Department of Chemistry, University of California, Berkeley, California 94702, United States.
J Am Chem Soc. 2021 Aug 4;143(30):11741-11750. doi: 10.1021/jacs.1c05346. Epub 2021 Jul 26.
The Pd-catalyzed asymmetric α-arylation of carbonyl compounds is a valuable strategy to form benzylic stereocenters. However, the origin of the stereoselectivity of these reactions is poorly understood, and little is known about the reactivity of the putative diastereomeric arylpalladium enolate intermediates. To this end, we report the synthesis and characterization of a series of diphosphine-ligated arylpalladium fluoroenolate complexes, including complexes bearing a metal-bound, stereogenic carbon and an enantioenriched chiral diphosphine ligand. These complexes reductively eliminate to form chiral α-aryl-α-fluorooxindoles with enantioselectivities and rates that are relevant to those of the catalytic process with SEGPHOS as the ancillary ligand. Kinetic studies showed that the rate of reductive elimination is slightly slower than the rate of epimerization of the intermediate, causing the reductive elimination step to impart the greatest influence on the enantioselectivity. DFT calculations of these processes are consistent with these experimental rates and suggest that the minor diastereomer forms the major enantiomer of the product. The rates of reductive elimination from complexes containing a variety of electronically varied aryl ligands revealed the unusual trend that complexes bearing more electron-rich aryl ligands react faster than those bearing more electron-poor aryl ligands. Noncovalent Interaction (NCI) and Natural Bond Orbital (NBO) analyses of the transition-state structures for reductive elimination from the SEGPHOS-ligated complexes revealed key donor-acceptor interactions between the Pd center and the fluoroenolate fragment. These interactions stabilize the pathway to the major product enantiomer more strongly than they stabilize that to the minor enantiomer.
钯催化的羰基化合物不对称 α-芳基化反应是形成苄基立体中心的一种有效策略。然而，这些反应的立体选择性的起源还没有被很好地理解，对于假定的手性芳基钯烯醇化物中间体的反应性也知之甚少。为此，我们报告了一系列双膦配体芳基钯氟代烯醇化物配合物的合成和表征，包括带有金属结合的手性碳和手性双膦配体的对映体富集的配合物。这些配合物通过还原消除形成手性α-芳基-α-氟代氧杂吲哚，具有与 SEGPHOS 作为辅助配体的催化过程相关的对映选择性和速率。动力学研究表明，还原消除的速率略慢于中间体的外消旋化速率，导致还原消除步骤对对映选择性的影响最大。这些过程的 DFT 计算与这些实验速率一致，并表明较小的非对映异构体形成产物的主要对映异构体。含有各种电子变化的芳基配体的配合物的还原消除速率揭示了一个不寻常的趋势，即含有更多富电子芳基配体的配合物比含有更多缺电子芳基配体的配合物反应更快。从 SEGPHOS 配体配合物还原消除的过渡态结构的非共价相互作用（NCI）和自然键轨道（NBO）分析揭示了 Pd 中心和氟代烯醇化物片段之间的关键供体-受体相互作用。这些相互作用比稳定次要对映异构体的相互作用更强烈地稳定主要产物对映异构体的途径。
