Pyridine reaction with organolithium reagents

Reaction with Organolithium Reagents. The fluorination of vinyl lithium derivatives with NFSi has been demonstrated in good yields with complete retention of configuration about the double bond. Phenyl lithium reacts rather poorly with A-fluorobenzenesulfonimide, but more complex phenyl lithium daivatives have been fluorinated to prepare fluoro- and polyfluoro-veratraldehydes as well as complex fluorinated polyaromatic compounds. Organolithium derivatives of heterocycles have been fluorinated by reaction with NFSi at low temperature. In this manner, fluoro-p3aroles and 2-fluoro-5-methylthieno[3,2-b]pyridine are prepared from their corresponding lithio-parent compounds (eq 16). ... 

Pyridine is an aromatic 6n electron heterocycle, which is isoelectronic with benzene, but electron deficient. Nucleophiles thus add almost invariably to carbon C2 of the imine-like C=N double bond. Perhaps the best known nucleophilic addition is the Chichibabin reaction with sodium amide in liquid ammonia, giving 2-aminopyr-idine. Reactions of the quinoline moiety of cinchona alkaloids can be more complex. Although expected 2 -addition can be achieved easily with organolithium reagents to yield 13 (Scheme 12.6) [9], LiAlH4, for example, has been shown to attack C4 en route to quincorine and quincoridine (Schemes 12.4 and 12.5). C4 selectivity is due to chelation of aluminum by the C9 OH oxygen. 

The reaction of pyridines with organolithium reagents afforded mainly 2-substituted pyridines through alkyl addition to generate a dearomatized hthium complex of dUiydropyridine. From this species, it has been though that ehmination of highly insoluble lithium hydride would yield the final... 

Benzamides (N-Bz) are formed by the reaction of amines with benzoyl chloride in pyridine or trimethylamine. The group is stable to pH 1-14, nucleophiles, organometallics (except organolithium reagents), catalytic hydrogenation, and oxidation. It is cleaved by strong acids (6N HCl, HBr) or diisobutylaluminum hydride. ... 

Reactions with nucleophiles occur at ring position C-4 (e.g. with Grignard reagents [137]), or at C-3 (with organolithium compounds). They are preparatively not as important as the Chichibabin or Ziegler reaction in pyridine ... 

When a phenyl ring on the backbone of polystyrene (represented by the solid sphere) is reacted with benzoyl chloride and aluminum chloride, the product is the benzoyl derivative 167 (this is a Friedel-Crafts acylation see Chapter 21, Section 21.3.3). If reacted with 168, the product is 169 (an acyl addition reaction of an organolithium reagent see Chapter 18, Section 18.4). When the methyl group of the pyridine unit in 169 is treated with phenyllithium to form the (pyridyllCHgLi derivative, reaction with formaldehyde leads to 170. If 170 is linked to iV-benzoyl 2 -0-isobutyladenosine-3 -monophosphate (171), the product is 172, in which the first nucleotide is bound to the polymer via the 3 position. 

Transformations related to the Chichibabin reaction take place when pyridines are treated with Grignard or organolithium reagents. 

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