Directed ortho Metallation Chemistry and Phosphine Synthesis: New Ligands for the Suzuki-Miyaura Reaction

Abstract

We describe the use of the phosphinic amide moiety as an effective directed ortho metallation group for the incorporation of various phosphino groups onto a benzene ring to generate phosphine ligands. These ligands were used to generate active palladium catalysts for the Suzuki-Miyaura reaction in which deactivated aryl bromides and some aryl chlorides were used as substrates. Surprisingly and interestingly, the (2-alkylphenyl)phosphine derivatives were found to be especially active. The stereoelectronic and electronic features of the ligands were probed by use of selenium oxidation products and Vaska’s rhodium complexes, respectively. Some unusual features were observed, specifically relating to the inductive effects of the alkyl side chains in relation to the electron-withdrawing­ phosphinic amide functions. The two probes were also compared, and the results were related to the catalytic data obtained from the Suzuki reactions. Quite unexpectedly, the ligands generate catalysts with good activity despite their being relatively electron-poor. This low electron density, resulting from the phosphinic amide functionality, renders them stable to oxidation and hydrolysis for over six months while exposed to air. Additionally, the use of the phosphinic amide directing group is unusual and rare, and has not, to our knowledge, been noted before in the preparation of phosphine ligands.

Key words

C-C bond formation - directed ortho metallation - ligand effects - palladium - Suzuki-Miyaura cross-coupling

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