Adachi Shinya, Saito Akira, Shibasaki Masakatsu
Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Org Lett. 2022 Jun 3;24(21):3901-3906. doi: 10.1021/acs.orglett.2c01624. Epub 2022 May 24.
Despite recent advances in reactions using alkylnitriles as carbon nucleophiles, diastereoselective direct catalytic asymmetric reactions, in which two consecutive chiral centers could be controlled, remain largely unexplored. Herein, we report the addition of alkylnitriles (such as propionitrile) to imines in the presence of a catalytic amount of a chiral pincer-type Ni-carbene complex and potassium 2,6-di--butyl-4-methylphenoxide (KBHT). BHT and molecular sieves were used as additives to improve the yields, diastereoselectivity, and enantiomeric ratio up to >99%, 90:10 /, and 97.5:2.5 er, respectively. The Mannich adducts can be readily converted to the corresponding β-amino acids.
尽管最近在使用烷基腈作为碳亲核试剂的反应方面取得了进展，但能够控制两个连续手性中心的非对映选择性直接催化不对称反应在很大程度上仍未得到探索。在此，我们报道了在催化量的手性钳型镍卡宾配合物和2,6-二叔丁基-4-甲基苯酚钾（KBHT）存在下，烷基腈（如丙腈）与亚胺的加成反应。使用BHT和分子筛作为添加剂，分别将产率、非对映选择性和对映体比例提高到>99%、90:10 /和97.5:2.5 er。曼尼希加合物可以很容易地转化为相应的β-氨基酸。
