RESUMO
The palladium-catalysed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.
Assuntos
Hidrocarbonetos Aromáticos/síntese química , Cetonas/síntese química , Paládio/química , Antipsicóticos/síntese química , Antipsicóticos/química , Catálise , Halogenação , Hidrocarbonetos Aromáticos/química , Cetonas/química , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/química , Proclorperazina/síntese química , Proclorperazina/química , Triptofano/análogos & derivados , Triptofano/síntese químicaRESUMO
A general methodology for the α-arylation of ketones using a nickel catalyst has been developed. The new well-defined [Ni(IPr*)(cin)Cl] (1 c) pre-catalyst showed great efficiency for this transformation, allowing the coupling of a wide range of ketones, including acetophenone derivatives, with various functionalised aryl chlorides. This cinnamyl-based Ni-N-heterocyclic carbene (NHC) complex has demonstrated a different behaviour to previously reported NHC-Ni catalysts. Preliminary mechanistic studies suggest a Ni(0)/Ni(II) catalytic cycle to be at play.
Assuntos
Complexos de Coordenação/química , Hidrocarbonetos Clorados/química , Cetonas/química , Metano/análogos & derivados , Níquel/química , Catálise , Cloretos , Metano/química , Estrutura MolecularRESUMO
A general catalytic protocol for the α-arylation of aryl ketones has been developed. It involves the use of a preformed, bench-stable Pd-N-heterocyclic carbene pre-catalyst bearing IHept as an ancillary ligand, and allows the coupling of various functionalized coupling partners at very low catalyst loading. Careful choice of the solvent/base system was crucial to obtain optimum catalyst performance. The pre-catalyst was also successfully tested in the synthesis of an industrially relevant compound.