Rhodium‐Catalyzed Asymmetric Hydroformylation of Unsaturated Nitriles.

Abstract

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

Catalytic Asymmetric Synthesis With Novel Monodentate Phosphorus Ligands

“…de Vries and co-workers reported the asymmetric hydroformylation of allyl cyanide using (R,S)-BINAPHOS as the ligand, which afforded the aldehyde b-18 with 66% ee in a 72:28 branched-to-linear ratio. 28 BINOL-based phosphoramidite ligands have also been used in this reaction, but the best result was to give b-18 in a 76:24 branched-to-linear ratio and only 18% ee. 28 Moreover, the reaction rate was low with only 31-45% conversion when the reaction was carried out in toluene at 60°C under 30 atm of CO and H 2 (1:1).…”

“…28 BINOL-based phosphoramidite ligands have also been used in this reaction, but the best result was to give b-18 in a 76:24 branched-to-linear ratio and only 18% ee. 28 Moreover, the reaction rate was low with only 31-45% conversion when the reaction was carried out in toluene at 60°C under 30 atm of CO and H 2 (1:1). Accordingly, it is apparent that this process is useful but quite demanding and it is necessary to improve the regioselectivity and enantioselectivity of this process to be practical.…”

“…These ligands have found a wide range of applications in metal-catalyzed asymmetric transformations such as hydrogenation, 7-15 1,4-addition of diethyl zinc [16][17][18][19][20][21][22] or boronic acid 23,24 to conjugated systems, hydrovinylation, 25,26 hydrosilylation, 27 hydroformylation, 19,28 intramolecular Heck reaction, 29,30 allylic alkylation, 31-34 amination [35][36][37] and etherification. 38,39 We have been developing a previously uninvestigated class of monophosphite and monophosphoramidite ligands based on readily accessible axially chiral biphenol units ( Figure 2).…”