CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
Org Biomol Chem. 2013 Sep 28;11(36):6195-207. doi: 10.1039/c3ob40853a.
A regioselective high yielding monochloro substitution (chlorohydrin formation) via Mitsunobu reaction is reported. In carbohydrates and sterically hindered non-sugars, only the primary hydroxyl group is chlorinated, whereas in the non-sugar 1,2- and 1,3-alcohols, predominantly the secondary chloride substitution occurs. The versatile methodology provides indirect access to epoxides with the retention of configuration, as against conventional Mitsunobu reaction which generates epoxides with inversion. The methodology was successfully used as a key step in the synthesis of optically active diastereoisomers of the antidepressant drug reboxetine from (R)-2,3-O-cyclohexylidene-d-glyceraldehyde in ∼43% overall yields.
本文报道了通过 Mitsunobu 反应实现的区域选择性高产单氯取代（氯醇形成）。在碳水化合物和位阻非糖中，只有伯羟基被氯化，而在非糖 1,2-和 1,3-醇中，主要发生仲氯取代。该多功能方法提供了间接生成保留构型的环氧化物的途径，与传统的 Mitsunobu 反应生成构型翻转的环氧化物相反。该方法成功地用于从（R）-2,3-O-环己叉基-d-甘油醛合成抗抑郁药雷佐皮汀的对映体异构体的关键步骤中，总收率约为 43%。
