Amine catalysis in the vinylic substitution of α-methylthio-α-arylmethylene Meldrum's acids and its absence in the substitution of methyl β-iodo-α-nitrocinnamate by amines

Abstract

Substitution of the iodine of (E)- and (Z)-methyl β-iodo-α-nitrocinnamates (5) by amines gives identical (Z)-enamines with aniline (Ani) and piperidine (Pip). No amine catalysis was observed with Pip, Ani, morpholine (Mor), or p-MeOC₆H₄NHMe (MMA) in MeCN nor with Pip or Mor in EtOH: k_Pip/k_Mor = 115–138 (MeCN), 3.3–6.9 (EtOH); k_MeCN/k_EtOH = 25.5 ± 2.2 (Pip), 0.79–1.16 (Mor); k_(Z)-5/k_(E)-5 = 1.3–2.9 (13.5 with MMA in MeCN). Replacement of the MeS group in six α-methylthio-α-arylmethylene Meldrum's acid (6-X) by Pip resulted in amine catalysis in MeCN and EtOH. In EtOH, the p-anisyl derivative (6-MeO) and in MeCN 6-MeO, 6-Me and 6-H displayed second order catalysis in Pip. Other 6-X compounds show orders between one and two in Pip with amine catalyzed (k_3B)/non-catalyzed (k₂) rate coefficient ratios of 281–731 (EtOH) and 504–635 (MeCN) at 30 °C. k_MeCN/k_EtOH = 3.0–4.9. In MeCN ΔH^‡ = −0.8 to −5.9 kcal mol⁻¹ and ΔS^‡ = −50 to −72 e.u. An intermediate zwitterion, 3a, is formed in all cases. For system 5 the rate of I⁻ expulsion from 3a exceeds its deprotonation rate, and the observed rate coefficient is composite: k_obs = k₁k₂/k₋₁ in MeCN (k₁ = rate coefficient of nucleophilic attack) but k_obs = k₁ in EtOH. In MeCN the deprotonation is faster than the expulsion rate of MeS⁻, and more so for 6-X with X = p-Br, p-CF₃, m,m′-(CF₃)₂. Different electrophilicities of 6-X, different extents of hydrogen bonding, steric and electronic effects account for the kinetic differences.