A Novel Procedure for the Synthesis of Epoxides Application of Simmons-Smith Reagents toward Epoxidation

Full text of DOI:10.1021/jo971773h

8628
J . Org. Chem. 1997, 62, 8628-8629
Sch em e 1. Ap p lica tion of Or ga n ozin c Rea gen ts
tow a r d Ep oxid a tion
A Novel P r oced u r e for th e Syn th esis of
Ep oxid es: Ap p lica tion of Sim m on s-Sm ith
Rea gen ts tow a r d Ep oxid a tion
Varinder K. Aggarwal,* Amjad Ali, and
Michael P. Coogan
Department of Chemistry, University of Sheffield,
Sheffield S3 7HF, United Kingdom
Received September 23, 1997
The Simmons-Smith reaction1 and recent modifica-
tions2 thereof has emerged as a powerful method for the
diastereo-3 and enantioselective cyclopropanation of al-
kenes.4 In view of their effectiveness as cyclopropanating
agents, it was surprising that Simmons-Smith reagents
had not been exploited further in organic synthesis.5
Motivated by this, and by our interest in catalytic
asymmetric epoxidation,6,7 we initiated a program focused
toward the use of Simmons-Smith reagents for the
synthesis of epoxides, and in this paper we report our
success in achieving this goal (Scheme 1).
Ta ble 1. Or ga n ozin c-Med ia ted Ep oxid a tion Rea ction s of
Ald eh yd es
We were intrigued by the possibility that Simmons-
Smith reagents could react with sulfides to generate
ylides (Scheme 1).8,9 These zinc-derived sulfur ylides
could then be used to generate epoxides from aldehydes
and might offer a more attractive alternative to the more
traditional routes to sulfur ylides, in terms of enhanced
chemoselectivity, stereoselectivity and milder reaction
conditions. A major concern, however, was whether the
sensitive epoxides would be compatibile with the reaction
conditions, in particular, whether they would survive in
the presence of EtZnCl, a potential Lewis acid.
Initially, we decided to investigate the reaction of zinc
carbenoids derived from Et2Zn and ClCH2I (e.g., EtZnCH2-
Cl 1, Scheme 1) with sulfides. Such species are implied
intermediates in the generation of active zinc carbenoids
by the Furukawa protocol3 and have been the subject of
recent structural investigation.10 We treated an aldehyde
with Et2Zn, ClCH2I (this is higher yielding than CH2I211),
and tetrahydrothiophene and were pleased to obtain
(1) Simmons, H. E.; Smith, R. D. J . Am. Chem. Soc. 1959, 81, 4256.
(b) Simmons, H. E.; Cairns, T. L.; Vladuchick, S. A.; Hoiness, C. M.
Org. React 1973, 20, 1.
(2) (a) Furukawa, J .; Kawabata, N.; Nishimura, J . Tetrahedron
1968, 24, 53. (b) Furukawa, J .; Kawabata, N.; Nishimura, J . Tetrahe-
dron Lett. 1968, 3495.
(3) For reviews on diastereoselective Simmons-Smith reactions,
see: Hoffmann, R. W. Chem. Rev. 1989, 89, 1841. (b) Hoveyda, A. H.;
Evans, D. A.; Fu G. C. Chem. Rev. 1993, 93, 1307.
(4) For recent reviews on enantioselective Simmons-Smith cylo-
propanations, see: (a) Salaun, J . Chem. Rev. 1989, 89, 1247. (b)
Charette, A. B.; Marcoux, J .-M. Synlett 1995, 1197. (c) Lautens, M.;
Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49-92. For general reviews
on organozinc chemistry see: (d) Knochel, P.; Singer, R. D. Chem. Rev.
1993, 93, 2117. (e) Motherwell, W. B.; Nutley, C. J . Contemp. Org.
Synth. 1995, 1, 219.
(5) For notable exceptions see: (a) Sidduri, A. R.; Knochel, P. J . Am.
Chem. Soc. 1992, 114, 7579. (b) McWilliams, J . C.; Armstrong, J . D.;
Zheng, N.; Bupathy, M.; Volante, R. P.; Reider, P. J . J . Am. Chem.
Soc. 1996, 118, 11970.
(6) (a) Aggarwal, V. K.; Abdel-Rahman, H.; J ones, R. V. H.; Lee, H.
Y.; Reid, B. D. J . Am. Chem. Soc. 1994, 116, 5973. (b) Aggarwal, V.
K.; Abdel-Rahman, H.; Li, F.; J ones, R. V. H.; Standen, M. Chem. Eur.
J . 1996, 2, 1024.
(7) Aggarwal, V. K.; Ford, J . G.; Thompson, A.; J ones, R. V. H.;
Standen, M. C. H. J . Am. Chem. Soc. 1996, 118, 7004.
(8) Cohen was the first to explore the reaction of Simmons-Smith
reagents with sulfides: Kozarych, Z.; Cohen, T. Tetrahedron Lett. 1982,
23, 3019.
