理论计算研究过渡金属-有机分子协同催化的酮的C-H或C-C键官能团化的催化机理及新催化体系的发展

选择性催化活化C-H生成新的C-X(X=C或杂原子)提供一种“原子经济”、简捷的合成方法。醛/酮的C-H与烯烃的加成反应属于这类反应。早期提出的金属-有机分子协同催化(MOCC)策略能有效地实现醛的C(sp2)–H官能团化和基于C-C活化的酮与烯烃的反应, 但不能完成酮的C(sp3)–H官能团化。基于MOCC, 实验近来实现了酮与烯烃的α-C(sp3)–H烷基化和C–C活化的[4+2]偶联反应。虽然MOCC在合成化学中崭露头角，但没有得到深入研究和发展。我们拟用计算化学的方法深入研究实验实现的MOCC催化的C–H活化和C–C活化反应的机理，解释实验上的困惑。基于机理认识，我们将进一步以计算为“实验”手段设计新的有机共催化剂、拓展现在唯一使用的铑和铑(I)/铑(III)氧化还原循环到其它金属及氧化还原循环并探索实现更具挑战性酮的C(sp3)–H官能团化。该研究将促进MOCC化学的丰富和发展。

C–H bond is ubiquitous in organic molecules. The construction of C–C and C–heteroatom bonds via directed C−H bond functionalization, which could offer an atom- and step-economic synthetic method to access complex molecules, is appreciated to be the “holy grail” in the area of transition metal (TM) catalysis, attracting extensive research effort. The addition of a C–H bond of ketone/aldehyde to olefin represents such a family of C–C bond forming reactions. Metal-organic cooperative catalysis (MOCC) which combines a TM catalyst and an organic cocatalyst to functionalize a C–H bond cooperatively is a conceptually new strategy proposed for aldehyde C(sp2)–H bond functionalization to avoid decarbonylation side reaction in hydroacylation of olefin and aldehyde. The strategy later on was also found to be effective in promoting ketone C-C bond activation/functionalization. Despite these early successes, the functionalization of less reactive C(sp3)–H bond of ketone remained to be a challenge for a relatively long period. Recently, Dong et al. have advanced the strategy greatly. By elaborating the two components of MOCC systems, they accomplished the challenging C(sp3)–H bond functionalization of ketone, achieving Cα-alkylation of ketones with simple olefins, and synthesized bridged ring systems from cyclobutanones and olefins via MOCC-mediated C–C bond activation of ketone. Although the MOCC strategy has demonstrated its power in organic synthesis, relatively less attention has been paid to this strategy, leaving room for further development. Herein we propose using computational chemistry to deeply understand the mechanisms of MOCC strategy by choosing experimentally realized MOCC-based catalytic reactions as representatives, including ketone Cα-alkylation with olefins via directed C(sp3)–H bond functionalization and the catalytic reactions via activating ketone C–C bond. In addition to understanding the mechanisms of MOCC, the computed mechanism will be used to solve experimental puzzles and to serve as a base for mechanism-based development. After deeply understanding the mechanisms, we will use computation as an “experimental” mean to explore new MOCC chemistry: designing new organic cocatalysts, expanding the hitherto sole use of rhodium metal to other TMs such as cobalt and nickel, expanding the hitherto exclusive use of the Rh(I)/Rh(III) redox cycling to other redox cycling of TMs such as Co(0)/Co(II), Ni(0)/Ni(II), and Ni(II)/Ni(IV) manifolds. On the basis of the above studies, we will ultimately challenge the C(sp3)–H bond functionalization of more general ketone (such as linear ketones and cyclohexanone) which have been attempted experimentally but are not efficient and develop new MOCC systems to carry out asymmetric ketone C-C bond activation based transformations with higher yield and enantiomeic selectivity. We expect that these studies will promote the enrichment and development of MOCC chemistry.