Straightforward Approach to Iminoxazines and Azetidinimines via 1,4-Additions of Chelated Enolates toward Nitroalkenes

Abstract

[reaction: see text] Chelated amino acid ester enolates undergo 1,4-addition toward nitroalkenes in a highly stereoselective fashion. Trapping the nitronates formed in the addition step with chloroformates or acyl chlorides gives rise to highly reactive intermediates that directly undergo cyclization. Depending on the N-protecting group (PG) used, iminoxazines or azetidinimines are formed in a simple one-pot protocol.

The Nitro to Carbonyl Conversion (Nef Reaction): New Perspectives for a Classical Transformation

“…[146] Upon reactiono fa dduct 214 with 2equivalents of methylc hloroformate, nitrileo xide derivatives 215 and 216 are formed and reactd ifferently according to the nature of the N-protecting group.T osylated derivatives 215 react through af our-membered ring transition state with the negatively charged nitrogen atom leading to azetidine imines 217.R ing closure of trifluoroacetylated intermediates 216 occurs involving the oxygena tom of the acyl group with formation of iminoxazines 218.…”

A Straightforward Approach towards Isoxazoline Amino Acid Esters by Domino Michael Additions/Nitrile Oxide Cycloadditions

“…As a first reagent we used methyl chloroformate, which gave good results in the Michael addition/iminooxazine formation. [22] In principle, 1 equiv. of chloroformate should be sufficient to generate the nitrile oxide, but with 1.2 equiv.…”

“…If the nitronates B formed in situ are hydrolyzed, the expected Michael addition products C are formed in good yields and reasonably good diastereoselectivities (depending on the metal salt used for chelation). [21] On the other hand, if ni-tronates B, obtained in the reaction of the zinc enolates, are trapped with an excess of acyl halides or chloroformates, the deprotonated amides undergo cyclization with the iminooxazines D. [22] In contrast, if SnCl 2 is used as a chelating metal salt, the formation of nitriles E is observed. [23] Shimizu reported, that nitronates can be converted into nitrile oxides by using chloroformates.…”

Chelated Ester Enolates as Versatile Nucleophiles for Direct Nucleophilic Attack on Aromatic Nitro Groups

“…Very recently, we reported the highly stereoselective 1,4-addition of these enolates D towards nitroalkenes (Scheme 4). 15 Interestingly the nitronates formed as inter- mediates could be trapped by acyl halides giving rise to nitriles 6 or different heterocycles, 16 depending on the reaction conditions and the protecting groups used.…”