Triazolium Salt Organocatalysis: Mechanistic Evaluation of Unusual Ortho-Substituent Effects on Deprotonation

Organocatalysis by N-heterocyclic carbenes is normally initiated by the deprotonation of precursor azolium ions to form active nucleophilic species. Substituent effects on deprotonation have an impact on catalytic efficiency and provide insight into general catalytic mechanisms by commonly used azolium systems. Using an NMR kinetic method for the analysis of C(3)-H/D exchange, we determined log kex–pD profiles for three ortho-substituted N-aryl triazolium salts, which enables a detailed analysis of ortho-substituent effects on deprotonation. This includes N-5-methoxypyrid-2-yl triazolium salt 7 and di-ortho-methoxy and di-ortho-isopropoxyphenyl triazolium salts 8 and 9, and we acquired additional kinetic data to supplement our previously published analysis of N-pyrid-2-yl triazolium salt 6. For 2-pyridyl triazoliums 6 and 7, novel acid catalysis of C(3)-H/D exchange is observed under acidic conditions. These kinetic data were supplemented by DFT analyses of the conformational preferences of 6 upon N-protonation. A C(3) deprotonation mechanism involving intramolecular general base deprotonation by the pyridyl nitrogen of the N(1)-deuterated dicationic triazolium salt is most consistent with the data. We also report kDO values (protofugalities) for deuteroxide-catalyzed exchange for 6–9. The protofugalities for 8 and 9 are the lowest values to date in the N-aryl triazolium series.

ortho-Substituent effect on the crystal packing and solid state speciation of aromatic C-nitroso compounds

The solid state behaviour of a short series aromatic C-nitroso compounds has been studied as a function of the electronic and steric nature of the ortho-substituent on the ring.

α-Alkylation of N–C Axially Chiral Quinazolinone Derivatives Bearing Various ortho-Substituted Phenyl Groups: Relation between Diastereoselectivity and the ortho-Substituent

2-Ethylquinazolin-4-one derivatives bearing various ortho-substituted phenyl groups were revealed to possess a stable C–N axially chiral structure at ambient temperature. The reactions of alkyl halides with the anionic species prepared from these quinazolinones were systematically explored. The α-alkylation reactions proceeded with diastereoselectivities ranging from 1:1 to >50:1, depending upon the steric bulk of the ortho-substituent, to afford products having the elements of axial and central chirality in high yields (85–98%).

The ortho-substituent on 2,4-bis(trifluoromethyl)phenylboronic acid catalyzed dehydrative condensation between carboxylic acids and amines

The ortho-substituent of boronic acid plays a key role in preventing the coordination of amines to the boron atom.

Divergent reaction pathways in gold-catalyzed cycloisomerization of 1,5-enynes containing a cyclopropane ring: dramatic ortho substituent and temperature effects

Gold-catalyzed cycloisomerization of 1,5-enynes containing a cyclopropane ring provides access to cyclobutane-fused 1,4-cyclohexadiene, 1,3-cyclohexadiene, tricyclic cyclobutene and biscyclopropane derivatives.