Huayou Hu

An unprecedented palladium-catalyzed double carbonylation for the construction of benzofuranone-linked ynones and amides has been developed. This double carbonylation reaction features operational simplicity, a broad substrate scope, good functional group compatibility, easy scale-up, as well as versatile transformations. The application of double carbonylation for the synthesis of other biologically and synthetically useful carbonyl-containing molecules is underway in our lab.

A base-promoted regioselective formal [3 + 2] annulation of pyridinium ylides with bromoalkynes is reported, producing a series of substituent-diverse indolizines in generally good yields. A mild K₂CO₃-promoted three-component formal [3 + 2] cyclization of pyridinium ylides and bromoalkynes at a 2:1 molar ratio delivered C2-acylmethylated indolizines, whereas C2-brominated indolizines were generated starting from pyridinium ylides bearing strong electron-withdrawing groups at the pyridinium unit by using 2,2,6,6-tetramethyl-1-piperidinyloxy as a dehydrogenating reagent. The current synthetic methodology offers a controllable and modular approach to access indolizines with different substitution patterns, featuring a wide substrate scope, good functional group compatibility, and complete regioselectivity without the demand of any transition-metal catalysts.

An unprecedented Pd-catalyzed cascade alkyne insertion/Heck/C-H activation reaction of o-iodophenyl alkenyl ethers and diarylacetylenes has been developed. Diversified tetracyclic-fused dihydroindeno[2,1-b]chromenes bearing a quaternary center were constructed in an efficient, straightforward, and atom-economic way with good to excellent yields. The protocol features high bonding efficiency, operational simplicity, broad substrate scope, and easy scale-up.

Pyrrolo[2,1-a]isoquinoline derivatives were synthesized from 2-aryl-pyrrolidines and alkynes via an oxidative dehydrogenation/cyclization coupling/dehydrogenative aromatization domino process.

A Pd-catalyzed carbonylative dearomatization of indoles using Co₂(CO)₈ as a safe CO source has been reported.

A Pd-catalyzed carbonylative dearomatization via an acyl Pd complex has been developed. Diversified carbonyl-containing spirocyclic indolenines with an all-carbon quaternary center were constructed in an efficient and straightforward way with good to excellent yields. The protocol features a simple catalytic system, operational simplicity, a broad substrate scope, easy scale-up, and versatile transformations. In addition, the asymmetric reaction was initially explored with moderate enantioselectivity.

A palladium-catalyzed dearomatization of indoles withalkynes hasbeen developed, providing an efficient route to access a variety ofsynthetically useful spirocyclohexaneindolenines in moderate to goodyields. The current method features a simple catalytic system, operationalsimplicity, and good functional group compatibility, which will contributesubstantially to the development of dearomatization to access spirocompounds. Besides, the ubiquitous existence of spiro molecules, includingspirocyclohexaneindolenines, in drugs and biological active moleculessuggests the potential application of this methodology in medicinalchemistry.

A simple and efficient method for the copper-catalyzed selective C5-H bromination and difluoromethylation of 8-aminoquinoline amides using ethyl bromodifluoroacetate as the bifunctional reagent.

We report a chelation-assisted C–H arylation of various indoles with sterically and electronically diverse (hetero)arylsilanes enabled by cost-effective Cp*-free cobalt catalysis. Key to the success of this strategy is the judicious choice of copper(II) fluoride as a bifunctional sliane activator and catalyst reoxidant. This methodology features a broad substrate scope and good functional group compatibility. The synthetic versatility of this protocol has been highlighted by the gram-scale synthesis and late-stage diversification of biologically active molecules.