Use of the N–O Bonds in N-Mesyloxyamides and N-Mesyloxyimides To Gain Access to 5-Alkoxy-3,4-dialkyloxazol-2-ones and 3-Hetero-Substituted Succinimides: A Combined Experimental and Theoretical Study

Abstract

The reactivity of N-mesyloxyamides and -imides with bases was studied based on the initial hypothesis of a possible [3,3]-rearrangement. While the intended α-sulfonyloxylation method could not be developed, the formation of valuable N-containing heterocyclic products was found. Treating N-mesyloxyamides with triethylamine gave fully substituted oxazolone products, which are masked α-amino acid derivatives. The products were identified by a computational approach, which revealed that α-lactams are first formed from an initial enolate by an intramolecular nucleophilic substitution. As strained intermediates, they readily rearrange to the oxazolone products. With a cyclic N-mesyloxyimide, elimination to a maleimide was found. This might indicate that sulfonyloxylation has taken place, but the corresponding product probably underwent elimination. Nucleophiles were then added to trap this suspected intermediate by substitution of methanesulfonate. That way, quaternary α-nitrogen- and α-oxygen-substituted succinimides could be formed, which represent a pharmacologically important class that has received much attention for its value in drug design.

Key words

α-amino acid derivatives - α-amino succinimides - DFT - enolates - α-lactams - microkinetic modeling - intrinsic bond orbitals - oxazolones - sulfonyloxylation

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