Suzuki−Miyaura Coupling of Aryl Carbamates, Carbonates, and Sulfamates

Abstract

The first Suzuki-Miyaura cross-coupling of carbamates, carbonates, and sulfamates is described. The method presented provides a powerful means to use simple derivatives of phenol as precursors to polysubstituted aromatic compounds, as exemplified by a concise synthesis of the antiinflammatory drug flurbiprofen.Transition metal-catalyzed cross-coupling reactions continue to play a vital role in modern synthetic chemistry. 1 Although cross-couplings of aryl halides and triflates are most common, recent studies have demonstrated the successful cross-coupling of simple and affordable phenolic derivatives. In 2008, notable achievements in this area include the Suzuki-Miyaura coupling of electron deficient aryl methyl ethers by Chatani, 2 and the Suzuki-Miyaura coupling of aryl pivalates, 3 which was reported simultaneously by our group, 4a and the group of Shi. 4b A conceptual advantage of these technologies, compared to methodologies involving halides and sulfonates, is the potential to direct the installation of other functional groups onto an aromatic ring prior to cross-coupling (Figure 1). In practice, however, the ability to use methyl ethers (R = Me) and pivalates (R = OC(O)CMe 3 ) in this sense is somewhat limited. 5 Given the importance of polyfunctionalized aromatics in medicine, ligands for catalysis, and materials chemistry, we sought to address this problem. In this communication, we describe the first Suzuki-Miyaura couplings of aryl carbamates, carbonates, and sulfamates. Moreover, we disclose a concise synthesis of the anti-inflammatory drug flurbiprofen (1) 6 using this methodology.neilgarg@chem.ucla.edu. Supporting Information Available: Detailed experimental procedures and compound characterization data (PDF). This material is available free of charge via the Internet at http://pubs.acs.org. Of the potential phenolic derivatives to be studied, aryl carbamates and sulfamates were considered ideal because of their ready availability and pronounced stability to a variety of reaction conditions. Furthermore, these substrates can be used to direct the installation of functional groups at both the ortho and para positions (via ortho-lithiation chemistry pioneered by Snieckus7 and electrophilic aromatic substitution,8 respectively). Although nickelcatalyzed Kumada couplings of these substrates have been documented, 7b,9 cross-coupling under milder, more attractive Suzuki-Miyaura conditions have not been reported. Of note, the oxidative addition of a metal into the aryl C-O bond of an aryl carbamate or sulfamate presents a considerable challenge. NIH Public AccessDespite this difficulty, we have found that the Suzuki-Miyaura coupling of aryl carbamates with aryl boronic acids proceeds in the presence of NiCl 2 (PCy 3 ) 2 , K 3 PO 4 , and heat, with toluene as solvent (Table 1). That NiCl 2 (PCy 3 ) 2 could be used to facilitate the desired transformation is advantageous,10 as this readily available complex shows marked stability to air and water, and can be used on the bench-top rather than in a gl...

An Improvement of Nickel Catalyst for Cross-coupling Reaction of Arylboronic Acids with Aryl Carbonates by Using a Ferrocenyl Bisphosphine Ligand

“…10,11 However, the use of a carbonate leaving group has been limited to naphthyl substrates. Here, we developed a new catalyst for the reaction of aryl carbonates.…”

Nickel-Catalyzed Cross-Coupling Reactions of Unreactive Phenolic Electrophiles via C–O Bond Activation

“…Garg reported that aryl pivalates can be coupled with arylboronic acids in the presence of a NiCl 2 (PCy 3 ) 2 catalyst [42], while Shi employed arylboroxines as nucleophiles in the presence of 0.88 equivalents of water, allowing for the cross-coupling of aryl acetates, pivalates and benzoates [43]. Both groups also extended their nickel-catalyzed protocols to the Suzuki-Miyaura type reactions of aryl carbamates [44,45]. Snieckus simultaneously reported on the nickel-catalyzed cross-coupling of aryl carbamates using a 10:1 mixture of an aryl carbamate and an arylboroxine [46,47].…”

State‐of‐the‐Art in Metal‐Catalyzed Cross‐Coupling Reactions of Organoboron Compounds with Organic Electrophiles

“…Direct cross-coupling reactions of aryl carbamates, however, are notoriously difficult because of the carbonyl C-O bond that is weaker than the Ar-O bond (according to Houk's calculations, the energy difference of the two bonds in question is 22.4 kcal/mol) [68]. Similar to the scenario with aryl carboxylates, the groups of Garg [69] and Snieckus [70] were able to utilize Ni-catalyzed systems to overcome this difficulty, successfully realizing cross-coupling reactions of various aryl carbamates with aryl boronic acids or boroxines (Eqs. (15) and (16) boroxine (1 : 10 ratio) is essential to obtain more reliable and reproducible results.…”

“…In addition to carbamates, sulfamates are also valuable electrophiles in Suzuki-Miyaura cross-couplings. Garg and coworkers [68,69] found that the same catalytic system could be applied to cross-coupling reactions of organosulfamates (Eq. (15), Scheme 2.19).…”