Chiral 1,2‐Dialkenyl Diaziridines: Synthesis, Enantioselective Separation, and Nitrogen Inversion Barriers

Abstract

trans-1,2-Disubstituted diaziridines form stable enantiomers at ambient conditions because of the two stereogenic pyramidal nitrogen atoms. Functionalized trans-1,2-disubstituted diaziridines can be utilized as a chiral switching moiety between two enantiomeric states in more complex molecular structures. However, the synthesis of functionalized diaziridines is quite challenging, because of the limited tolerance of reaction conditions that can be applied. Here we present a strategy to make trans-1,2-disubstituted diaziridines accessible as versatile building blocks in C-C-bond formations, i.e., the Heck reaction, and therefore introducing aryl substituents. The synthesis of trans-1,2-dialkenyl diaziridines with terminal alkenyl substituents and their stereodynamic properties are described.

Diastereoselective synthesis of substituted diaziridines from simple ketones and aldehydes

“…As the reaction moves forward (spectrum in green, blue and purple), the ratio of these benzylic protons shifts to the complete disappearance of imine 1b benzylic protons after 3.5 h. The new resonance corresponds to the benzylic protons in the diaziridine ring in a trans stereochemical relationship to the alkyl chain from the aldehyde substrate. 18 Throughout the duration of this experiment, we did not observe the formation of non-chiral intermediates. These results indicate that the diastereoselective step may be a concerted step; however, a pathway going through a highly organized ionic transition state towards the formation of the diaziridine product is also viable given the experimental results.…”

Configurational Lability of Imino‐Substituted Ethano Tröger Bases. Insight on the Racemization Mechanism

“…2 [3] In fact, upon quaternization of one of the two nitrogen atoms, transient aminal ring opening occurs; the resulting Supporting information for this article is available on the WWW under https://doi.org/10.1002/hlca.201900021 1 The two aromatic units adopt a nearly perpendicular orientation and hence the V-shape geometry denomination. 2 Complexation with metal complexes like methyltrioxorhenium leads, contrary to what has been reported, to the full racemization of TB-1. In fact, in Table 2 of reference [28], the space group is P2 1 /c which is centrosymmetric.…”

“…Tertiary amines comprising of three different substituents are chiral motifs, usually isolated in racemic form by virtue of the configurational instability of the Natom; the barrier for the nitrogen inversion (enantiomerization) is typically in the range of 6 -7 kcal/ mol. [1,2] Only few mono or polycyclic derivatives present configurationally stable stereogenic nitrogen atoms. One particularly important class of such compounds is that of Tröger bases (TBs, 1).…”

“…[36] Recently, TB 1 was treated with aryl α-imino carbenes; these intermediates are generated from the corresponding N-sulfonyl-1,2,3-triazoles [37 -42] under Rh (II)-catalysis at 80°C. [43] Original polycyclic indolinebenzodiazepines 4 resulted from the transformation through a cascade of [1,2]-Stevens rearrangement, Friedel-Crafts, Grob fragmentation, and aminal formation reactions (Scheme 3). [43] As the nature of the reagents and intermediates is comparable in both transformations 1!3 and 1!4, a high enantiospecificity was expected for the latter reaction.…”

Recent Advances in the Preparations and Synthetic Applications of Oxaziridines and Diaziridines

“…A novel synthetic route towards alkenyl diaziridines 176 was established by Trapp and co-workers in 2014. [86] The initial Mitsunobu reaction between 4pentanol 175 and phthalimide, followed by hydrazine mediated reduction delivered ammonium salt 175I, which on reaction with formaldehyde and sodium hypochlorite with NaOH base afforded diaziridine 176 in moderate yield (Scheme 47). The synthetic credibility of 176 was investigated following the Pdcatalyzed Heck reactions of 176 with versatile building block 177 to yield diaziridine fused macrocycle 178.…”