Aryl bromides, cross-coupling with

A decarboxylative approach to cross-coupling was explored with pico-linic acids (Scheme 38) (13T5732).The advantages of this approach are the stable and inexpensive starting materials when compared to organometallics and boronic acids. Under optimized conditions, a number of aryl bromides were coupled with picolinic acid. Lower yields were seen when the aryl bromides had electron-withdrawing groups (NO2 or CN).The yields were also moderate to poor when picolinic acid was coupled with 1- or 2-bro-monaphthalene or 2-bromopyridine. 2-Quinolinic acid coupled with bro-mobenzene in moderate yield. 

Activated aryl chlorides, which are close in reactivity to unactivated aryl bromides, underwent reaction with the original P(o-tol)3-ligated catalyst.58 Nickel complexes, which catalyze classic C—C bond-forming cross-couplings of aryl chlorides, 9-64 also catalyzed aminations of aryl chlorides under mild conditions.65,66 However, the nickel-catalyzed chemistry generally occurred with lower turnover numbers and with a narrower substrate scope than the most efficient palladium-catalyzed reactions. 

The sequential approach is also common in proposals written by synthetic chemists (a multistep synthesis is inherently step by step). Vyvyan (excerpt 13N), for example, proposes a strategy to synthesize a select group of heliannuols (alleo-pathic natural products isolated from the sunflower) in an optically pure form. One approach that he will explore involves enantioselective cross-coupling reactions between an alkyl zinc reagent and an aryl bromide. He begins with experiments that will utilize recently developed catalysts and produce products with known optical rotation data. Subsequent reactions are described that will lead potentially to the desired stereospecific heliannuols A and D. 

In 1995 Soderquist and Ftirstner independently reported that alkynylborates 67, prepared in situ from 9-OMe-9-BBN and alkynylmetals, effectively cross-couple with aryl and alkyl bromides using a Pd catalyst under base-free conditions at 60 °G. Soderquist and co-workers also reported on the synthesis of alkynylborinates 68, which are easier to isolate (Figure... 

Lithium triethyl(l-methylindolyl-2)borate has been introduced as a convenient source of indolyl residue for carbonylative cross-coupling with aryl iodides, alkenyl iodides, or triflates. The reaction requires elevated CO pressure and high loading of catalyst (5mol.%) (Equation (15)). Aryl and alkenyl bromides, as well as aryl iodides... 

Subsequently, a copper-catalyzed cross-coupling [with substoichiometric amounts of copper(l) iodide and N,N -dimethylethylenediamine (DMEDA)] between aryl halides and sulfoximines was developed [52]. In this case, both aryl bromides and aryl iodides reacted well. For the conversion of the former substrates an in-situ copper-catalyzed aryl Finkelstein reaction [53] had to be performed first, as shown in Scheme 2.1.1.22 for the preparation of 64 starting from bromobenzene (62). 

Zapf, A. Beller, M. Palladium/phosphite catalyst system for efficient cross coupling of aryl bromides and chlorides with PhB(OH)2. 

The first examples of microwave-assisted cross-couplings with organo-zinc compounds were reported in 2001, as shown in Scheme 70. Aryl- as well as alkylzinc bromides were effectively coupled with short reaction times [155]. 

Most recently, Monteiro et al. have reported that cyclopalladated compounds derived from the ortho-metalation of benzylic tert-butyl thioethers are excellent catalyst precursors for the Suzuki cross-coupling reaction of aryl bromides and chlorides with phenylboronic acid under mild reaction conditions. A broad range of substrates and functional groups are tolerated in this protocol, and high catalytic activity is attained (Eq. (58)) [93]. 

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