SN2′ versus SN2 Reactivity: Control of Regioselectivity in Conversions of Baylis-Hillman Adducts

TiCl4-induced Baylis-Hillman reactions of a,p-unsaturated carbonyl compounds with aldehydes yield the (Z)-2-(chloromethyl)vinyl carbonyl compounds 5, which react with 1,4-diazabicyclo[2.2.2]octane (DABCO), quinuclidine, and pyridines to give the allylammonium ions 6. Their combination with less than one equivalent of the potassium salts of stabilized carbanions (e.g. malonate) yields methylene derivatives 8 under kinetically controlled conditions (S(N)2' reactions). When more than one equivalent of the carbanions is used, a second S(N)2' reaction converts 8 into their thermodynamically more stable allyl isomers 9. The second-order rate constants for the reactions of 6 with carbanions have been determined photometrically in DMSO. With these rate constants and the previously reported nucleophile-specific parameters N and s for the stabilized carbanions, the correlation log k (20 degrees C)=s(N + E) allowed us to calculate the electrophilicity parameters E for the allylammonium ions 6 (-19 < E <-18). The kinetic data indicate the S(N)2' reactions to proceed via an addition-elimination mechanism with a rate-determining addition step.