Enantioselective Desymmetrization of Curcumins with 3‐Olefinic Oxindoles for the Synthesis of Spirocyclohexanoneoxindoles

Abstract

An enantioselective desymmetrization of curcumins with 3‐olefinic oxindoles involving a cascade double‐Michael addition strategy provides direct access to spirocyclohexanone‐oxindoles with complete regio‐ and diastereoselectivities and excellent enantioselectivities, besides good to excellent yields. The products possess three contiguous chiral centers and multiple reactive functionalities. The observed selectivities were rationalized by transitions state energy calculations at B3LYP//6‐31g(d) level of DFT.

The Michael donor–acceptor reactivity of curcumins in the synthesis of diverse multi-functional scaffolds

“…45 To date, asymmetric reactions with curcumins have been scarcely explored and, to fill this gap, our group introduced an enantioselective reaction of curcumin 23 with 3-alkylideneoxindole carboxylates 43, which offered spirocyclic compounds 44 in the presence of cinchonine derived thiourea catalyst C5 (Scheme 13). 46 The racemic product 44 was synthesized using TMG as base and CH 3 CN as solvent.…”

Regio- and stereoselective synthesis of functionalized tetrahydro-benzochromenes and hexahydrochromenochromenones via [4 + 2] annulation of curcumins with nitrochromenes

“…Surprisingly, the Michael donor–acceptor ability of curcumin remained unexplored until we first reported the reaction of curcumins with nitroalkenes leading to functionalized cyclohexanones via a double Michael reaction (Scheme 1a) and to dihydrofurans via Michael addition followed by intramolecular O -alkylation. 11 Subsequently, catalytic asymmetric single Michael 12 and double Michael (Scheme 1a) 13 additions to nitroalkenes, double Michael reaction with alkylidenemalononitrile (Scheme 1b and c) 14 and chalcones (Scheme 1d), 15 enantioselective double Michael reaction with 2-arylidene-1,3-indanediones (Scheme 1e) 16 have also been reported. Curcumin also participated in a single Michael addition to azodicarboxylates, 15 S N 2′ reaction followed by intramolecular oxa-Michael addition in the synthesis of furans, 17 and Michael addition followed by intramolecular O -alkylation in the synthesis of dihydrofurans.…”