Borrowing Hydrogen Reactions Catalyzed By Ruthenium And Iridium Catalysts Bearing 2-hydroxypyridyl Fragment

The borrowing hydrogen principle（BH）,also called hydrogen autotransfer,is a powerful approach to form carbon-carbon and carbon-nitrogen bond in one-step process to obtain more complicated products.The strategy is a cascade reaction,which relies on the dehydrogenation of alcohols,the condensation of corresponding carbonyls with amines or carbon nucleophiles,and the hydrogenation of the unsaturated intermediates.It is more efficient to use the tractable,renewable and economic alcohols as the alkylating agents when compared with traditional method s,and water is the only by-product.All these advantages have brought it great attention and it is regarded by pharmaceutical companies as one of the key areas of green chemistry.The earliest research in this field has focused on the use of ruthenium and iridium complexes as catalysts,which are normally more active than base metals.However,most of the ligands were unstable and intricate to synthsize.Most of the catalatic reaction were in relatively harsh catalytic conditions with poor reaction selectivity and limited substrate range.Combined with the recent research on hydroxy-pyridine synergistic catalysts in our group,a series of ruthenium and iridium catalysts containing 2-hydroxypyridyl group were designed to catalyze the synthesis of various N-heterocycles,alcohols,ketones and amines by borrowing hydrogen reaction,which has important implications for green chemistry.The main research contents are as follows:TheNNN-typeligandcontaininga2-hydroxypyridine（HO-C₅H₃N-CO-C₅H₃N-C₅H₄N）（3-3）was synthesized and reacted with[Ru（CO）₂Cl₂]to obtain the complex[（HO-C₅H₃N-CO-C₅H₃N-C₅H₄N）Ru（CO）Cl₂]（3-5）.The molecular structure of 3-5 was further confirmed by X-ray crystallography.The synthesis of pyridines,quinolines and pyrroles could be achieved by using 0.2 mol%complex 3-5 from amino alcohols and secondary alcohols in refluxing toluene after 6～12 h in the presence of potassium tert-butanol.The separation yields of some compounds were higher than 90%.The ligand（CH₃O-C₅H₃N-C₅H₃N-CO-C₆H₄-PPh₂）（4-2）and the tetradentate ruthenium complex[{CH₃O-C₅H₃N-C₅H₃N-CH（O）-C₆H₄-PPh₂}Ru（CO）（PPh₃）]Cl（4-5）were designed and synthesized.The pyridone structure of complex 4-6 was formed by the unusual carbon-oxygen bond cleavage of the methoxy containing complex 4-5.The possible mechanism of methoxy fracture of complex 4-5 was investigated.It showed that when there was a small amount of neutral H₂O in the refluxing tetrahydrofuran,the carbon-oxygen bond fracture could be realized by S_N2mechanism.While in the presence of KOH,it transformed into S _NAr mechanism.The transformation of 4-8a and 4-8b to 4-9 indicates it has certain universality that the coordination of ruthenium activates the O-CH₃ bond of a 2-methoxypyridyl group.Furthermore,these complexes were tested as catalysts forβ-alkylation of secondary alcohols with primary alcohols,and they exhibited similar activity.The yields for most substrates was above 90%in 90 min with 0.5 mol%complex 4-5.The simple ligand（HOC₅H₃CH₂C₅H₃OH）（5-2）and iridium complex[Cp*Ir（HOC₅H₃CH₂C₅H₃OH）（Cl）][Cl]（5-3）were designed and synthesized.The complex[Cp*Ir（HOC₅H₃CH₂C₅H₃OH）（H₂O）[OTf]₂（5-4）was obtained by interaction of 5-3 with Ag OTf.1 mol%complex 5-3 was applied to catalyze N-methylation of amines using methanol as the C₁ source.The reactions were conducted in the air for 12 h with a weak base（K₂CO₃）,and the monomethylated products could be obtained in the yields higher than 90%.The ligand（C₅H₄CH₂C₅H₃OH）（6-3）and the iridium complex(Cp*Ir（C₅H₄CH₂C₅H₃OH）（Cl）][Cl]（6-8）were designed,and the complex[Cp*Ir Cl（C₅H₄CH₂C₅H₃O）]（6-13）was obtained with base.At the same time,NN ligands containing different hydroxyl groups and methoxy groups were designed and synthesized,and a series of bidentate iridium complexes were synthesized.The activity of the iridium complexes to catalyze the monoalkylation of aromatic amines with tertiary amines was investigated.Complex 6-8 showed highest catalytic activitiy,and complex 6-13 was the intermediate of the catalytic reactions.The catalytic reactions were conducted under the relatively mild condition of 120℃in methanol,and there was no additional bases.NR₃·HCl can promote the N-alkylation aniline with triethylamine,and the yields reached up to 94%.The reactions were highly selective and there were no by-products,such as imine derivatives and disubstituted aniline products.