Copper oxidative cross-coupling

The synthesis of sodium channel inhibitor 1 [82] illustrates the utility of the /V-oxide strategy by using it not only to form the biaryl carbon-carbon bond, but also to form the C4 carbon-nitrogen bond. Diaryl ether 3, prepared by a copper catalyzed cross-coupling of 4-fluorophenol and l-bromo-4-iodobenzene [83], was coupled... 

This chiral copper(ll) complex was also effective in the oxidative cross-couplings between two electronically different polycyclic phenols, generally giving good yields and high enantioselectivity [42]. 

A newly introduced method for a one-pot unsymmetrical biaryl construction takes advantage of an initial selective iodination of one of the coupling partners, followed by copper-catalyzed cross-coupling. Since the mechanism by which an arene undergoes iodination varies by the nature of the arene, the iodination step needed to be worked out for each type of arene (i.e., electron-rich, electron-poor, both 5- and 6-membered aromatics and heteroaromatics, etc.). Common to each set of conditions is the use of molecular iodine as the oxidant. Moreover, Cul complexed by phenanthroline could be used in all cases. The base and solvent, therefore, were two key parameters that need to be varied. Reaction temperatures in all cases are between 100 °C and 135 and reaction times can vary from hours to, often, days. Yields in most cases tend to be moderate. The method does not apply to two electron-rich arenes. Also, arenes with protons that are of pKa greater than that of DMSO i.e., 37) are not amenable as they fail to form the intermediate copper species required for the... 

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. 

Copper-mediated oxidative cross-coupling of 2-pyrrolylboronic acid 51 with TMSCF3 provided another selective approach to 2-trifluoromethylpyrrole. Reaction proceeds in mild conditions to give A -TIPS-2-trifluoromethylpyrrole 52 in 48 % yield [27]. 

Senecal TD, Parsons AT, Buchwald SL (2011) Room temperature aryl trifluoromethylation via copper-mediated oxidative cross-coupling. J Org Chem 76 1174-1176... 

The copper-catalyzed oxidative cross-coupling of geminal diarylalkenes and secondary phosphine oxides was also described (Scheme 24). ... 

Copper-catalyzed C—H and C—X bond activations have attracted much attention because they can convert a C—H bond directly into a C—C or C—FG bond. These transformations meet the basic requirements of green chemistry [82], One elegant example of a cascade reaction related with the copper-catalyzed C—H bond activation is the copper-catalyzed C—H oxidation/cross-coupling of indole with a-amino carbonyl compounds (Scheme 5.80). 

Abstract During the last decades a powerful set of protocols featuring C(sp )-N bond formation have emerged as convenient alternatives for the assembly of enamine and enamides. Those methods consist of mostly palladium-catalyzed oxidative amidations of alkenes and both palladium- and copper-catalyzed cross-couplings between generally vinyl halides or pseudohalides and amines or amides. In this review recent advances in both types of processes will be disclosed. Additionally, the synthetic value of the title processes will be illustrated by describing relevant total syntheses of natural products involving vinylation process as the key step. 

Several new methods for oxidative coupling of enolates, enol silanes, and enamines have been reviewed and illustrated with reference to natural product synthesis. Copper(II)-catalysed oxidative cross-coupling of aldehydes and alkylbenzenes, to form benzyl esters on reaction with t-BuOOH, has been demonstrated. ... 

Palladium(II) and copper(I) co-catalytic twofold activation of a C-H bond resulted in the chemo- and regio-selective oxidative cross-coupling between two non-benzofused... 

Copper(I) complexed with 1,10-phenanthroline has been used in the arylation of imidazo[l,2-a]pyridines by aryl bromides, iodides, and triflates to give products, (139), substituted at the 3-position. The mechanism is likely to involve initial deprotonation at the 3-position followed by cupration and oxidative addition of the aryl halide. The copper-mediated cross-coupling of indoles with 1,3-azoles is assisted by chelation of a, readily removed, 2-pyrimidyl group and leads to products such as (140). In this reaction, two carbon-hydrogen substitutions are required and it is likely that initial cupration of the 1,3-azole is followed by chelation-assisted formation of a bis(heteroaryl) copper species before oxygen-promoted reductive elimination... 

A copper-mediated oxidative cross-coupling reaction of terminal allies with readily available a-silyldifluoromethylphosphonates (216) has been developed by Qing and co-workers. Thus, a series of synthetically useful a,a-difluoropropargylphosphonates (217) has been obtained in moderate yields and with excellent functional group compatibility (Scheme 72). ... 

A catalytic version of the coupling was also developed, by using 10 mol % of CuCl2 and 20 mol % of sparteine 1 (silver chloride was used as a stoichiometric oxidant to regenerate the copper (II) oxidant). This catalytic system was applied to the asymmetric cross-coupling leading to 101 in a 41% yield and 32% ee. 

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