Copper-Catalyzed Trifunctionalization of Alkynes: Rapid Formation of Oxindoles Bearing Geminal Diboronates

A copper-catalyzed trifunctionalization of alkynes that provides rapid access to oxindoles bearing a geminal diboronate side chain, highlighted by the simultaneous formation of one C−C bond and two C−B bonds, is reported. This new reaction features simple reaction conditions (ligand-free catalysis), a general substrate scope, and excellent chemoselectivity. Mechanistic study revealed a reaction sequence constituted by, in the order, borylation, intramolecular cross-coupling, hydroboration, which has been rarely documented.     

Nickel‐Catalyzed 1,2‐Diarylation of Alkenyl Carboxylates: A Gateway to 1,2,3‐Trifunctionalized Building Blocks

A nickel‐catalyzed conjunctive cross‐coupling of alkenyl carboxylic acids, aryl iodides, and aryl/alkenyl boronic esters is reported. The reaction delivers the desired 1,2‐diarylated and 1,2‐arylalkenylated products with excellent regiocontrol. To demonstrate the synthetic utility of the method, a representative product is prepared on gram scale and then diversified to eight 1,2,3‐trifunctionalized building blocks using two‐electron and one‐electron logic. Using this method, three routes toward bioactive molecules are improved in terms of yield and/or step count. This method represents the first example of catalytic 1,2‐diarylation of an alkene directed by a native carboxylate group.     

Direct Synthesis of Disubstituted 3-Isoquinolinone Derivatives through the Construction of C−N,C=O,and C(sp2)−C(sp3) Bonds under Transition-Metal-Free Conditions

The efficient three-component cascade coupling reaction of 3-haloisoquinolines, haloalkanes, and sp³-carbon nucleophiles (acetophenone or nitromethane) led to a series of structurally novel 1,2-disubstituted-3-isoquinolinones through the formation of C(sp³)−C(sp²), C−N, and C=O bonds. The NaOAc-promoted reaction described in this work is simple to operate, environment friendly, and highly selective.     

The Mechanism of Copper-Catalyzed Trifunctionalization of Terminal Allenes

A highly selective copper-catalyzed trifunctionalization of allenes has been established based on diborylation/cyanation with bis(pinacolato)diboron (B₂pin₂) and N-cyano-N-phenyl-p-toluenesulfonamide (NCTS). The Cu-catalyzed trifunctionalization of terminal allenes is composed of three catalytic reactions (first borocupration, electrophilic cyanation, and second borocupration) that provide a densely functionalized product with regio-, chemo- and diastereoselectivity. Allene substrates have multiple reaction-sites, and the selectivities are determined by the suitable interactions (e.g., electronic and steric demands) between the catalyst and substrates. We employed DFT calculations to understand the cascade copper-catalyzed trifunctionalization of terminal allenes, providing densely-functionalized organic molecules with outstanding regio-, chemo- and diastereoselectivity in high yields. The selectivity challenges presented by cumulated π-systems are addressed by systematic computational studies; these give insight to the catalytic multiple-functionalization strategies and explain the high selectivities that we see for these reactions.