Pyridylzinc halides

Treatment of the (—)-menthone-derived 2/7-1,3-benzoxazin-4(3//)-one 202 with triflic anhydride gave the triflate 203 in quantitative yield. Palladium-catalyzed cross-coupling of 203 with 2-pyridylzinc halide resulted in formation of an approximately 3 1 mixture of the 4-(2-pyridyl)-2//-l,3-benzoxazine 204 and a 4-imino-l,3-benzodioxane derivative 205 (Scheme 36). Compound 205 was formed by the isomerization of 203, which occurred with complete retention of stereochemistry. The 4-(2-pyridyl)-l,3-benzoxazine derivative 204 was applied in enantioselective allylic alkylations of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate as a chiral ligand inducing a 62% ee in the product <2005JOM(690)2027>. 

Ketones are formed from pyridylzinc halides on acylation with acid chlorides or anhydrides in reactions with benzoyl chloride or benzoic anhydride, pyridyl ketones (307) are formed in moderate yields. Reactions with 3-iodoquinoline gave the 3-benzoyl derivative 308. Organostannanes may be a better choice for ketone formation (see above). 

Aryl-aryl coupling by reaction of halides with organozinc reagents is a useful and mild route for the formation of some mixed biaryls. Such a process has been used in the reaction of pyridylzinc reagents with various iodoaromatic compounds giving good yields of coupled products (equation 65)484 87. 

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). 

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). 

Preparation and Cross-Coupling of2-Pyridyl and 3-Pyridylzinc Bromides 85 Table 3.35 Coupling reactions of P2 P6 with heteroaryl halides. 

Electron-deficient as well as electron-rich aryl boronic acids proved to be competent partners in the reaction, but electron-deficient boronic acids required higher temperatures. Boronic acids containing aryl halides (I, Cl) were also competent partners, providing a functional handle for further elaboration. Both primary and secondary amines have been utilised as coupling partners. A limitation of this chemistry is the inability to use nitrogen-based heterocycles due to either protodeboronation or the instability of the electron-poor sulfonyl chloride intermediate. Buchwald and coworkers later found that pyridylzinc reagents could be coupled with 2,4,6-trichlorophenyl chlorosulfate (TCPC) to access pyridine sulfonates without a transition metal catalyst." The pyridine sulfonates were subsequently treated with amines to generate sulfonamides. 

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