Enantioselective Functionalization of Difluorocyclopropenes Catalyzed by Chiral Copper Complexes: Proposal for Chiral gem-Dimethyl and tert-Butyl Analogues

Abstract

The highly enantioselective copper/chiral phosphine-catalyzed hydro-, bora-, and carbo-metalations of difluorocyclopropenes with PHMS [H-Si], H-BPin, (BPin)2, and (CH3)2Zn [Zn-Me] are shown to regiodivergently afford highly enantioenriched and functionalized difluorocyclopropanes. These examples can be viewed as the first successful syntheses of “chiral” gem-dimethyl and tert-butyl analogues.

The preparation and properties of 1,1-difluorocyclopropane derivatives

“…Consequently, the enantioselective functional group interconversions on prochiral or racemic difluorocyclopropane and difluorocyclopropene derivatives have provided important ways of obtaining enantiomerically pure cyclopropanes. The key reactions in this context are the enzyme-catalyzed formation and hydrolysis of esters and the hydrogenation of difluorocyclopropenes [73,79].…”

“…Recently, Mikami and co-workers reported the enantioselective hydrocupration of difluorocyclopropenes in the presence of chiral diphosphine ligands using stoichiometric hydride sources that included polymethylhydrosiloxane (PMHS) and organoboranes (Scheme 35) [79].…”

Asymmetric Transfer Hydrogenation of gem‐Difluorocyclopropenyl Esters: Access to Enantioenriched gem‐Difluorocyclopropanes

“…Alternatively, chemo‐enzymatic processes can be used, as illustrated by the kinetic resolution of racemic diacetate IX , which afforded optically active alcohol X and diacetate (−)‐ IX through a lipase‐catalyzed ester hydrolysis . Very recently, the enantioselective reduction of aryl gem ‐difluorocyclopropenes XI into aryl gem ‐difluorocyclopropanes XII by hydrocupration was disclosed (Scheme C) . Herein, we report a catalytic enantioselective approach toward disubstituted functionalized gem ‐difluorocyclopropanes, capitalizing on the asymmetric transfer hydrogenation of gem ‐difluorocyclopropenyl carboxylates A into gem ‐difluorocyclopropyl esters B in the presence of Noyori‐Ikariya ruthenium(II) complex and isopropanol as hydrogen donor (Scheme D).…”

Copper‐Catalyzed Enantioselective Hydrosilylation of gem‐Difluorocyclopropenes Leading to a Stereochemical Study of the Silylated gem‐Difluorocyclopropanes

“…As indicated by the intensive studies on synthesis of chiral cyclopropanes, [12] enantio‐controlled saturation process of the C=C double bond in cyclopropene is a promising and efficient approach to optically active gem ‐difluorocyclopropanes. Scheme 1a denotes a recently reported enantioselective synthesis of chiral gem‐ difluorocyclopropanes via hydrocupration of homochiral gem ‐difluorocyclopropenes followed by treatment with (deuterio)alcohols [13] . Use of polymethylhydrosiloxane (PMHS) as a hydrido source was successful, and the regio‐controlled hydrocupration furnished the corresponding chiral gem ‐difluorocyclopropanes as formal reduction products of the cyclopropenes in moderate to good enantiomeric excesses (up to 90 % ee).…”