Copper-Catalyzed Insertion into Heteroatom-Hydrogen Bonds with Trifluorodiazoalkanes.

Copper-catalyzed Si-H, B-H, P-H, S-H, and N-H insertion reactions of 2,2,2-trifluoro-1-diazoethane and 1-aryl 2,2,2-trifluorodiazoethanes generated a large number of new fluorine-containing chemical entities for medicinal chemists. With selected Si-H and B-H insertion reactions, we demonstrate successful extension to asymmetric catalysis.

Iodine(III)-Mediated para-Selective Direct Imidation of Anilides.

The direct, nucleophilic imidation of acetanilide derivatives has been performed under mild, iodine(III)-mediated or -catalyzed conditions, employing lithium triflimide as the nitrogen source. The reaction exhibits exclusive regioselectivity for the para position and shows a good tolerance for varied functional groups at both the ortho or meta positions. Preliminary mechanistic data suggest that the LiNTf2 reagent plays a key role in the reactivity.

Diversity-oriented approach to CF3CHF-, CF3CFBr-, CF3CF2-, (CF3)2CH-, and CF3(SCF3)CH-substituted arenes from 1-(diazo-2,2,2-trifluoroethyl)arenes.

Arenes substituted with perfluoroalkyl groups are attractive targets for drug and agrochemical development. Exploiting the carbenic character of donor/acceptor diazo compounds, a diversity-oriented synthesis of perfluoroalkylated arenes, for late stage fluorofunctionalization, is described. The reaction of 1-(diazo-2,2,2-trifluoroethyl)arenes with HF, F/Br, F2, CF3H, and CF3SH sources give direct access to a variety of perfluoroalkyl-substituted arenes presenting with incremental fluorine content. The value of this approach is also demonstrated for radiochemistry and positron emission tomography with the [(18)F]-labeling of CF3CHF-, CF3CBrF-, and CF3CF2-arenes from [(18)F]fluoride.

Oxidative para-triflation of acetanilides.

Direct triflation of acetanilide derivatives with silver triflate has been accomplished under mild iodine(III)-mediated oxidative conditions. The reaction shows excellent regioselectivity for the para position and tolerates a range of ortho and meta substituents on the aromatic ring. This method is also compatible with the preparation of arylnonaflates in synthetically useful yields.

Modulating reactivity and diverting selectivity in palladium-catalyzed heteroaromatic direct arylation through the use of a chloride activating/blocking group.

Through the introduction of an aryl chloride substituent, the selectivity of palladium-catalyzed direct arylation may be diverted to provide alternative regioisomeric products in high yields. In cases where low reactivity is typically observed, the presence of the carbon-chlorine bond can serve to enhance reactivity and provide superior outcomes. From a strategic perspective, the C-Cl bond is easily introduced and can be employed in a variety of subsequent transformations to provide a wealth of highly functionalized heterocycles with minimal substrate preactivation. The impact of the C-Cl functional group on direct arylation reactivity has also been evaluated mechanistically, and the observed reactivity profiles correlate very well with that predicted by a concerted metalation-deprotonation pathway.

Establishment of broadly applicable reaction conditions for the palladium-catalyzed direct arylation of heteroatom-containing aromatic compounds.

Conditions for the palladium-catalyzed direct arylation of a wide range of heterocycles with aryl bromides are reported. Those conditions employ a stoichiometric ratio of both coupling partners, as well as a substoichiometric quantity of pivalic acid, which results in significantly faster reactions. An evaluation of the influence of the nature of the aryl halide has also been carried out.

Intramolecular Pd(II)-catalyzed oxidative biaryl synthesis under air: reaction development and scope.

New reaction conditions for intramolecular palladium(II)-catalyzed oxidative carbon-carbon bond formation under air are described. The use of pivalic acid as the reaction solvent, instead of acetic acid, results in greater reproducibility, higher yields, and broader scope. This includes the use of electron-rich diarylamines as illustrated in the synthesis of three naturally occurring carbazole products: Murrayafoline A, Mukonine, and Clausenine. A variety of side products have also been isolated, casting light on competing reaction pathways and revealing new reactivity with palladium(II) catalysis.

Activation and functionalization of benzylic derivatives by palladium catalysts.

Palladium-catalyzed transformations of aryl halides and pseudo-halides involving carbonylation, carbon-carbon and carbon-heteroatom bond-forming reactions, etc. are very well documented, and have already been reviewed several times. The metal-catalyzed activation of benzylic derivatives is much less described. However, during the last decades, a number of papers have shown the interest offered by benzylic derivatives (halides, carbonates, acetates, phosphonates) in selective catalytic reactions for organic synthesis, most of them in the presence of palladium catalysts. The purpose of this tutorial review is to highlight selected examples of palladium-catalyzed transformations involving reactive benzylic derivatives.

Heck-Suzuki-Miyaura domino reactions involving ynamides. An efficient access to 3-(arylmethylene)isoindolinones.

[reaction: see text] Substituted 3-(arylmethylene)isoindolin-1-ones can be efficiently synthesized in a stereoselective manner from various ynamides and boronic acids by palladium-catalyzed Heck-Suzuki-Miyaura domino reactions.