Synthesis of oxazolidinones: rhodium-catalyzed C–H amination of N-mesyloxycarbamates

Abstract

N-Mesyloxycarbamates undergo intramolecular C-H amination reactions to afford oxazolidinones in good to excellent yields in the presence of rhodium(ii) carboxylate catalysts. The reaction is performed under green conditions and potassium carbonate is used, forming biodegradable potassium mesylate as a reaction by-product. This method enables the production of electron-rich, electron-deficient, aromatic and heteroaromatic oxazolidinones in good to excellent yields. Conformationally restricted cyclic secondary N-mesyloxycarbamates furnish cis-oxazolidinones in high yields and selectivity; DFT calculations are provided to account for the observed selectivity. trans-Oxazolidinones were prepared from acyclic secondary N-mesyloxycarbamates using Rh(oct). The selectivity was reverted with a cytoxazone N-mesyloxycarbamate precursor using large chiral rhodium(ii) carboxylate complexes, affording the corresponding cis-oxazolidinone. This orthogonal selectivity was used to achieve the formal synthesis of (-)-cytoxazone.

Tuning Triplet Energy Transfer of Hydroxamates as the Nitrene Precursor for Intramolecular C(sp3)–H Amidation

“…This result led us to envision to develop alternative types of triplet acceptors to enable the desired cyclization. In fact, there are several precedents showing the activation of hydroxamates via photoredox catalysis to generate amidyl radicals. − In addition, hydroxamates were used as a metal nitrenoid precursor by the action of transition metal catalysts. ,− …”

Rhodium(ii)-catalyzed C–H aminations using N-mesyloxycarbamates: reaction pathway and by-product formation

“…Experimentally, the reaction between N -mesyloxycarbamate A and potassium acetate or sodium 2-ethylhexanoate (known to be soluble in organic solvents) produced the potassium or sodium N -mesyloxycarbamate salt as a white precipitate (Scheme 3). 12 The rhodium catalyst was not necessary for salt generation to occur. When the deprotonation with potassium acetate was studied in silico , all three models afforded potassium N -mesyloxycarbamate salts ( Salt-K ) with a small energy barrier of 0.5 to 4.0 kcal mol –1 (Fig.…”

“…Significant advantages are associated with metal-catalyzed C–H amination via nitrene insertion, including mild reaction conditions as well as high chemo- and stereoselectivities 5,6. Among these processes, intramolecular metal-catalyzed C–H aminations with carbamate derivatives afford oxazolidinones in good to excellent yields,7–12 whereas intermolecular reactions produce amines bearing readily removable carbamate protecting groups (Scheme 1). 13–16 Very recently, the synthesis of γ-lactams via C–H amidation was reported using tailored iridium catalysts 17.…”

“…Understanding the pathway producing these products may lead to ways to control the reaction to avoid their formation. Herein, the results of an in-depth mechanistic study with N -sulfonyloxycarbamates, known to produce oxazolidinones10–12 and carbamate-protected amines13–15 in high yields and selectivities (eqn (1) and(2)), are reported. The nature of the active amination reagent (metal nitrenoid vs. metal nitrene), the resting state of the catalyst, the rate-determining step, the mechanism (stepwise or concerted) and the pathway responsible for the formation of the by-products will be addressed in this computational study.…”

Recent Advances in the Synthesis and Ring‐Opening Transformations of 2‐Oxazolidinones

“…Subsequently, In 2017, Lebel and colleagues introduced convergent rhodium(II)‐catalyzed intramolecular C−H amination of N ‐mesyloxycarbamate 64 for the synthesis of oxazolidinones 65 using ethyl acetate or methanol as a solvent (Scheme 17). [32] Several palpable merits of this strategy are simple operation, easily removable biodegradable low molecular weight byproducts, and insensitivity for humidity. The results showed that the use of 3 mol% of rhodium(II) triphenylacetate dimer complex Rh 2 (tpa) 4 as the catalyst was the best choice.…”