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Title: Direct, enantioselective, and nickel(II) catalyzed reactions of N-azidoacetyl thioimides with trimethyl orthoformate: a new combined methodology for the rapid synthesis of lacosamide and derivatives
Author: Teloxa, Saul F.
Kennington, Stuart C. D.
Camats Gangonells, Marc
Romea, Pedro
Urpí Tubella, Fèlix
Aullón López, Gabriel
Font Bardia, Ma. Mercedes
Keywords: Anticonvulsius
Síntesi asimètrica
Compostos de níquel
Asymmetric synthesis
Nickel compounds
Issue Date: 8-Apr-2020
Publisher: Wiley-VCH
Abstract: A direct and highly enantioselective reaction of N-azidoacetyl-1,3-thiazolidine-2-thione with trimethyl orthoformate catalyzed by Tol-BINAPNiCl2 in the presence of TESOTf and 2,6-lutidine is reported. The heterocyclic scaffold can be easily removed by addition of a wide array of amines to give the corresponding enantiomerically pure 2-azido-3,3-dimethoxypropanamides in high yields. Appropriate manipulation of the N-benzyl amide derivative provides an efficient access to the antiepileptic agent lacosamide through a new enantioselective C−C bond-forming process. DFT computational studies uncover clues for the understanding of the remarkable stereocontrol of the addition of a nickel(II) enolate to a putative oxocarbenium intermediate from trimethyl orthoformate.
Note: Versió postprint del document publicat a:
It is part of: Chemistry-A European Journal, 2020, vol. 26, num. 49, p. 11540-11548
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ISSN: 0947-6539
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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