Palladium-Catalyzed Multicomponent Synthesis of 2-Imidazolines from Imines and Acid Chlorides

We describe the palladium-catalyzed multicomponent synthesis of 2-imidazolines. This reaction proceeds via the coupling of imines, acid chlorides and carbon monoxide to form imidazolinium carboxylates, followed by a decarboxylation. Decarboxylation in CHCl3 is found to result in a mixture of imidazolinium and imidazolium salts. However, the addition of benzoic acid suppresses aromatization, and generates the trans-disubstituted imidazolines in good yield. Combining this reaction with subsequent nitrogen deprotection provides an overall synthesis of imidazolines from multiple available building blocks

An Electrophilic Approach to the Palladium-Catalyzed Carbonylative C–H Functionalization of Heterocycles

A palladium-catalyzed approach to intermolecular carbonylative C–H functionalization is described. This transformation is mediated by P^<i>t</i>Bu₃-coordinated palladium catalyst and allows the derivatization of a diverse range of heterocycles, including pyrroles, indoles, imidazoles, benzoxazoles, and furans. Preliminary studies suggest that this reaction may proceed via the catalytic formation of highly electrophilic intermediates. Overall, this provides with an atom-economical and general synthetic route to generate aryl-(hetero)­aryl ketones using stable reagents (aryl iodides and CO) and without the typical need to exploit pre-metalated heterocycles in carbonylative coupling chemistry

A Palladium-Catalyzed Carbonylation Approach to Acid Chloride Synthesis

We describe a new approach to acid chloride synthesis via the palladium-catalyzed carbonylation of aryl iodides. The combination of sterically encumbered phosphines (P^<i>t</i>Bu₃) and CO coordination has been found to facilitate the rapid carbonylation of aryl iodides into acid chlorides via reductive elimination from (^<i>t</i>Bu₃P)­(CO)­Pd­(COAr)­Cl. The formation of acid chlorides can also be exploited to perform traditional aminocarbonylation reactions under exceptionally mild conditions (ambient temperature and pressure), and with a range of weakly nucleophilic substrates

Chiral Phosphorus-Based 1,3-Dipoles: A Modular Approach to Enantioselective 1,3-Dipolar Cycloaddition and Polycyclic 2‑Pyrroline Synthesis

The design of a new class of chiral 1,3-dipoles for enantioselective cycloaddition reactions is reported. These phosphorus-based dipoles are easily formed (from imines, acid chlorides, and chiral phosphites), rigidly chiral, and undergo intramolecular alkene cycloaddition with high enantioselectivity. Overall, this provides a straightforward and modular approach to synthesize chiral 2-pyrrolines and pyrrolidines in up to 99% ee