One-Pot Synthesis of N-Substituted β-Amino Alcohols from Aldehydes and Isocyanides

A practical two‐stage one‐pot synthesis of N‐substituted β‐amino alcohols using aldehydes and isocyanides as starting materials has been developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon–carbon bon...

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Bibliographic Details
Published in:	Chemistry : a European journal Vol. 21; no. 21; pp. 7808 - 7813
Main Authors:	Cioc, Răzvan C., van der Niet, Daan J. H., Janssen, Elwin, Ruijter, Eelco, Orru, Romano V. A.
Format:	Journal Article
Language:	English
Published:	Weinheim WILEY-VCH Verlag 18.05.2015 WILEY‐VCH Verlag Wiley
Subjects:	Albuterol - chemical synthesis Albuterol - chemistry Alcohols Aldehydes Aldehydes - chemical synthesis Aldehydes - chemistry amino alcohols Amino Alcohols - chemical synthesis Amino Alcohols - chemistry Asymmetry Bronchodilator Agents - chemical synthesis Bronchodilator Agents - chemistry Chemistry Chemistry, Multidisciplinary Combinatorial Chemistry Techniques Cyanides - chemical synthesis Cyanides - chemistry Drugs isocyanide Lewis base Lewis bases Physical Sciences salbutamol Science & Technology Synthesis Tolerances Upgrading INSERTION salbutamol amino alcohols Lewis bases DISCOVERY isocyanide MULTICOMPONENT REACTIONS aldehydes ALPHA-ADDITIONS CHEMISTRY AGENTS PASSERINI-TYPE REACTIONS INHIBITORS DERIVATIVES AGONIST
ISSN:	0947-6539, 1521-3765, 1521-3765
Online Access:	Get full text
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Summary:	A practical two‐stage one‐pot synthesis of N‐substituted β‐amino alcohols using aldehydes and isocyanides as starting materials has been developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon–carbon bond disconnection, this protocol complements traditional approaches that involve amines and various carbon electrophiles (epoxides, α‐halo ketones, β‐halohydrins). Medicinally relevant products can be prepared in a concise and efficient way from simple building blocks, as demonstrated in the synthesis of the antiasthma drug salbutamol. Upgrading the synthesis to an enantioselective variant is also feasible. Retrosynthesis revisited: A practical and general two‐stage one‐pot synthesis of N‐substituted β‐amino alcohols using aldehydes and isocyanides as starting inputs is described (see scheme). Medicinally relevant compounds can be prepared in a concise and efficient way from simple building blocks, as demonstrated by the synthesis of the antiasthmatic drug salbutamol. The reaction can readily be made asymmetric by using a chiral Lewis base catalyst.
Bibliography:	CHEM21 - No. 115360 ArticleID:CHEM201500210 ark:/67375/WNG-WZ21R7KK-7 istex:FE484017B7F5367858FAF3CF730E66E96479D3C6 European Union EFPIA companies ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0947-6539 1521-3765 1521-3765
DOI:	10.1002/chem.201500210