Mechanism of nickel-catalyzed direct carbonyl-Heck coupling reaction: the crucial role of second-sphere interactions.

We present a detailed DFT mechanistic study on the first Ni-catalyzed direct carbonyl-Heck coupling of aryl triflates and aldehydes to afford ketones. The precatalyst Ni(COD)2 is activated with the phosphine (phos) ligand, followed by coordination of the substrate PhOTf, to form [Ni(phos)(PhOTf)] for intramolecular PhOTf to Ni(0) oxidative addition. The ensuing phenyl-Ni(ii) triflate complex substitutes benzaldehyde for triflate by an interchange mechanism, leaving the triflate anion in the second coordination sphere held by Coulomb attraction. The Ni(ii) complex cation undergoes benzaldehyde C[double bond, length as m-dash]O insertion into the Ni-Ph bond, followed by ß-hydride elimination, to produce Ni(ii)-bound benzophenone, which is released by interchange with triflate. The resulting neutral Ni(ii) hydride complex leads to regeneration of the active catalyst following base-mediated deprotonation/reduction. The benzaldehyde C[double bond, length as m-dash]O insertion is the rate-determining step. The triflate anion, while remaining in the second sphere, engages in electrostatic interactions with the first sphere, thereby stabilizing the intermediate/transition state and enabling the desired reactivity. This is the first time that such second-sphere interaction and its impact on cross-coupling reactivity has been elucidated. The new insights gained from this study can help better understand and improve Heck-type reactions.

Ni-Catalyzed Reductive Coupling of Electron-Rich Aryl Iodides with Tertiary Alkyl Halides.

This work illustrates the reductive coupling of electron-rich aryl halides with tertiary alkyl halides under Ni-catalyzed cross-electrophile coupling conditions, which offers an efficient protocol for the construction of all carbon quaternary stereogenic centers. The mild and easy-to-operate reaction tolerates a wide range of functional groups. The utility of this method is manifested by the preparation of cyclotryptamine derivatives, wherein successful incorporation of 7-indolyl moieties is of particular interest as numerous naturally occurring products are composed of these key scaffolds. DFT calculations have been carried out to investigate the proposed radical chain and double oxidative addition pathways, which provide useful mechanistic insights into the part of the reaction that takes place in solution.

Enantioselective Tandem Cyclization of Alkyne-Tethered Indoles Using Cooperative Silver(I)/Chiral Phosphoric Acid Catalysis.

Reported is the enantioselective synthesis of tetracyclic indolines using silver(I)/chiral phosphoric acid catalysis. A variety of alkyne-tethered indoles are suitable for this process. Mechanistic studies suggest that the in situ generated silver(I) chiral phosphate activates both the alkyne and the indole nucleophile in the initial cyclization step through an intermolecular hydrogen bond and the phosphate anion promotes proton transfer. In addition, further modifications of the cyclization products enabled stereochemistry-function studies of a series of bioactive indolines.

Aluminum(i) ß-diketiminato complexes activate C(sp2)-F and C(sp3)-F bonds by different oxidative addition mechanisms: a DFT study.

DFT computations reveal different reaction mechanisms for the oxidative addition of C(sp2)-F and C(sp3)-F bonds to the Al(i) complexes: a concerted mechanism for C(sp2)-F and a stepwise mechanism for C(sp3)-F involving fluoride transfer and the formation and recombination of an ion pair.