2‐Methylene‐1,2‐dihydropyridines (2‐pyNHOs): Highly Nucleophilic Enamines

Abstract

The high reactivity of 2‐methylene‐1,2‐dihydropyridines also known as 2‐methylpyridinium derived N‐heterocyclic olefins (2‐pyNHOs) has been recognized in organic synthesis, yet a quantification of their nucleophilicity is lacking. Herein we used stopped‐flow photometry to determine the nucleophilicity of a series of 2‐pyNHOs from the kinetics of their reactions with quinone methides and benzhydrylium ions as reference electrophiles in four organic solvents at 20 °C. The kinetic data was evaluated by using the Mayr‐Patz equation, lg k(20 °C) = sN(N + E), which gave nucleophilicity parameters N (and sN). With N in the range of 19.4 to 21.2 (in DMSO), 2‐pyNHOs exceed the reactivity of classical enamines, such as pyrrolidino‐cyclopent‐1‐ene. The addition of 2‐pyNHOs to quinone methides resulted in the formation of zwitterionic adducts with pyridinium and phenolate moieties. Subsequent tautomerization yielded entirely neutral pyridine‐2(1H)‐ylidene‐phenol species in several cases. Formation of the zwitterionic adducts from 2‐pyNHOs and neutral electrophiles was almost equally fast in the polar solvents acetonitrile and DMSO, but proceeded one to two orders of magnitude slower in the less polar solvents dichloromethane or THF.