Stereocontrolled alkylative construction of quaternary carbon centers.
Stereocontrolled alkylative construction of quaternary carbon centers.
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DOI：
10.1021/ja806021y
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发表时间：
2008-10-08
影响因子：
15
通讯作者：
Myers, Andrew G.
中科院分区：
文献类型：
--
作者：
Kummer, David A.;Chain, William J.;Morales, Marvin R.;Quiroga, Olga;Myers, Andrew G.
介绍了用于形成伪麻黄碱酰胺的α，α-二取代烯醇酸酯的立体定义的方案，随后在非对映选择性烷基化反应中实施了这些方案。α，α-二取代的伪麻黄胺底物的直接烷基化在一系列底物上被证明是有效的和非对映选择性的，例如非对映异构体伪麻黄碱α-甲基丁酰胺的烷基化，其中两种底物都被发现进行了α-C-H键与α-C-烷基的立体定向取代，并保留了立体化学。这是由顺序的立体特异性烯醇化和烷基化反应引起的，其中烷基卤化物攻击E-和Z-烯醇酸酯的共同π面，被认为是与伪麻黄碱醇盐侧链相反的。伪麻黄碱α-苯基丁酰亚胺发生了高度立体选择性而不是立体特异性的α-烷基化反应，证据表明这是由于容易的烯醇异构化。此外，我们还表明，通过将烷基锂试剂共轭加成到α，α-烷基-α-不饱和伪麻黄胺的S顺式构象上，可以以高度立体控制的方式生成α，β-二取代伪麻黄胺烯醇酸酯，提供与直接去质子化相同意义的α，α-二取代烯醇底物。介绍了将α-季铵盐类伪麻黄碱酰胺产品转化为光学活性羧酸、酮、伯醇和醛的方法。
Protocols for the stereodefined formation of α,α-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of α,α-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine α-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the α-C-H bond with α-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common π-face of the E- and Z-enolates, proposed to be that opposite the pseudoephedrine alkoxide side-chain. Pseudoephedrine α-phenylbutyramides are found to undergo highly stereoselective but not stereospecific α-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that α, α-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an α-alkyl-α,β-unsaturated pseudoephedrine amide, providing α,α-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the α-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes.
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影响因子：
5.2
作者：
Chain, William J.;Myers, Andrew G.
通讯作者：
Myers, Andrew G.
影响因子：
15
作者：
MEYERS, AI;COLLINGT.EW
通讯作者：
COLLINGT.EW
影响因子：
5.2
作者：
Reyes, Efraim;Vicario, Jose L.;Uria, Uxue
通讯作者：
Uria, Uxue
影响因子：
5.2
作者：
Boeckman, RK;Boehmler, DJ;Musselman, RA
通讯作者：
Musselman, RA
影响因子：
0.6
作者：
Castro, Alejandro;Ramirez, Johana;Gnecco, Dino
通讯作者：
Gnecco, Dino