New insights into the biphasic “CO-free” Pauson-Khand cyclisation reaction through combinedin situspectroscopy and multiple linear regression modelling

Abstract

“CO-free” carbonylations are catalytic reactions, which strive to replace toxic synthesis gas with less harmful surrogate molecules like formaldehyde. This study sheds light on the mechanism of the biphasic, Rh-catalysed Pauson-Khand type cyclisation reaction by applyingin situRaman spectroscopy together with NMR, dynamic light scattering measurements, and quantum chemical calculations. The reaction is particularly challenging to analyse as the Rh-catalyst features different ligands in the aqueous and organic phase. To tackle this challenge, a novel approach was designed, couplingin situRaman spectroscopy with an advanced data analysis model in the form of multiple linear regression. This fruitful combination of highly specific vibrational spectroscopy with state-of-the-art data analysis allowed not only identification of a new reaction mechanism, but also identification of parameters to accelerate the “CO-free” Pauson-Khand cyclisation,i.e.using mononuclear Rh-phosphine complexes with labile ligands, small organic micelles formed by an increased surfactant concentration, low formaldehyde concentration, and elevated temperature. This novel knowledge-driven optimisation protocol is superior to simple qualitative optimization routines and can be transferred to other reactions and spectroscopy techniques.