Taming Nitrene Reactivity with Silver Catalysts

Abstract

Nitrene transfer (NT) is a convenient strategy to directly transform C–H bonds into more valuable C–N bonds and exciting advances have been made to improve selectivity. Our work in silver-based NT has shown the unique ability of this metal to enable tunable chemo-, site-, and stereoselective reactions using simple N-dentate ligand scaffolds. Manipulation of the coordination environment and noncovalent interactions around the silver center furnish unprecedented catalyst control in selective NT and provide insights for further improvements in the field.1 Introduction1.1 Strategies for Nitrene Transfer1.2 Brief Summary of Chemocatalyzed Nitrene Transfer1.3 Focus of this Account2 Challenges in Chemocatalyzed Nitrene Transfer2.1 Reactivity Challenges2.2 Selectivity Challenges2.3 Chemoselective Nitrene Transfer2.4 Site-Selective Nitrene Transfer2.5 Enantioselective Nitrene Transfer3 Summary and Perspective3.1 Future Opportunities and Challenges3.2 Conclusion

Solvent Effects on the Chemo‐ and Site‐Selectivity of Transition Metal‐Catalyzed Nitrene Transfer Reactions: Alternatives to Chlorinated Solvents**

“…The 1,3‐aminoalcohol moiety is common in pharmaceuticals and bioactive natural products. Intramolecular amination of sulfamates via NT favors the formation of 6‐ over 5‐member rings, due to a more favorable 7‐member transition state dictated by the longer O−S bonds in sulfamates compared to the O−C bonds in the analogous carbamates [2b] . Indeed, sulfamate 3 (Scheme 2) formed only 4 , irrespective of the catalyst (Ag, Rh or Fe) or solvent.…”

“…Amination of 3° C(sp 3 )−H vs. 2° benzylic C−H bonds with sulfamate nitrene precursors . Achieving good site‐selectivity between two competing γ C−H bonds, such as an electron‐rich 3° C(sp 3 )−H and a weaker benzylic C−H bond in 6 (Scheme 3) to furnish 3‐amino‐1‐propanols 7 and 8 , is challenging [2b–e] . We first wanted to determine solvent scope with eight different catalysts, then ascertain the impact of catalyst and solvent on the site‐selectivity to furnish 7 and 8 (Schemes 3–4).…”

“…As shown in Scheme 4, Ag(tpa)OTf favors 7 , while ( t Bubpy) 2 AgOTf strongly prefers 8 in certain solvents. Computational studies suggested that non‐covalent interactions in the Ag(tpa)OTf nitrene transition state bias selectivity towards 7 , [2b,d] where the aromatic ring of 6 participates in a π‐π stacking or Ag‐π interactions with a pyridine on the bound ligand. All solvents preferred 7 in varying ratios of 7 : 8 using this catalyst; HTE data agreed with results from larger scale reactions performed in typical glassware (see Section XIII in the Supporting…”

“…Such catalysts, with the exception of tailored porphyrin ligands for Co designed by the Zhang group, [8] tend to show selectivity only for specific types of C−H bonds and modifying the supporting ligands to tune selectivity is challenging. In contrast, simple N‐dentate ligands on Ag(I) salts enable controlled chemo‐, [2f,g] site‐ [2b,c,e] and stereoselective [2h,i] transformations, where the right combinations of silver(I) salts and sp 2 nitrogen‐containing ligands enforce diverse coordination environments at the metal nitrene that predictably impact reaction selectivity.…”

Regio- and Enantioselective Catalytic δ-C–H Amidation of Dioxazolones Enabled by Open-Shell Copper-Nitrenoid Transfer

“…Regarding the site-selective nitrene transfer to form azacycles with five- or six-membered rings, notable progresses have been made, primarily through the ligand control approaches. − For instance, Du Bois et al modulated the steric properties of the ligands employed on the dirhodium catalysts to functionalize stronger but less hindered C–H bonds . Schomaker elegantly showcased the importance of ligands in controlling the ring size of cyclic carbamates via silver-catalyzed nitrene transfer and also proposed that the regioselectivity could be tuned by a sophisticated interplay of multiple factors, including the C–H bond dissociation energy (BDE) and steric/electronic environment around the in situ generated nitrenoid species .…”