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

• DOI: 10.1021/acs.orglett.0c00342
• Publication Date: 2020-02-04T13:25:34Z
• Authors: Chibueze I. Onyea...; Xinxin Shao; Steven J. Malcolmson
• Keywords: Alkadienes; Alkylation; Molecular Structure; Coordination Complexes; Stereoisomerism; Amines; 01 natural sciences; Catalysis; Palladium; 0104 chemical sciences

We describe a strategy for the enantio- and diastereoselective synthesis of homoallylic α-trifluoromethyl amines by the catalytic hydroalkylation of terminal dienes. Trifluoromethylsubstituted 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.