Diarylborinic Acid Derivatives as a Catalytic Iminium Ion Generator in the Mannich-Type Reaction Using Secondary Amines, Aldehydes, and Ketene Silyl Acetals

Abstract

Reactions of secondary amines, aldehydes, and ketene silyl acetals were efficiently promoted by catalytic amounts of diarylborinic acid esters, Ar₂B(OR), affording β-amino esters selectively with no formation of the corresponding β-hydroxy esters.

Key words

boron-based catalyst - β-amino acids - iminium ion intermediate - ketene silyl acetal - nucleophilic additions

References and Notes

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13

General Procedure for the Ph ₂ BOMe-Catalyzed Mannich-Type Reaction
To a solution of Ph₂BOMe (3.9 mg, 0.02 mmol) in DMSO (1.0 mL) were added amine 3 (0.4 mmol), aldehyde 2 (0.4-0.6 mmol), and ketene silyl acetal 4 (0.8 mmol). The mixture was stirred for 12 h at 60 °C, quenched with ice water, and extracted with EtOAc. The organic layer was washed with H₂O, and aqueous layer was extracted with EtOAc. The combined organic layer was dried over Na₂SO₄ and evaporated under vacuum. The crude 5 was purified by silica gel column chromatography. The imine-containing products 8 and 10 could not be purified by column chromatography, but were isolated by bulb-to-bulb distillation.

14

The imine-amine conjugate 7 exists as the cyclized aminal form, which may be in equilibrium with the imine form shown in the scheme.