Asymmetric Synthesis of Organophosphorus Compounds

This thesis explores the asymmetric synthesis of organophosphorus compounds through two different strategies: anion-binding organocatalysis (Chapter 2) and auxiliary-based stepwise stereospecific displacements at phosphorus (Chapter 3). Firstly, the synthesis of P-stereogenic α-aminophosphinates through a three-component dearomatization reaction, using isoquinolines, TrocCl, and pro-chiral phosphonites was explored (Scheme 1). The aim was to achieve selectivity at both the C- and P-centres through a chiral close-anion pair mechanism induced by a suitable anion-binding organocatalyst. The screening of a library of organocatalysts yielded moderate to excellent enantioselectivity and good to excellent yields (up to 96% ee, 24 examples), but the levels of diastereoselectivity were low. Silylphosphonites derived from enantiopure H-menthyl phenylphosphinate, were investigated as nucleophiles and their use was identified as a viable method of obtaining both high enantio- and diastereoselectivity in this class of reaction. Secondly, this thesis also describes an efficient approach to synthesizing enantioenriched P-stereogenic phosphines in a one pot manner starting from dichlorophosphines (Scheme 2). This was enabled using an easily accessible half-salan auxiliary which forms a “masked P-Cl bond” and a P-O bond in situ, which can be stereospecifically displaced using a combination of aryl and alkyl Grignard reagents. The resulting phosphines can be transformed into phosphine oxides, sulfides and boranes (up to 93% ee, 13 examples). Detailed NMR spectroscopic and computational investigations support the formation of a “masked P-Cl” species, responsible for the high selectivity of this method.