Nickel-Catalyzed Intramolecular Desulfitative C—N Coupling: A Synthesis of Aromatic Amines

Abstract

A nickel-catalyzed intramolecular CN coupling reaction via SO2 extrusion is presented. The use of a catalytic amount of BPh3 allows the transformation to take place under much milder conditions (60 °C) than previously reported CN coupling reactions by CO or CO2 extrusion (160–180 °C). In addition, this method displays good functional group tolerance and versatility, as it can be applied to the synthesis of dialkyl aryl amines, alkyl diaryl amines, and triaryl amines. The robustness of the desulfitative CN coupling is demonstrated by three high-yielding gram-scale reactions.

Ni-catalyzed C–S bond construction and cleavage

“…Taking advantage of the strong coordination between B and O, the authors successfully reduced the reaction temperature by adding BPh 3 . 106…”

Photocatalytic Late-Stage Functionalization of Sulfonamides via Sulfonyl Radical Intermediates

“… 8 Furthermore, endeavors to demonstrate the synthetic utility of sulfonamides in hydroaminations, 9 as directing groups in C–H activation, 10 and as precursors for C–N coupling reactions, have been reported. 11 However, it is intriguing to note that in many medicinal agents, construction of the sulfonamide unit is often performed early in the synthetic route and that their latent reactivity is seldom exploited. This has resulted in sulfonamides being viewed as terminal functional groups.…”

“…With the importance of aza-sulfur pharmacophores continually growing, a diverse selection of methods has been established for their synthesis, with approaches to sulfonamides being most common . Furthermore, endeavors to demonstrate the synthetic utility of sulfonamides in hydroaminations, as directing groups in C–H activation, and as precursors for C–N coupling reactions, have been reported . However, it is intriguing to note that in many medicinal agents, construction of the sulfonamide unit is often performed early in the synthetic route and that their latent reactivity is seldom exploited.…”

Ni(cod)(duroquinone)-Catalyzed C–N Cross-Coupling for the Synthesis of N,N-Diarylsulfonamides

“…We determined that the low yields obtained for 3ak and 3ap were not due to thermal extrusion of SO 2 or Nicatalyzed loss of SO 2 ; these products are stable when heated in the presence and absence of Ni(cod)(DQ). 27 A variety of sulfonamides can be used as coupling partners (Figure 4). Sulfonamides bearing electron-donating substituents on either the N-aryl or S-aryl group generated higher yields of the products (3c and 3fb, 85% and 85%) compared to sulfonamides bearing electron-withdrawing substituents (3bb and 3hb, 60% and 47%).…”

“…Bromothiophenes can be coupled by using the sodium salts of the sulfonamides in the absence of additional bases ( 3ap and 3aq , 51% and 54%). We determined that the low yields obtained for 3ak and 3ap were not due to thermal extrusion of SO 2 or Ni-catalyzed loss of SO 2 ; these products are stable when heated in the presence and absence of Ni­(cod)­(DQ) …”