Summary The biaryl motif is a building block in many drugs, agrochemicals, and materials, and as such it is highly desirable as a synthesis target. The state-of-the-art process for biaryl synthesis from ubiquitous carboxylic acids is decarboxylative cross-coupling involving loss of carbon dioxide (CO 2 ). However, the scope of these methods is severely limited, mainly due to specific substitution required to promote decarboxylation. The present report implements a decarbonylative version with loss of carbon monoxide (CO) that enables to directly engage carboxylic acids in a Suzuki-Miyaura cross-coupling to produce biaryls as a general method with high cross-coupling selectivity using a well-defined Pd(0)/(II) catalytic cycle. This protocol shows a remarkably broad scope (>80 examples) and is performed in the absence of exogenous inorganic bases. In a broader context, the approach shows promise for routine applications in the synthesis of biaryls by carefully controlled decarbonylation of prevalent carboxylic acids.

Fleeting intermediates constitute dynamically stepwise mechanisms. They have been characterized in molecular dynamics trajectories, but whether these intermediates form a free energy minimum to become entropic intermediates remains elusively defined. We developed a computational protocol known as entropic path sampling to evaluate the entropic variation of reacting species along a reaction path based on an ensemble of trajectories. Using cyclopentadiene dimerization as a model reaction, we observed an entropy maximum along the reaction path which originates from an enhanced conformational flexibility as the reacting species enter into a flat energy region. As the reacting species further approach product formation, unfavorable entropic restriction fails to offset the potential energy drop, resulting in no free energy minimum along the post-TS pathway. Our results show that cyclopentadiene dimerization involves an entropy maximum that leads to dynamic intermediates with elongated lifetimes, but the reaction does not involve entropic intermediates.

Herein, we describe a highly selective method for the direct decarbonylative step-down reduction of carboxylic acids to arenes, proceeding via well defined Pd(0)/(II) catalytic cycle.

The Lewis acid-promoted generation of destabilized vinyl cations from β-hydroxy diazo ketones leads to an energetically favorable 1,2-shift across the alkene followed by an irreversible C–H insertion to give cyclopentenone products. This reaction sequence overcomes typical challenges of counter-ion trapping and rearrangement reversibility of vinyl cations and has been used to study the migratory aptitudes of nonequivalent substituents in an uncommon C­(sp2) to C­(sp) vinyl cation rearrangement. The migratory aptitude trends were consistent with those observed in other cationic rearrangements; the substituent that can best stabilize a cation more readily migrates. However, density functional theory calculations show that the situation is more complex. Selectivity in the formation of one conformational isomer of the vinyl cation and facial selective migration across the alkene due to an electrostatic interaction between the vinyl cation and the adjacent carbonyl oxygen work in concert to determine which group migrates. This study provides valuable insight into predicting migration preferences when applying this methodology to the synthesis of structurally complex cyclopentenones that are differentially substituted at the α and β positions.