Asymmetric Hydrogenation of Ketones and Imines with Poly-Coordinated Chiral Catalysts

设计了一系列具有手性双膦配体和二胺配体的Ru配合物，并将其应用于酮的不对称氢化反应。所得结果如下：1)以甘露醇为原料合成了手性1，4-二胺Iphan。TolBINAP/Iphan-Ru络合物有效地催化了1-四丙酮及其类似物在异丙醇存在下的不对称氢化反应。反应在底物与催化剂的摩尔比(S/C)高达55,000的条件下完成，得到了对映体过量(Ee)高达99%的手性醇。2)TolBINAP/PICA-Ru催化剂(PICA=α-PICA)实现了叔烷基酮的不对称加氢反应。一系列空间位阻的酮在20大气压下氢化反应的S/C高达100,000，生成手性醇的效率高达98%。3)建立了手性双膦配体和手性二胺配体的Ru络合物文库，用于各种酮不对称氢化反应中手性催化剂的系统筛选。为此，以氨基酸为原料合成了一系列手性1，2-二胺配体。其中一个手性的N，N-二甲基-1，2-二胺，DMApen，显示出独特的性质。TolBINAP/DMapen-Ru催化剂催化芳基乙二醛缩醛加氢生成α-羟基缩醛，产率高达98%。4)在碱性条件下，手性Ru络合物催化芳香族亚胺加氢反应。一系列芳香族、脂肪族和乙烯基醛的氰硅化反应，在常温下S/C高达100,000。专题1)至3)已扩展到与化学工业的合作项目。该研究员(大仓武)在2007年获得了日本科学促进会的JSPS奖。

A series of ruthenium complexes with both chiral diphosphine and diamine ligands was designed and applied to asymmetric hydrogenation of ketones. The obtained results are described below1) Chiral 1,4-diamine IPHAN was prepared from mannitol. The TolBINAP/IPHAN-Ru complex effectively catalyzed asymmetric hydrogenation of 1-tetralones and their analogues in a base containing 2-propanol. The reaction was completed with a substrate-to-catalyst molar ratio (S/C) as high as 55,000 to afford the chiral alcohols in up to 99% enantiomeric excess (ee). Substituted 2-cyclohexenones were also converted to the allylic alcohols in high ee.2) The TolBINAP/PICA-Ru catalyst (PICA=α-picolylamine) achieved asymmetric hydrogenation of tert-alkyl ketones. A series of sterically hindered ketones was hydrogenated with an S/C as high as 100,000 at 20 atm H_2 to produce the chiral alcohols in up to 98% ee.3) A library of Ru complexes with chiral diphosphine ligands and chiral diamine ligands was made for systematic screening of chiral catalysts in asymmetric hydrogenation of various ketones. For this purpose, a series of chiral 1,2-diamine ligands was prepared from amino acids. Among of them a chiral N,N-dimethyl-1,2-diamine, DMAPEN, showed unique features. The TolBINAP/DMAPEN-Ru catalyzed hydrogenation of arylglyoxal dialkylacetals afforded the α-hydroxy acetals in up to 98% ee.4) Aromatic imines were hydrogenated with chiral Ru complexes under basic conditions.5) LiCl, one of the simplest lithium salts, efficiently catalyzed a reaction of aldehydes and (CH_3)_3SiCN under solvent free conditions. The cyanosilylation of a series of aromatic, aliphatic, and vinylic aldehydes completed with an S/C as high as 100,000 at ambient temperature.Topics 1) to 3) have expanded into collaboration projects with chemical industries.The investigator (Takeshi Ohkuma) received JSPS Prize from Japan Society for the Promotion of Science in 2007.