Asymmetric Direct Vinylogous Michael Reaction of Activated Alkenes to Nitroolefins Catalyzed by Modified Cinchona Alkaloids

Abstract

[reaction: see text] The first organocatalytic and asymmetric direct vinylogous Michael reaction that employs the electron-deficient vinyl malononitriles as the nucleophilic species has been reported. The novel transformations exhibit exclusive gamma-selectivity and high diastereo- and enantioselectivity in the addition to nitroolefins, which give the multifunctional products with two vicinal chiral centers.

Recent applications of Cinchona alkaloids and their derivatives as catalysts in metal-free asymmetric synthesis

“…A direct vinylogous Michael addition that utilises electron-deficient malononitriles such as 104 as the nucleophilic Michael donor in addition reactions to nitroolefins 12 displayed exclusive g-selectivity and high diastereo-and enantioselectivity, giving multifunctional products 105 with two adjacent chiral centres (Scheme 39). 68 Natural quinine and quinidine were tested as catalysts together with three commercially available modified Cinchona alkaloid catalysts, (DHQD) 2 AQN 103a, (DHQD) 2 PHAL 103b and (DHQD) 2 PYR 103c, of which 103c was found to be the most efficient catalyst for the transformation. A similar observation regarding 103c was reported by Jørgensen and co-workers.…”

Asymmetric Organocatalysis

“…An asymmetric direct vinylogous Michael reaction of activated vinyl malononitriles to nitroolefins catalyzed by modified cinchona alkaloid [DHQD] 2 PYR was reported by Chen (Scheme 61) [135]. Highly functionalized products with two vicinal chiral centers were generated with exclusive g-selectivity and high diastereoand enantioselectivity.…”

Cinchona‐Catalyzed Nucleophilic Conjugate Addition to Electron‐Deficient CC Double Bonds

“…Sharpless bis-cinchona alkaloids such as [DHQD] 2 PYR (163a) have proved to serve as highly efficient catalysts for the asymmetric vinylogous Michael addition of the electron-deficient vinyl malonitriles 164 as the nucleophilic species to nitroolefins 124 [50]. This process exhibited exclusive g-regioselectivity and high diastereoand enantioselectivity.…”