Strategies for successful Suzuki-Miyaura cross-couplings with thienylboronic acids: From model studies to dye structures

Abstract

Suzuki-Miyaura cross-coupling is a convenient way for preparing thienyl containing dyes and bioactive molecules. However, reactions with thienylboronic acids can be troublesome. To understand these reactions in more depth, we herein present our investigation into the cross-coupling of (5-formylthiophen-2-yl)boronic acid with 4-bromoanisole as a model reaction. The study includes variations of catalyst, base, aryl halide type, temperature and reaction medium. A key to succeed with such cross-couplings is a highly active catalyst, and sufficient solubility of both the boronic acid and the aryl halide. XPhos precatalysts proved to be the best system for the model reaction, while other catalysts might be applicable provided that more boronic acid is added, or an aryl iodide is used as cross-coupling partner. The XPhos 4th generation precatalyst was also efficient for the construction of mono- and di-thiophene-2-carbaldehyde substituted phenothiazines and a triarylamine dye precursor. However, each cross-coupling pair needs fine tuning of the reaction medium to maximize yield.