Csp2-H functionalization of phenols: an effective access route to valuable materials via Csp2-C bond formation.

In the vast majority of top-selling pharmaceutical and industrial products, phenolic structural motifs are highly prevalent. Non-functionalized simple phenols serve as building blocks in the synthesis of value-added chemicals. It is worth mentioning that lignin, being the largest renewable biomass source of aromatic building blocks in nature, mainly consists of phenolic units, which enable the production of structurally diverse phenols. Given their remarkable applicability in the chemical value chain, many efforts have been devoted to increasing the molecular complexity of the phenolic scaffold. Among the key techniques, direct functionalization of Csp2-H is a powerful tool, enabling the construction of new Csp2-C bonds in an economical and atomic manner. Herein we present and summarize the large plethora of direct Csp2-H functionalization methods that enables scaffold diversification of simple, unprotected phenols, leading to the formation of new Csp2-C bonds. In this review article, we intend to summarize the contributions that appeared in the literature mainly in the last 5 years dealing with the functionalization of unprotected phenols, both catalytic and non-catalytic. Our goal is to highlight the key findings and the ongoing challenges in the stimulating and growing research dedicated to the development of new protocols for the valorization of phenols.

POLITAG-M-F as Heterogeneous Organocatalyst for the Waste-Minimized Synthesis of ß-Azido Carbonyl Compounds in Batch and under Flow Conditions.

We herein report a waste minimization protocol for the ß-azidation of α,ß-unsaturated carbonyl compounds using TMSN3. The selection of the appropriate catalyst (POLITAG-M-F), in combination with the reaction medium, resulted in enhanced catalytic efficiency and a low environmental footprint. The thermal and mechanical stability of the polymeric support allowed us to recover the POLITAG-M-F catalyst for up to 10 consecutive runs. The CH3CN:H2O azeotrope has a 2-fold positive effect on the process, increasing the efficiency of the protocol and minimizing waste generation. Indeed, the azeotropic mixture, used as a reaction medium and for the workup procedure, was recovered by distillation, leading to an easy and environmentally friendly procedure for product isolation in high yield and with a low E-factor. A comprehensive evaluation of the environmental profile was performed by the calculation of different green metrics (AE, RME, MRP, 1/SF) and a comparison with other literature available protocols. A flow protocol was defined to scale-up the process, and up to 65 mmol of substrates were efficiently converted with a productivity of 0.3 mmol/min.