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Enantio- and Diastereoselective Synthesis of Homoallylic α-Trifluoromethyl Amines by Catalytic Hydroalkylation of Dienes

Chibueze I. Onyeagusi, Xinxin Shao, Steven J. Malcolmson

2020Organic Letters44 citationsDOIOpen Access PDF

Abstract

We describe a strategy for the enantio- and diastereoselective synthesis of homoallylic α-trifluoromethyl amines by the catalytic hydroalkylation of terminal dienes. Trifluoromethyl-substituted isatin-derived azadienolate nucleophiles undergo γ-selective alkylation with a Pd-DTBM-SEGPHOS catalyst, which additionally promotes regioselective addition to the diene and delivers products in up to 86% yield, 10:1 dr, and 97.5:2.5 er.

Topics & Concepts

ChemistryTrifluoromethylCatalysisOrganic chemistryCombinatorial chemistryAlkylFluorine in Organic ChemistryAsymmetric Synthesis and CatalysisCyclopropane Reaction Mechanisms
Enantio- and Diastereoselective Synthesis of Homoallylic α-Trifluoromethyl Amines by Catalytic Hydroalkylation of Dienes | Litcius