Nitrogen-substituted alkyllithiums

The first clearly authenticated preparation of an isoindole was reported by Wittig et in 1951. It was found that elimination from isoindolinium bromides and iodides with bases such as aryl- and alkyllithium afforded 2-substituted isoindoles in variable yields. For instance, 2,2-dimethylisoindolinium bromide (5) on treatment with one equivalent of phenyllithium in ether under nitrogen, evolved methane and gave 2-mcthylisoindole (6) in 74% yield. With methyl-lithium as base, a slightly lower yield was obtained. 

Oxazolidinone-Substituted Carbanions. Oxazolidinone-substituted organostannanes readily undergo transmetalation with alkyllithium reagents to the organolithium derivatives which then can undergo nucleophilic addition reactions. -Substituted oxazolidinones can act in this capacity as both a nitrogen source and source of chirality (eq 60). Although the a-stereoselection... 

The reaction of alkyllithium reagents with acyclic and cyclic tosylhydrazones can lead to mixtures of elimination (route A) and addition (route B) products (Scheme 22). The predominant formation of the less-substituted alkene product in the former reaction (Shapiro Reaction) is a result of the strong preference for deprotonation syn to the N-tosyl group. Nucleophilic addition to the carbon-nitrogen tosyl-hydrazone double bond competes effectively wiA a-deprotonation (and alkene formation) if abstraction of the a-hydrogens is slow and excess organolithium reagent is employed. Nucleophilic substitution is consistent with an Su2 addition of alkyllithium followed by electrophilic capture of the resultant carbanion. 

Substituted 5-chloro-l,2,3-thiadiazoles react with simple hetero nucleophiles by displacement of the chlorine, but reaction with aryl- and alkyllithiums gives alkynyl-thioethers via attack at sulfur and then ring cleavage with loss of nitrogen. A similar ring cleavage occurs, but by a different mechanism, when the... 

Tt has been known for 40 years that alkyllithium compounds will react with specifically substituted aromatic compounds to effect metalation —that is, replace an aromatic proton with a metal ion. More recently the orientation in a variety of such metalations has been worked out resulting in the identification of substituents that have been demonstrated to direct metalation to an aromatic proton adjacent to said substituents. This, then, is the reaction that is now called the directed metalation reaction. Since many of these substituents contain a directing nitrogen atom, it is appropriate that this process be reviewed here. 

Chloride is a better leaving group than alkoxide or aroxide, whereas the latter outpaces dialkylamides. Phosphorus-bound heterosubstituents, if cleverly selected, can be displaced stepwise (Scheme 1-Al). Thus, adding an alkyllithium in three consecutive steps to 2-chloro-3-methyl-l,3,2-oxazaphospholidine (51), first the halogen is substituted selectively, next the five-membered ring (of 52) is opened by rupture of the P-0 bond, and eventually the nitrogen-attached side chain (of 53) is substituted to afford the final phosphine. 

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