Alkylations lithiated aldimines

Fraser and coworkers152 examined the lithiation and alkylation of aliphatic ketimines of cyclohexanone 90 and found that the reaction proceeded to give >99% syn and axial isomer 91. Although some anti-axial (92) and aw/z -equatorial (93) alkylation products were also isolated, this was attributed to isomerization of the sjw-axial product. Similar results were obtained on alkylation of aliphatic aldimines which have been shown to give syn and anti products in a 96 4 ratio153. The electronic factor responsible for the preferential stabilization of the syn, or destabilization of the anti, lithiated aldimine was estimated to have a magnitude of at least 18 kJ mol-1. 

Whitesell and Whitesell" have tabulated some of the many types of electrophilic reagents that C-al-kylate metallated imines. These are potent nucleophiles and undergo substitution reactions even with weakly electrophilic species such as epoxides and oxetanes. Lithiated ketimines and aldimines have been frequently used in reactions with alkylating agents containing latent 2-keto (or aldehydo) groupsor 3-keto (or aldehydo) groups. ... 

Fortunately, the use of lithiated hydrazones derived from (S)- or ( )-l-amino-2-methoxymethylpyiro-lidine (SAMP or RAMP) as nucleophiles for asymmetric alkylations have provided a solution to the problems described above with metallated acyclic ketimines and aldimines. Lithiated SAMP or RAMP hydrazones of cyclic ketones are also alkylated in high yields. A major advantage of these chiral hydrazones is that their derivatives of aldehydes, acyclic and cyclic ketones all yield mainly ( )cc-. (Z)cN-Iithiated species on deprotonation with LDA in ethereal solvents under kinetic control. The ( )cc-configuration obtains as a result of the minimization of steric interactions in the usual closed transition... 

Butyllithium. 13, 56 14, 63-68 15, 59-61 17, 59-60 18, 74-77 19, 54-59 20, 62-65 lithiation. Various uses of BuLi for deprotonation include ethers that subsequently react with aldimines to provide precursors of pyrrolidin-3-ones. 2-Alkylidene tetrahydro-furans are readily prepared via alkylation of 2-sulfonylmethylenetetrahydrofuran.-... 

Further work on the alkylation of carbanions derived from cyclohexyl aldimines has appeared, and the lithiated cyclohexylimine derivative has proved to be the intermediate of choice in mono- and di-a-alkylations of crotonaldehyde. ... 

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