Ramberg-Backlund transformation

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. 

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. 

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 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. 

Boekelheide and his collaborators [407] have described a two-step sequence for transforming sulfide linkages to carbon-carbon double bonds — Stevens rearrangement of sulfur ylides and Hofmann elimination — which they found particularly useful for the synthesis of cyclophane derivatives, such as the [2.2]metaparacyclophane-l,9-diene shown. The Ramberg-Backlund rearrangement (see Section 4.3.2) was unsatisfactory for such highly strained molecules. 

Ramberg-Backlund rearrangement of fused dihydrothiepine 1,1-dioxides obtained via [6n+4n] cycloaddition (Section 13.03.5.2) led to benzannulated polycycles <1996JOC7644, 1999JA8237>. The rearrangement was conducted by the sequential treatment of dihydrothiepin 1,1-dioxides 102-106 with Bu OK and A-chlorosuccinimide (NCS) or. V-iodosiiccinimidc (NIS) at —105 °C, followed by the addition of another equivalent of the base (Scheme 13). The benzannulated product 111 was transformed to (-l-)-estradiol 112. 

The Ramberg-Backlund reaction, a novel carbon-carbon bond forming transformation, was discovered in 1940 when ethyl chloroethylsulfone 1, upon treatment with NaOH, was shown to form a mixture of cis and trans 2-butene. (Fig. 1) (7).The reaction has been used sporadically over the intervening years and has just received a comprehensive review in 2003.(2-8 )... 

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. 

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 third halogenative Ramberg-Backlund reaction is the Vedejs modification.16 He treated substrate 14 with NaH and C2CU in DME at room temperature and obtained alkene 15 in l.T ratio of E/Z. However, the Vedejs modification, albeit mild, is limited to sulfones in which the a-position bears a single hydrogen, an ester, and another substituent as exemplified by transformation 16W. 16 It does not work for simple, unactivated sulfones. 

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... 

Li, J. J. Ramberg-Backlund olefin synthesis. In Name Reactions for Functional Group Transformations , Li, J. J., Corey, E. J., Eds. John WUey Sons Hoboken, NJ, 2007, pp 386-404. (Review). 

Review articles have featured advances in the cycloisomerization of l,n-allenynes and Rn-allenenes, " reactions for synthesis of quaternary centres bearing a nitrogen substituent, " the Ramberg-Backlund reaction transforming a-halosulfones into alkenes, " and ring expansion of l,2-benzisoxazol-3-ones with a Vilsmeier reagent system, POCI3 and dimethylformamide (Scheme 75). " ... 

The overall process involving addition of a-bromomethanesulfonyl bromide to olefins and subsequent dehydrobromination followed by base-promoted viny-logous Ramberg-Backlund reaction constitutes a three-step transformation of olefins into 1,3-dienes (Scheme 14) [107]. Conjugated dienes are also available from the Ru(II)-catalyzed reaction of alkenesulfonyl chlorides with olefins [108],... 

---