Organocatalytic activity of cinchona alkaloids: which nitrogen is more nucleophilic?

The cinchona alkaloids 1a-d react selectively at the quinuclidine ring with benzyl bromide and at the quinoline ring with benzhydrylium ions (diarylcarbenium ions). The kinetics of these reactions have been determined photometrically or conductimetrically and are compared with analogous reactions of quinuclidine and quinoline derivatives. Quantum chemical calculations [MP2/6-31+G(2d,p)//B3LYP/6-31G(d)] show that the products obtained by attack at the quinuclidine ring (N(sp3)) of quinine are thermodynamically more stable when small alkylating agents (primary alkyl) are used, while the products arising from attack at the quinoline ring (N(sp2)) are more stable for bulkier electrophiles (Ar(2)CH). In some cases, rate and equilibrium constants for their reactions with benzhydrylium ions could be determined. These data gave access to the Marcus intrinsic barriers, which are approximately 20 kJ mol(-1) lower for attack at the N(sp3)-center than at the N(sp2)-center.