Hydrogen Bond Donor-Catalyzed One-Pot Transformations of 2,2-Disubstituted Epoxides: Synthesis of Functionalized Nitrile-Rich Derivatives

J Org Chem. 2024 Dec 17. doi: 10.1021/acs.joc.4c02111. Online ahead of print.

Abstract

A practically intriguing catalytic domino methodology has been developed for the synthesis of highly functionalized pyran and ethene-1,1,2-tricarbonitrile derivatives in a single-pot operation. The gem-dicyano olefins and the corresponding epoxide were taken as the reactive partners in the presence of a hydrogen bond donor (HBD)-catalyzed condition. The reaction was found to be highly efficient in terms of the formation of sequential C-C and O-C bonds along with an exceptional CSp2-CSp coupling step through a metal-free organocatalytic pathway. This strategy has been further utilized on ester-substituted epoxides, although the results differ from those with gem-dicyano epoxides. The process remains versatile and effective across a wide range of substrates. This catalytic protocol has been proven to be very generalized with varieties of substrate scope. A low catalyst loading, ambient reaction conditions, and satisfactory yields of all of the products are the vital features of this approach. Moreover, the overall atom-economic outcome along with the synergistic reactivity pattern between the activated epoxide and the malononitrile derivatives is also very significant to address the originality of this process. Spectroscopic analysis is utilized to validate the mechanistic interpretation.