Bi(III)-Catalyzed Enantioselective Allylation Reactions of Ketimines

Abstract

Summary Chiral homoallylic amines not only are found in pharmaceutically relevant compounds but also serve as versatile building blocks for chemical synthesis. However, catalytic allylation of ketimines with allylboronates, an attractive approach to synthesize chiral homoallylic amine scaffolds remain scarce. Herein, we develop a highly enantioselective allylation of isatin-derived ketimines with boron allylation reagents catalyzed by a Bi(OAc) 3 -chiral phosphoric acid catalyst system. The reactions are remarkably efficient and mild, most of which were completed in less than an hour at room temperature with only 1/2 mol% (Bi(OAc) 3 /CPA) catalyst loading. A wide range of chiral 3-allyl 3-aminooxindoles were obtained in excellent yields and enantioselectivities. The synthetic utility was demonstrated by efficient formal synthesis of (+)-AG-041R and (−)-psychotriasine. Preliminary mechanism was studied by control experiments and theoretical calculations.

Asymmetric Catalytic Ketimine Mannich Reactions and Related Transformations

“…In 2019, Li and coworkers described the development of an enantioselective asymmetric allylation of isatin-derived ketimines with allylboronates promoted by a binary acid system containing bismuth acetate and chiral phosphoric acid (Scheme 41) [127]. It is notable that most of the ketimines investigated were allylated in less than an hour at room temperature with only 1 mol% of Bi(OAc) 3 and 2 mol% of chiral phosphoric acid 48.…”

Chiral Aldehyde Catalysis Enables Direct Asymmetric Substitution Reaction of N-Unprotected Amino Acids with Halohydrocarbons

“…The clinical candidate compound (+)-AG-041R is a gastrin/CCK-B receptor antagonist with an IC50 of 1.1 nmol. [60][61][62][63][64][65] Few catalytic asymmetric methodologies have been developed for preparing this compound, [66][67][68][69][70][71][72][73][74][75][76] but we envisioned that its core oxindole unit can be constructed from our arylation product by a reduction of the nitro group and an in situ intramolecular amidation reaction, and a new catalytic asymmetric synthetic route for this clinical candidate was anticipated. As we discussed in the section on substrate scope, the diethyl aspartate 1b reacted smoothly with 2-nitro fluorobenzene 2a under the optimal reaction conditions, and product 3o was obtained in 52% yield with > 99% ee.…”

Recent Advances in Asymmetric Catalysis Using p‐Block Elements

“…[30] When considering the heavier group 15 elements, bismuth has gained popularity in catalysis in recent years, [31] and has also been found to show applications in enantioselective synthesis. For example, Bi(OAc) 3 /chiral phosphoric acid (CPA) systems have been utilised for enantioselective allylation reactions, [32][33][34][35][36] difluorocarbonylations, [37] and aza-Friedel-Crafts reactions. [38] In this mini-review we will highlight the key discoveries made in recent years (since 2016) in enantioselective catalysis employing borane, FLPs, bismuth, and aluminium as p-block catalysts.…”