Furkert Daniel P, Husbands Stephen M
Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Org Lett. 2007 Sep 13;9(19):3769-71. doi: 10.1021/ol0713988. Epub 2007 Aug 21.
The first asymmetric synthesis of the trans-3,4-dimethyl-4-arylpiperidine opioid antagonist scaffold is reported. C-3 stereochemistry was established via CBS reduction and stereoselective anti-SN2' cuprate displacement of the derived allylic phosphonate. The resultant vinyl bromide was then elaborated to the target compound by Suzuki coupling and trans-selective 4-methylation. Extension of this methodology should allow general enantioselective access to highly substituted piperidine ring systems.
报道了反式-3,4-二甲基-4-芳基哌啶阿片样物质拮抗剂骨架的首次不对称合成。通过CBS还原和衍生的烯丙基膦酸酯的立体选择性反式SN2'铜酸盐取代反应确定了C-3立体化学。然后通过铃木偶联和反式选择性4-甲基化将所得的乙烯基溴转化为目标化合物。这种方法的扩展应该能够实现对高度取代的哌啶环系统的一般对映选择性合成。
