3- pyridylzinc bromide

Pyridylzinc bromide, a commercially available reagent, was used in the synthesis of a series of bipyridyl derivatives (7.20.). Activated coupling partners, such as 2-chloro-4-cyanopyridine, reacted readily at room temperature in the presence of a palladium based catalyst, while less electron deficient halopyridines were coupled at elevated temperatures.27 The same approach was also extended to the preparation of other heterobiaryls.28... 

Propylzinc bromide Butylzinc bromide Cyclohexylzinc bromide 3-Ethoxy-3-oxopropylzinc bromide Phenylzinc bromide 2-Pyridylzinc bromide 2-Thienylzinc bromide... 

Hodgetts has shown that C2 chlorides and C4 and C5 bromides all participate in Negishi coupling with 2-pyridylzinc bromide in approximately 70% yield. Stambuli did not attempt Negishi coupling of the halooxazoles, probably due to the lability of the thioether under Negishi-like conditions. ... 

Scheme 4.41 Pd-catalyzed cross-coupling of 2-pyridylzinc bromide [158].

In general, the preparation of 2-pyridyl organometallics is mostly performed by lithiation of 2-halopyridine at cryogenic conditions followed by transmetal-lation with an appropriate metal halide. As mentioned previously, this procedure causes some limitations on the use of the 2-pyridyl organometallics. In our study, readily available 2-bromopyridine was treated at it with active zinc prepared by the Rieke method [138]. The oxidative addition of the active zinc to carbon-bromine bond was completed in an hour at refluxing temperature to give rise to the corresponding 2-pyridylzinc bromide (PI). 

Table 3.30 Coupling reaction of 2-pyridylzinc bromide (PI) with benzoyl chlorides. ... 

Prior to the Pd-catalyzed coupling reaction with a variety of aryl halides, a preliminary test was performed using a Pd(0) catalyst to find any effect of substituents in the C—C bond forming reactions. Several different types of 2-pyridylzinc bromides (Table 3.32, P1-P6) were coupled with 3-iodothiophene in the presence of 1 mol% of Pd(PPhs)4 in THF at rt, and the results are summarized in Table 3.32. In general, good yields (Table 3.32, entries 1, 3, and 4) were obtained from using 2-pyridylzinc bromide (PI), 4-methyl-2-pyridylzinc bromide (P3), and 5-methyl-2-pyridylzinc bromide (P4). Reactions with 3-methyl-2-pyridylzinc bromide (P2), 6-methyl-2-pyridylzinc bromide (P5), and 6-methoxy-2-pyridylzinc bromide (P6) resulted in moderate yields (Table 3.32, entries 2, 5, and 6). 

As described in many previous reports, bipyridine units are very important for many natural products as well as many molecules used in material chemistry [141]. Significantly, this structural moiety can be readily prepared utilizing 2-pyridylzinc bromides. As described in Table 3.36, not only symmetrical 2,2 -bipyridine (7a) but also several different types of unsymmetrical 2,2 -bipyri-dines (7b-7h) were prepared in moderate yields. Again, the coupling reaction was completed in the presence of lmol% Pd(PPh3)4 in THF at rt, and, in general, 3-methyl-2-pyridylzinc bromide (P2) and 6-methyl-2-pyridylzinc bromide (P6) produced 2,2 -bipyridines, 7e and 7h, in low yields (Table 3.36, entries 5 and 8). It should be emphasized that the preparation of bipyridines using readily available 2-pyridylzinc bromides (P1-P6) could be a very practical approach because considerable effort has been directed toward the preparation of unsymmetrical 2,2 -bipyridines. 

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... 

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. 

Interestingly, unsymmetrical amino-bipyridines were produced from the coupling reactions of 2-pyridylzinc bromides with halogenated aminopyri-dines under the conditions used previously. As shown in Scheme 3.11, 2-amino-5-iodopyridine reacted with PI to afford 2,3-bipyridine (s2a) in 59% isolated yield in the presence of lmol% of Pd(PPhs)4 catalyst (route A, Scheme 3.11). 

We have demonstrated a practical synthetic route for the preparation of 2-pyridyl and 3-pyridyl derivatives. It has been accomplished by utilizing a simple coupling reaction of readily available 2-pyridylzinc bromides and 3-pyridylzinc bromides, which were prepared via the direct insertion of active zinc to the corresponding bromopyridines, or they can be purchased (Rieke... 

In a 50 ml round-bottomed flask, isobutyryl chloride (1.27 g, 12 mmol) and 10 ml of THF were placed. Next, 20 ml of 0.5 M solution of 2-pyridylzinc bromide (PI) in THF (lOmmol) was added into the reaction flask via a syringe. The resulting mixture was stirred at rt for 4h. The reaction was monitored by GC analysis, quenched with saturated NH4CI solution, and then extracted with ether (30mix3). Combined organics were washed with saturated NaHCOs solution and brine and then dried over anhydrous MgS04. A vacuum distillation gave 0.94 g of 2-methyl-l-pyridin-2-yl-propan-l-one (2d) as a colorless oil in 63% isolated yield. 

Pd[P(Ph)3]4 (O.lOg, lmol%) and 4-iodophenol (l.lOg, Smmol) were placed in a 50ml round-bottomed flask. Next, 20ml of 2-pyridylzinc bromide (PI)... 

In 2010, Andreas Leitner and coworkers [174] at BASF reported the preparation of a very stable 2-pyridylzinc bromide (an sp organometallic nucleophile) on a multi-kilogram scale using Rieke technology and its application in the Negishi-Baba cross-coupling reaction. 

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