Kinetics and Mechanism of Michael-type Reactions of Ethyl Propiolate with Alicyclic Secondary Amines in H2O and MeCN: Solvent Effect on Reactivity and Transition-State Structure

The amines studied in this study are less reactive toward ethyl propiolate (3) in MeCN than in H2O although they are 7 to 9 pK(a) units more basic in the aprotic solvent. The reactivity morpholine and deuterated morpholine toward 3 is found to be identical, indicating that proton transfer occurs after rate-determining step (RDS). The fact that kinetic isotope effect is absent excludes a stepwise mechanism in which proton transfer occurs in RDS as well as a concerted mechanism in which nucleophilic attack and proton transfer occur concertedly through a 4-membered cyclic transition state (TS). Thus, the reactions have been concluded to proceed through a stepwise mechanism in which proton transfer occurs after RDS. Bronsted-type plots are linear with small beta(nuc) values, i.e., beta(nuc) = 0.29 in H2O and beta(nuc) = 0.51 in MeCN, indicating that bond formation is not advanced significantly in RDS. The small beta(nuc) value also supports the conclusion drawn from the study of kinetic isotope effect.