Department of Chemistry , Indian Institute of Technology Bombay , Powai, Mumbai 400076 , India.
Department of Chemistry , University of California Berkeley , Berkeley , California 94720 , United States.
J Am Chem Soc. 2019 Jan 16;141(2):998-1009. doi: 10.1021/jacs.8b11062. Epub 2018 Dec 28.
The use of more than one catalyst in one-pot reaction conditions has become a rapidly evolving protocol in the development of asymmetric catalysis. The lack of molecular insights on the mechanism and enantioselectivity in dual-catalytic reactions motivated the present study focusing on an important catalytic asymmetric Heck-Matsuda cross-coupling. A comprehensive density functional theory (M06 and B3LYP-D3) investigation of the coupling between a spirocyclic cyclopentene and 4-fluorophenyl diazonium species under a dual-catalytic condition involving Pd(dba) (dba = trans, trans-dibenzylideneacetone) and chiral 2,2'-binaphthyl diamine (BINAM)-derived phosphoric acids (BDPA, 2,2'-binaphthyl diamine-derived phosphoric acids) is presented. Among various mechanistic possibilities examined, the pathway with explicit inclusion of the base (in situ generated sodium bicarbonate/sodium biphosphate) is found to be energetically more preferred over the analogous base-free routes. The chiral phosphate generated by the action of sodium carbonate on BDPA is found to remain associated with the reaction site as a counterion. The initial oxidative addition of Pd(0) to the aryl diazonium bond gives rise to a Pd-aryl intermediate, which then goes through the enantiocontrolling migratory insertion to the cyclic alkene, leading to an arylated cycloalkene intermediate. Insights on how a series of noncovalent interactions, such as C-H···O, C-H···N, C-H···F, C-H···π, lp···π, O-H···π, and C-F···π, in the enantiocontrolling transition state (TS) render the migration of the Pd-aryl to the si prochiral face of the cyclic alkene more preferred over that to the re face are utilized for modulating the enantioselectivity. Aided by molecular insights on the enantiocontrolling transition states, we predicted improved enantioselectivity from 37% to 89% by changes in the N-aryl substituents of the catalyst. Subsequent experiments in our laboratory offered very good agreement with the predicted enantioselectivities.
在不对称催化发展中，一锅法反应条件下使用多种催化剂已成为一种快速发展的方法。双催化反应中缺乏对机理和对映选择性的分子认识，这促使我们进行了目前的研究，重点是重要的催化不对称 Heck-Matsuda 交叉偶联反应。本文采用综合密度泛函理论（M06 和 B3LYP-D3）研究了在双催化条件下，含钯（dba）（dba=反式，反式-二苄基丙酮）和手性 2,2'-联萘二胺（BINAP）衍生磷酸（BDPA，2,2'-联萘二胺衍生磷酸）的螺环环戊烯与 4-氟苯基重氮物种之间的偶联反应。在所考察的各种可能的机理中，发现包含碱（原位生成的碳酸氢钠/磷酸氢二钠）的途径在能量上比类似的无碱途径更有利。由碳酸钠与 BDPA 作用生成的手性磷酸与反应位点保持缔合，作为抗衡离子。Pd(0)与芳基重氮键的初始氧化加成产生 Pd-芳基中间体，然后通过对映体控制的迁移插入到环状烯烃中，生成芳基化的环烯烃中间体。一系列非共价相互作用，如 C-H···O、C-H···N、C-H···F、C-H···π、lp···π、O-H···π 和 C-F···π，在对映体控制过渡态（TS）中的作用的深入了解，使得 Pd-芳基向环状烯烃的 si 面迁移比向 re 面迁移更有利于对映体选择性。借助对映体控制过渡态的分子见解，我们通过改变催化剂的 N-芳基取代基，预测对映选择性从 37%提高到 89%。我们实验室随后的实验与预测的对映选择性非常吻合。
