Enantioselective Redox-Neutral Rh-Catalyzed Coupling of Terminal Alkynes with Carboxylic Acids Toward Branched Allylic Esters

We report on the first enantioselective variant of the atom-economic and redox-neutral coupling of carboxylic acids with terminal alkynes under rhodium catalysis utilizing the chiral, bidentate (<i>R</i>,<i>R</i>)-Cp-DIOP ligand. This represents the first example of this convenient asymmetric access to valuable branched allylic esters. The utility of this methodology is demonstrated by both a reaction performed on large scale and a short three-step synthesis of two naturally occurring γ-butyrolactones. A stereochemical model explaining the observed absolute configuration of the products based on DFT calculations is given

Mechanistic Investigations of the Rhodium Catalyzed Propargylic CH Activation

Previously we reported the redox-neutral atom economic rhodium catalyzed coupling of terminal alkynes with carboxylic acids using the DPEphos ligand. We herein present a thorough mechanistic investigation applying various spectroscopic and spectrometric methods (NMR, <i>in situ</i>-IR, ESI-MS) in combination with DFT calculations. Our findings show that in contrast to the originally proposed mechanism, the catalytic cycle involves an intramolecular protonation and not an oxidative insertion of rhodium in the OH bond of the carboxylic acid. A σ-allyl complex was identified as the resting state of the catalytic transformation and characterized by X-ray crystallographic analysis. By means of ESI-MS investigations we were able to detect a reactive intermediate of the catalytic cycle