Asymmetric Synthesis of 3,3-Disubstituted Isoindolinones Enabled by Organocatalytic Functionalization of Tertiary Alcohols

Abstract

An enantioselective intramolecular heterocyclization with in situ generated 3-hydroxyisoindolinone-derived N-acyliminium ions has been successfully accomplished. In the presence of a catalytic amount of a chiral phosphoric acid, functionalized 3,3-disubstituted isoindolinones bearing N-acyl-N,O-acetal moieties were obtained with good yields and a high level of stereocontrol (up to 98:2 er). This efficient method proceeds under mild conditions and exhibits broad scope with respect to both 3-hydroxyisoindolinones and hydroxyl partners.

Key words

N-acyliminium ion - chiral phosphoric acid - 3,3-disubstituted isoindolinones - N-acyl-N,O-acetal - enantioselective

Publication History

Received: 07 July 2022

Accepted after revision: 10 August 2022

Article published online:
23 September 2022

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