Asymmetric hydroformylation of crotononitrile (1) and ally cyanide (2) was probed with the view to develop a synthesis for (R)-4-amino-2-methyl-butan-1-ol. Hydroformylation of 1 under a variety of conditions mainly led to hydrogenated product. Hydroformylation of 2 with Rh/tris(2,4-ditert-butylphenyl) phosphite gave good selectivity to the formylated nitrile with an n/iso of 77:23. Asymmetric hydroformylation of 2 could be accomplished in 66% ee using Rh/(R,S)-BINAPHOS.

Aldehydes Aldehydes P 0170Rhodium-Catalyzed Asymmetric Hydroformylation of Unsaturated Nitriles. -In an attempt to prepare (R)-4-amino-2-methylbutan-1-ol, key intermediate in the synthesis of a new Tachykinin NK 1 receptor antagonist, the formation of its precursor aldehyde (III) by hydroformylation of crotononitrile or allyl cyanide (I) is studied. Crotononitrile is not useful since hydrogenation of the internal double bond is highly favored over hydroformylation. Several rhodium catalyst-ligand combinations are tested in the hydroformylation of allyl cyanide (I), and best results are obtained for the bulky phosphite ligand tris(di(tert-butyl)phenyl) phosphite (conditions D). First attempts towards an asymmetric hydroformylation reveal the best results to be obtained for the phosphine-phosphite ligand BINAPHOS. -(LAMBERS-VERSTAPPEN, M. M. H.; DE VRIES*, J. G.; Adv. Synth. Catal. 345 (2003) 4, 478-482; Adv. Synth. Catal., DSM Res. Life Sci., NL-6160 MD Geleen, Neth.; Eng.) -Mischke 28-078