Experimental and Computational Development of a Conformationally Flexible Template for the meta-C-H Functionalization of Benzoic Acids
Experimental and Computational Development of a Conformationally Flexible Template for the meta-C-H Functionalization of Benzoic Acids
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DOI：
10.1021/jacs.7b03296
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发表时间：
2017-08-09
影响因子：
15
通讯作者：
Yu, Jin-Quan
中科院分区：
文献类型：
--
作者：
Fang, Lizhen;Saint-Denis, Tyler G.;Yu, Jin-Quan
通过实验和计算工作，设计了用于苯甲酸间-CH烯化的构象灵活模板。新设计的模板有利于银钯异二聚体的低势垒过渡态，并证明当天然底物的功能手柄与目标C-H键之间的距离减小时，延长模板以实现间位选择性是可行的。对邻位、间位和对位 C-H 裂解过渡态的分析确定，新的模板构象优化了间位过渡态的腈和钯银二聚体之间的相互作用，使钯能够以中等至良好的产率和通常较高的区域选择性裂解间位 C-H 键。区域选择性完全由模板控制；动力学实验表明，单保护氨基酸配体存在时，速率增加了 4 倍。使用玻尔兹曼。所有可访问的 C-H 激活过渡态的分布，可以以合理的精度通过计算预测许多研究模板中的元选择性。报告的结构能和畸变能可用于进一步开发迄今为止尚未探索的芳烃底物的元-C-H 活化模板。
A conformationally flexible template for the meta-CH olefination of benzoic acids was designed through both experimental and computational efforts. The newly designed template favors a silver palladium heterodimer low barrier transition state, and demonstrates that it is feasible to lengthen templates so as to achieve meta-selectivity when the distance :between the functional handle of the native substrate and target C-H bond decreases. Analysis of the ortho-, meta-, and para-C-H cleavage transition states determined-that the new template conformation optimizes the interaction between: the nitrile and palladium silver dimer in the meta-transition state, enabling palladium to cleave meta-C-H bonds with moderate-to-good yields and generally high regioselectivity. Regioselectivity is governed exclusively by the template,;and kinetic experiments reveal that there is a 4-fold increase in rate in the presence of monoprotected amino acid ligands. Using a Boltzmann. distribution of all,accessible C-H activation transition states, it is possible to computationally predict-meta-selectivity in a number of investigated templates with reasonable accuracy. Structural and distortion energies reported may be used for the further development of templates for meta-C-H activation of hitherto unexplored arene substrates.