Preparation of Enantiomerically Enriched (2R,3R)- or (2S,3S)-trans-2,3-Diaryloxiranes via Camphor-Derived Sulfonium Ylides

Abstract

Easily available D-(+)-camphor-derived sulfides 3, 4, 6, and 7 were employed for enantioselective epoxidation via an ylide route. When benzylated or methylated sulfides were used as reagents or mediators for benzylidene transfer, stoichiometric and catalytic epoxidations were realized, respectively. Opposite asymmetric induction was achieved only when sulfides containing exo- (3 and 4) and endo- (6 and 7) alkylthio groups were used. That is, both (+)- and (-)-trans-diaryloxiranes could be obtained in excellent yields and moderate to good ee values under extremely mild conditions from the same chiral pool-derived reagents. A nonbonded interaction between the free OH in the ylides from sulfides (3, 6, and 7) and the carbonyl group of aldehydes controls the approach of the substrates to the ylidic carbon preferentially at one specified face and therefore leads to a more efficient asymmetric induction than that in the case of the ylide from methyl-protected hydroxylated sulfides 4, which cannot cause such an interaction. The same opposite asymmetric induction was also observed in the catalytic reaction with methyl-protected hydroxylated sulfide 4b and unprotected hydroxylated sulfide 3b.

Stereoselective synthesis of three-membered ring compounds via ylide routes

“…However, the ylide and carbenoids methodologies can only be applied to an activated imine, that is C¼N double bonds with an N-electron-withdrawing group, such as p-tolylsulfonyl (Ts) [8,10,12,13,14,16], diphenylphosphinoyl (DPP) [15] or 2-(trimethylsilyl)ethylsulfonyl (SES) [17]. No report has appeared for the reaction of a nonactivated imine with a semistablized or stablized ylide.…”

“…A catalytic version of this reaction was achieved by employing methyl sulfides and high yields and enantioselectivities were obtained [10].…”

A New Chiral Organosulfur Catalyst for Highly Stereoselective Synthesis of Epoxides

“…Recently, the chiral ylide route has become one of the most important strategies for optically active epoxides because it combines the formation of a carbon-carbon bond and an epoxidation into one reaction. [2][3][4][5][6] Although there are many reports on employing chiral sulfides to catalyze epoxidation reactions via sulfonium ylides, very successful cases are still limited.…”

“…[2a, [3][4][5][6] Aggarwal et al found that chiral sulfonium ylides could be formed by the reaction of sulfides with diazo compounds under the catalysis of CuA C H T U N G T R E N N U N G (acac) 2 or Rh 2 A C H T U N G T R E N N U N G (OAc) 4 , affording an elegant synthesis of trans-diaryl epoxides in high yields with excellent distereoselectivities and enantioselectivities (up to 94% ee). [3] In these processes, although novel sulfides were used as organocatalysts, metal complexes were also neccessarily employed.…”

Direct Utilization of Naturally Occurring Sulfides for the Asymmetric Epoxidation of Aldehydes Mediated by Catalytic Ylides

“…Synthesis of the chiral sulfides required 3 to 5 synthetic steps from camphor, [25][26][27] pulegone, 28 mannitol, 29 tartaric acid 30 or by an enzymatic reduction, 31 or a resolution. 32 Our present approach was of the utmost simplicity, i.e.…”