Participation of β-Ketothioamides in N-Heterocyclic Carbene-Catalyzed [3 + 3] Spiroannulation: Asymmetric Synthesis of Functionalized Spiro-piperidinone Derivatives

J Org Chem. 2018 Dec 21;83(24):15245-15255. doi: 10.1021/acs.joc.8b02520. Epub 2018 Nov 30.

Abstract

An N-heterocyclic carbene-catalyzed asymmetric [3 + 3] spiroannulation of β-ketothioamide was successfully developed. β-Ketothioamides exhibit an unusual reactivity to undergo a previously challenging lactamization reaction, and the desired spiro-piperidinone derivatives containing two vicinal stereogenic centers were synthesized in good to high yields with high stereoselectivities, whose structure can be converted to the corresponding imide and δ-lactam derivatives smoothly.