Haloaromatic coupling reaction

Essentially, two types of unsaturated bifunctional compound display the capability of being condensed in high yield, via a transition metal-catalysed carbon-carbon coupling reaction, into their requisite generic high molecular weight polymers plus a small molecule non-conjugated acyclic dialkenes and haloaromatic derivatives. 

C-H activation of aromatics for cross-coupling reactions without preparing haloaromatics... 

Z. H. Zhou and T. Yamamoto, Research on carbon-carbon coupling reactions of haloaromatic compounds mediated by zerovalent nickel complexes — preparation of cyclic oligomers of thiophene and benzene and stable anthrylnickel(II) complexes, J. Organomet Chem., 414, 119-127 (1991). 

With the preliminary results, we expanded this methodology to the coupling reactions with a variety of haloaromatic compounds. The results are described... 

Since Pd(ll) catalysts along with an appropriate ligand have been used in the coupling reactions of organozinc reagents with haloaromatic amines and alcohols [142], it seemed reasonable to try these conditions. The coupling reactions worked well with 2-pyridylzinc bromide (la), and the results are summarized in Table 3.37. The reaction of PI with 4-iodoaniline in the presence... 

Preparation and Cross-Coupling of2-Pyridyl and 3-Pyridylzinc Bromides 89 Table 3.37 Coupling reaction with haloaromatic amines. 

The reaction of PI with 4-iodoaniline in the presence of lmol% Pd(PPhs)4 provided 2-(4-aminophenyl)pyridine (8a) with similar results (89% isolated yield, Table 3.37, entry 6). 3-lodoaniline and 2-iodoaniline were also coupled with PI under the same conditions (Table 3.37, condition C), affording the aminophenyl pyridines (8d and 8e) in 64% and 74% isolated yields, respectively (Table 3.37, entries 7 and 8). Another successful coupling reaction (Table 3.37, entry 9) was achieved from a sterically hindered 3-methyl-2-pyridylzinc bromide (P2), resulting in 68% isolated yield with the formation of 8f. Unfortunately, no satisfactory coupling reaction occurred with 4-bromoaniline using the Pd(0) catalyst (Table 3.37, entry 10). With the results obtained from the coupling reactions with haloaromatic amines, it can be concluded that the Pd(0)-catalyzed reaction of 2-pyridylzinc bromides works effectively with iodoaromatic amines and also the relatively more reactive bromoaromatic amines. 

Many pharmacologically active compounds have been synthesized using 5-bromoisoquinoline or 5-bromo-8-nitroisoquinoline as building blocks.6 7 8 9 10 11 The haloaromatics participate in transition-metal couplings 81012 and Grignard reactions. The readily reduced nitro group of 5-bromo-8-nitroisoquinoline provides access to an aromatic amine, one of the most versatile functional groups. In addition to N-alkylation, TV-acylation and diazotiation, the amine may be utilized to direct electrophiles into the orthoposition. 

In a modified version of the Suzuki reaction arylboronates or boranes are utilized instead of arylboronic acid. Under the action of phosphine-free palladium catalysts NaBPh4 and tra(l-naphtyl)borane were found suitable phenyl-sources for arylation of haloaromatics in fully or partially aqueous solutions at 20-80 °C with good to excellent yields (Scheme 6.12) [32-34]. Aryl halides can be replaced by water-soluble diaryliodonium salts, At2IX (X = HSO4, BF4, CF3COO) in the presence of a base both Ar groups take part in the coupling [35]. 

The radical nucleophilic substitution is perfectly suited for tandem reactions [180]. Recent examples have been reported by the Rossi group (Scheme 66). Dihydrobenzofuranes and dihydroindoles substituted at the 3-position were prepared from ortho-functionalized haloaromatic compounds in high yields [181]. The nucleophiles involved in the initial electron transfer and subsequent coupling are varied. In particular, starting form naphthyl derivative 210, phosphinyl anions lead to tricyclic phosphine oxide 211 (after oxidation) in 98% yield. 

There is one paper in the literature for which the critical assessment of regiochemical control in the direct synthesis of PPPs does not apply. In 1978 and subsequent years, Yamamoto reported on the reaction between di-haloaromatic compounds and Mg metal in the presence of various low valency Ni catalysts [27,28]. When 1,4-dibromobenzene (2), 1 equiv of Mg, and dichloro-Ni(bi-pyridyl) in refluxing tetrahydrofuran is used, an exclusively para-linked, low molecular weight PPP (IR) is obtained (Fig. 8.1). The superiority of this very mild coupling process over other direct methods becomes immediately apparent if Yamamoto s material is visually compared with, e.g., Kovacic s. Whereas the former material is slightly yellow, the latter is black. 

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