Ramberg-Backlund reaction, sulfone synthesis

Most thiirene dioxides (and oxides) have been prepared through a modified Ramberg-Backlund reaction as the last crucial cyclization step, as illustrated in equation 40 for the benzylic series . Synthesis of thiirene dioxides requires two major modifications of the originally employed reaction first, the inorganic base has to be replaced by the less basic and less nucleophilic triethylamine - and second, the aqueous media has to be substituted by an aprotic organic solvent (e.g. methylene chloride). Under these mild reaction conditions the isolation of aryl-substituted thiirene dioxides (and oxides) is feasible . In fact, this is the most convenient way for the preparation of the aryl-disubstituted three-membered ring sulfones and sulfoxides. ... 

Alkene synthesis.1 This sulfone can be subjected to successive alkylation in the order shown in equation (I) to give a tetraalkylated derivative, but the fourth alkylation requires elevated temperatures and an activated reagent such as benzyl bromide. The alkylated derivatives on treatment with base undergo a Ramberg-Backlund reaction to give alkenes. 

Exercise 21-24 a. Sulfur dioxide is an angular molecule that can be represented as having a nonbonding electron pair in an sp2 hybrid orbital and one vacant p orbital on sulfur. Use this formulation to derive a thermally allowed transition state for the reversible 1,4-cycloaddition of S02 to 1,3-butadiene (Section 13-3C). b. The three-membered ring sulfone, shown below, is very unstable and rapidly dissociates to S02 and ethene. This process is used for the synthesis of alkenes by the dissociation of cyclic sulfones (Ramberg-Backlund reaction). Determine whether the transition state for the thermally favorable reaction is conrotatory or disrotatory. 

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. ... 

The Ramberg-Backlund reaction has also been applied to the synthesis of cyclopentadienes. For example, the a-chloro sulfone (12), a single unidentified diastereoisomer, was converted regiospecifi-cally into the cyclopentadiene (13). In principle, the acidity of the product requires the use of at least 2 equiv. of base for optimum yields, but, in practice, more than 1 equiv. of Bu"Li causes appreciable polymerization. 

In 1977, de Waard at the University of Amsterdam conceived and prosecuted a novel approach that he dubbed the Michael-induced Ramberg-Backlund (MIRB) olefin synthesis. 24,25 The reaction of dienyl sulfone 25 with one equivalent of sodium phenylsulfinate produced the Michael-induced Ramberg-Backlund product 26 in 40% yield. 

As far as polyenes are concerned, the Ramberg-Backlund reaction is an extremely powerful tool in putting the double bonds together. Herein just two examples are listed. Cao applied the Chan modification on a group of allylic dienylic sulfones and achieved the stereoselective synthesis of substituted all-tram-1,3,5,7-octatetraenes as exemplified by transformations 9899. 55 Polyene 101 was produced from sulfone 100 using the Chan modification as well.56... 

In a formal total synthesis of steroid brassindole, sulfide 102 was used as the substrate of the Ramberg-Backlund reaction.57 Chlorination of 102 followed by oxidation with m-CPBA, and treatment of the resulting chloro-sulfone with potassium t-butoxide, provided symmetrical olefin 103. 

Hart assembled olefin 109 convergently from benzyl bromide 106 by taking advantage of the Ramberg-Backlund reaction.59 As depicted below, the Sn2 displacement of benzyl bromide 106 with thiol 107 led to sulfide 108. Oxidation of 108 to the sulfone, followed by the Myers modification delivered alkene 109, an intermediate for the synthesis of C-aryl glycosides related to chrysomycins. 

The Ramberg-Backlund reaction converts a-halo sulfones into alkenes in the presence of a base with extrusion of S02. The a-metallated intermediates formed by the action of a polar base undergo 1,3-elimination with formation of unstable thiirane dioxides of type 83 that decompose into alkenes - - SO2 (cheletropic elimination). Halogenation is done under basic conditions using CBr2F2. The reactions has been applied to the synthesis of C-glycosides of type 84, as illustrated in Scheme 22.23. " ... 

The Ramberg-Backlund rearrangement was the key step in the total synthesis of the marine alkaloid manzamine C by D.l. MaGee and E.J. Beck. The azacycloundecene ring was stereoselectively formed by exposing the a-chloro sulfone to a strong base. The use of weaker bases either resulted in no reaction or gave rise to mixtures of ( )- and (Z)-alkenes. 

Internal alkylation takes place on reaction of a-haloalkyl alkyl sulfones with bases and produces epi-sulfones as intermediaries. These intermediates are usually unstable and provide alkenes by thermal extrusion of sulfur dioxide. This reaction, known as the Ramberg-Backlund rearrangement, has been widely used in synthesis and has been thoroughly reviewed (Scheme 107, entry e).36-3. 43<.473... 

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