Divergent rhodium-catalyzed electrochemical vinylic C–H annulation of acrylamides with alkynes

Abstract

Abstractα-Pyridones and α-pyrones are ubiquitous structural motifs found in natural products and biologically active small molecules. Here, we report an Rh-catalyzed electrochemical vinylic C–H annulation of acrylamides with alkynes, affording cyclic products in good to excellent yield. Divergent syntheses of α-pyridones and cyclic imidates are accomplished by employing N-phenyl acrylamides and N-tosyl acrylamides as substrates, respectively. Additionally, excellent regioselectivities are achieved when using unsymmetrical alkynes. This electrochemical process is environmentally benign compared to traditional transition metal-catalyzed C–H annulations because it avoids the use of stoichiometric metal oxidants. DFT calculations elucidated the reaction mechanism and origins of substituent-controlled chemoselectivity. The sequential C–H activation and alkyne insertion under rhodium catalysis leads to the seven-membered ring vinyl-rhodium intermediate. This intermediate undergoes either the classic neutral concerted reductive elimination to produce α-pyridones, or the ionic stepwise pathway to produce cyclic imidates.

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…Mei and co-workers continued on their electrochemical transition metal catalysis strategy 334 and elaborated the synthesis of α-pyridones and α-pyrones via electrochemical C−H activation (Scheme 193). 335 In this report, the authors employed a series of acrylamides and alkynes. Depending on the substituents on nitrogen atom and reaction temperature, a variety of structurally diverse α-pyridones and α-pyrones were produced accordingly in excellent yields.…”

Alkyne–alkenyl coupling at a diruthenium complex

“…9,27–30 To the best of our knowledge, the coupling reaction between simple alkenyl ligands and external alkynes has been unexplored heretofore. On the other hand, the coupling of alkynes with alkenyl molecules is of ultimate relevance in metal-mediated organic synthesis, 31–36 and the alkyne insertion into metal–alkenyl bonds constitutes a key step of the important Dötz reaction. 37–39…”

The Renaissance of Electro‐Organic Synthesis for the Difunctionalization of Alkenes and Alkynes: A Sustainable Approach

“…However it was seen that Ntosyl and N-phenyl acrylamides yield the corresponding αpyrones and α-pyridones respectively (Scheme 58). [117] The electrochemical reaction proceeds by CÀ H activation, alkyne addition and migratory addition to yield the seven membered rhodacycle intermediate. This intermediate can either undergo reductive elimination to yield α-pyridone or ionic reductive elimination to form α-pyrones.…”