Development of an enantioselective, kilogram-scale, rhodium-catalysed 1, 4-addition

…, DRJ Hose, JD Moseley, AJ Parker, I Patel…

Index: Brock, Sally; Hose, David R.J.; Moseley, Jonathan D.; Parker, Alexandra J.; Patel, Ian; Williams, Andrew J. Organic Process Research and Development, 2008 , vol. 12, # 3 p. 496 - 502

Full Text: HTML

Citation Number: 36

Abstract

A rhodium-catalysed 1, 4-addition of an arylboron species to an α, β-unsaturated ester was the key chirality-inducing step in the synthesis of an API. We describe herein the development of this chemistry, including optimization of reagent charges, reaction conditions, and metal recovery, in order to allow manufacture at multikilogram scale. A key result was the unexpected discovery that the use of a minimal quantity of an alcohol, ...