Metal-catalyzed nitrogen-atom transfer methods for the oxidation of aliphatic C-H bonds

Abstract

For more than a century, chemists have endeavored to discover and develop reaction processes that enable the selective oxidation of hydrocarbons. In the 1970s, Abramovitch and Yamada described the synthesis and electrophilic reactivity of sulfonyliminoiodinanes (RSO(2)N═IPh), demonstrating the utility of this new class of reagents to function as nitrene equivalents. Subsequent investigations by Breslow, Mansuy, and Müller would show such oxidants to be competent for alkene and saturated hydrocarbon functionalization when combined with transition metal salts or metal complexes, namely those of Mn, Fe, and Rh. Here, we trace our own studies to develop N-atom transfer technologies for C-H and π-bond oxidation. This Account discusses advances in both intra- and intermolecular amination processes mediated by dirhodium and diruthenium complexes, as well as the mechanistic foundations of catalyst reactivity and arrest. Explicit reference is given to questions that remain unanswered and to problem areas that are rich for discovery. A fundamental advance in amination technology has been the recognition that iminoiodinane oxidants can be generated in situ in the presence of a metal catalyst that elicits subsequent N-atom transfer. Under these conditions, both dirhodium and diruthenium lantern complexes function as competent catalysts for C-H bond oxidation with a range of nitrogen sources (e.g., carbamates, sulfamates, sulfamides, etc.), many of which will not form isolable iminoiodinane equivalents. Practical synthetic methods and applications thereof have evolved in parallel with inquiries into the operative reaction mechanism(s). For the intramolecular dirhodium-catalyzed process, the body of experimental and computational data is consistent with a concerted asynchronous C-H insertion pathway, analogous to the consensus mechanism for Rh-carbene transfer. Other studies reveal that the bridging tetracarboxylate ligand groups, which shroud the dirhodium core, are labile to exchange under standard reaction conditions. This information has led to the generation of chelating dicarboxylate dinuclear rhodium complexes, exemplified by Rh(2)(esp)(2). The performance of this catalyst system is unmatched by other dirhodium complexes in both intra- and intermolecular C-H amination reactions. Tetra-bridged, mixed-valent diruthenium complexes function as effective promoters of sulfamate ester oxidative cyclization. These catalysts can be crafted with ligand sets other than carboxylates and are more resistant to oxidation than their dirhodium counterparts. A range of experimental and computational mechanistic data amassed with the tetra-2-oxypyridinate diruthenium chloride complex, [Ru(2)(hp)(4)Cl], has established the insertion event as a stepwise pathway involving a discrete radical intermediate. These data contrast dirhodium-catalyzed C-H amination and offer a cogent model for understanding the divergent chemoselectivity trends observed between the two catalyst types. This work constitutes an important step toward the ultimate goal of achieving predictable, reagent-level control over product selectivity.

FIGURE 1

Selective C–H oxidation as a general method for C–N bond formation.

FIGURE 2

C–H amination through photolytic azide decomposition.

FIGURE 3

Intramolecular C–H amination en route to (−)-N-methylwelwitindolinone C isothiocyanate.

FIGURE 4

Oxidative cyclization of carbamate and sulfamate esters.

FIGURE 5

Oxazaphosphinane synthesis through rhodium-catalyzed amination.

FIGURE 6

Metrical parameters for alkoxysulfonamide derivatives.

FIGURE 7

Proposed mechanism for dirhodium-catalyzed C–H amination.

FIGURE 8

Sulfilimine formation supports intermediacy of iminoiodinane oxidant.

FIGURE 9

Efficient preparation and high performance of Rh₂(esp)₂.

FIGURE 10

Novel dirhodium strapped carboxylate catalysts.

FIGURE 11

Catalyst choice influences positional selectivity.

FIGURE 12

Heterocyclic acetals available through α-ethereal and α-aminal C–H insertion.

FIGURE 13

Competitive aziridination and C–H insertion reactions.

FIGURE 14

Divergent stereochemical outcomes in sulfamate and sulfamide C–H insertion reactions.

FIGURE 15

Asymmetric intramolecular C–H amination of aryl-substituted sulfamate esters.

FIGURE 16

Catalyst SAR data highlights the influence of remote steric groups on reaction performance.

FIGURE 17

Competitive aziridination versus allylic C–H amination. Product ratios were estimated by ¹H NMR integration.

FIGURE 18

[Ru₂(hp)₄Cl] for selective, intramolecular allylic C–H amination.

FIGURE 19

Results support a stepwise C–H abstraction/radical rebound mechanism for [Ru₂(hp)₄Cl]-catalyzed amination.

FIGURE 20

Generation of ¹⁵N-isotopomers through intermolecular C–H amination.

FIGURE 21

Intermolecular oxidation with TcesNH₂ favors benzylic C–H centers.

FIGURE 22

Chemo- and diastereoselective intermolecular amination of allylic C–H bonds.

FIGURE 23

Intermolecular olefin aziridination.

FIGURE 24

Ketone and aziridine byproducts identified in intermolecular C–H oxidation.

FIGURE 25

Spectroscopic characterization of a mixed-valent Rh₂(II,III) dimer.

FIGURE 26

Intermolecular C–H amination mediated by Ce⁴⁺ oxidant.