(9) For another use of sulfur ylides derived from Simmons-Smith
reagents, see: Bhat, L.; Thomas, A.; Ila, H.; J unjappa, H. Tetrahedron
1992, 48, 1037.
a
Product ratios are based on analysis by gas chromatography
and/or 1H NMR. Yields refer to isolated products.
b
epoxide in high yield (Table 1).12 Aromatic and aliphatic
aldehydes worked well, and the reaction even tolerated
(10) (a) Charrette, A. B.; Marcoux, J . F. J . Am. Chem. Soc. 1996,
118, 4539. (b) Denmark, S. E.; Edwards, J . P.; Wilson, S. R. J . Am.
Chem. Soc. 1992, 114, 2592. (c) Denmark, S. E.; Christenson, B. L.;
O’Connor, S. P. Tetrahedron Lett. 1995, 13, 2219. (d) Denmark, S. E.;
O’Connor, S. P. J . Org. Chem. 1997, 62, 584.
S0022-3263(97)01773-8 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 25, 1997 8629
unsaturated aldehydes (entry 6) without undergoing
cyclopropanation. This indicated that reaction of the zinc
carbenoid with the sulfide was much more rapid than
reaction with the alkene. R-Alkoxy (entries 7 and 8) and
R-amino aldehydes (entries 9 and 10) also reacted
smoothly, giving epoxides but as mixtures of diastereo-
isomers. In all cases, the diastereoselectivity was similar
to that observed in reactions of trimethylsulfonium ylide
with the aldehydes.13 However, in no case was any
racemization detected, whereas it has been reported that
in the case of the aldehyde derived from phenylalanine
substantial racemization occurs in the ylide epoxidation
process.14 The epoxide derived from phenylalanine (entry
10) is extremely important as it is a key intermediate in
the syntheses of many HIV protease inhibitors.14,15 The
mild conditions reported here makes this method com-
petitive with other literature methods.
In summary, we have developed a novel application of
organozinc reagents toward the epoxidation of carbonyl
compounds via the intermediacy of sulfur ylides. Ongo-
ing studies include the design and synthesis of chiral
sulfides for asymmetric epoxidation.
Ack n ow led gm en t. We thank Hesham Abdel Rah-
man for carrying out preliminary studies and the
Engineering and Physical Sciences Research Council
(EPSRC) for support.
(11) For comparative studies of the two reagents in cyclopropanation
see: Denmark, S. E.; Edwards, J . P. J . Org. Chem. 1991, 56, 6974.
(12) Sample experimental details (Table 1, entry 1): St yr en e
Oxid e. To a solution of diethyl zinc (1.82 mL of a 1.1 M solution in
toluene, 2.0 mmol) in 1,2-dichloroethane (6 mL) was added chlor-
oiodomethane (0.14 mL, 2.0 mmol) at -15 °C, under an atmosphere
of nitrogen. The reaction mixture was stirred for 15 min before the
addition of tetrahydrothiophene (0.26 mL, 3.0 mmol) and benzaldehyde
(0.10 mL, 1.0 mmol). The reaction mixture was allowed to warm to
ambient temperature and then stirred for 48 h. The reaction mixture
was diluted with CH2Cl2 (10 mL) and washed with NH4Cl (5 mL). The
aqueous phase was extracted with CH2Cl2 (3 × 20 mL), and the
combined organic phases were dried (MgSO4) and concentrated in
vacuo. The crude product was purified by column chromatography
(eluant: 10% EtOAc/Petrol) to afford styrene oxide as a colorless oil
(78 mg, 74%): δH (CDCl3) (250 MHz) 7.25 (5H, m), 3.85 (1H, dd J )
4.5 Hz, 3.0 Hz, CHOCH2), 3.30 (1H, dd, J ) 5.0 Hz, 4.5 Hz, CH2O),
2.85 (1H, dd, J ) 5.0 Hz, 3.0 Hz, CH2O).
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, spectral data and methods for determination of
enantiomeric excess of epoxides derived from chiral aldehydes
(5 pages).
J O971773H
(14) Ng, J . S.; Przybyla, C. A.; Liu, C.; Yen, J . C.; Muellner, F. W.;
Weyker, C. L. Tetrahedron 1995, 51, 6397. The R-alkoxy aldehyde
(entry 7) is even more prone to racemization than the R-amino aldehyde
(entry 10) but again none was detected.
(15) Beaulieu, P. L.; Lavallee, P.; Abraham, A.; Anderson, P. C.;
Boucher, C.; Bousquet, Y.; Duceppe, J . S.; Gillard, J .; Gorys, V.;
GrandMaitre, C.; Grenier, L.; Guindon, Y.; Guse, I.; Plamondon, L.;
Soucy, F.; Valois, S.; Wernic, D.; Yoakim, C. J . Org. Chem. 1997, 62,
3440 and references therein.
(13) (a) For addition to protected glyceraldehyde see: Hagen, S.;
Anthosen, T.; Kilas, L. Tetrahedron 1979, 35, 2583. (b) For addition
to amino aldehydes see: Reetz, M. T.; Binder, J . Tetrahedron Lett.
1989, 30, 5425.