Experimental and DFT Studies Explain Solvent Control of C–H Activation and Product Selectivity in the Rh(III)-Catalyzed Formation of Neutral and Cationic Heterocycles

A range of novel heterocyclic cations
have been synthesized by
the Rh­(III)-catalyzed oxidative C–N and C–C coupling
of 1-phenylpyrazole, 2-phenylpyridine, and 2-vinylpyridine with alkynes
(4-octyne and diphenylacetylene). The reactions proceed via initial
C–H activation, alkyne insertion, and reductive coupling, and
all three of these steps are sensitive to the substrates involved
and the reaction conditions. Density functional theory (DFT) calculations
show that C–H activation can proceed via a heteroatom-directed
process that involves displacement of acetate by the neutral substrate
to form charged intermediates. This step (which leads to cationic
C–N coupled products) is therefore favored by more polar solvents.
An alternative non-directed C–H activation is also possible
that does not involve acetate displacement and so becomes favored
in low polarity solvents, leading to C–C coupled products.
Alkyne insertion is generally more favorable for diphenylacetylene
over 4-octyne, but the reverse is true of the reductive coupling step.
The diphenylacetylene moiety can also stabilize unsaturated seven-membered
rhodacycle intermediates through extra interaction with one of the
Ph substituents. With 1-phenylpyrazole this effect is sufficient to
suppress the final C–N reductive coupling. A comparison of
a series of seven-membered rhodacycles indicates the barrier to coupling
is highly sensitive to the two groups involved and follows the trend
C–N+ > C–N > C–C (i.e., involving
the formation of cationic C–N, neutral C–N, and neutral
C–C coupled products, respectively).

本研究通过铑(III)催化的氧化C-N与C-C偶联反应，以1-苯基吡唑、2-苯基吡啶、2-乙烯基吡啶为底物，与炔烃（4-辛炔、二苯乙炔）反应，合成了一系列新型杂环阳离子。该类反应依次经历初始C-H活化、炔烃插入以及还原偶联三个步骤，且这三步均对所涉及的底物与反应条件具有显著敏感性。密度泛函理论（Density Functional Theory, DFT）计算结果表明，C-H活化可通过杂原子导向路径进行：中性底物取代乙酸根配体，形成带电中间体。该步骤（可生成阳离子型C-N偶联产物）因此在极性更强的溶剂中更易进行。同时存在一条无需乙酸根配体取代的无导向C-H活化路径，该路径在低极性溶剂中更具优势，最终生成C-C偶联产物。相较于4-辛炔，二苯乙炔更易发生炔烃插入步骤，但还原偶联步骤则呈现相反的活性趋势。二苯乙炔片段还可通过与其中一个苯基（Phenyl, Ph）取代基的额外相互作用，稳定不饱和七元铑环中间体。当底物为1-苯基吡唑时，该稳定效应足以抑制最终的C-N还原偶联步骤。对一系列七元铑环中间体的对比分析表明，偶联反应的能垒与所涉及的两个基团高度相关，其活性趋势为：阳离子型C-N偶联 > 中性C-N偶联 > 中性C-C偶联（即分别对应阳离子C-N产物、中性C-N产物与中性C-C产物的生成）。