A Mechanistic Study of the Stereochemical Outcomes of Rhodium‐Catalysed Styrene Aziridinations

Abstract

The stereoselective, rhodium-catalysed aziridination of styrene derivatives with a chiral Nmesyloxycarbamate was found to be highly substrate dependent. A density functional theory (DFT) study is herein reported to elucidate the stereochemical outcome of the aziridination process. Rhodium acetate was initially used as a model catalyst, followed by computational studies conducted with Rh 2 [(S)-nttl] 4 . Both singlet and triplet rhodium nitrene species were identified as intermediates affording concomitant concerted and radical pathways. In the latter case, the radical intermediate appears to undergo a direct ring closure via a minimum energy crossing point (MECP) between the triplet and closed-shell singlet surfaces. Exceptionally for the m-Br-styrene aziridination, an alternative radical pathway with a carbon-carbon bond rotation was observed, accounting for the observed 74:26 mixture of diastereomers. The computational analysis also suggests little control of the metal nitrene conformation with Rh 2 (OAc) 4 with the chiral N-mesyloxycarbamate: two conformers were located affording two diastereomers of the aziridine and correlating our experimental results. On the other hand, only one conformer was found for the nitrene generated from the chiral Nmesyloxycarbamate and Rh 2 [(S)-nttl] 4 . The so-called "all-up" conformer of Rh 2 [(S)-nttl] 4 was not only the most stable metal nitrene species, but also afforded the lowest energy transition state. The calculated dr for p-Br-styrene aziridination agrees with the observed experimental result. The combination of experimental and computational results offers a detailed mechanistic picture, providing insights for further catalyst development to enhance reactivity and selectivity.

Theoretical study of enantioenriched aminohydroxylation of styrene catalyzed by an engineered hemoprotein

“…Alma et al [ 26 ] demonstrated a nitrene radical intermediate in the Co‐porphyrin‐catalyzed aziridination of alkene, which occurs via the stepwise mechanism. Azek et al [ 27 ] elucidated that both singlet and triplet rhodium nitrene species are identified in the evolution of the aziridination process.…”

Rhodium-Catalyzed Sulfimidation Reactions: A Computational Study

“…The sulfimidation of thioanisole with singlet Rh-nitrenes 9 and 10 displayed an overall free activation barrier, whereas singlet Rh-nitrene 11 shows 5.0 kcal mol –1 activation free energy (Figure ). The sulfimidation of thioethers is thus an easier process in comparison to rhodium nitrene aziridination and C–H amination reactions, something that is also observed experimentally…”

“…Experimental evidence suggests that the rhodium nitrenoid species (L 4 Rh-N­( OMs )­R) might be the reactive intermediate in the amination of thioethers. This is in sharp contrast with what was observed in C–H and CC amination reactions using the same catalytic system . To establish the factors that govern the mechanism (Rh-nitrenoid vs rhodium nitrene), a density functional theory (DFT) study investigating rhodium­(II)-catalyzed thioether amination is reported herein.…”

“…Previous computational studies showed that coordination of the potassium anion of N -mesyloxycarbamate 1 (resulting from the deprotonation of 1 with KOAc) with Rh 2 (OAc) 4 afforded potassium rhodium nitrenoid 3 , which upon the elimination of KOMs, produced rhodium nitrene 9 . While the formation of potassium rhodium nitrenoid 3 is exergonic (Δ G = −14.9 kcal mol –1 ), the production of rhodium nitrene 9 is an endergonic process, (Δ G = 5.3 kcal mol –1 ) (Figure ).…”

“…The reaction and activation energies were calculated using Kohn–Sham DFT with the Perdew–Burke–Ernzerhof (PBE) approximation for the exchange-correlation energy . The PBE pure functional has been previously identified as a suitable method to afford reliable results with rhodium carboxylate dimer-derived nitrene species in C–H and CC amination reactions . Dispersion effects were treated using the DFT-D3 method developed by Grimme by additional single-point energy calculations. , Solvent effects were accounted for by additional single-point energy calculations, using the solvation model based on density (SMD) in CH 2 Cl 2 (ε = 8.93), performed on the gas-phase optimized geometries.…”