Nucleophilic Addition to Olefins. 4. Structure-Reactivity Relationships in the Reactions of Amines with Substituted Benzylidene Meldrum's Acids. Evidence for Intramolecular Proton Transfer to Carbon

Article abstract of DOI:10.1021/ja00536a035

The reactions of piperidine and morpholine with benzylidene Meldrum's acid (1-H) and its p-OMe and p-NMe2 derivatives (1-OMe, 1-NMe2) in water are characterized by a fast and slow kinetic process.The fast reaction refers to the formation of a zwitterionic adduct (T_A^+/-) which is in rapid acid-base equilibrtium with T_A^- (eq 1).The slow process leads, via an iminium ion, to the respective benzaldehyde and Meldrum's acid anion (eq 3) whereby protonation of T_A^- on carbon, to form T_A⁰, is rate limiting.The effect of the substituents in the olefin on rate (K₁) and equilibrium constants (K₁) for adduct formation indicate that the transition state is located approximately halfway between reactants and products (δ log K₁/δ log K₁ = 0.40 - 0.45).On the other hand, β_nuc is extremely low (0.07 -0.12), suggesting that C-N bond formation has made very little progress in the transition state.These data then suggest an imbalanced transition state for which two different and possibly complementary explanations are proposed.According to the first, rehybridization of the benzylic carbon (site of nucleophlic attack) is ahead of C-N bond formation.In the second it is assumed that some negative charge is localized on the benzylic carbon in the transition state but delocalized into the (COO)2C(CH3)2 moiety in the product, as has been suggested for the nitroalkane anomaly.Prhotonation of T_A^- on carbon by morpholinium ion is retarded 1000-fold owing to a steric effect; carbon protonation by the hydronium ion occurs mainly by prior equilibrium protonation on nitrogen, to form T_A^+/-, followed by an intramolecular proton switch, T_A^+/- -> T_A⁰ (eq 3), through an intermediate water molecule.