By the Ramberg-Backlund reaction

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 . 

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. 

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. 

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... 

Cyclic sulfones have been prepared by RCM in what appears to be a general process <02OL427> (Scheme 56). These sulfones readily undergo the Ramberg-Backlund reaction to form cyclic dienes in excellent yields. 

For applications of the Ramberg-Backlund reaction to the synthesis of C-glycosides reported by our group and by the Taylor group, see refs (72-22) Belica, P. S. Franck, R. W. Tetrahedron Lett. 1998,39, 8225. 

The Ramberg-Backlund reaction involves a thiirane-1,1-dioxide intermediate 58 as shown in Scheme 8. J ng etal. determined the mechanisms of reaction of thiirane-1,1-dioxide 59 with hydroxide ion in water <1996PAC825>. Two pathways were identified, the one first order and the other second order in hydroxide. The first step is formation of a trigonal bipyramidal mono-anion 60 formed by attack of OH at S of the sulfone. That anion then reacts with water to afford ethane sulfonate anion 61 or with a second OH to afford ethene and sulfite anion via 62 or 63 (Scheme 9). Some rate constants and equilibrium constants were determined. 

A novel tandem process has been reported " for the preparation of allylic amines, ethers, and sulfides from a-bromo-a, jS-unsaturated sulfones. The process is believed to proceed via an initial conjugate addition followed by proton exchange and Ramberg-Backlund rearrangement (see Scheme 75). A new variant of the Ramberg-Backlund reaction has been described in which a, /f-epoxy sulfones (319), on treatment with base, are converted into a range of mono-, di-, and tri-substituted allylic alcohols (320). 

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. 

Carotene has been prepared by treating the a,a -dianion generated from starting sul-phone with bromine or iodine followed by rearrangement (equation 25). Utilizing the Ramberg-Backlund reaction, an interesting cyclic enediyne has been made (equation 26). ... 

Thiols may be converted into alkenes with one extra carbon atom by successive chloromethylation, oxidation at sulfur, and Ramberg-BScklund rearrangement. If the original thiol is prepared by free radical addition of H2S to an alkene, the sequence constitutes a one-carbon homologation of alkenes. Although these transformations were at one time important applications of the Ramberg-Backlund reaction, they have hardly been used in recent years. 

Incorporation of deuterium at the vinylic positions of alkenes can be carried out very efficiently by performing the Ramberg-BScklund reaction in D2O. Finally, the recently developed Michael-induced and vinylogous modifications of the Ramberg-Backlund reaction offer useful approaches to conjugated dienes and polyenes. 

It is now widely accepted that a-halo sulfones are converted into alkenes under the basic conditions of the Ramberg-Backlund reaction via intermediate thiirane 1,1-dioxides (Scheme 7). Experimental data in support of this mechanism were first put forward by Bordwell in 1951, and extensive studies carried out since that time, particularly by Bordwell and Paquette in the late 1960s and early 1970s, have substantiated this overall scheme and have provided further insight into the mechanisms of the individual steps. Very little additional work concerning the mechanism of the reaction has been published since 1975. Consequently, only a summary of the essential features is presented here, and readers are referred to the detailed reviews, written by the leaders of the key research groups themselves, for the full data which support the following broad outline. ... 

Variations of the Ramberg-Backlund reaction have been described in which the usual halide ion is replaced by p-toluenesulfonate or p-toluene-, alkane- or trifluoromethane-sulfinate leaving groups. For example, Meyers has described a single transformation of the Ramberg-Backlund type of an a-tosyloxy sulfone (Scheme 9). The reaction is surprisingly slow, nearly 1000 times slower than that of the corresponding a-chloro sulfone under the same conditions, and this, of course, limits its value in synthesis. Another problem is the fact that the precursors are not easy to prepare. 

An example of sulfinate functioning as a leaving group is shown in equation (16), ° while another forms the basis of a useful synthesis of 3-cyclopentenones (Scheme 22). Zwanenburg has reported a transformation related to the Ramberg-Backlund reaction in which the halide leaving group is replaced by sulfinate and, in addition, the usual sulfone is replaced by sulfoxide. ... 

In 1964, Paquette reported that although the 9,10-double bond of simple phenanthrenes can be formed using the Ramberg-Backlund reaction (NaOH in aqueous dioxane), the sterically crowded 4,5-dimethyl-phenanthrene cannot be made by this method. Staab has now shown that the highly strained proton sponge 4,5-bis(dimethylamino)phenanthrene (15) can be prepared using Meyers modification of the re-... 

The generally accepted mechanism of the Ramberg-Backlund reaction (Scheme 39) involves the deprotonation of the a-chlorosulfone by the base to give the sulfonyl carbanion (92). The latter undergoes an intramolecular nucleophilic attack on the a-carbon atom with elimination of the chloride anion and formation of the episulfone (93), which is unstable and extrudes sulfur dioxide to yield the alkene (Scheme 39).6 The Ramberg-Backlund reaction, unlike the Julia reaction, yields mainly the (Z)-alkene from acyclic starting materials. 

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