C-Alkylation of Phenolate Anions

Early examples of this reaction involved cyclizations of 4-substituted phenols tethered to alkyl sulfonates and halides [3]. CycMzalions involving carbonyl electrophiles (aldehydes, ketones) and imines have been reported as well, but esters are not sufiSciently electrophilic to react [2]. Subsequent studies established that the facility of these so-called Ai-n cyclizations was strongly affected by the size of the newly formed ring in the order 3 5 6 4. Since the vast majority of alkylative dearomatizations involve intramolecular cyclizations (thereby avoiding competitive 0-aDcylation reactions), stereoelectronic effects operative in the transition states (resembling the TS of an Sjj2 reaction) are crucially important. These sometimes subtle effects can result in differential reactivity of structurally similar substrates [4]. 

Many alkylative dearomatizations proceed with complete stereoselectivity due to conformational rigidity of the cyclization substrates. Diastereoselective dearomatization of more flexible substrates is possible provided nonbonding interactions encountered in the Sj.j2-like transition states are sufficient to differentiate prochiral faces of the phenolate anions. For example, benzoate 

Chiral phase-transfo catalyst (25 mol%) CSOH-H2O, CH2CI2 

SCHEME 15.4 Asymmetric dearomatization of a phloroglucinol-based substrate. 

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