Copper-catalyzed transmetallation

As shown in the proposed reaction scheme [Scheme 5-3] [42a], this protocol is based on the discovery of Cul-catalyzed transmetallation in amine [45] and is constructed by a combination of two catalytic cycles A and B. There is no evidence for the acceleration of the reductive elimination step (step iii, from 76 to 74 in Scheme 5-3), although a coordination of the copper ion to or alkynyl group is expected. 

CO insertion prior to the transmetallation step. The mechanism of nickel-catalyzed coupling reactions is less established. Early studies indicated that homocoupling processes occur by oxidative addition through radical intermediates and possible intermediacy of Ni(I) and Ni(III) complexes. The copper-catalyzed cross-coupling reactions likely occur by transmetallation prior to oxidiative addition of the aryl halide. Iron-catalyzed reactions likely occur by low-valent, even sub-valent, species. 

In the same year, Roland and coworkers described a chiral silver-NHC complex with a tert-butyl substituted backbone for copper-catalyzed addition of Et2Zn to 2-cyclohexanone. However, the addition product was isolated in low enantioselectivity (23% ee) [77]. Later on, Alexakis et al. modified the carbene structure to improve the enantioselectivity (Scheme 3.51) [78]. By using the chiral silver-NHC salt 90 to transmetallate and generate the Cu catalyst, the asymmetric conjugate addition of diethylzinc to 2-cycloheptanone was achieved in good yield (95%) and enantioselectivity (93% ee). 

Alternatively, copper salts can themselves be engaged in transmetalation with a nucleophilic coupling partner to give organocopper intermediates, which then either enter the Pd-catalyzed... 

Another recent disclosure examined silicon-to-copper transmetallation as a mild means of synthesizing alkenyl-copper reagents from stable precursors. The method requires activation of the silyl group by an allylic alcohol. Again, the silanes in this work are produced by circuitous means but should be accessible by ruthenium-catalyzed hydrosilylation. Treatment of the silyl alcohol with a stoichiometric amount of copper(l) /rz -butoxide results in the C-to-O migration of the silyl group to produce a vinylcuprate shown to be competent for subsequent allylation to produce 1,4-diene products (Scheme 17). 

Concerning the lithium-zinc transmetallation from intermediate 331, it has been used (THF, room temperature) to perform a palladium-catalyzed Negishi cross-coupliug reaction with aryl bromides - and a 8 2 regioselective allylation in the presence of copper cyanide. 346 and 347 were, respectively, obtained (Scheme 101). 

In light of these significant challenges, Evans and Leahy reexamined the rhodium-catalyzed allylic alkylation using copper(I) enolates, which should be softer and less basic nucleophiles [23]. The copper(I) enolates were expected to circumvent the problems typically associated with enolate nucleophiles in metal-allyl chemistry, namely ehmina-tion of the metal-aUyl intermediate and polyalkylation as well as poor regio- and stereocontrol. Hence, the transmetallation of the lithium enolate derived from acetophenone with a copper(I) hahde salt affords the requisite copper] I) enolate, which permits the efficient regio- and enantiospecific rhodium-catalyzed allylic alkylation reaction of a variety of unsymmetrical acychc alcohol derivatives (Tab. 10.3). 

---