Suzuki−Miyaura Cross-Coupling of Aryl Carbamates and Sulfamates: Experimental and Computational Studies

Abstract

The first Suzuki–Miyaura cross-coupling reactions of the synthetically versatile O-aryl carbamate and O-sulfamate groups is described. The transformations utilize the inexpensive, bench-stable catalyst NiCl2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups (EDGs, EWGs) are tolerated, in addition to those that possess ortho substitutents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative additions with carbamates and sulfamates occur via a five-centered transition state, resulting in the exclusive cleavage of the Ar–O bond. Water is found to stabilize the Ni–carbamate catalyst resting state, and thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest.

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

“…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]. A close inspection of the reactions conditions developed for Suzuki-Miyaura cross-couplings for aryl esters and carbamates indicates that the presence of a suitable amount of water is crucial for achieving an efficient catalysis.…”

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

“…This advantage along with other attributes such as ready availability and stability under a variety of different conditions make them attractive substrates in the Suzuki-Miyaura cross-coupling reaction. 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.…”

“…In order to understand the selective Ar-O bond oxidative addition over the weaker carbonyl C-O bond, Houk and coworkers conducted DFT calculations on the possible transition states for the oxidatively inserted Ni(II) species [68]. As expected from the experimental outcome, the five-centered cyclic transition state 100 that arose from the selective cleavage of the Ar-O bond was found to be lower in energy compared to the three-centered transition state 101 that arose from selective carbonyl C-O bond cleavage.…”

“…To demonstrate the advantages associated with utilizing carbamates as crosscoupling partners, a synthetic application of the methodology was reported by Garg, Snieckus, and coworkers (Scheme 2.20) [68]. Thus, in this synthesis of disubstituted pyridine 108, the carbamate group of 105 was first used as a directing group for the installation of a boronyl substituent through DoM.…”

“…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).…”