Stereoselective synthesis of 2-dienyl-substituted piperidines using an eta4-dienetricarbonyliron complex as the stereocontrolling element in a double reductive amination cascade.
In the presence of NaBH(OAc)(3), a 1,5-keto-aldehyde, contained within a side-chain of an eta(4)-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 CuCl(2) 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.
Williams
Iwan
I
School of Chemistry, University of Birmingham, Edgbaston, Birmingham, UKB15 2TT.
Reeves
Keith
K
Kariuki
Benson M
BM
Cox
Liam R
LR
D000447:Aldehydes / Q000737:chemistry; D001894:Borohydrides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D058085:Iron Compounds / Q000737:chemistry*; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000447:Aldehydes; D001894:Borohydrides; D058085:Iron Compounds; D010880:Piperidines