Sustainable Access to π-Conjugated Molecular Materials via Direct (Hetero)Arylation Reactions in Water and under Air

Abstract

Direct (hetero)arylation (DHA) is playing a key role in improving the efficiency and atom economy of C–C cross coupling reactions, so has impacts in pharmaceutical and materials chemistry. Current research focuses on further improving the generality, efficiency and selectivity of the method through careful tuning of the reaction conditions and the catalytic system. Comparatively fewer studies are dedicated to the replacement of the high-boiling-point organic solvents dominating the field and affecting the overall sustainability of the method. We show herein that the use of a 9:1 v/v emulsion of an aqueous Kolliphor 2 wt% solution while having toluene as the reaction medium enables the preparation of relevant examples of thiophene-containing π-conjugated building blocks in high yield and purity.

Sustainable Pd-Catalyzed Direct Arylation of Thienyl Derivatives with (Hetero)aromatic Bromides under Air in Deep Eutectic Solvents

“…As we could expect, recurring to flash chromatography caused a significant increase of E -factors, with values ranging between 351 and 4279 ( 5b , d , k ). However, all our values look similar to others calculated according to the same principles. , …”

“…However, all our values look similar to others calculated according to the same principles. 77,82 Eco-scale values ranged from 41 to 81: according to the original paper by Van Aken et al, 66 the reaction conditions in DESs can thus be ranked as "excellent" (Eco-scale >75) for the preparation of compounds 5c,e,g,i, and "acceptable" (Eco-scale >50) for compounds 5a,b,f,h,j. Therefore, "inadequate" (Ecoscale <50) values were obtained only for the preparation of 5d,k, mostly due to the lower isolated yields of those compounds.…”

Sustainable protocols for direct C–H bond arylation of (hetero)arenes

“…Beverina et al reported a representative example of sustainable direct C-H bond ortho-arylation of octafluorobiphenyl with an aryl bromide, performed in Kolliphor 2% in H 2 O/ toluene (9 : 1 v/v) mixture. 131 One of the most appealing features of the protocol is definitely the application of a micellar catalysis: the use of Kolliphor, which is an FDA-approved surfactant obtained by the reaction of castor oil with ethylene oxide, allowed for the development of micellar catalytic systems within which direct arylation reactions may occur. The key concept of micellar catalysis is related to the preferential accumulation of organic compounds within the lipophilic pockets formed by the self-assembly of surfactants in H 2 O.…”

“…Beverina and co-workers reported an extensive investigation of sustainable direct C-H bond arylation reactions of 2-(nhexyl)thiophene, 2,2′-bithiophene, 3,4-ethylenedioxythiophene and thieno[3,4-c]pyrrole-4,6-dione with aryl bromides, performed in Kolliphor 2% in H 2 O/toluene (9 : 1 v/v) mixture. 131 The use of Kolliphor allowed for the application of a micellar catalysis approach: direct C-H arylation reactions occurred within the lipophilic pockets of micelles, where thanks to the high concentration and local polarity effects, reactions are very efficient. In addition to the use of a micellar catalysis, the overall sustainability of the process was further confirmed by E-factors (i.e., the mass ratio between organic wastes and product) in all cases in the order of 10 2 (between 179 and 556), which are low values, considering that they also include purification.…”

“…141 More appealing from a sustainability point of view was instead the study of Beverina et al, who described a protocol for the direct C-H bond arylation of thieno[3,2-b]thiophene with aryl bromides under the micellar catalysis approach, performed in Kolliphor 2% in H 2 O/ toluene (9 : 1 v/v) mixture as the solvent. 131…”