Development of new P(V) catalysts for the asymmetric reduction of ketimines

The use of Lewis basic P(V) organocatalysts as a means of activating trichlorosilane toward the asymmetric reduction of ketimines has been examined. Screening of a first generation library of catalysts encompassing a diverse range of functionality identified the P-chiral scaffold to be the most effective. Examination of the literature however, showed no practical, robust and efficient means for the preparation of such species. As a result studies became centred upon the development of the N-phosphinoyl oxazolidinone 178. Addition of the appropiate aryl or alkyl Grignard reagent to the oxazolidinone 178 afforded the corresponding P-chiral phosphine oxide in excellent yield and complete enantiocontrol with studies suggesting an SN2(P) process in operation. Screening of the second generation library of P-chiral phosphine oxide catalysts identified the 2-anisyl species 172 to be the most selective delivering the N-PMP amine 107 in >95% yield and 29% ee. Mechanistic studies on the catalyst 172 demonstrated a [ML2] non-linear effect and led to the hypothesis that a bis-P-chiral phosphine oxide catalyst would confer higher enantioselectivity. Synthesis of the third generation bis-P-chiral catalyst 224 through expansion of the N-phosphinoyl oxazolidinone chemistry enabled isolation of the amine 107 in 70% conversion and 60% ee after four hours.EThOS - Electronic Theses Online ServiceGBUnited Kingdo