Bis(oxiranes) Containing Cyclooctane Core: Synthesis and Reactivity towards NaN3

Abstract

Reactions of oxirane ring opening provide a powerful tool for regio- and stereoselective synthesis of polyfunctional and heterocyclic compounds, widely used in organic chemistry and drug design. Cyclooctane, alongside other medium-sized rings, is of interest as a novel molecular platform for the construction of target-oriented leads. Additionally, cyclooctane derivatives are well known to be prone to transannular reactions, which makes them a promising object in the search for novel approaches to polycyclic structures. In the present work, a series of cyclooctanediones was studied in Corey-Chaykovsky reactions, and novel spirocyclic bis(oxiranes) containing cyclooctane core, namely, 1,5-dioxadispiro[2.0.2.6]dodecane and 1,8-dioxadispiro[2.3.2.3]dodecane, were synthesized. Ring opening of the obtained bis(oxiranes) upon treatment with sodium azide was investigated, and it was found that the reaction path is determined by the reciprocal orientation of oxygen atoms in the oxirane moieties. Diastereomers of the bis(oxiranes) with cis-orientation underwent independent ring opening, supplying corresponding diazidodiols, while in the case of stereoisomers with trans-orientation, domino-like reactions occurred, including intramolecular nucleophilic attack and the formation of a novel three- or six-membered O-containing ring. Summarily, a straightforward approach to polyfunctional compounds containing cyclooctane or oxabicyclo[3.3.1]nonane cores, employing bis(oxiranes), was elaborated.

Stereoselective Approach to Hydroxyalkyl-1,2,3-triazoles Containing Cyclooctane Core and Their Use for CuAAC Catalysis

“…On the other hand, the enhanced conformational flexibility inherent in such medium-ring molecules provides the attached hydroxy and triazolyl functionalities with access to new unusual spatial dispositions that can be useful for applications in medicinal chemistry and catalysis [42][43][44]. In previous work we have elaborated a synthetic approach to a series of azidoalcohols and diazidodiols, containing a cyclooctane core, via nucleophilic ring-opening of oxiranes [45]. The sequence of oxirane ring-opening upon treatment with an azide and following azide-alkyne cycloaddition reactions represents a straightforward approach to β-hydroxytriazoles, as was demonstrated recently [46] by the synthesis of a series of α-hydroxy-β-triazolotetrazoles from α,β-epoxynitriles.…”

“…Previously, we elaborated the stereoselective approach to azidoalcohols 5,6 and diazidodiols 7,8 based on the nucleophilic ring-opening of different diastereomers of bis(oxiranes) I,II [45] (Figure 3). Mono-and diazides 5-8 were investigated in the reaction with phenylacetylene (Schemes 3 and 4).…”

“…Nevertheless, performing the reaction in the presence of Cu(OAc)2•H 2O/NaAsc for 2 h, we managed to isolate azidoalcohol 10, containing oxabicyclo[3.3.1]nonane moiety (Scheme 3). Previously, we elaborated the stereoselective approach to azidoalcohols 5,6 and diazidodiols 7,8 based on the nucleophilic ring-opening of different diastereomers of bis(oxiranes) I,II [45] (Figure 3). Mono-and diazides 5-8 were investigated in the reaction with phenylacetylene (Schemes 3 and 4).…”

“…Column chromatography was performed on silica gel (Macherey-Nagel, Silica 60, 0.015-0.04 mm). Oxirane 1 and azides 5-8 were obtained via described methods [45]. All other starting materials were commercially available.…”

“…1-(Azidomethyl)cyclooctanol (2a) [45] Yield 59% (606 mg), colorless oil, Rf = 0.38 (light petrol:EtOAc 10:1). 1 H NMR (400 MHz, CDCl 3 ) δ, ppm: 1.31-1.87 (m, 15H, 7CH 2 + OH) and 3.26 (s, 2H, CH 2 -N 3 ).…”