By the Ramberg-Backlund

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. 

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 decomposition of cyclic sulfones and sulfoxides has attracted increasing attention recently in view of their relationship to cyclic fragmentation reactions and of the dramatic impact of the Woodward-Hoffman rules for intermolecular cycloaddition and electrocyclic ring opening reactions. The simplest cyclic sulfone known is 2,3-diphenyl thiirene-1,1-dioxide (A) which was isolated by Carpino and McAdams by the Ramberg-Backlund base catalyzed dehydrohalogenation of a, a -dibromodibenzylsulfone, viz. 

Ramberg-Backlund rearrangement. The key step in a synthesis of (+)-eremantholide A (4), involves ring contraction of the chloro sulfone 2 by the Ramberg-Backlund rearrangement. Thus treatment of 2 with this highly hindered base (1), 2.2 equiv., and HMPA (10 equiv.) in DME at 70° provides 3 in 82% yield. Use of less hindered bases results mainly in reduction of the chloro group. 

Predominantly Z- or E-y, S-unsaturated carboxylic acids are readily prepared by the Ramberg-Backlund rearrangement of the a-halosulphone intermediate... 

Reactions of (145) with potassium permanganate, performic acid, aqueous lithium carbonate, and silver acetate in acetic acid are described. Treatment of the cyclopentadiene-methyl a-bromovinyl sulphone adduct with sodium methoxide in dimethyl sulphoxide gives (141) by the Ramberg-Backlund rearrangement, but in refluxing aqueous 2N sodium hydroxide (146) is also formed. Good evidence in the latter case is presented for a homolytic mechanism. With added isopropyl alcohol, in addition to (146), products are obtained by hydrogen-atom abstraction. 

Oxidation to the sulfone followed by the Ramberg-Backlund reaction (halogenation, intramolecular displacement, chelotropic elimination of SO ) then dehvered 14, which was selectively reduced, leading to 15. 

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. ... 

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. 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. 

One of the earliest and most important discoveries in metal-catalyzed asymmetric synthesis is Sharpless s Ti-catalyzed epoxidation of allylic alcohols. A mere mention of all the total syntheses that have used this technology would require a separate review article Here, we select Trost s masterful total synthesis of solamin (100, Scheme 14), for its beautiful and multiple use of Sharpless s asymmetric epoxidation.1161 Optically pure epoxy alcohol 95 is converted to both epoxy iodide 96 and diol 97 The latter two intermediates are then united to give 98, which is oxidized and converted to dihydrofuran 99 by a Ramberg-Backlund transformation. The Re catalyzed butenolide annulation that is used to afford the requisite unsaturated lactone only adds to the efficiency of this beautiful total synthesis. 

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 (a -bromobenzyl)benzyldiphenylphosphonium salts (364) with amine bases has been shown to afford alkenes (366) with Z-selectivity. The reaction is believed to proceed via an e/it-phosphonium species (365) by a mechanism similar to that of the Ramberg-Backlund transformation. 

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