Vinyl-1,2,4-oxadiazoles Behave as Nucleophilic Partners in Morita–Baylis–Hillman Reactions

Abstract

We describe that vinyl-oxadiazoles function as a new and efficient nucleophilic partner for the Morita−Baylis− Hillman (MBH) reaction. The reaction between 5-vinyl-3-aryl-1,2,4-oxadiazoles and aromatic and aliphatic aldehydes, catalyzed by DABCO in the absence of solvent, showed high efficiency to afford a new class of heterocyclic MBH adducts with potential biological activity on yields up to 99% and short reaction times. These synthetically attractive adducts bear a heterocyclic scaffold of large pharmaceutical and commercial interest associated with a plethora of biological effects and technological applications. We also demonstrate their synthetic usefulness by a photoinduced addition reaction to a polyfunctionalized amino alcohol.

Catalyst-Free Conjugate Addition of Indolizines to In Situ-Generated Oxidized Morita–Baylis–Hillman Adducts

“…Less reactive t -butyl acrylate and acrylamide derivatives also furnished the desired compounds in good yields ( 9la and 9ma , Table ). The vinyl-oxadiazole MBH adduct 8n , which belongs to a class of MBH adducts recently discovered by our group, was successfully employed as the electrophile partner in this conjugate addition, resulting in rapid formation of the molecular-hybridized compound 9na with two biologically important heterocycles (Table ). …”

Aza-Morita–Baylis–Hillman Reaction with Vinyl-oxadiazoles: An Expeditious Approach to Access New Heterocyclic Arrangements

“…18 The 1,2,4-oxadiazole motif is also present in molecules used in material sciences, 19 polymers, 20 and organic chemistry. 21 These important features associated with our previously described results using vinyl-1,2,4-oxadiazoles in MBH reaction with aldehydes 13 prompted us to explore the potential of these aryl heterocycles as nucleophilic partners for other MBH reactions. In the present communication, we describe the results achieved in the development of an aza-MBH reaction between vinyl-oxadiazoles and N-sulfonylimines.…”

“…Inspired by the Chen group's results, we recently described an efficient MBH reaction with aldehydes using vinyl-1,2,4-oxadiazoles (Scheme 1, F), as the nucleophilic partners. 13 The compound 1,2,4-oxadiazole is a pharmacophore fragment, that is considered an ester bioisostere. 14 Many drugs have the 1,2,4-oxadiazole moiety present in their structures; these include L690548, a muscarinic agonist, used in Alzheimer treatment; 15a,b Libexin 15c and Perebron, 15d which are antitussive and anti-inflamatory agents, Cluster Syn lett respectively; and 5-HT 1D receptor agonists used to treat migraine (Figure 1).…”

“…We initiated our study by synthesizing the vinyl-oxadiazole 1a, which was promptly prepared in 89% yield, according the protocol described by Burns 22 and by the synthesis of N-benzenesulfonylimine 2a in quantitative yield. 23 We have previously established 13 DABCO as the best Lewis base for the MBH reaction between vinyl-1,2,4-oxadiazole 1a and aldehydes in the presence of acetic acid as an additive. For this reason, we decided to start our optimization work by using that system (DABCO/AcOH).…”

Systematic study of the substitution effect on the tetrel bond between 1,4-diazabicyclo[2.2.2]octane and TH3X

“…Using DABCO not only increases the yield of the Morita-Baylis-Hillman (MBH) reaction but also shows very pronounced regioselectivity. 48,49 Importantly, the MBH reaction of benzaldehyde with acrylamide under DABCO catalysis can be carried out in an aqueous system. 50 In addition, as a good linker, DABCO can also form structurally stable complexes with a variety of organic and organometallic compounds.…”