Cross-coupling of pyridines

Scheme 24 Pd-catalyzed oxidative cross-coupling of pyridine N-oxides with simple arenes...

Scheme 36 Oxidative cross-coupling of pyridine N-oxide derivatives with cycloalkanes...

E. Maerten, M. Sauthier, A. Mortreux, Y. Castanet, Tetrahedron, 2007, 63, 682-689. Palladium-N-heterocyclic carbene an efficient catalytic system for the carbonylative cross-coupling of pyridine halides with boronic acids. 

Scheme 8.24 Transition metal free cross-coupling of pyridine-JV-oxide with cycloalkanes.

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. 

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]. 

An alternate approach to the formation of pyridylboronic acids is the cross-coupling of a halopyridine with a diboronate ester (usually bis(pinacolato)diboron, 7.7.)9 The analogous reaction of 2-chloropyridine led to pyridine formation through protodeboronation. The product of the reaction, either after hydrolysis to the boronic acid or in the ester form, can be further reacted with another aryl halide to give a biaryl. In certain cases the reaction might also be carried out in a one-pot manner.10... 

Numerous studies involving similar amido derivatives of metals such as Ti (e.g. heterometallic cross-coupling of benzonitrile with carbon dioxide, pyridine, and benzophenone with mixed [Ti N(Bu )Ar 3] and [Mo N(Bu )Ar 3] systems), V (e.g. denitrogenation of a vanadium nitride by carbon disulfide and dioxide), Nb (e.g. the... 

The reaction of aryl and alkenyl halides with the Reformatsky reagent 237 in polar solvents affords a-arylacetates [105], Iodides of heterocyclic compounds such as pyridine, quinoline and pyrimidine react smoothly with Reformatsky reagents. The cross-coupling of 237 with 4-iodo-2,6-dimethyl- and 2-iodo-4,6-dimethylpyrimidine (236) occurs smoothly to form 238. But no reaction of 5-iodo-2,4-dimethylpyrimidine (239) takes place [106],... 

Pyridylmethylphosphinates can be accessed, albeit in low isolated yield, by palladium-catalyzed cross-coupling of 2- and 3-pyridylmethyl chlorides with anilinium hypophosphites <2005T6315>. For example, 3-chloromethylpyr-idine hydrochloride reacts with anilinium hypophosphite in the presence of Pd(OAc>2, dppf, 1,4-diazabicy-clo[2.2.2]octane (DABCO), and (BuOTSi as esterification agent to give butyl (pyridine-3-ylmethyl)phosphinate 53 in 46% yield (Equation 37). This transformation proceeds in 24% yield when performed on 2-chloromethylpyridine. 

Kumada reactions. Polyfunctional pyridines can be prepared by Pd(0)-catalyzed cross-coupling of functionalized arylmagnesium halides with chloro- or bromopyridines at temperatures as low as 40 C, e.g., Scheme 114... 

Suzuki-Miyaura cross-coupling of 343 with 2,4,6-trivinylcyclotriboroxane-pyridine complex proved to be a very efficient method for the generation of the styrenes 337, R2 = Boc in high yields (Scheme 104)188. The procedure was tolerant to all the aryl substituents attempted and to the three different nitrogen substituents. 

The disclosure of a one-pot directed ortho metalation-boronation and Suzuki-Miyaura cross-coupling of derivatized pyridines 44 to give substituted azabiaryls 45 provided an excellent protocol for the in situ utilization of pyridyl boronic acids whose isolation is known to be difficult <07JOC1588>. The disclosed method relies on the in situ compatibility of LDA and B(Oz-Pr)3 and proceeds in good to excellent yields for the multi-step process. The report details a comprehensive survey of pyridyl boronates and is expected to be of considerable value in the synthesis of bioactive molecules. 

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