Development of Highly Stereoselective Asymmetric Reactions Using P-Chiral Phosphine Ligands

本研究旨在开发具有极高对映选择性和催化活性的新型不对称催化剂。为了达到这一目的，我们基于膦-硼烷方法设计并制备了新的p手性膦配体。新合成的膦配体（QuinoxP^*和AlkynylP^*）不仅在铑催化的不对称氢化反应中，而且在铑或钯催化的碳-碳成键反应中，都被证明具有高达99.9%的对映选择性。研究了一种合成p -手性膦配体对映体的新方法。以(-)-sparteine为原料制备的关键中间体(S)-t-丁基甲基膦-硼烷经氢化铝锂的溴化还原反应转化为(R)-对映体。合成的(R)-对映体用于制备（R，R） t-Bu-喹诺酮^*。以(Z)-α-乙酰氨基乙酸酯为模型底物，R-（叔丁基甲基膦）（二叔丁基膦）甲烷为手性配体，研究了铑催化脱氢氨基酸不对称加氢反应的对映体选择机理。根据实验结果和DFT计算，认为在非螯合二氢化物形成螯合二氢化物的缔合过程中发生了对映体选择。

This study is directed toward the development of new asymmetric catalysts that exhibit exceedingly high enantioselectivity and catalytic activity. In order to achieve this purpose, we designed and prepared new P-chiral phosphine ligands based on the phosphine-borane methodology. The newly synthesized phosphine ligands (QuinoxP^* and AlkynylP^*) have been proved very high enantioselectivities up to 99.9% ee in not only rhodium-catalyzed asymmetric hydrogenation but also rhodium- or palladium-catalyzed carbon-carbon bond forming reactions.A new synthetic method for the synthesis of the counter enantiomers of P-chiral phosphine ligands has been studied. A key intermediate (S)-t-butylmethylphosphine-borane, which is prepared by the use of (-)-sparteine, was converted to (R)-enantiomer by the bromination and reduction with lithium aluminum hydride. The synthesized (R)-enantiomer was used for the preparation of (R,R) t-Bu- QuinoxP^*.Mechanistic study was carried out in order to investigate the enantioselection mechanism in the rhodium-catalyzed asymmetric hydrogenation of dehydroaminoacids using (Z)-α-acetamidocinnamate as a model substrate and R-(tert-butylmethylphosphino)(di-tert-butylphosphino)methane as the chiral ligand. Based on the experimental facts and DFT caluculation, it is concluded that the enantioselection takes place during the association step when the chelating dihydride is formed from the nonchelating dihydride.