Study On Manganese-catalyzed C–H Enaminylation And Electrochemically Oxidative C–X(X=N, P) Bonds Formation

Since the mid-seventies of the 20 th century,with the rapid development of synthetic chemistry,it has brought huge economic profits to people,at the same time,the resulting environmental problems have gradually begun to appear.Synthetic chemistry faces not only the challenge of creating increasingly complex molecules,but also the challenge of atomic economy and sustainable development.Sustainable chemistry is a broad framework,in which green chemistry is an important part of sustainable chemistry,which solves the problem of green synthesis and makes synthetic chemicals more benign to some extent.Therefore,in order to support the concept of green chemistry and sustainable chemistry,chemists should develop greener and greener chemical processes,a trend that is likely to become more evident in the coming decades.In this context,the transition metal-catalyzed C–H bond functionalization strategy and organic electrosynthesis strategy began to emerge.These two transformational synthesis strategies have different advantages compared with traditional organic chemistry.Among them,the transition metal-catalyzed C–H bond functionalization strategy has the advantages of few by-products,mild reaction conditions,simple and easily available starting materials,no need for pre-functionalization of substrates,so as to reduce the synthesis steps.On the other hand,the organic electrosynthesis strategy has the advantages of no additional redox agent,no catalyst and renewable reaction energy.It also provides chemists with a new tool to do more things with less money.Based on the idea of green chemistry,a series of environmentally friendly and highly selective functionalization and oxidation methods have been developed based on transition metal-catalyzed C–H bond functionalization and organic electrochemical strategies.The details are summarized as following:(1)Manganese-catalyzed C?H enaminylation: expedient access to indole-purine hybrids with anti-tumor bioactivities.The C–H enaminylation of novel 6-(1H-indol-1-yl)-purines with ketenimines was accomplished by means of eco-friendly aqueous manganese catalysis as well as rhenium catalysis with low catalyst loading.The versatile C–H enaminylation features unparalleled broad substrate scope with good yields,and high levels of chemo-,site-and regio-selectivity.The well-defined organometallic C–H functionalization sets the stage for the facile synthesis of indole–purine hybrids with antitumor bioactivities.(2)A catalyst-free,direct electrochemical synthesis of synthetically challenging medium-sized lactams through C–C bond cleavage has been developed.In contrast to previous typical amidyl radical cyclization,this electrosynthetic approach enabled stepeconomical ring expansion through a unique remote amidyl migration under mild,metaland external-oxidant-free conditions in a simple undivided cell.The strategy features unparalleled broad substrate scope with all ring sizes of(hetero)aryl-fused 8–11-membered rings and hetero atom-tethered rings,high yields,and good functional group tolerance.Our experimental and computational findings provided strong support for a SET-based reaction manifold.(3)Electrooxidation enables late-stage azolation of benzylic C?H bonds.The installation of azoles via C–H/N–H cross-coupling is significantly underdeveloped,particularly in benzylic C–H azolation due to the requirement for external chemical oxidants and the challenge in controlling the site-and chemo-selectivity.Herein,a late-stage azolation of benzylic C?H bonds enabled by electrooxidation is described,which proceeds in an undivided cell under mild,catalyst-and chemical-oxidant-free reaction conditions.The remarkable synthetic utility of our approach is highlighted by its easy scalability without overoxidation of products and ample scope with valuable functional groups.The approach can be directly used to install benzyl and azole motifs on highly functionalized drug molecules.(4)Electrochemically enabled phosphorylation and hydrophosphorylation of imine derivatives.The electrochemical phosphorylation of aldehyde hydrazones has been developed under exogenous oxidant-free conditions.The strategy provides expedient access to highly functionalized α-iminophosphine oxides with ample scope and broad functional group tolerance by means of mild,user-friendly electrolysis,in an undivided cell.