Ligand-controlled asymmetric arylation of aliphatic α-amino anion equivalents

Abstract

A palladium-catalyzed asymmetric arylation of 9-aminofluorene-derived imines using a chiral dialkylbiaryl phosphine as the supporting ligand has been developed. This transformation allows for enantioselective access to a diverse range of α-branched benzylamines.

Scheme 1. Proposed Pd-Catalyzed Arylation Reaction

Scheme 2. Pd-Catalyzed Arylation of Imine 2b

Reaction conditions: see Table 1. The rr (regioisomeric ratio, 3b to 5) was determined by ¹H NMR spectroscopy for the corresponding amines upon NaBH₄ reduction.

Scheme 3. Pd-Catalyzed Enantioselective Arylation Reactions^,

Reaction conditions: Ar–X (1 mmol, X = Br unless otherwise noted), 2 (1.15 mmol), NaOtBu (1.1 mmol). Isolated yields (averages of two runs) are shown. Boc = tert-butoxycarbonyl. Ts = p-toluenesulfonyl. The absolute configuration of 6c was assigned as S. See the Supporting Information for details. [(η-C₃H₅)PdCl]₂ (5 mol %), L7 (12.5 mol %), 2 (1.25 mmol), NaOtBu (1.2 mmol). The ee was determined for the corresponding N-Boc amine. 2 (1.05 mmol).