Alkylation, enolate ions side chain

An ion-pair derived from the substrate and solid NaOH forms a cation-assisted dimeric hydrophobic complex with catalyst 39c, and the deprotonated substrate occupies the apical coordination site of one of the Cu(II) ions of the complexes. Alkylation proceeds preferentially on the re-face of the enolate to produce amino acid derivatives with high enantioselectivity. However, amino ester enolates derived from amino acids other than glycine and alanine with R1 side chains are likely to hinder the re-face of enolate, resulting in a diminishing reaction rate and enantioselectivity (Table 7.5). The salen-Cu(II) complex helps to transfer the ion-pair in organic solvents, and at the same time fixes the orientation of the coordinated carbanion in the transition state which, on alkylation, releases the catalyst to continue the cycle. 

When / -dicarbonyl enolates are allowed to react with alkynyliodonium salts, typically in ter/-butyl alcohol or THF, alkynyl- and/or cyclopentenyl- -dicarbonyl compounds are obtained. The product compositions are largely regulated by the migratory aptitude of R in the alkynyl moiety and the availability of alkyl side chains for the MC-insertion (MCI) pathway (equation 45). These divergent modes of reactivity are nicely illustrated by the reactions of the 2-phenyl-1,3-indandionate ion with ethynylfphenyl)- and 4-methyl-1-hexynyl(phenyl)iodonium tetrafluoroborates (equation 1 15)27 2. 

In summary, Wardrop developed a synthetic route to azatricycle 15 (16 steps), which Snider had previously transformed to 19. Accordingly, a formal synthesis of racemic desmethylamino FR901483 was achieved, the key steps being (i) formation of the azaspirodecane ring by an N-methoxy-A-acylnitrenium ion-induced spirocyclization (ii) construction of the bridge framework by a 6-exo-trig radical cyclization, and (iii) installation of the C(6) p-methoxybenzyl side chain by Lewis acid-mediated alkylation of a silyl enol ether. 

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