The Aza-Payne Rearrangement: A Theoretical DFT Study of the Counter-Ion and Solvent Effects

Abstract

The aza-Payne reaction mechanism has been studied by theoretical DFT calculations. Three reaction pathways have been considered: two of them result in the formation of a three-membered ring, with either inversion (S N I, experimentally observed) or retention (S N R) at the substituted carbon. The third reaction path results in the formation of a fourmembered ring. The mechanisms were first studied in the gas phase with the bare anion (An − ). The role of the counterion (Li + ) was then analysed by study of the reaction with the neutral species (An − Li + ) in the gas phase. Results for the (An − Na + ) system are also presented. Finally, the role of the solvent (THF and H 2 O) was taken into account with the aid

Aza-Payne rearrangement of α,α-disubstituted-aziridinemethanols

“…Clean intramolecular S N 2 substitution is observed. 6 The aza-Payne reaction is reversible 5a and the epoxide can be favored over the aziridine if the nitrogen anion is well stabilized. For example, from ab initio calculations, the energy minimum of aza anion 6 was predicted to be 18.6 kcal/mol lower than that of oxa anion 5 5a (Scheme 2).…”

Diastereomerically and Enantiomerically Pure 2,3-Disubstituted Pyrrolidines from 2,3-Aziridin-1-ols Using a Sulfoxonium Ylide: A One-Carbon Homologative Relay Ring Expansion

“…In previous work directed toward the synthesis of tetrahydrofurans (Scheme ), compounds containing an oxygen substituent at either C-4 or C-5 of the epoxy alcohol were excellent substrates for the Payne rearrangement/one-carbon homologative ring-opening/ cyclization sequence to yield 2,3-disubstituted tetrahydrofurans. Likewise, these substrates (entries 1−4, Table ) performed well in the aza-Payne rearrangement by treatment with NaH in THF, as described by Ibuka . There were no notable disparities in the yields of epoxy amines utilizing either cis - or trans -disubstitituted aziridinols as substrates (Table , entries 1−8).…”

“…In contrast to the Payne rearrangement, the aza-Payne rearrangement of activated 2,3-aziridin-1-ols (Scheme ) has not received as much attention, despite its great potential for the synthesis of enantiomerically pure nitrogen-containing compounds . Ibuka and co-workers have described the aza-Payne rearrangement of a series of cis - and trans -2,3-disubstituted aziridin-1-ols, as well as the reaction of the resulting epoxy amines with a few selected nucleophiles, including organocuprates and amines. − A particularly useful feature of the aza-Payne rearrangement is that, under aprotic conditions, the equilibrium for both cis - and trans -disubstituted 2,3-aziridin-1-ols lies exclusively toward the epoxy amine. This may result from the greater ability of the activated amine to stabilize the negative charge under the basic reaction conditions and/or the greater thermodynamic stability of the epoxy amine vs the aziridinol .…”

Lewis Acid-Mediated Rearrangement of Activated Cyclic Amines: A Facile Synthetic Protocol for the Preparation of Amino Carbonyl Compounds

“…To confirm that the reaction in the cases of five- and six-membered rings (vide supra) proceeds via an epoxide as proposed in the mechanism described in Scheme , we thought of converting 8 into a similar epoxide 11 using aza-Payne rearrangement. Ibuka and co-workers have reported the aza-Payne rearrangement of a series of 2,3-disubstituted aziridine-1-ols, as well as the reaction of rearranged product with different nucleophiles, including organocuprates and amines to our knowledge, the aza-Payne rearrangement of α,α-disubstituted azetidinemethanol has not been studied.…”