Pyridines cross-coupling

Scheme 15 Imidazole-pyridine cross coupling at a rhenium center.

The cross-coupling of aromatic and heteroaromatic rings has been carried out extensively[555]. Tin compounds of heterocycles such as oxazo-lines[556,557], thiophene[558,559], furans[558], pyridines[558], and seleno-phenes [560] can be coupled with aryl halides. The syntheses of the phenylo.xazoline 691[552], dithiophenopyridine 692[56l] and 3-(2-pyridyl)qui-noline 693[562] are typical examples. 

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

A useful method for the preparation of functionalised thiazoles has been described. Palladium catalysed cross coupling reactions between 4-thiazolyl-5-acetyl triflates 36 and alkynes afforded 4-alkynyl-5-acetylthiazoles 37 in good yields (56-82%). If 37 is then treated with ammonia in methanol, thiazolo[5,4-c]pyridines 39 are formed, probably via the intermediate imine 38 which then undergos a regioselective 6-endo dig cyclisation <99EJOC3117>. 

The ortho-arylation of 2-arylpyridines with aryltin reagents is mediated by Wilkinson s catalyst. This cross-coupling procedure occurs at high temperatures and consequently, the prevention of double phenylation represents a major hurdle, which is often achieved by adding a methyl group to either the pyridine or aryl group (Equations (125) and (126)).1... 

The Liebeskind group cross-coupled 4-chloro-2-cyclobutenone 69 with 2-tribuylstannyl-benzothiazole to synthesize a-pyridone-based azaheteroaromatics [48], The adduct 70 underwent a thermal rearrangement to afford a transient vinylketene 71, which then intramolecularly cyclized onto the C—N double bond of benzothiazole, giving rise to thiazolo[3,2-a]pyridin-5-one 72. In another case, 2-acetyl-4-trimethylstannylthizaole (73) was coupled with an acid chloride 74 to form the desired ketone 75 [49]. 

Attempts to make oxazolylboronic acids failed probably due to the equilibrium between cyclic and acyclic valence bond tautomers of the lithiooxazoles. A somewhat relevant Suzuki coupling involved the Pd-catalyzed cross-coupling of 6-bromo-2-phenyloxazolo[4,5-6]pyridine with phenylboronic acid to provide 6-phenyl-2-phenyloxazolo[4,5-6]pyridine [15]. 

Chloro-P-carboline (25) has served as a common intermediate in palladium-catalyzed cross-coupling reactions, offering easy access to several pyridine alkaloids. In Bracher s total synthesis of perlolyrine (27), a P-carboline alkaloid, the Suzuki reaction of 25 with 5-formylfuranyl-2-boronic acid (26) formed the C-C bond between the pyridine and the furan rings <92LA1315>. Reduction of the resulting Suzuki adduct with NaBIL subsequently... 

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