Study On The Synthesis Of N-Heterocycles Via Transfer Hydrogenation Coupling Of Alcohols

Alcohols are a class of cost-effective and easily-available renewable resources that widely distribute in nature.Over the past two decades,the research on efficient,selective and green transformation of alcohols has been becoming a hot topic.At present,the hydrogen transfer coupling reaction is a super synthetic method to promote the utilization of alcohols.In which,In which,the alcohols are dehydrogenated by transition metal or other catalysts to form the aldehyde or ketone intermediates,which subsequent react with carbon-or N-nucleophiles to in-situ generate the alkenes or imines.Finally,the catalyst give the hydrogen back to the unsaturated chemical bonds to the intermediates,thus affording the products.Generally,such synthetic protocols do not need stoichiometric amount of oxidants and reductants as well as special high pressure equipment,and water is produced as the only by-product.Hence,the hydrogen transfer coupling reactions of alcohols possess extremely high step-and atom-economic efficiency.Meanwhile,nitrogen-containing heterocyclic compounds play a significantly important role in biomedical and functional materials,are a class of indispensable substances related to the people's livelihood and sustainable development.Hence,the utilization of alcohols with other reagents for the construction of nitrogen-containing heterocyclic products is of great significance in the progress of sustainable chemistry.Under this context,our research mainly contains the synthesis of novel N-heterocycles compounds via hydrogen transfer coupling strategy from alcohols.The details are as follows:(1)Synthesis of 1,2,3,4-tetrahydronaphthyridines from ortho-aminopyridyl methanols and alcohols through ruthenium-catalyzed selective hydrogen transfer coupling reaction.This synthetic protocol proceeds in an atom-and step-economic fashion together with the advantages of operational simplicity,broad substrate scope,water as the only by-product,no need for external reducing reagents such as high pressure H2 gas,offering a highly practical approach for accessing this type of structurally unique product.The product structure was confirmed by single crystal diffraction,and the control experiments and isotope labeling reaction proved that the reaction involves a hydrogen transfer process of alcohols and the possible mechanism was therefore proposed.(2)Hydrogen transfer-mediated direct ?-alkylation of aryl-1,8-naphthyridines with alcohols under transition metal catalyst-free Conditions.By employing abundant and sustainable alcohols as the alkylating reagents,this method enables the selective alkylation of the less-substituted pyridyl ring at the ?-position of aryl naphthyridines,affording the desired products in moderate to excellent yields upon isolation.The method proceeds under transition metal-free conditions in an atom-and step-economic fashion.Mechanistic investigations suggest the reaction undergoes a hydrogen transfer-mediated alkylation process.(3)Ruthenium-catalysed hydrogen transfer annulation protocol for direct synthesis of fused tetrahydro-pyrazine derivatives.By employing readily available Ru3(CO)12/Xantphos/t-BuOK as an efficient catalyst system,the protocol proceeds with unprecedented synthetic effectiveness including step-and atom-economy,no need for external high pressure H2 gas and short reaction time,offering an important basis for the transformation of vicinal diols resource into functionalized products.(4)Synthesis of tetrahydropyrido-fused pyrimidines via ruthenium-catalyzed selective transfer hydrogenation.The study demonstrates the first example of direct access to tetrahydropyrido-fused pyrimidines from ortho-aminopyridyl methanols and simple nitriles.This synthetic protocol proceeds via a sequence of dehydrogenative annulation and selective transfer hydrogenation of the challenging pyridyl nucleus,affording the products with the advantages of an easily available catalyst system,broad substrate scope and no need for additional high pressure H2 gas.In addition,DFT study revealed the origin of the unique selectivity for the transfer hydrogenation process.The work presented in this paper has represented a significant advancement in implementation of transer hydrogenative coupling strategy,endowing the potential for futher design of new reactions to construct semi-saturated fused N-heterocyclic products that are currently inaccessible or challenging to prepare with the conventional methods.(5)The application of tetrahydro-1,8-naphthyridine compounds in the synthesis of novel pincer ligands.A series of tetrahydro-1,8-naphthyridine derivatives were synthesized by hydrogen transfer coupling and palladium-carbon-catalyzed reduction reactions,which react with phosphorus reagents to afford new types of pincer ligands such as P^N^P,P^N^N and P^N^C ones in good yields..The ligands with novel non-symmetric N-heterocycles as skeletons features easy preparation,high stability and convenient structural modification.Among which,the asymmetric P^N^P ligands are currently rare.Finally,we synthesized the pincer ruthenium complexes with the use of P^N^P ligands and Ru metal precursor.