Structure–Reactivity Relationship Studies for Guanidine‐Organocatalyzed Direct Intramolecular Aldolization of Ketoaldehydes

Abstract

Structure–reactivity studies are performed to explore the reaction mechanism of the guanidine‐catalyzed intramolecular aldol reaction of ketoaldehydes. A large number of guanidine and guanidine‐like catalysts are synthesized and their properties studied. Kinetic profiles and pKa values of the catalysts are measured and correlated to reaction barriers calculated using density functional theory (DFT). The DFT calculations show that structural rigidity influences the pKa of the guanidines. Although the basicity is a very important factor in the catalysis, it is not sufficient to fully account for its catalytic efficiency. The availability of two aligned nitrogen reaction sites for proton shuttling in the transition state is an essential feature that helps to rationalize the reactivity pattern and the activation mode for this family of organocatalysts.

Organocatalytic controlled/living ring-opening polymerization of cyclotrisiloxanes initiated by water with strong organic base catalysts

“…The Brønsted basicity of TMnPG has been reported to be at least higher than TBN in CD 3 OD/D 2 O = 8/2 (w/w). 43 TMiPG showed a slightly lower catalytic activity than TMnPG presumably because of the higher steric hindrance of the isopropyl group than that of the propyl group. It is noteworthy that the undesired side reactions were much less frequent in the polymerization catalyzed by TMiPG and TMnPG in comparison with that catalyzed by other bases with comparable catalytic activity.…”

“…TBO (0.0036 h –1 ), a bicyclic guanidine with two five-membered rings, showed much lower catalytic activity than TBD and TBN, presumably due to its much lower Brønsted basicity than TBD and TBN. 43 TMGb (0.093 h –1 ), an acyclic tetramethylguanidine with an R–N C(N)–NH–R′ unit, showed 36 times higher catalytic activity than TMGa. The replacement of an H–N C(N)–NMe 2 unit of TMGa with an Me–N C(N)–NH–Me unit certainly contributed to the increase in the catalytic activity.…”

“…The R–N C(N)–NH–R′ unit in the guanidines B would simultaneously activate water or a silanol on a propagating polymer by the imino group and transfer the hydrogen atom on the amino group to an incoming monomer based on the ‘proton shuttling mechanism’ as depicted in Scheme 3a . 43 In contrast, the bases in the other categories are incapable of ‘proton shuttling’ and need to directly transfer the hydrogen atom as depicted in Scheme 3b . K s would increase as the acidity of the terminal silanol increases and the steric hindrance of the silanol decreases.…”