Nucleophiles Ramberg-Backlund reaction

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... 

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. 

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. ... 

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. 

The mechanism of the Ramberg-Backlund reaction is rather straightforward. When a-halosulfone 1 is treated with a strong base, deprotonation rapidly takes place to give a-anion 3, which undergoes a backside displacement (intramolecular nucleophilic substitution, SNi) to provide thiirane dioxide 4 (also known as episulfone) as the key intermediate.10 The Swi reaction with loss of halide is the rate-limiting step. Finally, the unstable 4 releases sulfur dioxide and the ring strain to deliver alkene 2. 

Taylor and Evans extended the substrate for the MIRB to other nucleophiles including methoxide, thiol, and amines in place of de Waard s sulfinate.26 For instance, Michael addition of benzylamine to bromo-vinylsulfone 27 gave the adduct as bromo-sulfone 28, which upon treatment with a base led to the Ramberg-Backlund reaction product 29 in 83% yield. 

Particularly useful in cyclic dialkyne chemistry is sulfide as a nucleophile. This is due to a discovery made by Regen and co-workers, who found that the yield of dialkyl sulfides is strongly enhanced when the sulfide reagent is first adsorbed onto AI2O3 thus, the substitution reaction takes place on the surface of the aluminum oxide. As the preparation of cyclic sulfides from dibromides is a stepwise process, these conditions were expected to increase the yield of cyclic sulfides dramatically as one end of the chain is immobilized after displacement of the first bromine [14]. Nicolaou first used this principle in the preparation of a series of cyclic thiadiynes [Eq. (6)] [15]. The cyclic thiadiynes prepared in this way are very useful as they can be converted to cyclic enediyne systems via the Ramberg-Backlund ring-contraction reaction (see below). 

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