Stereoselective synthesis of 2-dienyl-substituted piperidines using an η4-dienetricarbonyliron complex as the stereocontrolling element in a double reductive amination cascade?

Organic & Biomolecular Chemistry Pub Date: 2007-09-12 DOI: 10.1039/B710898B

Abstract

In the presence of NaBH(OAc)3, a 1,5-keto-aldehyde, contained within a side-chain of an η4-dienetricarbonyliron complex, undergoes a double reductive amination sequence with a series of primary amines, to provide the corresponding piperidine products in good to excellent yield. The dienetricarbonyliron complex functions as a powerful chiral auxiliary in this cascade process, exerting complete control over the stereoselectivity of the reaction, with the formation of a single diastereoisomeric product. The sense of stereoinduction has been confirmed by X-ray crystallography. Removal of the tricarbonyliron moiety can be effected with CuCl2 to afford the corresponding 2-dienyl-substituted piperidine in excellent yield. Attempted extension of this cyclisation strategy to the corresponding azepane ring system using a 1,6-keto-aldehyde as the cyclisation precursor was unsuccessful; in this case, the reaction stopped after a single reductive amination on the aldehyde to provide an acyclic keto-amine product.

Graphical abstract: Stereoselective synthesis of 2-dienyl-substituted piperidines using an η4-dienetricarbonyliron complex as the stereocontrolling element in a double reductive amination cascade
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