Ramberg-Backlund-type

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. 

A Ramberg-Backlund type reaction has been carried out on the a-halo sulfides ArCHClSCH2Ar, which react with r-BuOK and PPh3 in refluxing THF to give the alkenes ArCH—CHAr. 

There have been Ramberg-Backlund-type reactions in which the leaving group is not a halide ion. For example, treatment of the polyalkylated methyl triflone 365 is known to result in a Ramberg-Backlund reaction forming the corresponding olefin. Since methyl triflone 364 can be alkylated successively regiospecifically at the two carbon atoms, Hendrickson and coworkers used this reaction for the synthesis of some tailor-made olefins. 

Lawrence, N. J., Muhammad, E. Ramberg-Backlund type reactions of phosphonium salts. Tetrahedron Lett. 1994, 35, 5903-5906. Wladislaw, B., Marzorati, L., Russo, V. P. T., Zim, M. H., Di Vitta, C. Novel reaction decarboxylative Ramberg-Backlund rearrangement in some a-isopropylsulfonyl carboxylic esters. Tetrahedron Lett. 1995, 36, 8367-8370. 

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. 

A very different sulfur dioxide extrusion protocol has been applied to the total synthesis of (+)-estradiol (30) by Rigby and coworkers. In the event, the trimethylsilyl-substituted chromium thiepin complex 27 participated in a [6 r+4 r] cycloaddition reaction to provide a 70% yield of the structurally complex dihy-drothepin 28. Subsequent sulfur dioxide extrusion via a Ramberg-Backlund-type ring contraction gave tetracycle 29. The total synthesis of (+)-estradiol (30) was completed using a four-step sequence of standard reactions (eq 12). ... 

Potassium hydroxidelcarbon tetrachloride a,/ - thylenesulfonic acids from sulfones Ramberg-Backlund-type rearrangement... 

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

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. 

Chem. Lett. 1984, 833-836. For another variation of the Ramburg-Backlund reaction see Matusuyama, H. Miyazawa, Y. Kobayashi, M. Regioselective Alkylation and the Ramberg-Baecklund Type Reaction of a-( -tolylsulfonyl)thiane S,S-Dioxide. A New Route to the Synthesis of 3-Alkyl-3-Cyclopentenones Chem. Lett. 1986, 433—436. 

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. " ... 

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