The combined C-H functionalization/Cope rearrangement: discovery and applications in organic synthesis.
The combined C-H functionalization/Cope rearrangement: discovery and applications in organic synthesis.
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DOI：
10.1021/ar300013t
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发表时间：
2012-06-19
影响因子：
18.3
通讯作者：
Lian, Yajing
中科院分区：
文献类型：
--
作者：
Davies, Huw M. L.;Lian, Yajing
sp3 C-H键的立体选择性官能化方法的开发是一项具有挑战性的工作。该帐户描述了C-H官能化/科普重排（CHCR）组合的范围，这是一种在铑稳定的乙烯基卡宾和含有烯丙基C-H键的底物之间发生的反应。计算研究表明，CHCR反应是由氢化物从底物的烯丙基位置转移到类卡宾引发的，然后迅速地在发展中的铑结合的烯丙基阴离子和烯丙基阳离子之间形成C-C键。原则上，反应可以通过乙烯基卡宾和接近的底物的四个不同取向进行。CHCR反应的早期例子都是高度非对映选择性的，与通过椅过渡态进行的反应一致，其中乙烯基类卡宾采用S-顺式构象。最近的计算研究表明，其他过渡态的取向是积极的访问，这些结果指导了高度立体选择性CHCR反应的发展，通过船过渡态与乙烯基卡宾在一个S-顺式配置进行。CHCR反应在有机合成中有着广泛的应用。在一些新的方案中，CHCR反应作为有机化学中一些经典合成策略的替代品。CHCR反应是Michael反应、乙烯基化Mukaiyama羟醛缩合反应、串联Claisen重排/科普重排和串联羟醛缩合反应/Aldol-科普重排的合成等价物。在所有这些情况下，生成的产物具有非常高的非对映体控制。使用手性四羧酸二铑催化剂如Rh 2（S-DOSP）4或Rh 2（S-Pd 3）4，研究人员可以实现非常高水平的不对称诱导。CHCR反应的应用包括外消旋二氢萘的有效对映体分化和几种天然产物的全合成：（-）-colorphiasin A，（-）-elisapterosin B和（+）-erogorgiaene。通过将CHCR反应进一步级联，我们和其他研究人员实现了一类新的单胺再摄取抑制剂4-取代吲哚的不对称合成。
The development of methods for the stereoselective functionalization of sp3 C–H bonds is a challenging undertaking. This Account describes the scope of the combined C–H functionalization/Cope rearrangement (CHCR), a reaction that occurs between rhodium-stabilized vinylcarbenoids and substrates containing allylic C–H bonds. Computational studies have shown that the CHCR reaction is initiated by a hydride transfer to the carbenoid from an allyl site of the substrate, which is then rapidly followed by C–C bond formation between the developing rhodium-bound allyl anion and the allyl cation. In principle, the reaction can proceed through four distinct orientations of the vinylcarbenoid and the approaching substrate. The early examples of the CHCR reaction were all highly diastereoselective, consistent with a reaction proceeding via a chair transition state with the vinylcarbenoid adopting an s-cis conformation. Recent computational studies have revealed that other transition state orientations are energetically accessible, and these results have guided the development of highly stereoselective CHCR reactions that proceed through a boat transition state with the vinylcarbenoid in an s-cis configuration. The CHCR reaction has broad applications in organic synthesis. In some new protocols, the CHCR reaction acts as a surrogate to some of the classic synthetic strategies in organic chemistry. The CHCR reaction has served as a synthetic equivalent of the Michael reaction, the vinylogous Mukaiyama aldol reaction, the tandem Claisen rearrangement/Cope rearrangement, and the tandem aldol reaction/siloxy-Cope rearrangement. In all of these cases, the products are generated with very high diastereocontrol. With a chiral dirhodium tetracarboxylate catalyst such as Rh2(S-DOSP)4 or Rh2(S-PTAD)4, researchers can achieve very high levels of asymmetric induction. Applications of the CHCR reaction include the effective enantiodifferentiation of racemic dihydronaphthalenes and the total synthesis of several natural products: (−)-colombiasin A, (−)-elisapterosin B, and (+)-erogorgiaene. By combining the CHCR reaction into a further cascade sequence, we and other researchers have achieved the asymmetric synthesis of 4-substituted indoles, a new class of monoamine reuptake inhibitors.
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影响因子：
4.3
作者：
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影响因子：
15
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