Tosaki Shin-ya, Horiuchi Yoshihiro, Nemoto Tetsuhiro, Ohshima Takashi, Shibasaki Masakatsu
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Chemistry. 2004 Mar 19;10(6):1527-44. doi: 10.1002/chem.200305709.
We describe a new strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays. This strategy relies on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides promoted by the Sm-BINOL-Ph(3)As[double bond]O (1:1:1) complex, followed by a conversion of morpholinyl amides into ketones and diastereoselective ketone reduction. Highly enantio- (up to >99 % ee) or diastereoselective (up to >99.5:0.5) epoxidation was achieved using 5-10 mol % of the Sm complex to afford synthetically very useful, nearly optically pure alpha,beta-epoxy morpholinyl amides. Stereoselectivity of the epoxidation was controlled by the chirality of BINOL with overwhelming inherent diastereofacial preference for the substrate. Combination with the syn- and anti-selective ketone reduction with the highly catalyst-controlled epoxidation allowed for an iterative strategy for the syntheses of all possible stereoisomers of 1,3-polyol arrays. Eight possible stereoisomers of 1,3,5,7-tetraol arrays were synthesized with high to excellent stereoselectivity. Moreover, the efficiency of the present strategy was successfully demonstrated by enantioselective syntheses of several 1,3-polyol/alpha-pyrone natural products, for example, cryptocaryolone diacetate.
我们描述了一种用于对映选择性和非对映选择性合成1,3 - 多元醇阵列所有可能立体异构体的新策略。该策略依赖于由Sm - BINOL - Ph₃As=O（1:1:1）配合物促进的α,β - 不饱和吗啉基酰胺的高度催化剂控制的环氧化反应，随后将吗啉基酰胺转化为酮并进行非对映选择性酮还原。使用5 - 10 mol%的Sm配合物实现了高度对映选择性（高达>99% ee）或非对映选择性（高达>99.5:0.5）的环氧化反应，得到合成上非常有用的、几乎光学纯的α,β - 环氧吗啉基酰胺。环氧化反应的立体选择性由BINOL的手性控制，对底物具有压倒性的固有非对映面偏好。将非对映选择性酮还原与高度催化剂控制的环氧化反应相结合，为1,3 - 多元醇阵列所有可能立体异构体的合成提供了一种迭代策略。以高至优异的立体选择性合成了1,3,5,7 - 四醇阵列的八种可能立体异构体。此外，通过对几种1,3 - 多元醇/α - 吡喃酮天然产物（例如隐杯伞酮二乙酸酯）的对映选择性合成，成功证明了本策略的效率。
