Organolithiums amides

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. 

The presence of an amide on pcrhydrooxazolo[3,2-tf] pyridine skeleton allows for a substituent modification at the C-5 position. Among the possibilities are partial or full reduction of the amide as well as addition of organolithium reagents, respectively, starting from 323 <1998JOC1732>, 325<1999TL8965>, or 327 (Scheme 88). 

Hodgson DM, Stent MAH (2003) Overview of Organolithium-Ligand Combinations and Lithium Amides for Enantioselective Processes. 5 1-20 Hodgson DM, Tomooka K, Gras E (2003) Enantioselective Synthesis by Lithiation Adjacent to Oxygen and Subsequent Rearrangement. 5 217-250... 

Due to the high interest in metalation reactions with lithium amide or alkyllithiums, an indicator scale of lithium ion pairs in THF has been developed119. Aggregation studies have indicated that organolithium species exist predominantly, if not exclusively, as monomers in the 10-3-10-4 M concentration range. Particular attention has been devoted to the lithium and caesium ion-pair acidities of diphenylamine in THF120 that, at 25 °C, have been found to be 19.05 and 24.20, respectively. 

Hodgson DM, Stent MAH (2003) Overview of Organolithium-Ligand Combinations and Lithium Amides for Enantioselective Processes. 5 1-20... 

Enantiomeric excesses of up to 76% have been obtained for alkyllithium-aldehyde condensations using 3-aminopyrrolidine lithium amides as chiral auxiliaries. Addition of organolithiums to imines has been achieved with up to 89% ee, in the presence of C2-symmetric bis(aziridine) ligands. ... 

The association number of Li amides, such as LrN(SiMe3)2, organolithium compounds bound at the a-position to S or Se atoms, such as LiCH2SePh, and various transition metal complexes was determined at 0°C in THF or at —35°C in Et20, by differential vapor-pressure osmometry. The method allows handling compounds sensitive to autooxidation, moisture and temperature . ... 

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