1,3-Aminoalkohole als Bausteine in der asymmetrischen Synthese von Azetidinen, Azetidincarbonsäuren und Piperidin-3-olen

摘要

Four-membered cyclic amines – the azetidines – are an original class of compounds with limited occurrence in nature. Nevertheless enantiopure azetidines and in particular derivatives of the azetidine-2-carboxylic acid are used in medicine, crop protection and asymmetric catalysis. Despite these promising developments in azetidine chemistry, the lack of general enantioselective routes to these heterocycles is evident by the relatively low number of reports on azetidines and especially azetidine carboxylic acids in the literature.A versatile and efficient asymmetric synthesis of substituted azetidines with excellent diastereomeric and enantiomeric excesses (de = 93-99%, ee = 96-99%) in good overall yields starting from SAMP-hydrazones is described. Virtually stereoisomerically pure differently N,O-protected 1,3-amino alcohols were prepared as intermediates. By using the phenyl moiety as a synthetic equivalent of the carboxylic acid function, this protocol could also be applied to the synthesis of enantiopure azetidine-type alpha- and beta-amino acids. The alpha-amino acids were successfully deployed as organocatalysts.Furthermore he 1,3-amino alcohols were utilised in an asymmetric synthesis aimed at the preparation of prosopis alkaloid mimetics featuring an additional substituent compared to the naturally occurring alkaloids. A functionalised electrophile was employed in a diastereoselective alkylation of the dioxanone SAMP-hydrazone. The obtained aminoketon was cyclised by reductive amination, yielding an acetal protected piperidin-3-ol. Different protecting group strategies were examined in order to increase the moderate yields and diastereoselectivities.