A New Synthesis of 2-Methyleneaziridines

Abstract

A new synthetic route leading to 2-methyleneaziridines has been developed by base-induced 1,2-dehydrobromination of 2-(bromomethyl)aziridines. Several base-solvent pairs did not lead to 2-methyleneaziridines. Only potassium tert-butoxide in tetrahydrofuran afforded 2-methyleneaziridines in competition with the substitution products, i.e. 2-(tert-butoxymethyl)aziridines. Various attempted functionalizations of 1-(arylmethyl)-2-methyleneaziridines failed, but they proved to be excellent substrates for the synthesis of beta-lactam derivatives, i.e. 1-(arylmethyl)-2-iminoazetidines, through ring expansion with azides carrying electron-withdrawing substituents.

Mechanistic Considerations for the Consecutive Cyclization of 2,3-Dibromopropylamine Hydrobromide Giving a Strained Molecule, 1-Azabicyclo[1.1.0]butane

“…8) Thus, to clarify the first cyclization step, path A and/or path B, a competitive cyclization reaction of N-benzyl-2,3-dibromopropylamine hydrochloride (12) giving only two types of monocyclic products was examined. Treatment of 12 with n-BuLi under the same reaction conditions (entry 8 in Table 1) as in the case of 1 furnished aziridine 13 9) in 14% yield, a scarce amount of azetidine 14, and allylamine 15 10) in 47% yield together with recovery (33%) of 12, as shown in Chart 3 (HPLC analysis). The allylamine 15 was not derived from 13 or 14, respectively, under the same reaction conditions.…”

Ring Expansions of Nonactivated Aziridines and Azetidines

“…To close this section, an intriguing transformation reported by De Kimpe upon reaction of methylene-aziridines with sulfonyl azides leading to cyclic fourmembered amidines deserves a mention [75]. Upon cycloaddition between the alkene moiety of 110 and a sulfonyl azide, intermediate 111 is formed that decomposes to dipole 112, then evolving in a semipinacol-type rearrangement to deliver the imino-β-lactam derivative 113 in excellent yields (Scheme 28).…”

Synthesis of new functionalized aziridine-2- and azetidine-3-carboxylic acid derivatives of potential interest for biological and foldameric applications

“…Following a preliminary communication (Mangelinckx et al 2008), in the present paper, in-depth results are described on the synthesis and study of the reactivity of 2-(bromomethyl)aziridine-2-carboxylic esters and 3-bromoazetidine-3-carboxylic esters, the structures of which incorporate the synthetically important 2-(halomethyl)aziridine (Abbaspour Tehrani et al 2002;De Smaele et al 1998;De Kimpe et al 1997;D'hooghe et al 2006a;Mangelinckx et al 2009;Vervisch et al 2010), or 3-haloazetidine structural motif (Van Driessche et al 2006;Van Brabandt et al 2009). The bromo-substituted carbon atom can be advantageously used as a moiety for functionalization.…”

“…The bromo-substituted carbon atom can be advantageously used as a moiety for functionalization. Allylamines have proven to be suitable substrates for the synthesis of 2-(bromomethyl)aziridines and/or 3-bromoazetidines via bromination of the C-C double bond to the corresponding ,γ-dibromo amines followed by intramolecular ring closure (Abbaspour Tehrani et al 2002;De Smaele et al 1998;De Kimpe et al 1997;Hayashi et al 2004;Gensler 1948), or via electrophile-induced bromocyclization Rousseau 2000, 2002). This ring closure usually has high selectivity towards the formation of aziridines instead of azetidines.…”