCN, Me,SO, 90 "C; d, KOH, EtOH-H,O, refluxing; e, 4(R)-MCTT (5) ( 2 mol equiv), DCC, pyridine; f, piperidine (1mol equiv), THF, -78 "C; g, recrystallization from hexane-CH,Cl,.
This chemical chiral induction method is conceptually similar to the enzymatically enantioselective hydrolysis of 3-substituted glutaric acid esters with pig liver esterasel"?g and c u - ~ h y m o t r y p s i n . ~ ~ ~ Our work established the novel concept that the introduction of the two same chiral ligands, e.g., two 4(R)MCTT groups, into a symmetrical molecule having a prochiral center changes its original symmetrical environment into an unsymmetrical one.
he Figure 3. Perspective view of the crystallographic structure of compound 20. Ne
Figure 4. Perspective view of the crystallographic structure of compound 19.
Chiral Induction into cis -4-Cyclohexen-1,2-ylenebis(acetic acid). As an application of this novel method, we attempted chiral induction into cis-4-cyclohexen-1,2ylenebis(acetic acid) (41, which should have two extreme enantiomeric conformers 4a and 4b (Figure 5). As ring W 2 O 4_a H JY" e * conversion of the cyclohexene part freely a t room tem/" conformatlanal contormationall perature, 4a and 4b cannot be resolved. Resolution of this diastereomerlsrr >enantlometism I type usually requires a particularly high barrier energy for the ring conversion a t very low t e m p e r a t ~ r e . ~Highly ~ selective chiral induction into conformational enantiomers (e.g., diols 15 and 16) has been achieved via the enzyme discrimination procedure by Jones and his c o - w o r k e r ~ . ~ ~ , ~ ~ However, chemical chiral induction into the conformational enantiomers had not been reported. Figure 5. 4(R)-MCTT promoted discrimination between conformational enantiomers 4a and 4b. I
E
16
R:CH2OH
1 1 R=C02H
Compound 4 was derived from a commercially available dicarboxylic acid 17 via the sequence shown in Scheme V.% Usual treatment of 4 and 2 equiv of 4(R)-MCTT (5) with DCC in pyridine afforded diamide 19 (mp 128-128.5 "C) in 63.6% yield. Aminolysis of diamide 19 with 1equiv of piperidine in T H F a t -78 "C gave a yellow solid (63.8% yield), which contained a 94.0:6.0 ratio of the products according to HPLC analysis. The solid mixture was recrystallized to give the major component (mp 125-125.5 " C ) in overall 51.2% yield from 19 (Scheme V). The structure and absolute stereochemistry of the major product were clarified to be 20 by crystallographic X-ray analysis.27 A perspective view of the crystallographic structure of 20 is shown in Figure 3.21 As we expected 20 t o be useful as "a bifunctional and optically active synthon" for asymmetric synthesis of biologically active compounds, such as prostacarvacyclins (25) Cf. Goodbrand, H. B., Jones, J. B. J.Chem. Soc., Chem. Commun. 1977, 469.
(26) Bloomfield, J. J.; Fennessey, P. V. Tetrahedron Lett. 1964, 2273. (27) Crystallographic structures of compounds 19 and 20 and their data are available as supplementary material.
