Design and development of monodentate chiral phosphines and their applications to asymmetric synthsese

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The transition-metal catalyzed asymmetric synthesis is one of the most expedient and environmentally benign processes and attracts attention for practical use. In addition the design and development of chiral ligands for the transition-metal catalyzed reactions are most fascinating and a challenging task. We have succeeded in the development of new monodentate chiral phosphines, (1R, 2S, 5R, 6S)-2,6-dimethyl-9-phenyl-9-phosphabicyclo[3 .3.1]nonane and its enantiomer ((+)- and(-)-9-PBNs) from commercially available 1,5-dimethyl- 1,5-cyclooctadiene in 4 or 5 steps. Utilizing 9-PBNs coordinated with palladium, enantioselective carbon-carbon bond, carbon-nitrogen bond, and carbon-oxygen bond forming reactions through asymmetric allylic substitution reactions have been investigated in detail. The allylic alkylation of 1,3-diphenyl-2- propenyl acetate with dimethyl malonate using the catalyst from bis(benzylidene)palladium and (-)- 9-PBN was found to proceed efficiently and afford the allylated product with 94 %ee in quantitative yield. Extension to nitrogen nucleophiles instead of carbon ones has been investigated. The primary and secondary amines and the sodium salts of the sulfonamides and imide showed the enantiomeric efficacy of up to 98 %ee. Furthermore, trialkyl borates were found to serve as oxygen nucleophiles for asymmetric allylic substitution reaction and afford the corresponding ethers with up to 96 %ee. As further extension of this asymmetric synthesis using 9-PBNs we have investigated reaction of 2-cycloalkenyl esters and found that 2-substituted 2- cycloalkenyl methyl carbonates are suitable substrates for asymmetric allylic substitution reaction.