Diastereoselective nickel-catalyzed reductive couplings of aminoaldehydes and alkynylsilanes: application to the synthesis of D-erythro-sphingosine

A strategy for the nickel-catalyzed reductive coupling of alpha-aminoaldehydes with silyl alkynes has been developed. The process proceeds with exceptional regiocontrol and diastereoselectivity. A variety of protected serinal derivatives were examined, and Garner aldehyde afforded the highest chemical yields of an easily deprotected Coupling product. Use of a C-15 alkyne allowed a direct and efficient synthesis Of D-erythro-sphingosine. With this silyl alkyne of interest, coupling reactions were most efficient when trace water was employed with THF as solvent. Using this procedure, D-erythro-sphingosine was prepared by a short sequence, wherein the alkene stereochemistry, C-3 stereocenter, and the C-3-C-4 carbon-carbon bond were all efficiently installed by the key nickel-catalyzed coupiing process. (C) 2009 Elsevier Ltd. All rights reserved.