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

Functional Group Transposition: A Palladium-Catalyzed Metathesis of Ar–X σ‑Bonds and Acid Chloride Synthesis

We describe the development of a new method to use palladium catalysis to form functionalized aromatics: via the metathesis of covalent σ-bonds between Ar–X fragments. This transformation demonstrates the dynamic nature of palladium-based oxidative addition/reductive elimination and offers a straightforward approach to incorporate reactive functional groups into aryl halides through exchange reactions. The reaction has been exploited to assemble acid chlorides without the use of high energy halogenating or toxic reagents and, instead, via the metathesis of aryl iodides with other acid chlorides

Palladium Catalyzed, Multicomponent Synthesis of Fused-Ring Pyrroles from Aryl Iodides, Carbon Monoxide, and Alkyne-Tethered Imines

A palladium-catalyzed multicomponent route to polycyclic pyrroles is described. Pd­(P^<i>t</i>Bu₃)₂ was found to catalyze the coupling of (hetero)­aryl iodides, two equivalents of carbon monoxide and alkyne-tethered imines into 1,3-dipoles (Münchnones), which undergo spontaneous, intramolecular 1,3-dipolar cycloaddition to form polycyclic pyrroles. The systematic variation of the alkyne, tethered-imine, or aryl iodide can allow the buildup of a range of pyrrole derivatives, where any of the substituents can be independently varied. In addition, the same palladium catalyst can be employed in an initial Sonogashira-type coupling with aryl iodides, which upon the addition of CO can allow the novel tandem catalytic, five component synthesis of diversely substituted products

Palladium-Catalyzed Carbonylation of Aryl Chlorides to Electrophilic Aroyl-DMAP Salts

The palladium-catalyzed carbonylative coupling of aryl chlorides and 4-dimethylaminopyridine (DMAP) to generate electrophilic aroyl-DMAP salts is described. In contrast to classical carbonylation reactions, which often require nucleophiles to react with weakly electrophilic palladium-acyl intermediates, the high electrophilicity of aroyl-DMAP salts allows the acylation of a broad range of substrates. This transformation is mediated by a palladium-Xantphos catalyst, and mechanistic studies suggest the combination of ligand steric strain together with Pd(0) stabilization allows both the reductive elimination of a reactive ArCO–DMAP product and oxidative addition of the strong aryl-chloride bond. Overall, this transformation allows the generation of amides and esters from aryl chlorides with an array of nucleophiles and with good functional group compatibility

Multicomponent Coupling Approach to Cross-Conjugated Polymers from Vanillin-Based Monomers

We describe the use of vanillin-based monomers as a renewable feedstock for the synthesis of cross-conjugated polymers. This transformation exploits a catechyl-substituted phosphonite mediated multicomponent polymerization to convert vanillin-derived diimines, commercial diacid chlorides, and simple alkynes or alkenes into conjugated pyrrole-based polymers. The flexibility of the multicomponent polymerization has allowed for the efficient formation of families of vanillin-derived fluorescent polymers with tunable properties. This includes coupling vanillin with furan-based acid chlorides as the first cross-conjugated polymer composed of both components of lignocellulosic biomass

Intramolecular C–C Bond Coupling of Nitriles to a Diimine Ligand in Group 7 Metal Tricarbonyl Complexes

Dissolution of M­(CO)₃(Br)­(L^Ar) [L^Ar = (2,6-Cl₂-C₆H₃-NCMe)₂CH₂] in either acetonitrile [M = Mn, Re] or benzonitrile (M = Re) results in C–C coupling of the nitrile to the diimine ligand. When reacted with acetonitrile, the intermediate adduct [M­(CO)₃­(NCCH₃)­(L^Ar)]Br forms and undergoes an intramolecular C–C coupling reaction between the nitrile carbon and the methylene carbon of the β-diimine ligand

Copper-Catalyzed Petasis-Type Reaction: A General Route to α-Substituted Amides From Imines, Acid Chlorides, and Organoboron Reagents

A copper-catalyzed Petasis-type reaction of imines, acid chlorides, and organoboranes to form α-substituted amides is described. This reaction does not require the use of activated imines or the transfer of special units from the organoboranes and represent a useful generalization of the Petasis reaction

From Aryl Iodides to 1,3-Dipoles: Design and Mechanism of a Palladium Catalyzed Multicomponent Synthesis of Pyrroles

A palladium-catalyzed multicomponent synthetic route to polysubstituted pyrroles from aryl iodides, imines, carbon monoxide, and alkynes is described. To develop this reaction, a series of mechanistic studies on the [Pd­(allyl)­Cl]₂/P^<i>t</i>Bu₃ catalyzed synthesis of imidazolinium carboxylates from aryl iodides, imines, and carbon monoxide were first performed, including model reactions for each individual step in the transformation. These show that this reaction proceeds in a concurrent tandem catalytic fashion, and involves the in situ formation of acid chlorides, <i>N</i>-acyl iminium salts, and ultimately 1,3-dipoles, i.e., Münchnones, for subsequent cycloaddition. By employing a Pd­(P^<i>t</i>Bu₃)₂/Bu₄NCl catalyst, this information was used to design the first four-component synthesis of Münchnones. Coupling the latter with 1,3-dipolar cycloaddition with electron deficient alkynes or alkenes can be used to generate diverse families of highly substituted pyrroles in good yield. This represents a modular and streamlined new approach to this class of heterocycles from readily accessible starting materials