Synthesis of C2-Symmetric Sulfide and Its First Application in Highly Enantioselective Synthesis of Chiral Aziridines

Abstract

A C2-symmetric sulfide 6 has been synthesized from cheap l-tartaric acid. It was found that sulfide 6 could perform a tandem reaction with benzyl bromide and tosyl imines to give (2S,3S)-aziridines 9a–9g with good to excellent enantioseletivities (up to 96% ee).

Catalytic Asymmetric Darzens and Aza‐Darzens Reactions for the Synthesis of Chiral Epoxides and Aziridines

“…Huang et al . reported the preparation of chiral sulfonium ylide generated in situ from the C 2 ‐symmetric sulfide 116 , derived from L‐tartaric acid, and its use for the asymmetric aziridination of N ‐tosyl aldimines 114 with benzyl bromide ( 115 ) in the presence of potassium carbonate (Scheme ).…”

“…In contrast to the use of a stoichiometric amount of sulfide, the Chein group developed in 2014 an enantioselective catalytic sulfur ylide aziridination using 20 mol % of chiral (thiolan‐2‐yl)diphenylmethanol benzyl ether ( 125 ) as organocatalyst (Scheme ) . Thus, using organocatalyst 125 , a wide scope of trans ‐ N ‐diphenylphosphinic aziridines 126 have been prepared in good yields and enantioselectivities of up to 98 % ee .…”

Recent Developments in Asymmetric Aziridination

“…In 2007, Huang et al. have reported the synthesis of a novel chiral C 2 ‐symmetrical sulfide from L ‐tartaric acid and its application to an asymmetric domino reaction between benzyl bromide and tosylimines to form the corresponding aziridines 82. In this case, the sulfide reacted with benzyl bromide in the presence of potassium carbonate to generate the corresponding chiral sulfonium ylide in situ , which then reacted with an N ‐tosylimine to yield the aziridine.…”

Phosphorothioic Acids and Related Compounds as Surrogates for H2S—Synthesis of Chiral Tetrahydrothiophenes

“…Hauptman and co-workers demonstrated that rhodium complexes with chiral bis(phosphinite) ligands 5 are effective in asymmetric hydrogenation reactions. Metzner and co-workers showed that sulfur ylides derived from 6 – 7 can promote enantioselective epoxidation reactions while Huang demonstrated the utility of 8 in aziridinations. Aggarwal’s group used sulfur ylides derived from 9 as stereoselective epoxidation, cyclopropanation, and aziridination reagents …”

“…We outline here the more notable reports. Metzner and Huang’s preparation of 6 – 8 relied on the double displacement reaction of the corresponding mesylated diol with Na 2 S. Wang, Högberg, and Besada have also reported syntheses of chiral tetrahydrothiophenes. These methods were based on conjugate additions, sulfur ylides, or singlet oxygen-mediated rearrangements.…”