Cuprous chloride accelerated Stille reactions. A general and effective coupling system for sterically congested substrates and for enantioselective synthesis
Cuprous chloride accelerated Stille reactions. A general and effective coupling system for sterically congested substrates and for enantioselective synthesis
复制标题
DOI：
10.1021/ja991500z
复制
发表时间：
1999-08-25
影响因子：
15
通讯作者：
Corey, EJ
中科院分区：
文献类型：
--
作者：
Han, XJ;Stoltz, BM;Corey, EJ
Stille偶联反应的一个主要限制来自空间筛选，特别是在乙烯基锡烷组分中。例如，对于1-取代的乙烯基锡烷和芳基全氟烷基磺酸盐或卤化物，由于反应速率非常慢和竞争性的cine取代，通常观察到的产率可以忽略不计或较低。通过氯化亚铜作为偶联促进剂的发现和应用，这个问题已经在本工作中得到克服。因此，使用涉及Pd（PPh 3）（4）/CuCl/LiCl体系在厌氧条件下在二甲基亚砜溶液中在60 ℃下的偶联方案，可以以优异的产率进行各种各样的Stille偶联反应，否则这些反应会失败（表1）。该方法已被应用于手性1-（芳基乙基）烷基甲醇26，天然产物尼坎德烯酮的模型的对映选择性合成。氯化亚铜对Stille偶联的加速可以通过乙烯基锡烷->乙烯基铜（I）金属转移步骤的干预和随后ArPdX与乙烯基铜（I）中间体的加速偶联来解释。
A major limitation of Stille coupling reactions arises from steric screening, especially in the vinylstannane component. For example, with 1-substituted vinylstannanes and aryl perfluoroalkanesulfonates or halides negligible or low yields are generally observed, due to very slow reaction rates and competing cine substitution. This problem has been overcome in the present work through the discovery and application of cuprous chloride as an accelerant for coupling. Thus, using a protocol for coupling that involves the system Pd(PPh3)(4)/CuCl/LiCl under anaerobic conditions in dimethyl sulfoxide solution at 60 degrees C, a wide variety of Stille coupling reactions which otherwise fail can be effected in excellent yield (Table 1). The process has been applied to the enantioselective synthesis of the chiral 1-(arylethyl)alkylcarbinol 26, a model for the natural product nicandrenone. The acceleration of Stille coupling by cuprous chloride can be explained by the intervention of a vinylstannane --> vinylcopper(I) transmetalation step and a subsequent accelerated coupling of ArPdX with the vinylcopper(I) intermediate.