Organolithium with amides

Unlike organolithiums, lithium amides do not attack tin, so functionalisation of tin-containing molecules by deprotonation with LDA is still feasible 133... 

An extensive study of the decomposition of the N,N-dimethylbenzyl-anilinium ion 22 was recently carried out by Lepley and coworkers 93.99) As expected, displacement reactions occur exclusively with hydroxide and alkoxide, an orf/io-rearrangement occurs with amide, and a variety of products are formed with various organolithium reagents. The products found when butyllithium was employed are listed below. 

There is a rather useful reaction with amides. Organolithium reagents react with DMF to give aldehydes.. An example is the reaction of 231 with s c-butyllithium to give the aryl-lithium reagent (see sec. 8.5.F for directed ortho metalation reactions). Subsequent reaction with DMF and hydrolysis gave a 91% yield of aldehyde 232 in Yamaguchi s synthesis of the radulanins. ... 

DIRECTED METALATION OF ARENES WITH ORGANOLITHIUMS, LITHIUM AMIDES, AND SUPERBASES... 

Most successful approaches involving addition reactions in the presence of chiral additives utilize organolithium, organomagnesium and the recently introduced organotitanium reagents, which are known to coordinate with amines, ethers, metal amides and alkoxides. 

Alkyltriphenylphosphonium halides are only weakly acidic, and a strong base must be used for deprotonation. Possibilities include organolithium reagents, the anion of dimethyl sulfoxide, and amide ion or substituted amide anions, such as LDA or NaHMDS. The ylides are not normally isolated, so the reaction is carried out either with the carbonyl compound present or with it added immediately after ylide formation. Ylides with nonpolar substituents, e.g., R = H, alkyl, aryl, are quite reactive toward both ketones and aldehydes. Ylides having an a-EWG substituent, such as alkoxycarbonyl or acyl, are less reactive and are called stabilized ylides. 

The indolizinoquinoline 106 can be prepared by intramolecular acylation of the precursor 105. The organolithium derivative of 105 reacts intramolecularly with the amide this Parham-type reaction gives the triheterocyclic product in reasonable yield, and higher yields are obtained when the Weinreb-type methoxyamide (Rz = OMe) is used (Equation 21) <20030L1115>. 

Conversions of carboxylic acids to ketones are typically performed in stepwise fashion6 via intermediates such as acid chlorides,7 anhydrides,8 thioesters,9 or N-alkoxy amides,10 or by the direct reaction of carboxylic adds with lithium reagents.11 In this latter method trimethylsifyl chloride has been shown to be an effective reagent for trapping the tetrahedral alkoxide intermediates and for quenching excess organolithium reagent. 

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