Nickel-Catalyzed Kumada Coupling of Boc-Activated Aromatic Amines via Nondirected Selective Aryl C–N Bond Cleavage

Abstract

A nickel-catalyzed Kumada coupling of aniline derivatives was developed by selective cleavage of aryl C–N bonds under mild reaction conditions. Without preinstallation of an ortho directing group on anilines, the cross-coupling reactions of Boc-protected aromatic amines with aryl Grignard reagents afforded unsymmetric biaryls. Mechanistic studies by DFT calculations revealed that the nickel-mediated C–N bond cleavage is the rate-limiting step.

Electrophilicity Scale of Activated Amides: 17O NMR and 15N NMR Chemical Shifts of Acyclic Twisted Amides in N−C(O) Cross‐Coupling

“…Ta ble 2, entry 2). [18b] Ta ken together,t he data indicate that (1) the charged ensity at the nitrogen atom in twisted acyclica mides follows the inductive effect destabilizing N-substituent, (2) 15 NNMR can be used as ap redictive tool of the carbonyl electrophilicity in this class of compounds. However,i ts hould be noted that amide 8 (R = Ms) is an outlier,w hile aromatic N-acyl-pyrazole derivative 6 is not considered in this analysis due to aromatic nitrogen…”

“…ONMR and 15 NNMR chemical shifts of acyclic twisted and destabilized acyclic amides that have recently received major attention as precursors in N-C(O) cross-coupling by selectiveo xidative addition as well as precursors in electrophilic activation of N-C(O) bonds. Most crucially, we demonstrate that acyclic twisted amides feature electrophilicity of the carbonyl group that ranges between that of acida nhydrides and acid chlorides.…”

“…[14] Moreover,t he recently discovered s NÀCs cissionreactions capitalize on diminishing amidic resonanceincommonacyclic twistedamides. [15] However,d espite the fundamental importance of acyclic twisted amides in various areas of chemistry and biochemistry, electrophilicity scale of these important amides has not been reported.T he lack of electrophilic scale prevents the rational development of synthetic technologies, and more broadly affects the perceptiono ft he acyclic amide bond as the most stable carboxylic acid derivative as outlined in all undergraduate organic chemistry textbooks. [1,2,16] Herein, we report electrophilicity scale of acyclic twisted and destabilized acyclic amides by using 17 ONMR and 15 NNMR chemicals hifts.…”

“…We were further intrigued to measure 15 Figure 4p resentsagraphical representation of 15 NNMR shifts vs. amide. Remarkably,w e found an excellent linear correlation between 17 ONMR chemical shifts and 15 N NMR chemical shifts in the studies acyclic twisted amides (R 2 = 0.92, outlier analysis: N,N-Ph/Ms, 8) ( Figure 5).…”

“…Remarkably,w e found an excellent linear correlation between 17 ONMR chemical shifts and 15 N NMR chemical shifts in the studies acyclic twisted amides (R 2 = 0.92, outlier analysis: N,N-Ph/Ms, 8) ( Figure 5). Interestingly,t he most twisted amides 10-12 are characterized by the 15 ppm, which is in the range nitrogen of pyrroles (158 ppm, C 4 H 4 NH) and isonitriles (162 ppm, MeNC) rather than typical N,N-di-alkyl amides (104 ppm, DMAC cf. Ta ble 2, entry 2).…”