Catalyst speciation and deactivation in the ruthenium-mediated transformation of ethynyl-β-ionol to α,β-unsaturated esters for vitamin A synthesis

Abstract

The catalytic anti-Markovnikov addition of carboxylic acids to propargylic alcohols to furnish unsaturated esters is an appealing transformation due to its mild conditions, good selectivity and high atom economy. Treatment of the γ-hydroxy α,β-unsaturated esters with Brønsted acids gives access to enals which serve as important building blocks for the production of vitamins and aroma compounds from biogenic terpenes. Unfortunately, current turnover numbers (TON) for this ruthenium-catalysed reaction are too low for industrial application (<100). Here we present a detailed investigation into the speciation and deactivation of the most active [(dppe)Ru^II(MA)₂] catalyst in the anti-Markovnikov addition of carboxylic acids to ethynyl-β-ionol. Multi-nuclear high resolution FlowNMR spectroscopy gave insight into a range of kinetically relevant carboxylate complexes, allowed quantifying catalyst deactivation kinetics, and showed a pronounced influence of the carboxylic acid on catalyst stability. Systematic optimisation of reaction parameters resulted in significant improvements in catalyst productivity to reach TONs of >450 for ethynyl-β-ionol and >2000 for phenylacetylene.