No 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...

Catalytic intramolecular C-H amination has advanced as a general technology for chemical synthesis. 1 The utility of the heterocyclic products fashioned from such processes validates efforts to identify chiral transition-metal complexes capable of effecting asymmetric insertion (Figure 1). On a more fundamental level, the challenges associated with the design of a catalytic system able to support a reactive oxidant that can discriminate between two hydrogen atoms on a prochiral methylene center are significant. Nonetheless, success of this type has been realized in enantioselective C-H insertion reactions of diazoalkane derivatives and in select instances involving intra-and intermolecular C-Hamination. 2-5 This report describes the development and performance of Rh 2 (S-nap) 4 , a valerolactam-derived dirhodium complex that affords some of the highest levels of asymmetric control to date in cyclization reactions of sulfamate esters. The strong preference of this catalyst for promoting allylic C-H bond insertion is also highlighted.Our earliest efforts to identify chiral catalysts for asymmetric C-H amination focused primarily on dirhodium tetracarboxylate complexes derived from α-amino acids. In all cases examined, cyclized sulfamate products were formed with conspicuously poor enantiomeric induction (0-20% ee). Studies to evaluate % ee as a function of product conversion clearly established that the enantiomeric ratio was decreasing over the reaction time course. Such results are indicative of a change in catalyst structure owing to the lability of the bridging carboxylate groups. Our interest thus turned toward alternative classes of ligands including carboxamide-based designs. In principle, the strongly donating carboxamidate groups increase the capacity of the dirhodium centers for backbonding to the π-acidic nitrene ligand, thus affording a more stable and potentially more discriminating oxidant. 6,7 Unfortunately, simple dirhodium tetracarboxamidate complexes such as Rh 2 (cap) 4 1 are ineffective catalysts for C -H amination because of their propensity to undergo facile one-electron oxidation when combined with PhI(OAc) 2 or related hypervalent iodine reagents (Figure 2). 8 The resulting mixed-valent Rh 2+ /Rh 3+ dimer appears to be catalytically inactive for C-H amination. Accordingly, in order for a dirhodium carboxamide to promote nitrene-mediated insertion, we concluded that its oxidation potential would have to be increased significantly relative to that of Rh 2 (cap) 4 .The basis for the design of Rh 2 (S-nap) 4 4 was Rh 2 (PTPI) 4 2, a complex originally developed by Hashimoto for asymmetric alkene cyclopropanation (Figure 2). 9 The measured Rh 2+ / Rh 2+ →Rh 2+ /Rh 3+ redox potential for Rh 2 (PTPI) 4 is 120 mV vs SCE, marking the rather significant influence of the proximal phthalimide group on the donating strength of the carboxamidate ligand. 10 We reasoned that replacement of the phthalimide moiety with a 2°s ulfonamide would allow for intramolecular hydrogen bonding between the N-H and the E...

Chiral (salen)Al complex 1a catalyzes the highly enantioselective conjugate addition of carbon- and nitrogen-based nucleophiles to acyclic alpha,beta-unsaturated ketones. This methodology is tolerant of substantial variation of the ketone structure, providing access to a wide range of useful chiral building blocks in high yield and enantiomeric excess. Synthetic manipulations of the conjugate addition products are demonstrated, including the straightforward preparation of beta-amino ketones and highly enantioenriched carbo- and heterocyclic compounds.

No abstract

C‐H‐Insertion: Eine Methode für die intermolekulare Aminierung von C‐H‐Bindungen wird beschrieben, die limitierende Substratmengen und eine bequeme, Phenol‐abgeleitete Stickstoffquelle einsetzt. Selektivitäts‐ und mechanistische Studien ergeben, dass die sterische Wechselwirkung zwischen dem Substrat und dem aktiven Oxidans entscheidend für die Produktselektivität ist.

Metal-Catalyzed Oxidations of C-H to C-N Bonds

Intramolecular C-H amination with sulfamate esters occurs under the action of dinuclear Rh catalysts and iodine(III) oxidants, and has recently emerged as a powerful tool for synthesis. Insights gained through mechanistic studies of this process suggest that other terminal oxidants, including common halogenating agents such as NaOCl, could function to promote the cyclization reaction. Results described in this report demonstrate that the combination of NaOCl and 3 mol% Rh 2 (oct) 4 is effective in select cases for converting sulfamate substrates to the corresponding [1,2,3]-oxathiazinane-2,2-dioxide heterocycles. The mechanism for C-H functionalization, however, is distinct from that induced by hypervalent iodine reagents and likely involves the intermediacy of an N-centered radical. KeywordsC-H amination; catalysis; rhodium; bleach; oxathiazinane Catalytic methods for C-H and π-bond amination have emerged recently as selective and practical tools for fine chemicals synthesis. 1 Starting from any one of a number of amine derivatives (e.g., carbamates, ureas, guanidines, sulfamates, sulfonamides, sulfamides), intramolecular C-H insertion is effected under the action of a dinuclear Rh(II) catalyst and a diacyloxyiodobenzene oxidant (Figure 1). Experimental and theoretical studies suggest that this process occurs through an iodoimine (RN=IPh), which is intercepted by the Rh complex to generate a transient metallo-nitrene intermediate. 2,3 The reactive nitrenoid is capable of oxidizing C-H bonds and does so through a concerted asynchronous insertion step. Consideration of this mechanism as well as reports describing the application of chlora-and bromamine-T (TsN(Na)X) as "nitrene" equivalents have led us to examine alternative oxidants in place of PhI(O 2 CR) 2 . 4,5,6,7 These studies ask whether a surrogate species of the iodoimine can be generated in situ under conditions compatible with the dirhodium complex. The discovery of substitute oxidants for the C-H amination process has important practical consequences as well as the potential to bring with it the identification of new catalyst systems.The reported reactivity of haloamine-T salts with metal catalysts for C-H and π-bond functionalization led us to examine initially reactions of 1 with common halogenating agents (Figure 2). 6 The admixture of NaOCl and NaBr (i.e., NaOBr) under biphasic alkaline conditions (CH 2 Cl 2 , aqueous Na 2 HPO 4 ) affords N-bromosulfamate 2. 8 Although this material is not formed cleanly and attempts to isolate 2 were not made, the combination of these reagents and 3 mol% Rh 2 (oct) 4 results in an efficient cyclization event to furnish the corresponding [1,2,3]-oxathiazinane-2,2-dioxide 7 (eq 1). 9,10 While other brominating agents such as Nbromosuccinimide and Br 2 can be used in place of NaOCl/NaBr, none give results that are comparable to our optimized protocol. 11,12 jdubois@stanford.edu. Following these exploratory investigations, analysis of the reaction scope began to expose striking differences between this process...