Cu-catalyzed intermolecular oxyalkylation of styrenes under air: access to diverse iminolactones

Abstract

A practical, simple, and efficient copper-catalyzed highly regioselective oxyalkylation of styrenes and readily available a-bromoacetamides under air is realized. This reaction exhibits a wide range of functional group tolerance in styrenes and a-bromoacetamides to afford iminolactones.Difunctionalization of alkenes is a powerful tool for the synthesis of heterocycles through tandem two same or different C-X (X ¼ C, N, O, etc.) bond formations in organic synthesis. Although metal-free as well as transition-metalcatalyzed aminocarbonylation, aminoarylation, aminovinylation, aminoalkynylation, and aminooxygenation reactions of alkenes have been signicant developments in recent decades, 1 the selective oxyalkylation reactions of alkenes for their efficiency in synthesizing different types of oxygencontaining heterocycles remains challenging.2 N-Substituted iminolactones, which can be easily converted to g-lactones, are prevalently used as antibacterial agents, aldosterone inhibitors, and proper precursors for the preparation of a wide spectrum of natural compounds.3 However, the selective oxyalkylation of alkenes for the synthesis of N-substituted iminolactones are still rare. In this context, Lei and coworkers developed Ni-catalyzed cyclization of a-haloamides with alkenes through carbon-centered radical addition to the carbonyl oxygen of amides or esters (Scheme 1a).4 Recently, Nishikata and coworkers reported copper-catalyzed oxyalkylation of alkenes to afford iminolactone by controlling the reactivity of the oxygen nucleophile of the amide group (Scheme 1b).5 However, these methods require long reaction time, anhydrous solvent, inert atmosphere protection and sometimes even special apparatuses such as the glovebox to manipulate the reactions. Therefore, a practical and simple methodology towards effective intermolecular oxyalkylation of alkenes is highly desirable. Recently, we developed selectuor-mediated highly selective radical dioxygenation of alkenes and metal-free catalyzed C-O bond formation reactions directly from C-H bonds.6 As part of our ongoing study on difunctionalization of alkenes 6a,d and C-O bond formation reactions, we present herein our recent progress in copper-catalyzed highly regioselective oxyalkylation of styrenes and readily available a-bromoacetamides under air.We started our investigation by applying styrene 1a and 2-bromo-2-methyl-N-phenylpropanamide 2a in a model reaction to optimize the reaction conditions. To our delight, in the preliminary experiment of using 10 mol% of CuI as catalyst, the desired oxyalkylation proceeded to give the desired product 3a in 45% yield in the presence of 1,

The Fascinating Chemistry of α‐Haloamides

“…The divergent cyclo‐coupling process was strongly inhibited by the addition of TEMPO or BHT to the reaction mixture demonstrating that a radical process was involved. Thus, under weakly basic conditions and according to previous findings by Lv, the iminolactones C resulted through a multistep process commencing with the carbamoyl radical addition onto C=C double bond of the acrylate partners B . Afterward, a 5‐ endo cyclization followed by an oxidation‐deprotonation step gave compound C .…”

“…Lv and co‐workers developed a practical synthesis of iminolactones via a copper‐catalyzed cyclo‐coupling between styrenes B and readily available NHAr‐containing 2‐bromo‐2‐methyl propanamides A (Scheme ). They smoothly achieved the carbooxygenated compounds C by conducting the reaction at 100 °C in acetone, under air, provided that 1,10‐phenanthroline (Phen) was the ligand and K 2 CO 3 the base.…”

Copper-Catalyzed Modular Amino Oxygenation of Alkenes: Access to Diverse 1,2-Amino Oxygen-Containing Skeletons

“…The reaction with amide 4c gave iminolactone 5c in 35% yield, resulting from nucleophilic oxygen cyclization rather than nitrogen trapping. 14 Unsaturated 1,3-diones 4d–e were examined in this reaction as potential oxygen nucleophile via the enol form, with 5d formed in 31% yield. Oxime 4f afforded desired dihydroisoxazole product 5f under slightly modified conditions, with same efficacy on both 0.4 mmol and 2-mmol scales.…”

Radical Strategy for the Transition-Metal-Catalyzed Synthesis of γ-Lactones: A Review

“…29 The Lv group also reported, in 2017, a Cu-catalyzed highly regioselective oxyalkylation of styrenes with -bromoacetamides leading to iminolactones, which can be further converted into lactones. 30 In 2018, our group developed a copper-catalyzed intermolecular carboesterification of alkenes with -bromo esters for the synthesis of polysubstituted -lactone skeletons using H 2 O as the source of the oxygen atom in the newly formed ester group (Scheme 15). Among the many -bromo esters investigated, primary (R 3 = R 4 = H), secondary (R 3 = H, R 4 = alkyl, COR′), and tertiary (R 3 = alkyl, R 4 = alkyl, COR′) bromo esters were all tolerated and afforded good to excellent yields.…”