二酮的对映选择性氢化去对称化

Asymmetric hydrogenation of simple ketones is undoubtedly one of the most important synthetic methods for synthesis of the chiral secondary alcohols in organic chemistry. In sharp contrast, enantioselective hydrogenative desymmetrization of diketones, especially for 1,3-diketones due to the similar activity of two carbonyl groups, remains undeveloped. The main challenges include over-reduction, difficulty in control of enantio- and diastereoselectivity and the instability of the hydrogenation product (acid or base-catalyzed reversible Aldol reaction of β-hydroxy ketones). Herein, an enantioselective transition metal-catalyzed hydrogenation/transfer hydrogenative desymmetrization of 1,2-diketones and 1,3-diketones will be explored for synthesis of chiral α-hydroxy ketones and β-hydroxy ketones with adjacent α-tertiary or quaternary stereocenters, respectively. In addition, by combination of desymmetrization and remote control, enantioselective hydrogenative desymmetrization of 4-substituted cyclopentane-1,2-diones and 5-substituted cyclohexane-1,3-diones will be also explored for synthesis of chiral α- or β-hydroxy ketones bearing discrete stereocenters. At present, some of these proposals have been proved to be possible in our preliminary research.

对简单酮的不对称氢化目前已经取得很好的进展，成为合成手性二级醇最有效的方法，但是对二酮的选择性单氢化目前仍然是不对称催化领域的挑战性课题，主要困难有：1）容易过度氢化；2）对映选择性和非对映选择性控制困难；3）氢化产物容易消旋化（如：在酸或碱催化下，氢化产物a-羟基酮存在逆羟醛缩合反应消旋化途径）。针对上述难点，本项目计划开发活性适中且具有高度选择性氢化（转移氢化）催化剂，并且控制反应在中性或弱酸性条件下进行。主要探索1,3-二酮和1,2-二酮类化合物的氢化（转移氢化）去对称化反应；在此基础上，探索5-取代-1,3-环己二酮和4-取代-1,2-环戊二酮衍生物的氢化（转移氢化）去对称化，同时实现远程手性控制，构建多个非连续的手性中心。本项目研究为合成具有多个手性中心的α-或β-羟基羰基化合物提供一条有效的途径。目前，初步的研究结果证明了该项目的可行性。

对简单酮的不对称氢化目前已经取得很好的进展，成为合成手性二级醇最有效的方法，但是对二酮的选择性单氢化是不对称催化领域的挑战性课题，申请人设计、合成了2-取代-1,3-环戊二酮和5-取代-1,3-环己二酮衍生物的氢化（转移氢化）去对称化，同时实现远程手性控制，构建多个非连续的手性中心。本项目研究为合成具有多个手性中心的α-或β-羟基羰基化合物提供一条有效的途径。