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Catalytic Hydrogenation of Cyanohydrin Esters as a Novel Approach to N ‐Acylated β‐Amino Alcohols – Reaction Optimisation by a Design of Experiment Approach
Author(s) -
Veum Lars,
Pereira Silvia R. M.,
van der Waal Jan C.,
Hanefeld Ulf
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200500870
Subject(s) - chemistry , enantiopure drug , cyanohydrin , catalysis , yield (engineering) , organic chemistry , intramolecular force , substrate (aquarium) , solvent , acyl group , enantioselective synthesis , group (periodic table) , materials science , oceanography , geology , metallurgy
Abstract The catalytic hydrogenation of acylated cyanohydrins and subsequent intramolecular migration of the acyl group to yield pharmaceutically interesting N ‐acyl β‐amino alcohols is shown to be a successful one‐pot preparation method. The combination of a multistep DoE approach and high‐throughput methodology proved to be an effective strategy for the optimisation of the reaction. With the favoured catalyst/solvent combination of nickel on alumina in dioxane, both hydrogenation and acyl group migration proceeded smoothly, giving the N ‐acyl β‐amino alcohols in yields (determined by GC) of up to 90 % for aliphatic substrates and up to 50 % for benzylic ones, the latter being more prone to side reactions. No racemisation was found to occur at the chiral centre of an aliphatic molecule when an enantiopure cyanohydrin ester was used, though a minor decrease in ee was observed with a benzylic substrate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)