Palladium(II)-Catalyzed Regioselective syn-Hydroarylation of Disubstituted Alkynes Using a Removable Directing Group

A palladium­(II)-catalyzed regioselective <i>syn</i>-hydroarylation reaction of homopropargyl amines has been developed, wherein selectivity is controlled by a cleavable bidentate directing group. Under the optimized reaction conditions, both dialkyl and alkylaryl alkyne substrates were found to undergo hydroarylation with high selectivity. The products of this reaction contain a 4,4-disubstituted homoallylic amine motif that is commonly seen in drug molecules and other bioactive compounds

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. The methodology developed herein represents the first three-component 1,2-dicarbofunctionalization of non-conjugated alkenes involving a C­(sp³)–C­(sp³) reductive elimination step

Directed Nickel-Catalyzed 1,2-Dialkylation of Alkenes

A nickel-catalyzed conjunctive cross-coupling of non-conjugated alkenes, alkyl halides, and alkylzinc reagents is reported. Regioselectivity is controlled by chelation of a removable bidentate 8-aminoquinoline directing group. Under optimized conditions, a wide range of 1,2-dialkylated products can be accessed in moderate to excellent yields. To the best of our knowledge, this report represents the first example of three-component 1,2-dialkylation of non-conjugated alkenes to introduce differentiated alkyl fragments

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. The methodology developed herein represents the first three-component 1,2-dicarbofunctionalization of non-conjugated alkenes involving a C­(sp³)–C­(sp³) reductive elimination step

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. The methodology developed herein represents the first three-component 1,2-dicarbofunctionalization of non-conjugated alkenes involving a C­(sp³)–C­(sp³) reductive elimination step

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. The methodology developed herein represents the first three-component 1,2-dicarbofunctionalization of non-conjugated alkenes involving a C­(sp³)–C­(sp³) reductive elimination step

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 <i>O</i>-cyclopropylation, whereas with 2-pyridones, 2-hydroxybenzimidazoles, and 2-aminopyridines the reaction brings about <i>N</i>-cyclopropylation. The transformation is catalyzed by Cu­(OAc)₂ and 1,10-phenanthroline and employs 1 atm of O₂ as the terminal oxidant. This method is operationally convenient to perform and provides a simple, strategic disconnection toward the synthesis of cyclopropyl aryl ethers and cyclopropyl amine derivatives bearing an array of functional groups

Palladium(II)-Catalyzed Directed <i>anti-</i>Hydrochlorination of Unactivated Alkynes with HCl

A regio­selective <i>anti</i>-hydrochlorination of unactivated alkynes is reported. The reaction utilizes <i>in situ</i> 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. This method provides access to a broad array of substituted alkenyl chlorides in excellent yields and with high regio­selectivity. The products from this transformation were successfully derivatized via Stille coupling to a variety of trisubstituted alkene products. Reaction progress kinetic analysis was performed, shedding light on a possible mechanism for this catalytic process