A practical catalytic reductive amination of carboxylic acids.

Autor: Stoll EL; School of Chemistry, GlaxoSmithKline Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham 6 Triumph Road Nottingham NG7 2GA UK ross.denton@nottingham.ac.uk., Tongue T; School of Chemistry, GlaxoSmithKline Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham 6 Triumph Road Nottingham NG7 2GA UK ross.denton@nottingham.ac.uk., Andrews KG; School of Chemistry, GlaxoSmithKline Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham 6 Triumph Road Nottingham NG7 2GA UK ross.denton@nottingham.ac.uk., Valette D; GlaxoSmithKline Gunnels Wood Road Stevenage SG1 2NY UK., Hirst DJ; GlaxoSmithKline Gunnels Wood Road Stevenage SG1 2NY UK., Denton RM; School of Chemistry, GlaxoSmithKline Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham 6 Triumph Road Nottingham NG7 2GA UK ross.denton@nottingham.ac.uk.
Jazyk: angličtina
Zdroj: Chemical science [Chem Sci] 2020 Aug 12; Vol. 11 (35), pp. 9494-9500. Date of Electronic Publication: 2020 Aug 12.
DOI: 10.1039/d0sc02271c
Abstrakt: We report reductive alkylation reactions of amines using carboxylic acids as nominal electrophiles. The two-step reaction exploits the dual reactivity of phenylsilane and involves a silane-mediated amidation followed by a Zn(OAc) 2 -catalyzed amide reduction. The reaction is applicable to a wide range of amines and carboxylic acids and has been demonstrated on a large scale (305 mmol of amine). The rate differential between the reduction of tertiary and secondary amide intermediates is exemplified in a convergent synthesis of the antiretroviral medicine maraviroc. Mechanistic studies demonstrate that a residual 0.5 equivalents of carboxylic acid from the amidation step is responsible for the generation of silane reductants with augmented reactivity, which allow secondary amides, previously unreactive in zinc/phenylsilane systems, to be reduced.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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