Development and Application of New Chiral Ligand Systems Effective for Catalytic Asymmetric Carbon-Carbon Bond Formation

有效催化不对称碳-碳键形成的新型手性配体体系的开发和应用

• 批准号: 13672225
• 负责人: MORIMOTO Toshiaki
• 金额: $ 1.15万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672225/
• 关键词: chiral ligand; chiral catalyst; copper catalyst; phosphine ligand; conjugate addition; enone; diethylzinc; enantioselectivity; スルホンアミド配位子; 共役付加

New chiral P,N type ligands were designed and prepared starting from L-valinol and (R)-binaphthol for catalytic asymmetric conjugate addition of dialkylzinc to enones. By condensation of a chiral component, (S)-1-(diphenylphosphino)-3-methyl-2-butanamine, with pyridine-2-carboxylic acids and pyridine-2-carboxaldehydes, new amide-type and imine-type P,N ligands bearing pyridyl groups were obtained. For evaluation of the ligands, asymmetric conjugate addition of diethylzinc to 2-cyclohexen-1-one was carried out using copper triflate (1 mol%) as the catalyst. The pyridylmethylene derivatives (imine-type ligands) were found to be very efficient ligands having high enantioselectivity up to 95% ee, though the amide-type ligands showed lower enantioselectivity (below 66% ee). On the other hand, the enantioselectivity of the conjugate addition to an acyclic enone, chalcone, was lower and only a moderate selectivity (up to 71% ee) was obtained even by using the imine-type ligands. The enantioselectivity of the amide-type ligand was improved by alkylation of the NH group, and the smallest N-Me derivative showed the highest selectiveity (81% ee (cyclohexenone), 75% ee (chalcone)). Several N-sulfonyl derivatives of the chiral component were prepared and the selectivity of an N-(1R)-10-camphorsulfonyl derivative (73% ee) was better than that of the others in the reaction of 2-cyclohexen-1-one. An axially chiral 1,1'-binaphthyl ligand bearing both 2-tosylamino and 2'-diphenylphosphino groups was synthesized through a new convenient route using (R)-2-cyano-2'-phosphinyl-1,1'-binaphthyl as a synthetic intermediate. The new ligand was found to be highly efficient in the copper-catalyzed conjugate addition of diethylzinc to benzylideneacetones, showing high selectivity of 84-99% ee.

以l -缬丙醇和(R)-联萘酚为起始原料，设计并制备了新的P、N型手性配体，用于催化二烷基锌与烯酮的不对称共轭加成。通过手性组分(S)-1-（二苯基膦）-3-甲基-2-丁胺与吡啶-2-羧酸和吡啶-2-羧醛缩合，得到了新的酰胺型和亚胺型含吡啶基的P，N配体。为了评价配体，以三酸铜（1mol %）为催化剂，进行了二乙基锌与2-环己烯-1- 1的不对称共轭加成反应。吡啶基亚甲基衍生物（亚胺型配体）是非常有效的配体，具有高达95% ee的高对映选择性，而酰胺型配体的对映选择性较低（低于66% ee）。另一方面，偶联加到无环烯酮查尔酮的对映选择性较低，即使使用亚胺型配体，也只有中等的选择性（高达71% ee）。通过NH基团的烷基化，提高了酰胺型配体的对映选择性，最小的N-Me衍生物具有最高的选择性（ee（环己酮）81%,ee（查尔酮）75%）。手性组分的N-磺酰衍生物制备了几种，其中N-(1R)-10-樟脑磺酰衍生物（73% ee）在2-环己烯-1- 1反应中的选择性优于其他衍生物。以(R)-2-氰基-2'-膦基-1,1'-联萘基为中间体，通过新的便捷途径合成了含有2-甲氨基和2'-二苯基膦基的轴手性1,1'-联萘基配体。该配体在铜催化二乙基锌与苄基丙酮的共轭加成反应中具有很高的选择性，选择性为84-99%。

项目成果

Toshiaki Morimoto: "A new chiral 2-sulfonylamino-2'-phosphino-1,1'-binaphthyl ligand for highly enantioselective copper-catalyzed conjugate addition of diethylzinc to beozylideneacetones"Tetrahedron Letters. 45(in press). (2004)

Toshiaki Morimoto：“一种新的手性 2-磺酰氨基-2-膦基-1,1-联萘配体，用于高度对映选择性铜催化二乙基锌与苯亚甲基丙酮的共轭加成”四面体快报。