Nickel-Catalyzed Mono-Selective α-Arylation of Acetone with Aryl Chlorides and Phenol Derivatives.

The challenging nickel-catalyzed mono-α-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-α-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives. The methodology has been extended to the unprecedented coupling of acetone with phenol derivatives. Mechanistic studies allowed the isolation and characterization of key Ni0 and NiII catalytic intermediates. The Josiphos ligand is shown to play a key role in the stabilization of NiII intermediates to allow a Ni0 /NiII catalytic pathway. Mechanistic understanding was then leveraged to improve the protocol using an air-stable NiII pre-catalyst.

Functionalization of remote C-H bonds: expanding the frontier.

Novel tool set: New methodologies for the functionalization of remote CH bonds have been developed recently. In diverse approaches high selectivities are achieved for the functionalization of less reactive C(sp(2) )H as well as C(sp(3) )H bonds distal to any substituents.

Palladium-catalyzed carbonylative α-arylation to ß-ketonitriles.

A carbonylative α-arylation process employing unactivated nitriles for the first time is described. The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting ß-ketonitriles are obtained in good to excellent yields. The methodology also allows for a convenient (13) C-labelling of the generated carbonyl moiety.

Palladium-catalysed carbonylative α-arylation of acetone and acetophenones to 1,3-diketones.

Three COmponent -arylation: A carbonylative ketone -arylation process employing acetone for the first time, as well as acetophenones, is described (see scheme). The reaction tolerates a range of (hetero)aryl iodides and several functionalised aryl ketone coupling partners. Only low pressures of molecular CO are applied and no additional solvent is necessary.

A novel double carbonylation reaction of aryl halides: selective synthesis of 5-arylfuranones.

Double CO inCOrporation: An atom-efficient synthesis of 4-arylfuranones from aryl halides, two molecules of CO, and terminal alkenes is reported (see scheme). 18 different 4-arylfuranones were synthesized in up to 83 % yield in a straightforward manner and with high regioselectivity. The range of the new 4-arylfuranones synthesized demonstrates the value and novelty of this procedure.

More sustainable formation of C-N and C-C bonds for the synthesis of N-heterocycles.

Heterocycles made green: New methodologies for the synthesis of pyrroles were recently developed based on domino Ir- and Ru-catalyzed amination and alkylations of alcohols. The concept provides a greener approach to interesting N-heterocyclic compounds.

A selective palladium-catalyzed carbonylative arylation of aryl ketones to give vinylbenzoate compounds.

Preparation of enols: when treated with [{Pd(cinnamyl)Cl}(2)]/cataCXium A (nBuPAd(2), Ad=adamantyl) under an atmosphere of CO, aryl ketones react with aryl halides in a carbonylative C-O coupling reaction to form (Z)-vinyl benzoates.

Discrete iron complexes for the selective catalytic reduction of aromatic, aliphatic, and α,ß-unsaturated aldehydes under water-gas shift conditions.

Iron-catalyzed reductions: Selective iron-catalyzed reduction of aldehydes with hydrogen generated in situ by the water-gas shift reaction is presented (see scheme). The generality and selectivity of this mild procedure are demonstrated by the efficient reduction of various aromatic, aliphatic and α,ß-unsaturated aldehydes.

Palladium-catalyzed carbonylative Heck reaction of aryl bromides with vinyl ethers to 3-alkoxy alkenones and pyrazoles.

Three COming together: The first carbonylative Heck coupling reaction of aryl bromides and vinyl ethers leading to 1-aryl-3-alkoxy-2-propen-1-ones has been established (see scheme). Based on this coupling methodology, a novel one-pot synthesis of aryl-substituted pyrazoles was also realized.

Convenient and mild synthesis of nitroarenes by metal-free nitration of arylboronic acids.

A novel methodology for the direct nitration of arylboronic acids has been developed. By using inexpensive tert-butyl nitrite various aromatic nitro compounds are produced in moderate to good yields (45-87%) without the need of any catalyst.