Dispersion and Steric Effects on Enantio-/Diastereoselectivities in Synergistic Dual Transition-Metal Catalysis
Dispersion and Steric Effects on Enantio-/Diastereoselectivities in Synergistic Dual Transition-Metal Catalysis
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DOI：
10.1021/jacs.1c12664
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发表时间：
2022-01-20
影响因子：
15
通讯作者：
Houk, K. N.
中科院分区：
文献类型：
--
作者：
Li, Bo;Xu, Hui;Houk, K. N.
进行了全面的计算研究，以探索对映选择性 Cu/Pd 和立体发散 Cu/Ir 双催化合成 α,α-二取代 α-氨基酸（α-AAs）的机制。手性铜偶氮甲碱叶立德与外消旋 pi-烯丙基钯物种或立体纯 pi-烯丙基铱络合物进行容易的 α-烯丙基化，分别立体会聚或立体发散地提供单/双立构中心。 α中心的立体选择性由相对于前手性亲核试剂的α烯丙基化的面选择性控制。尽管过渡态组装明显相似，但计算模型和畸变/相互作用分析揭示了立体诱导的多种模式，其中铜甲亚胺叶立德物质可以利用有吸引力的色散相互作用和/或空间引起的畸变来选择性地拦截金属-π-烯丙基中间体。 Cu/Ir 系统中 β-立构中心的生成依赖于立体特异性生成的烯丙基铱配合物和电子控制的支化至线性选择性，而双 Cu/Pd 系统则由于空间因素和 pi-pi 堆积相互作用而产生线性单手性产物。这些研究在分子水平上证明了配体编码的手性信息如何转移到所得α-AA的α/β位点，以及区域/立体选择的模式如何通过过渡金属稳定的偶联伙伴的差异而改变。为了促进立体选择性催化的研究，展示了一套用于提取不对称诱导控制因素的分析工具。
Comprehensive computational studies were carried out to explore the mechanisms of enantioselective Cu/Pd and stereodivergent Cu/Ir dual-catalytic syntheses of alpha,alpha-disubstituted alpha-amino acids (alpha-AAs). A chiral copper azomethine ylide undergoes facile alpha-allylation with racemic pi-allylpalladium species or stereopure pi-allyliridium complex to stereoconvergently or stereodivergently furnish single/double stereocenters, respectively. Stereoselectivity at the alpha-center is controlled by the facial selectivity of alpha-allylation with respect to the prochiral nucleophile. Despite apparently similar transition-state assemblies, computational models and distortion/interaction analyses disclose versatile modes of stereoinduction wherein the copper azomethine ylide species can face-selectively intercept metal-pi-allyl intermediates utilizing attractive dispersion interactions and/or sterically caused distortions. Generation of the beta-stereocenter in the Cu/Ir system relies on a stereospecifically generated allyliridium complex and electronically controlled branched-to-linear selectivity, while the dual Cu/Pd system yields a linear monochiral product due to steric factors and pi-pi stacking interactions. The studies demonstrate on a molecular level how ligand-encoded chiral information is transferred to the alpha-/beta-sites of the resulting alpha-AAs and how the mode of regio-/stereoselection is altered by differences in transition-metal-stabilized coupling partners. To facilitate studies of stereoselective catalysis, a suite of analytical tools to extract controlling factors for asymmetric induction is demonstrated.