Influence of chelating silyl scavengers on the diastereoselectivity of chromium catalyzed pinacol cross couplings

Abstract

Abstract-The choice of the silyl scavenger shows a substantial influence on the diastereoselectivity of the chromium catalyzed pinacol cross coupling. In the case of the intramolecular cyclization, two competing effects are observed. If the silylation reagents contain chelating heteroatoms in the side chain, a remarkable trans-selectivity is observed. Conversely the cis-diols are preferred if bulky substituted scavengers are used. A suitable transition state model for this reaction is reported, based on formerly published results. Ó 2005 Elsevier Ltd. All rights reserved.Recently, we have reported a chromium catalyzed diastereoselective pinacol cross coupling.2 It was found that the diastereoselectivities of the coupling reactions are mainly substrate dependent (Scheme 1).3 Furthermore, we have reported an intramolecular cyclization of 2-methylene-a,x-dicarbonyl compounds by chromium catalyzed pinacol cross coupling. 4 In this case, the diastereoselectivities are mainly dependent on ring sizes and the substitution of the x-carbonyl group.The starting point of our catalytic cross coupling reaction of acroleins with aldehydes was a publication by Takai and co-workers reporting a chromium-mediated process using a high excess of chromium(II) chloride to couple vinylketones with various aldehydes.5 Takai described that changing the silyl scavenging reagent only had little effect on diastereoselectivities under his reaction conditions.Encouraged by former results dealing with the effect of different scavenger reagents in the homo pinacol coupling, 6 we tried to substitute our scavenging trimethylsilyl chloride (TMS-Cl) with acetyl chloride, which we thought to be suitable to liberate chromium(III) chloride from the intermediate chromium alcoholate. 7 We found that the reaction was no longer catalytic in chromium or proceeded very slow albeit with a dramatic increase in diastereoselectivity (coupling of ethyl acrolein with 3-phenylpropionic aldehyde: 23% de, syn, with TMS-Cl, 78% yield; 54% de, syn, with AcCl, 10% yield).Maintaining the apparently positive chelating effect in the side chain of the scavenger, we switched back to silyl chlorides of the type ROMe 2 Si-Cl.8 Although diastereoselectivities were not as high as in the case of acetyl chloride, a significant increase, compared to TMS-Cl, could be observed (50% de, syn, 83% yield).