Heterocycles 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 7V-fluorobenzenesulfonlmlde, but more complex phenyl lithium derivatives 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-pyrroles and 2-fluoro-5-methylthleno[3,2-b]pyrldlne are prepared from their corresponding llthlo-parent compounds (eq 16). ... 

Tandem reactions involving organolithium reagents (reactions with formation and participation of heterocycles) 03OPP445. 

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 enantioselective addition of the amino organolithium reagents consists of two stereo-controlled reactions, the asymmetric deprotonation (equation 14) and the following addition to electrophiles. The stereochemical course of the addition depends on the electrophile E. In the cases where heterocyclic enone or a,-unsaturated lactones are the electrophiles (entries 5-7), the addition proceeds with retention of configuration. In contrast, with the other electrophiles in Table 10 and trimethyltin chloride in equation 15, the addition proceeds with inversion of configuration. In the addition which proceeds with retention of configuration, a pre-complexation between the electrophiles and lithium may be involved (equation 16). 

Apart from nucleophilic substitution reactions, the chemistry of the halo derivatives of the 7r-deficient heterocycles is fairly similar to that of aromatic halides. Thus, heterobiaryls can be prepared by the Ullman reaction, and Grignard reagents and organolithium compounds can be prepared, although in many instances, and especially with Grignard reagents,... 

Similar displacement reactions can be applied to branched aminoalkyl heterocycles <86X5065). Another route to branched aminoalkylpyrroles involves addition of organolithium reagents to the dimethylaminomethylene derivatives that are formed by Vilsmeier-Haack reactions (Scheme 103). These can be isolated by treatment of the reaction mixture with NaH <87SC863>. 

Nucleophilic substitution reactions can be carried out on poly(methyl methacrylate) with heterocyclic organolithium reagents. " The reactions are conducted in homogeneous solutions in tetrahydrofuran or in benzene combined with hexamethylphosphoramide. Copolymers will form with tautomeric keto-j5-heterocyclic structures. The following heterocyclic reagents are useful 2-picolinyllithium, [(4,4-dimethyl-2-oxazole-2-yl)methyl]lithium, quinaldinyllithium, and [2-thiazole-2-yl-methyl]lithium. 

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