Corporate Research and Development Division, Takasago International Corporation, 1-4-11 Nishi-Yawata, Hiratsuka, Kanagawa 254-0073, Japan.
Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1-E4-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan.
Org Lett. 2021 Apr 16;23(8):3070-3075. doi: 10.1021/acs.orglett.1c00739. Epub 2021 Mar 29.
A highly efficient dynamic kinetic resolution of cyclic halohydrins was achieved by the asymmetric transfer hydrogenation of racemic α-haloketones. Bifunctional oxo-tethered Ru(II) catalysts could promote the reduction without deterioration of halogens. By structural tuning of the catalyst, chiral alcohols having halogen, ester, carboxamide, and sulfone functions were obtained variably with excellent diastereo- and enantioselectivities (up to >99:1 d.r. and >99.9 ee), which provided a concise synthetic approach to a dopamine D3 receptor ligand, (+)-PHNO.
通过外消旋 α-卤代酮的不对称转移氢化反应，实现了环状卤代醇的高效动态动力学拆分。双功能氧桥联钌（II）催化剂可以促进还原，而不会恶化卤素。通过催化剂的结构调整，获得了具有卤素、酯、酰胺和砜官能团的手性醇，具有优异的非对映选择性和对映选择性（高达＞99:1 d.r. 和＞99.9ee），为多巴胺 D3 受体配体（+）-PHNO 提供了一种简洁的合成方法。
