Asymmetric synthesis of 2-alkyl-perhydroazepines from [5,3,0]-bicyclic lactams
Asymmetric synthesis of 2-alkyl-perhydroazepines from [5,3,0]-bicyclic lactams
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DOI：
10.1021/jo001548r
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发表时间：
2001-02-23
影响因子：
3.6
通讯作者：
Weiser, MJ
中科院分区：
文献类型：
--
作者：
Meyers, AI;Downing, SV;Weiser, MJ
描述了一类新的[5，3，0]-双环内酰胺的合成和应用。由（R）-苯基甘氨醇与ω-酮酸脱水环化制得内酰胺4-6，为可分离的非对映体混合物（类似于2：1），产率低（类似于40%）。通过2-烯丙基-N-丙烯酰基恶唑烷的闭环复分解反应，实现了较高的化学产率（高达61%），8。顺式双环内酰胺4a和5a用铝烷或氢化锂铝进行立体选择性还原，得到2-位R构型的氮杂醇11 a和15 a，产率良好至中等（50-88%）。在差向异构体反内酰胺4 b和5 b的二异丁基氢化铝还原中也观察到高选择性，得到在C-2处具有S构型的氮杂醇11b和15 b。N-苄基部分的氢解裂解以良好的产率和良好的对映体过量（84-94%）得到手性2-取代的全氢氮杂卓（R）-和（S）-12。
The synthesis and utility of a novel class of [5,3,0]-bicyclic lactams are described. Produced by the cyclodehydration of (R)-phenylglycinol with omega -keto acids, lactams 4-6 were obtained as separable diastereomeric mixtures (similar to2:1) in low yields (similar to 40%). Higher chemical yield (up to 61%) was realized tia an alternate route involving ring closure metathesis of 2-allyl-N-acroyl oxazolidines, 8. Stereoselective reductions of the syn-bicyclic lactams, 4a and 5a, occurred with the use of alane or lithiumaluminum hydride, affording azepine alcohols, 11a and;15a, of the R configuration at the 2-position, in good to moderate yields (50-88%). High selectivity was also observed in the diisobutylaluminum hydride reduction of the epimeric anti lactams, 4b and 5b, affording azepine alcohols, 11b and 15b, of the S configuration at C-2. Hydrogenolytic cleavage of the N-benzyl moiety afforded chiral 2-substituted perhydroazepines, (R)- and (S)-12, in good yields and good enantiomeric excesses (84-94%).