Dehydrogenative reagent-free annulation of alkenes with diols for the synthesis of saturated O-heterocycles

Abstract

Dehydrogenative annulation reactions are among the most straightforward and efficient approach for the preparation of cyclic structures. However, the applications of this strategy for the synthesis of saturated heterocycles have been rare. In addition, reported dehydrogenative bond-forming reactions commonly employ stoichiometric chemical oxidants, the use of which reduces the sustainability of the synthesis and brings safety and environmental issues. Herein, we report an organocatalyzed electrochemical dehydrogenative annulation reaction of alkenes with 1,2- and 1,3-diols for the synthesis of 1,4-dioxane and 1,4-dioxepane derivatives. The combination of electrochemistry and redox catalysis using an organic catalyst allows the electrosynthesis to proceed under transition metal- and oxidizing reagent-free conditions. In addition, the electrolytic method has a broad substrate scope and is compatible with many common functional groups, providing an efficient and straightforward access to functionalized 1,4-dioxane and 1,4-dioxepane products with diverse substitution patterns.

Fig. 1

Reaction design. a Selected bioactive molecules containing the 1,4-dioxane moiety. b Oxidation of styrenyl alkenes via direct electrolysis. c Synthesis of O-heterocycles via annulation reactions of alkenes with diols

Fig. 2

Electrochemical gram scale reaction. Gram scale synthesis of 27

Fig. 3

Mechanistic rationale and cyclic voltammograms. a Mechanistic proposal. b Cyclic voltammograms recorded in MeCN/CH₂Cl₂ (6:1) with 0.1 M Et₄NPF₆ as the supporting electrolyte. 3 (2.6 mM). 1 (1.3 mM). SET, single-electron transfer

Fig. 4

Electrolysis of compound 4. a Electrolysis of 4 in the presence of triarylamine 3. b electrolysis of 4 in the absence of 3. Yields were determined by ¹H NMR using 1,3,5-trimethoxygenzene as the internal standard