A general catalytic hydrogen transfer-mediated α-functionalization of 1,8-naphthyridines is reported for the first time that benefits from a hydrogen transfer-mediated activation mode for non-activated pyridyl cores. The pyridyl α-site selectively couples with the C8-site of various tetrahydroquinolines (THQs) to afford novel α-functionalized tetrahydro 1,8-naphthyridines, a class of synthetically useful building blocks and potential candidates for the discovery of therapeutic and bio-active products. The utilization of THQs as inactive hydrogen donors (HDs) appears to be a key strategy to overcome the over-hydrogenation barrier and address the chemoselectivity issue. The developed chemistry features operational simplicity, readily available catalyst and good functional group tolerance, and offers a significant basis for further development of new protocols to directly transform or functionalize inert N-heterocycles.

Ag eneral catalytic hydrogen transfer-mediated afunctionalization of 1,8-naphthyridines is reported for the first time that benefits from ahydrogen transfer-mediated activation mode for non-activated pyridyl cores.T he pyridyl a-site selectively couples with the C8-site of various tetrahydroquinolines (THQs) to affordn ovel a-functionalized tetrahydro 1,8naphthyridines,aclass of synthetically useful building blocks and potential candidates for the discovery of therapeutic and bio-active products.T he utilization of THQs as inactive hydrogen donors (HDs) appears to be ak ey strategy to overcome the over-hydrogenation barrier and address the chemoselectivity issue.T he developed chemistry features operational simplicity,r eadily available catalyst and good functional group tolerance,a nd offers as ignificant basis for further development of new protocols to directly transform or functionalize inert N-heterocycles.Hydrogen transfer-mediated carbon-carbon and carbonheteroatom bond formations have emerged as powerful tools in synthetic organic chemistry,since they enable key steps in creation of various functionalized products. [1] Forexample,in addition to the hydrogen-borrowing methodologies extensively employed for N-alkylation [2] and C-alkylation, [3] Krische has demonstrated outstanding contributions on the coupling of alcohols with C À Cd ouble/triple bonds. [4] With the use formic acid as the hydrogen donor (HD), the Bruneau group has reported the non-directed C(sp 3 )ÀHb ond alkylation of saturated cyclic amines. [5] In addition, Li and the coworkers have illustrated the conversion of phenol derivatives into amines in the presence of HCO 2 Na. [6] Despite these significant achievements,the strategy of selective trapping of the transient partially hydrogenated N-heteroarenes remains ac hallenge,a lthough it would offer aw ay to access functionalized molecules that are inaccessible or difficult to prepare with existing methods.Thep yridyl ring is ubiquitous in bioactive molecules, functional materials,d yes,a grochemicals,p harmaceuticals, and natural products.H ence,t he direct transformation of pyridyl ring into functionalized frameworks is of significant importance.H owever,s uch ag oal, without the assistance of directing groups [7] or pre-installation of functionalities, [8] remains highly challenging.A sp art of our continuous research interest in construction of N-heterocycles by hydrogen transfer strategies, [9] we have recently demonstrated adirect reductive quinolyl b-C À Halkylation using formic acid as the hydrogen donor (HD). [10] Encouraged by this work, we set out to realize the direct a-functionalization of N-heteroarenes via ahydrogen transfer-mediated activation mode for non-activated pyridyl core.A ss hown in Scheme 1, in the presence of asuitable HD and catalyst (Cat), the first transfer hydrogenation (TH) of pyridyl ring of 2 would afford an allylic amine A and its tautomers (enamine B and imine C). Then, the nucleophile 1 (NuH) would undergo a-addition to imine C,t hereby releasing the...

By an external hydrogen transfer-mediated activation mode, we herein demonstrate a new palladium-catalyzed direct α,β-coupling of different types of N-heteroarenes. Such a selective coupling reaction proceeds with the advantages of operational simplicity, high atom-economical efficiency, and use of safe and abundant i-propanol as the activating agent, offering a practical way to access nitrogen bi-heteroarenes. Preliminary exploration has revealed that the obtained bis-1,10-phenanthroline 2qq' as a ligand is capable of improving a copper catalyst for C-C bond formation. The work reported in this paper has built an important basis for the creation of extended π-conjugated systems that are of high significance in biological, medicinal, materials and synthetic organic chemistry as well as catalysis.