Isocyanide based multicomponent reactions of oxazolidines and related systems

TETRAHEDRON

卷:66

Article; Proceedings Paper

Waller, Robert W.¹  Diorazio, Louis J.²  Taylor, Brian A.²  Motherwell, William B.¹  Sheppard, Tom D.¹ 

[1] UCL, Dept Chem, Christopher Ingold Labs, London WC1H 0AJ, England

[2] AstraZeneca, AstraZeneca Proc R&D, Macclesfield SK10 2NA, Cheshire, England

关键词: Multicomponent reactions;    Isocyanides;    Design of experiments;    Oxazolidines;    Ring-opening reactions;   

DOI  :  10.1016/j.tet.2010.05.083

来源: Elsevier

【 摘 要 】

N-Alkyloxazolidines react in a multicomponent reaction with carboxylic acids and isocyanides to give N-acyloxyethylamino acid amides. The previously reported reaction conditions were improved using a design of experiments approach (DoE). Under the optimised conditions, good yields of the N-acyloxyethylamino acid amide products are obtained both via a three- or four-component approach from N-alkylethanolamines, aldehydes/ketones, isocyanides and carboxylic acids. The reaction of oxazolidines without a nitrogen substituent was found to give either the expected Ugi products or the N-acyloxyethylamino acid amides depending on the choice of reaction conditions. Optimised reaction conditions were also developed for the ring-expansion of oxazolidines to morpholin-2-ones via reaction with an isocyanide followed by hydrolysis. The mechanistic pathway of the multicomponent reaction was briefly investigated using an O-18 labelling experiment. The carboxylic acid component can be replaced by a range of other acidic nucleophiles including thiobenzoic acid, thiophenol or 5-phenyltetrazole, which are incorporated via an alternative pathway. These latter reactions can also be applied to 2-aminotetrahydrofurans, 2-aminotetrahydropyrans or 4-hydroxybut-2-one, further extending the structural diversity of the multicomponent reaction products. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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