Theoretical study of the stereoselective additions of chiral alcohols to ketenes
Theoretical study of the stereoselective additions of chiral alcohols to ketenes
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DOI：
10.1021/ja035899
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发表时间：
2004-09-08
影响因子：
15
通讯作者：
Houk, KN
中科院分区：
文献类型：
--
作者：
Cannizzaro, CE;Houk, KN
1989年，默克公司的Larsen等人发现，将手性醇加入到酮类化合物中可以得到对映体富集的芳基丙酸，这种化合物因其抗炎治疗特性而受到重视。观察到的高1,4-不对称诱导（添加时为bbb99:1 dr，水解成酸后达到99% ee）是罕见的。基于B3LYP密度泛函理论计算的定量模型解释了(S)-乳酸甲酯、(S)-3-甲基-2-丁醇和(S)pantolactone对甲基苯基烯的立体选择性。中间体的构象过程可以影响反应的立体选择性，加成步骤或烯酸酯中间体的质子化反应都可能决定反应的立体选择性。
In 1989, Larsen et al. at Merck discovered that the addition of chiral alcohols to ketenes provided enantiomerically enriched aryl propionic acids, compounds valued for their therapeutic antiinflammatory properties. The high 1,4-asymmetric induction observed (>99:1 dr in the addition, and up to 99% ee after hydrolysis to the acid) is rare. A quantitative model based on B3LYP density functional theory calculations accounts for the stereoselectivity in the addition of (S)-methyl lactate, (S)-3-methyl-2-butanol, and (S)pantolactone to methylphenylketene. The conformational processes of the intermediates can impact the stereoselectivity of the process, and either the addition step, or the protonation of the enolate intermediate, may be stereoselectivity determining.