Intramolecular aldol additions, Marcus

Rate and equilibrium constants have been measured for representative intramolecular aldol condensations of dicarbonyls.60a For the four substrates studied (32 n = 2, R = Me n = 3, R = H/Me/Ph), results have been obtained for both the aldol addition to give ketol (33), and the elimination to the enone (34). A rate-equilibrium mismatch for the overall process is examined in the context of Baldwin s rales. The data are also compared with Richard and co-workers study of 2-(2-oxopropyl)benzaldehyde (35), for which the enone condensation product tautomerizes to the dienol60b (i.e. /(-naphthol). In all cases, Marcus theory can be applied to these intramolecular aldol reactions, and it predicts essentially the same intrinsic barrier as for their intermolecular counterparts. 

Intramolecular aldol reaction of (14) to give (16), promoted by lyate ion, has been found to proceed by rate-determining deprotonative formation of enolate intermediate (15) the intramolecular addition (/cc) occurs more rapidly than reprotonation of (15) by H2O or D2O ( hoh or A dod), c/ hoh = 35. However, when the reaction is catalysed by high concentrations of 3-substituted quinuclidine buffers, the enolate addition is rate determining and competitive with reprotonation of (15) k-Q /k (lmol ) increases from 7 to 450 as the acidity of the buffer acid increases from p/(bh = 11-5 to 7.5. The unexpectedly small Marcus intrinsic value for addition of (15) to the carbonyl group has been attributed to favourable interactions between the soft-soft acid-base pair. 

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