Copper-Catalyzed Chan-Lam Cyclopropylation of Phenols and Azaheterocycles.

Small molecules containing cyclopropane-heteroatom linkages are commonly needed in medicinal chemistry campaigns yet are problematic to prepare using existing methods. To address this issue, a scalable Chan-Lam cyclopropylation reaction using potassium cyclopropyl trifluoroborate has been developed. With phenol nucleophiles, the reaction effects O-cyclopropylation, whereas with 2-pyridones, 2-hydroxybenzimidazoles, and 2-aminopyridines the reaction brings about N-cyclopropylation.

Nickel-Catalyzed β,γ-Dicarbofunctionalization of Alkenyl Carbonyl Compounds via Conjunctive Cross-Coupling.

A nickel-catalyzed conjunctive cross-coupling between non-conjugated alkenes, aryl iodides, and alkylzinc reagents is reported. Excellent regiocontrol is achieved utilizing an 8-aminoquinoline directing group that can be readily cleaved to unmask net β,γ-dicarbofunctionalized carboxylic acid products. Under optimized conditions, both terminal and internal alkene substrates provided the corresponding alkyl/aryl difunctionalized products in moderate to excellent yields.

Palladium(II)-Catalyzed Directed anti-Hydrochlorination of Unactivated Alkynes with HCl.

A regioselective anti-hydrochlorination of unactivated alkynes is reported. The reaction utilizes in situ generated HCl as the source of both the Cl and H and is catalyzed by palladium(II) acetate, with loadings as low as 25 ppm. Removable picolinamide and 8-aminoquinoline bidentate directing groups are used to control the regioselectivity of the chloropalladation step and stabilize the resulting alkenylpalladium(II) intermediate for subsequent protodepalladation.