Synthesis of Functionalized Five-Membered Heterocycles from Epoxides: A Hydrogen-Bond Donor Catalytic Approach.

Abstract

The synthesis of highly functionalized five-membered oxa- and aza-heterocycles has been reported utilizing hydrogen-bond donor (HBD) catalysis. In this method, an epoxide was taken as a substrate and reacted with functionalized arylidene/alkylidene malononitrile derivatives in the presence of a newly designed HBD catalyst. In all the cases, the products 2,5-disubstituted tetrahydrofurans (2,5-THFs) were obtained in good to excellent yields (up to 86%) with high diastereoselectivity (dr up to 99:1) as a single regioisomer. The stereochemistry at the 2- and 5-positions of the five-membered ring has been confirmed by single-crystal X-ray analysis, and cis is found to be the major product. The same strategy has been further utilized to obtain substituted oxazolidines whenever the epoxide has been reacted with isocyanate as an electrophile. In order to induce enantioselectivity, a chiral epoxide has been reacted with both the electrophiles in the presence of the same catalyst system to afford the single stereoisomer of the final products. This synthetic methodology involves a low catalyst loading and ambient reaction condition and has been generalized with various substituents present in the starting electrophiles to produce the resultant products in acceptable yields and stereoselectivity.