Tandem α-cyano enamine enolate alkylations on bicyclic lactams:: Asymmetric carbocycle and heterocycle synthesis
Tandem α-cyano enamine enolate alkylations on bicyclic lactams:: Asymmetric carbocycle and heterocycle synthesis
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DOI：
10.1021/jo971920b
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发表时间：
1998-03-06
影响因子：
3.6
通讯作者：
Meyers, AI
中科院分区：
文献类型：
--
作者：
Schwarz, JB;Meyers, AI
氰基烯胺1和7用α，ω-二卤化物（或二卤化物等价物）烷基化，然后水解以显示内酰胺羰基，得到含有系留亲电体的内酰胺8和10。侧基卤化物在内酰胺烯醇化物上的分子内环化提供三环内酰胺9和13，其经受第二烯醇化物烷基化以形成季立构中心。在去甲麻黄碱三环内酰胺13的情况下，分子间是高度内选择性的，所得内酰胺14进行部分还原和水解辅助裂解，得到对映体纯的八甲酮16和17。从这种化学反应中合成了“伍德沃德酮”19，这是一种合成多种类固醇的中间体。最后，甲氧基甲基双环（或三环）内酰胺33显示经历手性助剂的非还原性裂解以提供含有季中心的3，4-二氢吡啶酮。
The alkylation of cyano enamines 1 and 7 with alpha,omega-dihalides (or dihalide equivalents), followed by hydrolysis to reveal the lactam carbonyl, provided lactams 8 and 10 containing a tethered electrophile. Intramolecular cyclization of the pendant halide onto the lactam enolate provided tricyclic lactams 9 and 13, which were subjected to a second enolate alkylation to form a quaternary stereocenter. In the case of nor-ephedrine tricyclic lactam 13, the intermolecular was highly endo selective, and the resultant lactams 14 were subjected to partial reduction and hydrolytic auxiliary cleavage to provide enantiopure octalones 16 and 17. From this chemistry came the synthesis of the "Woodward ketone" 19, an intermediate in the total synthesis of a number of steroids. Finally, the methoxymethyl bicyclic (or tricyclic) lactams 33 were shown to undergo nonreductive cleavage of the chiral auxiliary to provide 3,4-dihydropyridones containing a quaternary center.