| Popis: |
Palladium-catalyzed cross-coupling reactions have found extensive use in the synthesis of biaryls and aryl-substituted heteroaromatics. Although powerful, the classical palladium-catalyzed cross-coupling reactions (Hiyama, Negishi, Kumada, Stille, Suzuki) can suffer from common limitations such as extensive reaction times, environmentally unfriendly by-products or reagents, and are atom inefficient. This has generated much attention in the past decades to further improve upon, or expand this type of reactivity, leading to new alternatives. Unfortunately, many newly developed alternatives require the extensive use of co-catalysts and/or additives, or lack selectivity. Extending upon the decarboxylative cross-coupling protocol previously developed by Forgione and Bilodeau, this work utilizes heteroaromatic sulfinates as nucleophilic coupling partners. Heteroaromatic sulfinates have shown to be readily synthesized by lithiation of the corresponding heteroaromatic followed by quenching with sulfur dioxide gas, requiring little to no purification. Following extensive optimization, an environmentally benign desulfinylative cross-coupling protocol was developed requiring no co-catalyst or additives. The cross-coupling of heteroaromatic sulfinates and aryl bromides occurs in predominantly aqueous media utilizing an inexpensive catalyst system employing a palladium (II) source, and requires short reaction times. The scope of this newly developed reactivity encompasses thiophene and furan sulfinates, which can be coupled with electron-deficient, electron-neutral and electron-rich aryl bromides in moderate to near quantitative yields. |
