Highly enantioselective synthesis of glycidic amides using camphor-derived sulfonium salts. Mechanism and applications in synthesis
Highly enantioselective synthesis of glycidic amides using camphor-derived sulfonium salts. Mechanism and applications in synthesis
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DOI：
10.1021/ja0568345
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发表时间：
2006-02-15
影响因子：
15
通讯作者：
Winn, CL
中科院分区：
文献类型：
--
作者：
Aggarwal, VK;Charmant, JPH;Winn, CL
研究了一系列酰胺稳定的硫叶立德的反应，这些叶立德衍生自易于获得的樟脑衍生的锍盐，用于合成缩水甘油酰胺。测试伯酰胺、仲酰胺和叔酰胺，并且发现用叔酰胺观察到最高的对映选择性，其以良好至优异的产率、唯一的反式选择性和优异的对映选择性提供缩水甘油酰胺。该反应对芳香醛具有普遍性，但对脂肪醛具有更大的不对称选择性。用有机锂试剂处理环氧酰胺可以干净地转化为环氧酮。我们也能够实现选择性开环的环氧酰胺与各种亲核试剂，然后通过水解的酰胺，得到相应的羧酸。将该方法应用于目标化合物SK&F 104353的全合成。交叉实验和理论计算的结合表明，速率和选择性决定步骤是闭环，而不是甜菜碱形成的情况下，苯基稳定叶立德。
The reactions of a range of amide-stabilized sulfur ylides derived from readily available camphor-derived sulfonium salts for the synthesis of glycidic amides have been studied. Primary, secondary, and tertiary amides were tested, and it was found that the highest enantioselectivities were observed with tertiary amides, which provided glycidic amides in good to excellent yields, exclusive trans selectivity, and excellent enantioselectivities. The reaction was general for aromatic alclehydes, but aliphatic alclehydes gave more variable enantioselectivities. The epoxy amides could be converted cleanly into epoxy ketones by treatment with organolithium reagents. We were also able to effect selective ring opening of the epoxy amides with a variety of nucleophiles, followed by hydrolysis of the amide to yield the corresponding carboxylic acid. This methodology was applied to the total synthesis of the target compound SK&F 104353. A combination of crossover experiments and theoretical calculations has revealed that the rate- and selectivity-determining step is ring closure, not betaine formation as was the case for phenyl-stabilized ylides.