Intramolecular ortho-C-H activation and C-N/C-O cyclizations of phenyl amidines and amides have recently been achieved under Cu catalysis. These reactions provide important examples of Cu-catalyzed functionalization of inert C-H bonds, but their mechanisms remain poorly understood. In the present study the several possible mechanisms including electrophilic aromatic substitution, concerted metalation-deprotonation (CMD), Friedel-Crafts mechanism, radical mechanism, and protoncoupled electron transfer have been theoretically examined. Cu(Ⅱ)-assisted CMD mechanism is found to be the most feasible for both C-O and C-N cyclizations. This mechanism includes three steps, i.e. CMD with Cu(Ⅱ), oxidation of the Cu(Ⅱ) intermediate, and reductive elimination from Cu(Ⅲ). Our calculations show that Cu(Ⅱ) mediates the C-H activation through an six-membered ring CMD transition state similar to that proposed for many Pd-catalyzed C-H activation reactions. It is also interesting to find that the rate-limiting steps are different for C-N and C-O cyclizations: for the former it is concerted metalation-deprotonation with Cu(Ⅱ), whereas for the latter it is reductive elimination from Cu(Ⅲ). The above conclusions are consistent with the experimental kinetic isotope effects (1.0 and 2.1 for C-O and C-N cyclizations, respectively), substituent effects, and the reactions under O2 -free conditions.
Rhodium-catalyzed cross-coupling reactions of unactivated primary alkyl chlorides with diboron reagents have been developed as practical methods for the synthesis of alkylboronic esters. These reactions expand the concept and utility of Rh（I）-catalyzed cross-coupling of aliphatic electrophiles.
Recently we reported Pd-catalyzed decarboxylative cross-coupling of cyanoacetate salts with aryl halides and triflates. This reaction shows good functional group tolerance and is useful for the synthesis of-aryl nitriles. To elucidate the mechanism for this reaction, we now carry out a density functional theory study on the cross-coupling of potassium cyanoacetate with bromobenzene. Our results show that the decarboxylation transition state involving the interaction of Pd with the-carbon atom has a very high energy barrier of +34.5 kcal/mol and therefore, must be excluded. Decarboxylation of free ion (or tight-ion-pair) also causes a high energy increase and should be ruled out. Thus the most favored decarboxylation mechanism corresponds to a transition state in which Pd interacts with the cyano nitrogen. The energy profile of the whole catalytic cycle shows that decarboxylation is the rate-determining step. The total energy barrier is +27.5 kcal/mol, which is comprised of two parts, i.e. the energy barrier for decarboxylation and the energy cost for transmetallation.
