Parker Kathlyn A, Fokas Demosthenes
Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.
J Org Chem. 2006 Jan 20;71(2):449-55. doi: 10.1021/jo0513008.
[reaction: see text] The radical cyclization approach to the morphine alkaloids has been applied in an asymmetric synthesis of (-)-dihydrocodeinone. A chiral cyclohexenol (R-32), from the CBS reduction of the enone, is the source of chirality. The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, (-)-15b --> (+)-16, was followed by an unprecedented reductive hydroamination, completing the synthesis of (-)-dihydroisocodeine ((-)-17) in 13 steps from commercially available materials.
[反应：见正文] 吗啡生物碱的自由基环化方法已应用于（-）-二氢可待因酮的不对称合成中。烯酮经CBS还原得到的手性环己烯醇（R-32）是手性源。第一步关键反应是串联环化反应，其中立体化学由几何限制控制，（-）-15b →（+）-16，随后是前所未有的还原氢胺化反应，从市售原料出发，经13步反应完成了（-）-二氢异可待因（（-）-17）的合成。
