Discovery and Comparison of Homogeneous Catalysts in a Standardized HOT‐CAT Screen with Microwave‐Heating and qNMR Analysis: Exploring Catalytic Hydration of Alkynes.

A HOT‐CAT (homogeneous thermal catalysis) screen using microwave‐heating and quantitative NMR (qNMR) analysis has been developed for identification and comparison of catalyst activity in homogeneous metal‐based catalysis. The hydration of terminal alkynes to ketones or aldehydes served as a model reaction in this proof‐of‐concept study. Key aspects of the screen are the use of a high‐temperature setting (e. g. 160 °C) at a fixed, short reaction time (e. g. 15 min) for all samples. Analysis of crude reaction mixtures by a standardized, quantitative 1H NMR protocol gives a comprehensive picture of catalyst chemo‐ and regioselectivity, which permits broad comparisons and the discovery of non‐target reactivity. For catalytic alkyne hydration, data for 105 runs involving 81 catalyst systems with 15 different metals is presented. The activity of all established catalyst systems was reproduced, and new catalyst systems with Markovnikov hydration selectivity were discovered and applied to preparative runs, namely Cu2O−CSA (CSA=camphorsulfonic acid), Co(OAc)2−tetraphenylporphyrin−CSA and [IrCl(COD)]−CSA. [ABSTRACT FROM AUTHOR]