The Ramberg-Backlund reaction

Thiirane 1,1-dioxides extrude sulfur dioxide readily (70S393) at temperatures usually in the range 50-100 °C, although some, such as c/s-2,3-diphenylthiirane 1,1-dioxide or 2-p-nitrophenylthiirane 1,1-dioxide, lose sulfur dioxide at room temperature. The extrusion is usually stereospeciflc (Scheme 10) and a concerted, non-linear chelotropic expulsion of sulfur dioxide or a singlet diradical mechanism in which loss of sulfur dioxide occurs faster than bond rotation may be involved. The latter mechanism is likely for episulfones with substituents which can stabilize the intermediate diradical. The Ramberg-Backlund reaction (B-77MI50600) in which a-halosulfones are converted to alkenes in the presence of base, involves formation of an episulfone from which sulfur dioxide is removed either thermally or by base (Scheme 11). A similar conversion of a,a -dihalosulfones to alkenes is effected by triphenylphosphine. Thermolysis of a-thiolactone (5) results in loss of carbon monoxide rather than sulfur (Scheme 12). 

The a -halosulfone, required for the Ramberg-Backlund reaction, can for example be prepared from a sulfide by reaction with thionyl chloride (or with N-chlorosuccinimide) to give an a-chlorosulfide, followed by oxidation to the sulfone—e.g. using m-chloroperbenzoic acid. As base for the Ramberg-Backlund reaction have been used alkoxides—e.g. potassium t-butoxide in an etheral solvent, as well as aqueous alkali hydroxide. In the latter case the use of a phase-transfer catalyst may be of advantage. ... 

Cf. three-membered ring sulfones as intermediates of the Ramberg-Backlund reaction L. A. Paquette, Org. React., 25, 1 (1977). 

The formation of alkenes from thiirane dioxides may not be stereospecifically controlled in the presence of a sufficiently strong base and sufficiently acidic protons in the three-membered ring. Under such conditions (essentially those typical for the Ramberg Backlund reaction), epimerization via a carbanion intermediate produces an equilibrium mixture of thiirane dioxides19,99 and consequently a mixture of cis- and trans-alkenes. 

Since the Ramberg-Backlund reaction proceeds through the initial a-proton removal by base, followed by intramolecular nucleophilic substitution of a-carbanion 358 to form... 

Block and Aslam441 reported a novel variant of the Ramberg-Backlund reaction in which a,/J-unsaturated a -bromoalkyl sulfones 368 afforded 1,3-dienes upon treatment with base. Since a -bromoalkyl sulfones 368 can be obtained readily by the initial treatment of olefins with bromomethanesulfonyl bromide under photoirradiation and subsequent treatment with triethylamine, this reaction was utilized for preparation of dienes which contain one additional carbon over that of the corresponding olefin. Starting from the cyclic olefins 369-372 the 1,3-dienes 373-376 were obtained442. 

The Ramberg-Backlund reaction has been utilized for the preparation of polyenes. 1,3-Butadienyl allyl sulfones 398 and 399 were transformed into the tri- and tetra-enes 400 and 401 by alkylcuprate addition and the Ramberg-Backlund-type S02 extrusion449. Julia and coworkers450 carried out the Michael addition of various nucleophiles such as ethanol, t-butyl acetoacetate and phenyl thioacetone to allyl dienyl sulfones 402 and then converted them to diallyl sulfones 403. The sulfones were transformed into isoprenoid, 404 by the Ramberg-Backlund reaction. 

Finally, an electrochemical reduction of bis-a-bromobenzyl sulfone to stilbene195 and a spectacular, so-called bis-homoconjugative, version of the Ramberg-Backlund reaction, which converts the a-chlorosulfone 100 into the bridged cyclooctatriene derivative 101 (equation 63)196-197, have also been published. 

The Ramberg-Backlund reaction can be regarded as a type of extrusion reaction (see p. 1352). 

Ramberg-Backlund reaction of isomeric dichlorodisulfone 380 gave 1,4-dimethyl-Dewar benzene 381 and p-xylene. The Ramberg-Backlund reactions of dichlorosulfones, 382 (N = 2-5), were carried out and 1,4-polymethylene-Dewar benzenes 383 (n = 4,5) were obtained . 

The Ramberg-Backlund reaction of compound 384 gave the Bredt olefin 388, which was actually isolated . By reaction of chlorosulfones 385-387 and 392-394 (n = 2) with potassium t-butoxide the corresponding oxaproperanes 392-397 were obtained by the Ramberg-Backlund reaction, but only in low yields . In contrast, the reaction of the chlorosulfoxides 392, 393 and 394 n = 1) gave oxaproperanes 395, 396 and 397 under analogous conditions in 85-90, 25 and 85% yields, respectively . 

The subjects of this section are two reactions that do not actually involve carbo-cation intermediates. They do, however, result in carbon to carbon rearrangements that are structurally similar to the pinacol rearrangement. In both reactions cyclic intermediates are formed, at least under some circumstances. In the Favorskii rearrangement, an a-halo ketone rearranges to a carboxylic acid or ester. In the Ramberg-Backlund reaction, an a-halo sulfone gives an alkene. 

The Ramberg-Backlund Reaction. a-Halosulfones undergo a related rearrangement known as the Ramberg-Backlund reaction.91 The carbanion formed by deprotonation gives an unstable thiirane dioxide that decomposes with elimination of sulfur dioxide. This elimination step is considered to be a concerted cycloelimination. 

A recently developed application of the Ramberg-Backlund reaction is the synthesis of C-glycosides. The required thioethers can be prepared easily by exchange with a thiol. The application of the Ramberg-Backlund conditions then leads to an exocyclic vinyl ether that can be reduced to the C-nucleoside.95 Entries 3 and 4 in Scheme 10.6 are examples. The vinyl ether group can also be transformed in other ways. In the synthesis of partial structures of the antibiotic altromycin, the vinyl ether product was subjected to diastereoselective hydroboration. 

Scheme 10.6 gives some examples of the Ramberg-Backlund reaction. Entry 1 was used to prepare analogs of the antimalarial compound artemisinin for biological evaluation. The reaction in Entry 2 was used to install the side chain in a synthesis of the chrysomycin type of antibiotic. Entries 3 and 4 are examples of formation of C-glycosides. 

A phosphonium analogue of the Ramberg-Backlund reaction, which exhibits the same Z-stereoselectivity, has been used to form stilbenes by the action of amine bases on (a -bromobenzyl)benzyldiphenylphosphonium bromide. The reaction is believed to proceed via a strained ep/-phosphonium salt (Scheme 7) but the origin of the stereoselectivity is unknown. 

Treatment of an a-halosulfone 1 with base leads to extrnsion of sulfur dioxide and formation of an alkene 2. This reaction is referred to as the Ramberg-Backlund reaction, it usnaUy yields a mixture of E- and Z-isomers of the alkene. 

The Ramberg-Backlund reaction has been nsed for the preparation of strained nnsatnrated ring componnds that are difficnlt to obtain by other methods. A recent example is the synthesis of ene-diyne 5" that has been used as starting material... 

The reaction of an a-halo sulfone with a base to give an olefin is called the Ramberg-Backlund reaction.309 The reaction is quite general for a-halo sulfones with an a hydrogen, despite the unreactivity of a-halo sulfones in normal Sn2 reactions (p. 344). Halogen reactivity is in the order I > Br > Cl. Phase transfer catalysis has been used.310 In general, mixtures of cis and trans isomers are obtained, but usually the less stable cis isomer predominates. The mechanism involves formation of an episulfone and then elimination of... 

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