Chiral sulfinyl-based olefin ligands for rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to cyanoalkenes

【作者】 薛峰； 祝勇； 李长恭； 齐晓蕾；

【Author】 Feng Xue;Yong Zhu;Changgong Li;Xiaolei Qi;College of Chemistry and Chemical Engineering,Henan Institute of Science and Technology;

【机构】 河南科技学院化学化工学院；

【摘要】 The chiral 3,3-disubstituted propionitriles, which could be readily transformed into other useful functionalities, such as amine, aldehyde, and carboxylic acid groups, are versatile synthetic intermediates in many biologically active compounds and pharmaceutical agents. The most direct and attractive method to obtain chiral 3,3-diarylpropylnitriles would utilize the asymmetric 1,4-addition reaction of cyanoalkenes and aryl boronic acids. However, there has been no report on chiral sulfinyl-based olefin ligands applied in asymmetric addition of α,β-unsaturated nitriles, especially for the substrates without activation groups so far. In view of the fact that the marketing of single enantiomers is becoming more popular, the development of an asymmetric method is highly desirable. Hence, we first developed the catalytic system of the rhodium-catalyzed addition of arylboronic acids to cyanoalkenes without activation groups, in which chiral sulfinyl-based olefin ligands were applied to afford 45-57% yields and 50-60% enantioselectivities, the ligands bearing p-tolylsulfinyl group have shown to be more effective than those bearing tert-butylsulfinyl, p-methoxybenzenesulfinyl and 2-methoxy-1-naphthylsulfinyl groups. Moreover, the ligands with electron-donating groups were more beneficial on the terminal benzene ring of the alkene moiety. This study sets the stage for further exploration of this recently developed ligands in other asymmetric transformations and the development of other kinds of unique olefin ligands.更多还原

【Abstract】 The chiral 3,3-disubstituted propionitriles, which could be readily transformed into other useful functionalities, such as amine, aldehyde, and carboxylic acid groups, are versatile synthetic intermediates in many biologically active compounds and pharmaceutical agents. The most direct and attractive method to obtain chiral 3,3-diarylpropylnitriles would utilize the asymmetric 1,4-addition reaction of cyanoalkenes and aryl boronic acids. However, there has been no report on chiral sulfinyl-based olefin ligands applied in asymmetric addition of α,β-unsaturated nitriles, especially for the substrates without activation groups so far. In view of the fact that the marketing of single enantiomers is becoming more popular, the development of an asymmetric method is highly desirable. Hence, we first developed the catalytic system of the rhodium-catalyzed addition of arylboronic acids to cyanoalkenes without activation groups, in which chiral sulfinyl-based olefin ligands were applied to afford 45-57% yields and 50-60% enantioselectivities, the ligands bearing p-tolylsulfinyl group have shown to be more effective than those bearing tert-butylsulfinyl, p-methoxybenzenesulfinyl and 2-methoxy-1-naphthylsulfinyl groups. Moreover, the ligands with electron-donating groups were more beneficial on the terminal benzene ring of the alkene moiety. This study sets the stage for further exploration of this recently developed ligands in other asymmetric transformations and the development of other kinds of unique olefin ligands.更多还原