Basicities and Nucleophilicities of Pyrrolidines and Imidazolidinones Used as Organocatalysts

The
Brønsted basicities pKaH (i.e.,
pKa of the conjugate acids) of 32 pyrrolidines
and imidazolidinones, commonly used in organocatalytic reactions,
have been determined photometrically in acetonitrile solution using CH acids as indicators. Most investigated
pyrrolidines have basicities in the range 16 < pKaH < 20, while imidazolidinones are significantly less
basic (10 < pKaH < 12). 2-(Trifluoromethyl)­pyrrolidine
(A14, pKaH 12.6) and the
2-imidazoliummethyl-substituted pyrrolidine A21 (pKaH 11.1) are outside the typical range for pyrrolidines
with basicities comparable to those of imidazolidinones. Kinetics
of the reactions of these 32 organocatalysts with benzhydrylium ions
(Ar2CH+) and structurally related quinone methides,
common reference electrophiles for quantifying nucleophilic reactivities,
have been measured photometrically. Most reactions followed second-order
kinetics, first order in amine and first order in electrophile. More
complex kinetics were observed for the reactions of imidazolidinones
and several pyrrolidines carrying bulky 2-substituents, due to reversibility
of the initial attack of the amines at the electrophiles followed
by rate-determining deprotonation of the intermediate ammonium ions.
In the presence of 2,4,6-collidine or 2,6-di-tert-butyl-4-methyl-pyridine, the deprotonation of the initial adducts
became faster, which allowed the rate of the attack of the amines
at the electrophiles to be determined. The resulting second-order
rate constants k2 followed the correlation
log k2(20 °C) = sN(N + E), where electrophiles
are characterized by one parameter (E) and nucleophiles
are characterized by the two solvent-dependent parameters N and sN. In this way, the organocatalysts A1–A32 were integrated in our comprehensive
nucleophilicity scale, which compares n-, π-, and σ-nucleophiles.
The nucleophilic reactivities of the title compounds correlate only
poorly with their Brønsted basicities.