Highly enantioselective synthesis induced by chiral primary alcohols due to deuterium substitution
Highly enantioselective synthesis induced by chiral primary alcohols due to deuterium substitution
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DOI：
10.1021/ja002992e
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发表时间：
2000-11-29
影响因子：
15
通讯作者：
Soai, K
中科院分区：
文献类型：
--
作者：
Sato, I;Omiya, D;Soai, K
位阻同位素效应引起了相当大的注意。例如，已经报道了氘化四氰蒽醌二甲烷中的结构立体同位素效应，9,10 -二氢菲衍生物2b的外消旋化和[2.2]偏对环蒽的翻转中的构象动力学同位素效应，以及4-哌酮衍生物还原中的立体同位素效应。从有机立体化学和生物化学的角度来看，具有手性的氢被氘取代的手性化合物是很重要的。这些对映体的手性主要是由于碳-氘键和碳氢键的长度差别很小；碳-氘键的时间平均长度（0.1099 nm）仅比碳氢键短0.0004 nm。因此，不像其他常见的对映体，其手性是由于原子核中质子数的不同，这些同位素对映体被认为在不对称反应和识别中只表现出非常小的差异。事实上，同位素对映体直到最近才用手性固定相（csp）高效液相色谱（HPLC）分离。另一方面，尽管最近在不对称催化方面取得了进展，但尚不清楚是否有同位素对映体可以在高对映选择性合成中作为手性诱导剂。迄今为止所报道的同位素对映体诱导的不对称合成的对映选择性和动力学分辨率都极低。在手性氘化喹啉衍生物存在的情况下，对烯酮进行MeOH的对映选择性加成，根据旋光度，产物的光学纯度仅为0.13%，并且只研究了手性诱导剂的一种对映体。外消旋r -苯基丁酸酐与对映异构氘化醇的动力学拆分，水解后得到光学纯度仅为0.1-0.6%的r -苯基丁酸。因此，由同位素对映体诱导的高对映选择性合成是一个具有挑战性的问题。我们在这里报道了一个前所未有的高度对映选择性合成手性化合物由伯醇- r -d的同位素对映体诱导。
Steric isotope effects have attracted considerable attention. 1 For example, a structural steric isotope effect in deuterated tetracyanoanthraquinodimethane, 2a conformational kinetic isotope effects in the racemization of a 9, 10-dihydrophenanthrene derivative2b and in the flipping of [2.2] metaparacyclophanes, 2c and a steric isotope effect in the reduction of a 4-piperidone derivative have been reported. 2dChiral compounds whose chirality is due to the replacement of hydrogen by deuterium are important from the standpoint of organic stereochemistry and biochemistry. 3 The chirality of these enantiomers is mainly due to the very small difference between the lengths of carbon-deuterium and carbon-hydrogen bonds; the time-averaged carbon-deuterium bond length (0.1099 nm) is shorter than the carbon-hydrogen bond by only 0.0004 nm. 4 Thus, unlike other usual enantiomers whose chirality is due to the difference in the number of protons in the atomic nucleus, these isotopic enantiomers are considered to show only very small differences in asymmetric reactions and recognition. In fact, isotopic enantiomers were only quite recently separated analytically using HPLC with a chiral stationary phase (csp). 5 On the other hand, despite the recent advances in asymmetric catalysis, 6 it is unclear whether any isotopic enantiomer can act as a chiral inducer in highly enantioselective synthesis. The enantioselectivities that have been reported so far in asymmetric synthesis7 and kinetic resolution8 induced by isotopic enantiomers have been extremely low. Enantioselective addition of MeOH to a ketene in the presence of a chiral deuterated quinuclidine derivative gave a product with an optical purity of only 0.13% based on the optical rotation, and only one enantiomer of the chiral inducer was investigated. 7 Kinetic resolution of racemic R-phenylbutyric anhydride with enantiomerically deuterated alcohols gives, after hydrolysis, R-phenylbutyric acid with an optical purity of only 0.1-0.6%. 8 Thus, highly enantioselective synthesis induced by isotopic enantiomers is a challenging problem. We report here an unprecedented highly enantioselective synthesis of a chiral compound induced by the isotopic enantiomer of primary alcohol-R-d.