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. 2017 Jun 21;139(24):8126-8129.
doi: 10.1021/jacs.7b04937. Epub 2017 Jun 6.

Enantioselective CuH-Catalyzed Hydroacylation Employing Unsaturated Carboxylic Acids as Aldehyde Surrogates

Yujing Zhou  1 , Jeffrey S Bandar  1 , Stephen L Buchwald  1
Affiliations

Enantioselective CuH-Catalyzed Hydroacylation Employing Unsaturated Carboxylic Acids as Aldehyde Surrogates

Yujing Zhou et al. J Am Chem Soc. .

Abstract

The direct asymmetric copper hydride (CuH)-catalyzed coupling of α,β-unsaturated carboxylic acids to aryl alkenes to access chiral α-aryl dialkyl ketones is reported. A variety of substrate substitution patterns, sensitive functional groups, and heterocycles are tolerated in this reaction, which significantly expands the range of accessible products compared with existing hydroacylation methodology. Although mechanistic studies are ongoing, we propose that CuH-catalyzed silylation of unsaturated acids occurs to access a uniquely effective acyl electrophilic coupling partner.

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Figures

Scheme 1
Scheme 1
Previous work in hydroacylation using (a) aldehydes, (b) aryl anhydrides, and (c, this work) α,β-unsaturated carboxylic acids to access chiral α-aryl ketones.
Scheme 2
Scheme 2
(a) Discovery and (b) SAR of CuH-catalyzed tandem hydroacylation and 1,4-reduction with unsaturated acyl electrophiles.a a yields determined by 1H NMR analysis of crude reaction mixture, (S,S)-Ph-BPE = 1,2-Bis((2S,5S)-2,5-diphenylphospholano)ethane.
Scheme 3
Scheme 3
Currently proposed pathway for hydroacylation.
Scheme 4
Scheme 4
The use of (a) acrylic acid and (b) β-ethoxyacrylic acid to access chiral ethyl ketones.a a Yields represent average isolated yields of two runs, performed with 1 mmol of alkene.
See this image and copyright information in PMC

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