Novel Reactions of Disubstituted 1,2‐Dioxetanes with Olefins as π‐Nucleophiles: Cycloadditions via 1,6‐Dipoles

Abstract

In view of their ability to serve as an efficient source of excited carbonyl products, I ,2-dioxetanes have been the subject of intensive investigation for almost twenty years." J However, aside from unimolecular fragmentations in excited carbonyl compounds, only little was hitherto known about the chemical transformations of these strained peroxides. One of the first reactions of 1,2-dioxetanes with heteroatomic nucleophiles to be reported was their deoxygenation by phosphanes.r21 Biphylic insertion into the peroxide bond first yields a pentacovalent intermediate, which, after thermal elimination of phosphane oxide affords the epoxide. Also the reaction of dioxetanes with sulfidesr3] generates epoxides, whereas lithium aluminum h~dride,[~I t h i~l s [~l and biologically relevant reductants,16] such as ascorbic acid or NADH, reduce 1,2-dioxetanes to 1,Zdiols. Moreover, although reactions of cyclic acyl peroxides['] with x-nucleophiles, e.g. olefins, are quite common, such transformations do not appear to be known in the case of dioxetanes. In this communication we report the cycloaddition of 3,3-disubstituted 1,2-dioxetanes 1 with electron-rich olefins 2 to afford unusual products, whose structure depend on the type of olefin and solvent employed (Scheme 1, Table 1). The dioxetane 1 a was synthesized as described in the literature.[*] The previously unknown halogen-substituted derivatives 1 b and lc['I were prepared from the corresponding p-bromohydroperoxides according to the usual Kopecky method.l4] The reaction of dioxetane l c with tetraethoxyethene 2a and 1 ,4-dioxene 2 b, electron-rich olefins without allylic hydrogen, afforded the dioxane derivatives 3 in good yields; cleavage of the dioxetane into carbonyl fragments occurred only to a small extent (Table l), and deoxygenation to epoxides was not observed. The moisture-sensitive orthoester product 3a (m.p. 47-48 "C) showed characteristic singlets at 6 = 108.8 and 109.4 in the I3C-NMR spectrum (CDCI,, 63 MHz) for the orthoester carbon atoms. The cycloadduct 3b formed from dioxetane 1 c and 1 ,Cdioxene 2 b, was established as its cis isomer (coupling between the acetal protons: J = 1.6 Hz) and was isolated as the diastereomeric mixture (52:48). In contrast, reaction of the 2,3-dimethylbenzo-l,4-dioxene 2c with dioxetane l c furnished the ene product 4a as the main product (two diastereomers, 59:41), together with appreciable amounts of a-bromoacetophenone as cleavage product from dioxetane 1 c (Table 1). Epoxides or cycloadducts 3 were not observed. In a similar way, 1,2-dimethylcyclopentene 2d and 2,3-dimethyl-2-butene 2e gave with dioxetane l c the corresponding ene products, namely the pmethylene-fY-hydroxy ethers 4 b, c; two diasteromers (77 : 23) were found for the ene product derived from olefin 2d. No cycloadducts 3 were detected, but cleavage into carbonyl products and deoxygenation of the dioxetane 1 c leading to 2-bromomethyl-2-phenyloxirane, together with the corresponding oxygen transfer products 1,2-dimethyl-I ,2-epoxycyclopentane 5 a[' l a ] a...

Steric and Stereoelectronic Control of the Mode Selectivity as a Function of Alkene Structure in the Reaction with Dimethyl α-Peroxy Lactone: Cycloadducts and Ene Products versus Epoxides

“…In this context, we recall our previous studies on the reaction of 3,3-disubstituted 1,2-dioxetanes with electron-rich olefins, which as π-type nucleophiles react by S N 2 attack on the sterically less hindered oxygen atom of the peroxide bond in the four-membered ring peroxide to afford mainly cycloadducts and ene products, while the epoxidation reaction was hardly significant 1c. Methanol trapping experiments definitively showed that 1,6-dipolar intermediates intervened.…”

“…The oxidation of olefins by cyclic peroxides has been studied over the last decades from both the synthetic and mechanistic point of view. The earliest mechanistic studies have been carried out with cyclic peroxides such as phthaloyl peroxide 1a and more recently α-methylene β-peroxy lactones 1b and 1,2-dioxetanes 1c.…”

“…The oxidation of olefins by cyclic peroxides has been studied over the last decades from both the synthetic and mechanistic point of view. The earliest mechanistic studies have been carried out with cyclic peroxides such as phthaloyl peroxide 1a and more recently α-methylene β-peroxy lactones 1b and 1,2-dioxetanes 1c. During the last few years, the dioxiranes 1d have acquired special importance because of their effective epoxidation of electron-rich as well as electron-poor olefins under mild conditions.…”

Synthesis and use of cyclic peroxides

“…The 4-acetoxyazetidone derivative 233 has been synthesized from methyl 3(R)-hydroxybutyrate via the endoperoxide 234 (Scheme 60).' 18 Although thermal rearrangement of 234 in the presence of sodium acetate provides 233 (22%), improved yields of 233 can be obtained by treatment of 234 with hydrogen peroxide followed by acetic anhydride prior to thermolysis. The [4+2] cycloaddition of singlet oxygen to a protected guanosine derivative affords the corresponding thermally labile adduct 235 as a mixture of isomers.'…”

Syn-Dihydroxylation of Alkenes Using a Sterically Demanding Cyclic Diacyl Peroxide

“…Notwithstanding the pioneering work of Greene and Adam, the reactivity of cyclic peroxides toward nucleophiles as well as olefins still does not yet fully exploit the potency for novel carbon–oxygen bond-forming reactions . Dioxiranes are known to give epoxides upon reaction with alkenes, whereas 1,2-dioxetanes and dimethyl α-peroxy lactones produce mixtures of peroxides, cycloadducts, and ene products. , Concurrently, with the growing attention for metal-free organic reactions, CAPs have become attractive because of their potent ability in dioxygenation of electron-rich olefins under mild conditions. A few known CAPs have been employed with phthaloyl and cyclopropyl malonoyl peroxides, resulting in appreciably increased reactivity, with the latter being superior due to its higher relative reactivity, diastereoselectivity, and ease of preparation .…”