DFT and Experimental Exploration of the Mechanism of InCl3-Catalyzed Type II Cycloisomerization of 1,6-Enynes: Identifying InCl2+ as the Catalytic Species and Answering Why Nonconjugated Dienes Are Generated
DFT and Experimental Exploration of the Mechanism of InCl3-Catalyzed Type II Cycloisomerization of 1,6-Enynes: Identifying InCl2+ as the Catalytic Species and Answering Why Nonconjugated Dienes Are Generated
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DOI：
10.1021/jo301471w
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发表时间：
2012-10-05
影响因子：
3.6
通讯作者：
Yu, Zhi-Xiang
中科院分区：
文献类型：
--
作者：
Zhuo, Lian-Gang;Zhang, Ji-Ji;Yu, Zhi-Xiang
InCl 3和其他In（III）物种已被广泛用作许多反应中的催化剂。然而，这些反应的真实的催化物种是什么？通过对InCl_3催化1，6-烯炔环化异构化反应的机理和区域选择性的DFT计算和实验研究，我们提出该反应的催化物种是原位生成的InCl_2+。进一步的电喷雾电离高分辨质谱（ESI-HRMS）支持乙腈溶液中InCl 2+的存在。InCl 2+作为催化物质的这一发现表明，由In（III）物质催化的其他反应也可以具有阳离子In（III）物质作为真实的催化剂。DFT计算表明，InCl 3催化1，6-烯炔环异构化反应的催化循环是从InCl 2+开始的.与底物的炔配位，产生乙烯基阳离子。然后乙烯基阳离子的非经典环丙烷化到底物的烯烃部分得到高烯丙基阳离子，其经历涉及[1，3]-碳位移的新型高烯丙基阳离子重排，得到更稳定的高烯丙基阳离子15。最后，InCl 2+阳离子配位辅助的非共轭[1，2]-氢化物位移提供最终的非共轭二烯产物。在环化异构化反应中优先生成非共辄二烯而不是共辄二烯主要是由于两个原因：InCl 2+在[1，2]-H位移过渡态中与烯烃部分的配位不利于产生与带正电荷的烯烃相邻的阳离子的共轭[1，2]-H位移，并且InCl 2+与非共轭二烯产物的配位比与共轭二烯的配位更强，使得非共轭[1，2]-H移位过渡态的能量比共轭[1，在哈蒙德假设的基础上，得到了2]-H转移过渡态。DFT计算预测，如果1，6-烯炔的炔部分中的给电子甲基取代基被H原子取代，则共轭[1，2]-H位移将变得有利。这种产生共轭二烯的预测已经在实验上得到了验证。用计算方法研究了InCl_3催化1，6-烯炔环化异构化反应中得到H型产物而不是I型产物的原因。
InCl3 and other In(III) species have been widely applied as catalysts in many reactions. However, what are the real catalytic species of these reactions? Through DFT calculations and experimental investigation of the mechanism and regioselectivity of InCl3-catalyzed cycloisomerization reactions of 1,6-enynes (here all discussed 1,6-enynes are ene-internal-alkyne molecules), we propose that the catalytic species of this reaction is the in situ generated InCl2+. Further electrospray ionization high-resolution mass spectroscopy (ESI-HRMS) supported the existence of InCl2+ in acetonitrile solution. This finding of InCl2+ as the catalytic species suggests that other reactions catalyzed by In(III) species could also have cationic In(III) species as the real catalysts. DFT calculations revealed that the catalytic cycle of the cycloisomerization of 1,6-enynes catalyzed by InCl3 starts from InCl2+. coordination to the alkyne of the substrate, generating a vinyl cation. Then nonclassical cyclopropanation of the vinyl cation to the alkene part of the substrate gives a homoallylic cation, which undergoes a novel homoallylic cation rearrangement involving a [1,3]-carbon shift to give the more stable homoallylic cation 15. Finally InCl2+ cation coordination assisted nonconjugated [1,2]-hydride shifts deliver the final nonconjugated diene products. The preference of generating nonconjugated dienes instead of conjugated dienes in the cycloisomerization reaction is mainly due to two reasons: coordination of the InCl2+ to the alkene part in [1,2]-H shift transition states disfavors the conjugated [1,2]-H shifts that generate cations adjacent to the positively charged alkene, and coordination of InCl2+ to the nonconjugated diene product is stronger than coordination to the conjugated diene, making nonconjugated [1,2]-H shift transition states lower in energy than conjugated [1,2]-H shift transition states, on the basis of the Hammond postulate. DFT calculations predicted that the conjugated [1,2]-H shifts could become favored if the electron-donating methyl substituent in the alkyne moiety of the 1,6-enyne is replaced by a H atom. This prediction of producing a conjugated diene has been verified experimentally. Rationalization about why type H rather than type I products were obtained using InCl3 as the catalyst in the cycloisomerization of 1,6-enynes has also been investigated computationally.