Synthesis of Chiral Bulky Monophosphite Ligands and Their Application in Cu-Catalyzed Asymmetric Conjugate Addition of Diethylzinc to Cyclic Enones

A series of new bulky monophosphite ligands were synthesized from axially chiral BINOL and highly sterically hindered adamantanecarbonyl chloride. These ligands were applied to the Cu-catalyzed asymmetric 1,4-conjugate addition of diethylzinc to cyclic enones and were found to have moderate enantioselectivities (up to 61% ee). The stereochemically matched combination of (S)-BINOL in ligand (S)-(2-(adamantane-1-carboxylic acid)-1,1′-binapthalen-2′-yl)-((S)-1,1′-binaphthalen-2,2′-yl)phosphite induces a moderate enantioselectivity. The sense of enantioselectivity is mainly controlled by the configuration of the 2,2′-o, o-(1,1′-binaphthyl)-dioxo-phosphite moiety of the ligands.

摘要：以联萘酚和大位阻的金刚烷酰氯为原料, 经两步合成了系列新型手性单齿亚磷酸酯配体, 并应用于铜催化的二乙基锌对环烯酮的不对称 1,4-共轭加成反应. 结果表明, 产物收率和对映选择性最高分别为 95% 和 61%. 配体 (S)-(2-(adamantane-1-carboxylic acid)-1,1’-binapthalen-2’-yl)-((S)-1,1’-binaphthalen-2,2’-yl)phosphite [(S,S)-3a]的两个 (S)-联萘酚构型是匹配的组合, 产物的绝对构型主要由配体中 2,2’-二氧膦-1,1’-联萘酚的构型控制. 

Graphical abstractA series of new bulky monophosphite ligands derived from BINOL and adamantanecarbonyl chloride were employed in Cu-catalyzed enantioselective 1,4-conjugate addition of diethylzinc to cyclic enones (up to 61% ee).Figure optionsDownload full-size imageDownload as PowerPoint slide