FELIX A. KORTMANN, PETER HERMSEN, ANDRÉ H. M. DE VRIES
InnoSyn B.V., Geleen, The Netherlands

Abstract

Visible light-induced decarboxylative borylation was successfully implemented and scaled-up as key step in a novel route towards vaborbactam. The transformation was carried out in a falling-film photoreactor on a 10 g-scale. Under mild conditions (420 nm blue LEDs, RT, 4 h) the N-hydroxyphtalimide redox active ester was converted to the corresponding pinacolato boronates in 78% isolated yield. Other borylation methodologies, both photochemical as well as organometallic, showed inferior results in comparison experiments.

INTRODUCTION

Photochemistry comprises the chemical reactions of atoms or molecules that have been electronically excited by light of an the appropriate wavelength, which can be absorbed by the substrate. Thus, an overlap in wavelengths between the emitted light and those absorbed by the substrate is required. Alternatively, a sensitizer or photocatalyst can be used to absorb radiation and transfer its energy to the substrate (1).

According to the Lambert-Beer law,  the intensity of the light decreases logarithmically with the path length traveled through the medium. For practical reasons, most photochemical reactions are done in solution. In industrial photochemistry, high substrate concentrations are preferred. However, for substrates with an assumed molar extinction coefficient of 350, already at a mere 0.5 mol/l concentration of substrate, the incoming light is absorbed within a 0.1 mm thick zone (see Figure 1, left, grey curve). The photo reaction takes place exclusively in this zone and as consequence, most of the reaction medium in traditional immersion type photo reactors (Pförtne ...