Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine
Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine
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DOI：
10.1039/b308410h
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
Smith, NM
中科院分区：
文献类型：
--
作者：
Hermet, JPR;Porter, DW;Smith, NM
合成了三种手性二胺，并在 N-(叔丁氧基羰基)吡咯烷的锂化-取代中作为金雀花碱替代物进行了评估。金雀花样二胺{(1S*, 2R*, 8R*)-10-甲基-6,10-二氮杂三环[6.3.1.0(2,6)]十二烷和(1S*, 2R*, 9R*)-11-甲基-7,11-二氮杂三环[7.3.1.0(2,7)]十三烷}的合成和尝试拆分（通过包合物）形成）被报告。不幸的是，只能解析二氮杂三环[7.3.1.0(2,7)]十三烷化合物。描述了从天然产物(-)-金雀花碱开始制备(1R,2S,9S)-11-甲基-7,11-二氮杂三环[7.3.1.0(2,7)]十三烷的替代路线。这个简单的三步路线提供了克量的(+)-金雀花替代物。路线中的中间体 (1R, 5S, 12S)-3-甲氧基羰基-十氢-1,5-亚甲基吡啶并[1,2-a][1,5]重氮星-8-酮的 X 射线晶体学使本文中描述的所有三环二胺的立体化学得以明确建立。使用标准方法从 (S)-脯氨酸和解析的 2-哌啶乙醇开始制备另外两种二胺。这些二胺缺乏(-)-金雀花碱的双吡啶骨架，并且被发现具有极差的对映选择性。结论是，对于 N-Boc 吡咯烷的不对称锂化取代，仅需要刚性双吡啶骨架和 (-)-金雀花碱四个环中的三个即可实现高对映选择性。此外，研究表明二胺(1R,2S,9S)-11-甲基-7,11-二氮杂三环[7.3.1.0(2,7)]十三烷是第一个成功的(+)-金雀花碱替代品。
Three chiral diamines were synthesised and evaluated as sparteine surrogates in the lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine. The synthesis and attempted resolution of sparteine-like diamines {(1S*, 2R*, 8R*)-10-methyl-6,10-diazatricyclo[6.3.1.0(2,6)]dodecane and (1S*, 2R*, 9R*)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane} ( via inclusion complex formation) are reported. Unfortunately, it was only possible to resolve the diazatricyclo[7.3.1.0(2,7)] tridecane compound. An alternative route to (1R, 2S, 9S)-11-methyl-7,11-diazatricyclo[ 7.3.1.0(2,7)]tridecane starting from the natural product, (-)-cytisine, is described. This simple three-step route furnished gram-quantities of a (+)-sparteine surrogate. X-Ray crystallography of an intermediate in the route, (1R, 5S, 12S)-3-methoxycarbonyl-decahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, enabled the stereochemistry of all of the tricyclic diamines described in this paper to be unequivocally established. Two other diamines, starting from (S)-proline and resolved 2-piperidine ethanol, were prepared using standard methods. These diamines lacked the bispidine framework of (-)-sparteine and were found to impart vastly inferior enantioselectivity. It was concluded that, for the asymmetric lithiation-substitution of N-Boc pyrrolidine, a rigid bispidine framework and only three of the four rings of (-)-sparteine are needed for high enantioselectivity. Furthermore, it is shown that diamine (1R, 2S, 9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane is the first successful (+)-sparteine surrogate.