Oxidative Cyclization of Sulfamate Esters Using NaOCl - A Metal-Mediated Hoffman-Löffler-Freytag Reaction

Abstract

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...

A manganese catalyst for highly reactive yet chemoselective intramolecular C(sp3)–H amination

“…These data further support a stepwise mechanism for manganese that proceeds through H–atom abstraction followed by rapid radical rebound from the base metal catalyst. In contrast to aminations that proceed via free radical intermediates 21,38,39 , this mechanistic feature of metallonitrene chemistry allows C—H amination reactions to proceed stereospecifically with high functional group tolerance, and enables the prospect of tuning the catalyst to control selectivity during functionalization 6 .…”

“…We hypothesized that a metal catalyst capable of transferring bound nitrenes to C(sp 3 )—H bonds via a stepwise mechanism with attenuated radical character of the metallonitrene oxidant relative to iron would achieve higher reactivity while maintaining chemoselectivity 20 . Low reactivity observed under iron catalysis with aliphatic C(sp 3 )—H bonds coupled with reports that sulfamate ester N -centered free radicals are unreactive towards intramolecular aminations of 3° C(sp 3 )—H bonds 21 suggested to us that a metallonitrene with diminished radical character would be more reactive. Although nature rarely uses manganese metal species to mediate oxidations, early studies using synthetic metalloporphryins as models for cytochrome P450 demonstrated that manganese and iron oxos react via mechanistically analogous one electron pathways, with manganese exhibiting significantly higher C—H hydroxylation reactivity 22 .…”

Sulfamate Esters Guide Selective Radical‐Mediated Chlorination of Aliphatic C−H Bonds

“…To our knowledge, there are no general strategies for aliphatic γ-C–H functionalization guided by a masked alcohol. [4,5] Herein described are the first experiments to demonstrate that sulfamate esters [6,7] can mediate 1,6-hydrogen-atom transfer (HAT) processes to guide the light-promoted chlorination of unactivatedγ-C(sp 3 )–H centers.…”

“…In unguided C–H functionalization reactions, proximity to inductively electron-withdrawing groups deactivates C–H bonds to oxidation. This phenomenon is evident when 3,7-dimethyloctanol is masked with an electron withdrawing group, and engages in undirected fluorination, [33] oxygenation, [34] amination, [35] azidation, [36] or trifluoromethylthiolation [37] processes that functionalize C(7) in preference to C(3). By contrast, the sulfamate ester-guided chlorination installs chlorine at the electronically deactivated C(3) position (entries 2–3).…”

Site-selective bromination of sp3 C–H bonds

“…A variety of transition metal salts were tested in conjunction with 3 equivalents each of NaBr and NaOCl, a reagent combination known to generate hypobromite in situ and used previously for the oxidative cyclization of sulfamate esters. 56 While little to no reaction ensued in the presence of catalytic Mn 3+ , Co 2+ , Cu 2+ , and Ni 2+ ( Table 1 , entries 1–4), switching to Rh 2 (oct) 4 ( Table 1 , entry 5) afforded a marked increase in conversion to brominated product 2 . The choice of dirhodium complex had a clear influence on reaction performance, as catalysts bearing hydrophobic ligands such as octanoate or triphenylacetate ( Table 1 , entries 5–7) out-performed others tested ( Table 1 , entries 8, 9), likely owing to the greater solubility of these complexes in dichloromethane.…”