Tandem diastereo- and enantioselective preparation of aryl and alkyl cyclopropyl carbinols with three adjacent stereocenters using perhydrobenzoxazines and diethylzinc

Abstract

The enantio-and diastereoselective one-pot ethylation/cyclopropanation is efficiently promoted by a chiral perhydrobenzoxazine. The catalytic system tolerates a wide range of di-and trisubstituted α,β-unsaturated aldehydes and has been found to be highly diastereo-and enantioselective. Enals leading to intermediates lacking allylic strain or with either A 1,2 or A 1,3 strain afford the corresponding syn hydroxycyclopropanes very selectively. While α-methyl enals are successfully ethylated/cyclopropanated, the presence of bulky substituents at alpha position of the enal constitutes a limitation to the substrate scope. The use of 1,1-diiodoethane allows the obtention of the corresponding enantioenriched cyclopropylcarbinol, which bears carbon-substituents at all three positions of the ring, with good enantiocontrol, although moderate diastereoselectivity. A procedure for the asymmetric one-pot arylation/cyclopropanation of enals is proposed, which involves the use of triarylboroxin, diethylzinc and diiodomethane.

Diastereoselective Fluorocyclopropanation of Chiral Allylic Alcohols Using an α-Fluoroiodomethylzinc Carbenoid

“…In comparison to other halocyclo­propanations, the stereoselective synthesis of fluorocyclo­propanes from fluoro-substituted carbenoids is relatively understudied, mainly in part due to the lack of suitable methods for the efficient generation of the reagent. The diastereoselective transfer of carbenoids using chiral secondary allylic alcohols is an efficient strategy to synthesize 1,2,3-substituted halocyclo­propanes, , containing up to four stereocenters (Scheme ). We reasoned that this strategy could be applied toward the stereoselective formation of fluoro-substituted cyclopropanes.…”