James Sanderson

In the presence of catalytic [{IrCp*Cl₂}₂] and Ag₂CO₃, Li₂CO₃ as the base, and acetone as the solvent, benzoic acids react with arenediazonium salts to give the corresponding diaryl-2-carboxylates under mild conditions. This CH arylation process is generally applicable to diversely substituted substrates, ranging from extremely electron-rich to electron-poor derivatives. The carboxylate directing group is widely available and can be removed tracelessly or employed for further derivatization. Orthogonality to halide-based cross-couplings is achieved by the use of diazonium salts, which can be coupled even in the presence of iodo substituents.

Directing rather than removed: In the presence of catalytic [{IrCp*Cl₂}₂], benzoic acids react with arenediazonium salts to give the corresponding diaryl-2-carboxylates. If desired, the carboxylate directing group can be removed by in situ protodecarboxylation.

See the light of day: Light is the fastest way of transferring energy and information through space, and in chemistry it can perform the dual role of reactant and product. Sunlight, a really unique reactant, represents our ultimate energy source. Chemists are engaged in designing systems for the conversion of light into electrical or chemical energy and vice versa to create a more sustainable way of life.

Functionalized secondary alkyllithium reagents obtained by I/Li exchange from the corresponding secondary alkyl iodides undergo two successive transmetalations with Me₃SiCH₂ZnBr⋅LiBr and CuBr⋅2 LiCl⋅Me₂S to provide functionalized secondary alkylcopper compounds with high retention of configuration. These alkylcopper derivatives react further with electrophiles such as alkynyl esters, acid chlorides, allylic chlorides, ketals, ethylene oxide, and 3-iodocyclopentanone with high retention of configuration. A related sequence of transmetalations with MeMgI and LaCl₃⋅2 LiCl allows a retentive addition of secondary alkyllithium reagents to acetone. The influence of the solvent on the configurational stability of secondary alkylzinc reagents is described.

Configurationally retentive domino transmetalations of nonstabilized functionalized secondary alkyllithium compounds with Me₃SiCH₂ZnBr⋅LiBr and CuBr⋅ 2 LiCl⋅Me₂S allow the preparation of secondary alkylcopper compounds with retention of configuration (TBDPS=tert-butyldiphenylsilyl). Trapping with a range of electrophiles (acid chlorides, ethylene oxide, alkynyl esters, ketals, allylic chlorides) afford various open-chain acyclic products.

The Mitsunobu reaction is renowned for its mild reaction conditions and broad substrate tolerance, but has limited utility in process chemistry and industrial applications due to poor atom economy and the generation of stoichiometric phosphine oxide and hydrazine byproducts that complicate purification. A catalytic Mitsunobu reaction using innocuous reagents to recycle these byproducts would overcome both of these shortcomings. Herein we report a protocol that is catalytic in phosphine (1-phenylphospholane) employing phenylsilane to recycle the catalyst. Integration of this phosphine catalytic cycle with Taniguchi’s azocarboxylate catalytic system provided the first fully catalytic Mitsunobu reaction.

Make it catalytic: A catalytic Mitsunobu reaction using innocuous reagents to recycle the stoichiometric phosphine oxide and hydrazine byproducts was developed. The reported protocol is catalytic in 1-phenylphospholane and uses phenylsilane to recycle the catalyst. Integration of this phosphine catalytic cycle with Taniguchi’s azocarboxylate catalytic system provided the first fully catalytic Mitsunobu reaction.

Stable CO linkages are generally unreactive in cross-coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross-couplings because the strong CO bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron-catalyzed cross-coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 °C, 2 h) with a ligand-free catalyst (1–2 mol %).

Iron clad: Acetates are underutilized electrophiles in metal-catalyzed cross-coupling reactions because of the strong alkenyl CO bond and their propensity to engage in unwanted reactions. Combination of a ligand-free low-valent Fe catalyst with nucleophilic organomagnesium reagents, low temperature, and short reaction times results in highly selective cross-couplings with alkenyl acetates.

A cobalt-catalyzed cross-coupling between 3- and 4-iodopiperidines and Grignard reagents is disclosed. The reaction is an efficient, cheap, chemoselective, and flexible way to functionalize piperidines. This coupling was used as the key step to realize a short synthesis of (±)-preclamol. Some mechanistic investigations were conducted that highlight the formation of radical intermediates.

Scaffold synthesis: A cobalt-catalyzed cross-coupling between iodopiperidines and Grignard reagents is reported (see scheme; PG=protecting group). A large variety of 3- and 4-substituted piperidines were synthesized and the method was applied to a short synthesis of (±)-preclamol. This work constitutes one of the rare examples of cross-couplings involving 3-halogeno piperidines.

Disclosed herein is a Rh^III-catalyzed chelation-assisted activation of unreactive CH bonds, thus enabling an intermolecular amidation to provide a practical and step-economic route to 2-(pyridin-2-yl)ethanamine derivatives. Substrates with other N-donor groups are also compatible with the amidation. This protocol proceeds at room temperature, has a relatively broad functional-group tolerance and high selectivity, and demonstrates the potential of rhodium(III) in the promotive functionalization of unreactive CH bonds. A rhodacycle having a SbF₆⁻ counterion was identified as a plausible intermediate.

Giving direction: The title reaction leads to the successful functionalization of unreactive CH bonds in the presence of directing groups (DGs). A rhodacycle having a SbF₆⁻ counterion was isolated and is proposed to be a plausible intermediate.