Lipase-catalyzed resolution of (2R*,3S*)- and (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol at low temperatures and determination of the absolute configurations of the four stereoisomers.
Lipase-catalyzed resolution of (2R*,3S*)- and (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol at low temperatures and determination of the absolute configurations of the four stereoisomers.
复制标题
在低温下脂肪酶催化拆分 (2R*,3S*)- 和 (2R*,3R*)-3-甲基-3-苯基-2-氮丙啶甲醇，并测定四种立体异构体的绝对构型。
DOI：
10.1021/jo048243n
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
T. Ema
中科院分区：
文献类型：
--
作者：
T. Sakai;Yu Liu;H. Ohta;T. Korenaga;T. Ema
[反应：见正文]脂肪酶催化拆分(2R*，3S*)-3-methyl-3-phenyl-2-aziridinemethanol，(+/-)-2，在低温下合成了有用的(2S，3S)-2及其醋酸酯(2S，3R)-2a，具有(2S)-选择性(-40℃时E=55)，而类似的(2R*，3R*)-3-methyl-3-phenyl-2-aziridinemethanol，(+/-)-3反应，得到(2S，3S)-3及其醋酸酯(2R，3R)-3a，具有(2R)-选择性(E=73，-20℃)。以苯甲酸叔丁酯7a为原料，经Neber反应制得化合物(+/-)-1a，再与甲基溴化镁进行非对映选择性加成反应制得化合物(+/-)-2。叔丁酯是促进该反应所必需的。为了确定(2S，3R)-2a的绝对构型，通过甲基溴化镁对3-苯基-2H-氮杂环-2-甲醇(S)-10进行非对映选择性甲基化，通过三步反应独立合成了对映体(2S，3R)-2。(2S，3S)-3的绝对构型由相应的N-(S)-2-(6-甲氧基-2-萘基)丙酰基(S，S，S)-13的X-射线分析确定。
[reaction: see text] Lipase-catalyzed resolution of (2R*,3S*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-2, at low temperatures gave synthetically useful (2R,3S)-2 and its acetate (2S,3R)-2a with (2S)-selectivity (E = 55 at -40 degrees C), while a similar reaction of (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-3, gave (2S,3S)-3 and its acetate (2R,3R)-3a with (2R)-selectivity (E = 73 at -20 degrees C). Compound (+/-)-2 was prepared conveniently via diastereoselective addition of MeMgBr to tert-butyl 3-phenyl-2H-azirine-2-carboxylate, (+/-)-1a, which was successfully prepared by the Neber reaction of oxime tosylate of tert-butyl benzoyl acetate 7a. The tert-butyl ester was requisite to promote this reaction. For determination of the absolute configuration of (2S,3R)-2a, enantiopure (2S,3R)-2 was independently prepared in three steps involving diastereoselective methylation of 3-phenyl-2H-azirine-2-methanol, (S)-10, with MeMgBr. The absolute configuration of (2S,3S)-3 was determined by X-ray analysis of the corresponding N-(S)-2-(6-methoxy-2-naphthyl)propanoyl derivative (S,S,S)-13.