Guanidine–Guanidinium Cooperation in Bifunctional Artificial Phosphodiesterases Based on Diphenylmethane Spacers; <i>gem</i>-Dialkyl Effect on Catalytic Efficiency

Diphenylmethane derivatives <b>1</b>–<b>3</b>, decorated with two guanidine units, are effective catalysts of HPNP transesterification. Substitution of the methylene group of the parent diphenylmethane spacer with cyclohexylidene and adamantylidene moieties enhances catalytic efficency, with <i>gem</i>-dialkyl effect accelerations of 4.5 and 9.1, respectively. Activation parameters and DFT calculations of the rotational barriers around the C–Ar bonds indicate that a major contribution to the driving force for enhanced catalysis is entropic in nature

Ribonuclease Activity of an Artificial Catalyst That Combines a Ligated Cu^II Ion and a Guanidinium Group at the Upper Rim of a <i>cone</i>-Calix[4]arene Platform

A <i>cone</i>-calix­[4]­arene derivative, featuring a guanidinium group and a Cu^II ion ligated to a 1,4,7-triazacyclononane (TACN) ligand at the 1,3-distal positions of the upper rim, effectively catalyzes the cleavage of 2-hydroxypropyl <i>p</i>-nitrophenyl phosphate (HPNP) and a number of diribonucleoside 3′,5′-monophosphates (<i>N</i>p<i>N</i>′). Kinetic and potentiometric measurements support the operation of a general-base/general-acid mechanism and demonstrate that the hydroxo form of the ligated Cu^II ion is the sole catalytically active species. Rate enhancements relative to the background hydrolysis reaction at 1 mM catalyst concentration are 6 × 10⁵-fold for HPNP and cluster around 10⁷-fold with the most favorable catalyst–<i>N</i>p<i>N</i>′ combinations

Organocatalytic synthesis of benzazetidines by trapping hemiaminals with protecting groups

Benzazetidines are highly strained and inherently unstable heterocycles. There are only few methodologies for assem-bling these compounds. Here, a protocol is presented to trap an elusive cyclic, 4-membered hemiaminal structure. This method affords several benzazetidine in moderate to good yields (up to 81%), it uses inexpensive materials and does not require catalysts based on transition metals. The high ring strain energy of these benzazetidine systems was estimated by DFT calculations to be about 32 kcal mol-1. This synthesis can be applied also on gram scale with reac-tion yield essentially unchanged