CuH-Catalyzed Asymmetric Reduction of α,β-Unsaturated Carboxylic Acids to β-Chiral Aldehydes

Abstract

The copper hydride (CuH)-catalyzed enantioselective reduction of α,β-unsaturated carboxylic acids to saturated aldehydes is reported. This protocol provides a new method to access a variety of β-chiral aldehydes in good yields, with high levels of enantioselectivity and broad functional group tolerance. A reaction pathway involving a ketene intermediate is proposed based on preliminary mechanistic studies and density functional theory calculations.

Figure 1

(a) General Access to β-Chiral Aldehydes (b) Racemic and (c) Asymmetric Transformation from α,β-Unsaturated Carboxylic Acids to Saturated Aldehydes (This work)

Scheme 1. (a) Discovery and (b) Model Reaction of Unsaturated Acid Reduction Protocol^{a, ,}

^a (S,S)-Ph-BPE = 1,2-Bis((2S,5S)-2,5-diphenylphospholano)ethane.

Scheme 2

Proposed Mechanisms and Preliminary Mechanistic Studies

Scheme 3. One-pot Transformation from α, β-Unsaturated Carboxylic Acids to Chiral Amines^a

^a Reactions were conducted on 0.50 mmol scale. See the Supporting Information for detailed conditions.