Alkenylation of pyridines

Ruthenium vinylidene intermediates have also been proposed in the mechanism of the coupling of unactivated alkenes with terminal alkynes to afford 1,3-dienes as a mixture of two isomers, linear and branched derivatives. The linear one was favored [56] (Eq. 42). The same system has allowed the ruthenium-catalyzed alkenylation of pyridine [57]. 

Another example is the ruthenium-catalysed alkenylation of pyridine which is performed in the presence of the same catalyst precursor RuCl(Cp)(PPh3)2 (20 mol %)/NaPF6 (20 mol %) at 150 °C [63]. The use of trimethylsilylalkynes, which are also known to produce vinylidene complexes rather than terminal alkynes, avoids the dimerization of the alkyne and favours the formation of the (E)-vinylpyridine (Scheme 17). The reaction has been applied to a variety of silylated alkynes and substituted pyridines (Fig. 8). 

Scheme 9 Nickel-catalyzed alkenylation of pyridine JV-oxide using alkynes...

A catalyst system composed of Ni(COD)2, amino-NHC (38) and AlMes was demonstrated to promote C-4 selective alkenylation of pyridine and quinoline derivatives. A small amount of C-3 alkenylation species was also obtained as side products in most cases (Scheme 14.63). Stoichiometric reaction of Ni(COD)2 with amino-NHC/AlMcg results in complex 39. Complex 39 can react stoichiometrically or catalytically with allgmes to generate the alkenylated product in good yield. The coordination mode of this intermediate may account for the paraMeta-selectivity over orffto-selectivity. ... 

Alkylation and alkenylation of pyridine N-oxides 26 (or analogs) are important tools to obtain diverse substituted pyridines used as precursor in... 

Scheme 13 Ni-catalyzed selective C2-alkenylation of pyridine W-oxides.

Highly regioselective C4-alkylation and alkenylation of pyridines were achieved simultaneously by the groups of Hiyama and Nakao (2010JA13666) and Ong (2010JA11887) via Nickel/Lewis acid cooperative... 

Scheme 33 Ni/Lewis acid catalyzed C4-alkylation/alkenylation of pyridine.

Scheme 53 Pd-catalyzed alkenylation of pyridine, pyrazine, quinoxaline, and pyrida-zine A/-oxides.

C3-selective alkenylation of pyridine can be promoted via a palladium/ phenantroline catalytic system (23 131) (Scheme 62). By analogy with... 

C2-Alkenylated pyridines were found to be obtained through the sequence of the Pd-catalyzed direct alkenylation of pyridine N-oxides and following deoxygenation (Scheme 18.62) [60]. 

Yu and co workers [62] succeeded in performing the C3-alkenylation of pyridines primarily, accompanied by formation of minor amounts of C2- and C4-alkenylated pyridines (Scheme 18.64). 

Shih and coworkers prepared adducts of several organoaluminum compounds with an NHC featuring a pendant JV-t-butylethylamine branch. The resulting complexes were found to undergo insertion reactions with benzaldehyde, with the carbonyl carbon inserting between the C—A1 bond [29]. These trimethylaluminum complexes have also been used in conjunction with [Ni(cod)2] to facilitate the meta- and j ara-alkenylation of pyridine (with 4-octyne) [135]. These complexes were compared to the corresponding triphenylborane adduct and found to be generally more reactive and more prone to react with imsaturated substrates [136]. 

Olefination via Pd(II) C—H functionalization is not limited to carbon-based arenes. Olefination of the C-2 position of pyridines can be accomplished through the A-oxide. Intra-molecular-directed alkenylation of pyridines leading to... 

SCHEME 5.13 Nickel-catalyzed alkenylation of pyridine A -oxides with alkynes. 

The direct C2 alkenylation of pyridines could be achieved by the use of a Lewis acid cocatalyst, such as trimethylaluminum, dimethyl-, or diphenylzinc. Trimethylaluminum favored formation of dienes 60, zinc-based Lewis acids preferentially gave monoenes 59 (Scheme 5.14). ... 

Hiyama, Nakao and coworkers were able to achieve direct C3/C4 alkenylation of pyridines 67 nsing the highly hindered NHC ligand IMes (l,3-(2,4,6-trimethylphenyl) imidazol-2-ylidene), and trimethylaluminum as Lewis acid cocatalyst (Scheme 5.16).2°... 

SCHEME 5.17 Nickel-catalyzed C3/C4 alkenylation of pyridines and fused pyridines. 

Nickel-Catalyzed C3/C4 Alkenylation of Pyridines and Fused Pyridines... 

The C2 regioselective alkenylation of pyridine is carried out using reaction conditions similar to the nickel-catalyzed arylation in the presence of stoichiometric amount of an unsymmetrical aikyne) (eq 32). ... 

Scheme 41 Formation of 1,3-dienes by linear coupling of phenylacetylenes with olefins and regio- and stereoselective a-alkenylation of pyridines...

Figure 1.17 Pd-catalyzed mefa-selective alkenylation of pyridine in the presence of an MPAA coligand (experiment R = "Bu computed R = Et) [46].

---