Multicomponent Cyclizative 1,2‐Rearrangement Enabled Enantioselective Construction of 2,2‐Disubstituted Pyrrolinones

Abstract

The 1,2‐rearrangement reaction is one of the most important approaches to construct carbon‐carbon bonds in organic synthesis. However, the development of catalytic asymmetric 1,2‐rearrangements is still far from mature and often suffers from problems such as complex substrates, single product structure, and lack of synthetic application. Multicomponent reaction has been recognized as a robust tool for the synthesis of diverse and tunable products from readily available starting material. Conceptionally and practically, the development of multicomponent asymmetric 1,2‐rearrangements is highly desirable. In this regard, we report herein a three‐component benzilic acid‐type rearrangement of 2,3‐diketoesters, aromatic amines and aldehydes for the asymmetric construction of synthetically challenging pyrrolinones bearing aza‐quaternary stereocenters. To the best of our knowledge, this reaction represents the first example of organocatalyzed multicomponent asymmetric 1,2‐rearrangements.

Diverting the Mannich reaction to access 2,2-disubstituted indolin-3-ones by merging 1,2-aryl migration and copper-catalyzed aerobic oxidation

“…Instead of being directly captured by the nucleophile, the resulting acyl iminium intermediate might undergo a kinetically favored intramolecular aryl attack on the electrophilic ketone by the PMP motif (Scheme 1B). Inspired by Zhu and Wu's pioneering work on anionotropic 1,2-rearrangement, 12 we assume that a 1,2-aryl migration would take place subsequently, affording a 2-substituted indolin-3-one skeleton. However, the domino flow could be driven forward when a compatible oxidant is present.…”