Synthesis Of Isoquinoline Derivatives Via Transition-Metal Catalyzed Carbene Insertion Reactions

Poly cyclic nitrogen-containing heterocycles has attracted wide attention due to their important application in the synthesis of bioactive compounds.Developing novel and efficient methods to synthesize nitrogen-containing heterocyclic compounds remains an attractive synthetic task in recent years.As significant caibene species,diazo compounds and isocyanides play important roles in the synthesis of nitrogen-containing heterocycles based on their unique reactivitives.Based on the long-standing research interest on the synthesis of privilagded heterocycles,we herein developed efficient Ru?II?-catalyzed C-H bond activation/annulation of cyclic amides with 1,3-diketone-2-diazo compounds and inert C?sp³?-C?sp³?bond cleavage reactions for the synthesis of isoquinoline derivatives.We have developed an efficient and practical method for the synthesis of8H-isoquinolino[1,2-b]quinazolin-8-one derivatives via ruthenium catalyzed C-H bond activation reactions.Diverse nitrogen-containing poly cyclic compounds were synthesized effectively under mild conditions.The reaction proceeds through consecutive C-H bond activation,carbene insertion and annulation reaction with water and N₂ as the only byproducts,revealing the environmental benignity of this reaction.We have developed a divergent route to multi-substituted isoquinolines through a C-C bond cleavage from ethyl-3-benzyl-3,4-dihydroisoquinoline-3-carboxylate derivatives.A novel rearrangement reaction involving C-C bond cleavage and the formation of a new C-C bond in a sodium hydride-promoted synthesis of 1-?isoquinolin-3-yl?-2-phenylethan-1-ones was developed.As an electron-withdrawing group,the cyclic imine could contribute to increase of the acidity of the cyclic C-H bond,facilitating the aromatization process.When ethyl-3-benzyl-3,4-dihydroisoquinoline-3-carboxylatesweretreatedwith N-bromosuccinimide,ethyl isoquinoline-3-carboxylates were selectively formed via a radical pathway.These reactions proceeded smoothly in moderate to excellent yields under transition-metal-free conditions,and a wide range of functional groups were tolerated.