Understanding the Differential Performance of Rh₂(esp)₂ as a Catalyst for C−H Amination

Abstract

The continued development of selective and efficient reaction technologies for C-H amination necessitates a deeper understanding of the factors that affect catalyst stability. 1 Our earliest mechanistic studies on carbamate and sulfamate ester oxidation indicated that dinuclear rhodium-tetracarboxylate catalysts were subject to rapid ligand exchange, a process believed to initiate catalyst decomposition. 2 These findings motivated the design and synthesis of Rh 2 (esp) 2 , a complex derived from two, chelating bis-carboxylate ligands, which exhibits superior performance for C-H amination reactions (Figure 1). 3 While it appears that Rh 2 (esp) 2 is less prone to ligand exchange than other simple tetracarboxylate systems (e.g., Rh 2 (OAc) 4 ), we have noted an alternate pathway for catalyst arrest that involves competing one-electron oxidation to a mixed-valence Rh 2+ /Rh 3+ dimer. We now provide evidence that reduction of the Rh 2+ /Rh 3+ dimer and reconstitution of the active Rh 2+ /Rh 2+ catalyst is occurring under the oxidizing reaction conditions. The rate of this peculiar reduction event is clearly coupled to catalyst turnover number and reaction efficiency. These data have led us to propose that the differential performance of Rh 2 (esp) 2 derives from the unusual kinetic stability of the mixed-valence dimer vis-à-vis other dirhodium tetracarboxylate complexes.The advent of Rh 2 (esp) 2 has enabled the efficient and selective intermolecular amination of benzylic C-H bonds. 4 When this reaction is conducted, a rather striking color change from green to deep red is witnessed as the reagents are mixed. The species responsible for the red color has been identified as a mixed-valence [Rh 2 (esp) 2 ] + dimer. 4 A large body of circumstantial evidence appears to correlate the formation of this red complex with the reactivity of the C-H bond undergoing oxidation (i.e., [Rh 2 (esp) 2 ] + forms when the C-H bond is slow to intercept the reactive Rhnitrene intermediate). Similar phenomena are observed with tetracarboxylate complexes such as Rh 2 (O 2 C n Pr) 4 , though the effectiveness of such catalysts for intermolecular amination reactions does not compare with Rh 2 (esp) 2 . Given the nearly identical potentials for one-electron oxidation of Rh 2 (esp) 2 and Rh 2 (O 2 C n Pr) 4 (1130 mV and 1150 mV vs SCE, respectively), we hypothesized that differences in catalyst performance between these two Rh complexes are linked to differences in the kinetic stability of the respective mixed-valence species. To test this idea, we have generated the one-electron oxidized adduct, [Rh 2 (esp) 2 ] + , by treating Rh 2 (esp) 2 with Cl 3 CCH 2 OSO 2 NH 2 (TcesNH 2 ) and PhI(O 2 C n Pr) 2 in the absence of substrate. 5,6 UV/visible spectroscopy confirms that this species is persistent in solution for >5 min (Figure 2). 7 Conversely, the solution of mixed-valence dimer derived from Rh 2 (O 2 C n Pr) 4 bleaches to a pale yellow within 60 s of mixing the reactants. An apparent link between reaction performance and the lifetime of th...

Capturing fleeting intermediates in a catalytic C–H amination reaction cycle

“…Structural assignments of the m/z 1,186.9057 signal as [5] + and the m/z 1,080.0535 signal as [1•3] + are supported by the close correspondence of predicted and experimental isotope profiles ( Fig. 4C and Fig.…”

“…In our experience, the oxidation of substrate by Rh-nitrene 6 seems to correlate with competitive formation of a mixed-valent (Rh 2+ /Rh 3+ ) dimer 8 that visibly colors the reaction solution red. Previous studies show that this red species is generated when Rh 2 (esp) 2 1, sulfamate 2, and oxidant 3 are mixed in solution (e.g., 0.3 mM 1 in chlorobenzene) (4,5,11). In this report, we provide direct evidence for the formation of species 8.…”

“…mass spectrometry | transient intermediates | C-H oxidation | catalysis C atalytic methods for selective C-H oxidation rely on the exquisite choreography of a series of ligand substitution and redox events (1,2) and in some instances, the controlled generation of a hyperreactive electrophile (3)(4)(5). The Du Bois laboratory has developed an amination protocol that uses the catalyst bis [rhodium(α,α,α′,α′-tetramethyl-1,3-benzenedipropionic acid)], hereafter designated as Rh 2 (esp) 2 , to promote both intra-and intermolecular oxidation reactions (1,2).…”

“…+ , which appears to result from reaction of the nitrenoid oxidant (4,5,11). The fast rates of the on-and off-path steps in this catalytic process and the transient nature of the reactive Rh-nitrene have confounded direct detection of many of the proposed reaction intermediates.…”

Rhodium‐Catalyzed Synthesis of 2,3‐Disubstituted Indoles from β,β‐Disubstituted Stryryl Azides

“…[1] Sequential reaction processes that involve metal nitrenes are rare despite their electrophilicity, [2] which enables reaction with carbonhydrogen bonds or olefins. [3][4][5][6] Our mechanistic study of rhodium(II)-catalyzed carbazole formation from biaryl azides which suggested that CÀN bond formation preceded CÀH bond cleavage through a 4p-electron-5-atom electrocyclization. [7] Consequently, we anticipated that substrates lacking functionalizable C À H bonds might participate in a migratorial process where a new C À C bond is formed in addition to the C À N bond.…”