A Cascade Reaction of Cinnamyl Azides with Acrylates Directly Generates Tetrahydro-Pyrrolo-Pyrazole Heterocycles

Abstract

Developing reactions to generate complex and modular building blocks in a concise and direct fashion remains a contemporary synthetic challenge. This work describes a stereoselective cascade reaction between allylic azides and acrylates that directly generates tetrahydro-pyrrolo-pyrazole ring systems. These products contain up to four contiguous stereocenters, two of which may be tetrasubstituted carbon atoms attached to a nitrogen atom.Over 30 examples are provided with an average isolated yield of 71% (ranging from 40% to 94%). The reaction was easily scaled to use more than one gram of starting material, and the products can be readily diversified.

Hybrid of the 1,2,3‐triazole nucleus and sesquiterpene skeleton as a potential antitumor agent: Hemisynthesis, molecular structure, Hirshfeld surface analysis, density functional theory, and in vitro cytotoxic and apoptotic effects

“…The C Cl bond lengths average 1.767 (10) Å, are in good agreement with the Cl C bond length of 1.764 (6) Å reported for the related compound [21]. The bond distances N3-C10a, C10a-C7a, C7a-N1, N1-N2, and N2-N3 are 1.443 (12) Å, 1.538 ( 14) Å, 1.517 (13) Å, 1.267 (11) Å, and 1.368 (11) Å, respectively, with agrees with C N, N═N, N N C C, and bond length found in the literature for the compound having triazoles heterocycles [27].…”

“…The global reactivity indexes are potent tools that can explain the reaction mechanism and are measured through the global electron density transfer value [26,27]. As presented in Table 1, the electronic chemical potential of compounds 3 (A1 = À4.446 eV) is higher than that of R1 (À4.207 eV); consequently, the transfer of charge will be more favored from dipolarophile to dipole.…”

Azides in the Synthesis of Various Heterocycles

“…Optimization of the reaction in the scope of the substrate, incorporating methyl or phenyl group adjacent to the azide, for compound 70o a diastereomer was observed. Furthermore, cyclic azide resulted in the formation of tricyclic compounds 70u-w, as demonstrated in Scheme 34 [28]. Previously, a cycloaddition reaction was reported between cinnamyl azide and methyl acrylates to obtain the tetrahydro-pyrrole-pyrazole [26,27].…”

“…Previously, a cycloaddition reaction was reported between cinnamyl azide and methyl acrylates to obtain the tetrahydro-pyrrole-pyrazole [26,27]. Recently, Carlson et al [28] developed the previously mentioned procedure via stereoselective interaction between allylic azides and acrylates in high yields. The development includes (i) secondary and tertiary azides, (ii) the use of an enantioenriched azide, (iii) cinnamyl azides substituted at the α or β-carbon, (iv) derivatization of the products, and (v) additional Michael acceptors.…”

“…Optimization of the reaction in the scope of the substrate, incorporating methyl or phenyl group adjacent to the azide, for compound 70o a diastereomer was observed. Furthermore, cyclic azide resulted in the formation of tricyclic compounds 70u-w, as demonstrated in Scheme 34 [28].…”