Synergistic catalysis: enantioselective cyclopropanation of alkylidene benzoxazoles by Pd(ii) and secondary amine catalysis. Scope, limitations and mechanistic insight

Abstract

An enantioselective synergistic cascade cyclopropanation/NHC catalyzed ring opening has been reported. DFT calculations have been performed to confirm the mechanism.

Synergistic Catalysis for Asymmetric [3 + 2] Cycloadditions of 2-Indolylmethanols with α,β-Unsaturated Aldehydes

“…On the other hand, the Shi group has described a cooperative catalysis-enabled asymmetric α-arylation of aldehydes employing 2-indolylmethanols as arylation reagents . Based on the superiority of cooperative catalysis and our continuing efforts in using chiral diarylprolinol silyl ethers as an effective promoter for activation of 2-enals, we design the asymmetric [3 + 2] cycloaddition of 2-indolylmethanols and α,β -unsaturated aldehydes, which was catalyzed by a synergistic catalytic system consisting of Brønsted acids (BH) and secondary amines, providing rapid access to various cyclopenta­[ b ]­indole derivatives (Scheme c).…”

Recent progress in asymmetric synergistic catalysis – the judicious combination of selected chiral aminocatalysts with achiral metal catalysts

“…The final stereochemical outcome arises from the stereospecific inversion of this centre occurring from the Si face of the trans -enamine for the 2 R diastereomer but from the Re face for the 2 S diastereoisomer. 60 This model did not incorporate the secondary coordination of the palladium to the iminium ion as previously postulated.…”

Combined Power of Organo‐ and Transition Metal Catalysis in Organic Synthesis

“…Moreover, the stereoselectivity of the cyclopropanation reaction that is responsible for unusual cis conformation in the product was explained by a thorough mechanistic study. [47] In 2020, Luo et al introduced an arene-containing chiral primary amine as a dual aminocatalyst and ligand in the asymmetric allylic alkylation of α-branched β-ketocarbonyls 28. [48] The π-coordinating chiral primary amine catalyst can be successfully applied in the asymmetric allylation reactions of vinylethylene carbonates (VEC)'s 29 (Scheme 17), vinyl epoxides, or simple allylic alcohols.…”

“…Further, the applicability of this reaction was demonstrated for cascade cyclopropanation and ring‐opening reaction which prevents some of the limitations of the simple Michael addition between alkyl‐benzoxazoles and enals. Moreover, the stereoselectivity of the cyclopropanation reaction that is responsible for unusual cis conformation in the product was explained by a thorough mechanistic study [47] …”