Sulfones elimination with base

The sulfonyl halides (ArSOjCl) convert the alcohol into a sulfonate (ArSOjOR), which is a better leaving group than the hydroxyl group. This allows a range of nucleophilic substitutions to be carried out, many of which parallel those found with alkyl halides. Alkyl halides such as iodides are formed by the nucleophilic substitution of the sulfonate by an iodide ion. The reaction in this case proceeds with inversion of configuration. Treatment of the sulfonate esters with bases such as sodium methoxide or collidine (2,4,6-trimethylpyridine), or even just heating them, can lead to the elimination of toluene-4-sulfonic acid and the formation of an alkene. 

In E2 elimination with bases like KOH and CH30Na, most alkyl halides give Saytzeflf orientation. Certain other compounds (quaternary ammonium salts, Sec. 23.5, for example) give Hofmann orientation. Alkyl sulfonates fall in between. With each kind of compound, orientation is affected—sometimes drastically—by the choice of base and solvent, and by stereochemistry. (The percentage of 1-hexene from 2-hexyl chloride, for example, jumps from 33% in CH ONa/ CH3OH to 91% in /-BuOK//-BuOH, evidently for steric reasons.) In all this, we should remember that orientation is a matter of relative stabilities of competing transition states these stabilities are determined by electronic factors—alkene character and carbanion character—with superimposed conformational factors. 

The 2,2 -bis(phenylthiomethyl) dispiroketal (dispoke) derivative is cleaved by oxidation to the sulfone, followed by treatment with LiN(TMS)2. The related bromo and iodo derivatives are cleaved reductively with LDBB (lithium 4,4 -di- -butylbiphenylide) or by elimination with the P4- -butylphosphazene base and acid hydrolysis of the enol ether. The 2,2-diphenyl dispiroketal is cleaved with FeCl3 (CH2CI2, rt, overnight)." The dimethyl dispiroketal is cleaved with TFA, and the allyl derivative is cleaved by ozonolysis followed by elimination. ... 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

The synthesis of 4,5-disubstituted triazoles shown in Scheme 208, carried out on a polymer support with microwave assistance, is based on a similar principle. In the first step, sulfinate 1248 is converted to sulfone 1249. Condensation with aldehydes provides vinyl sulfones 1250. Cyclocondensation of sulfones 1250 with sodium azide generates corresponding triazoline intermediates that eliminate sulfinate 1248 to provide triazoles 1251 in moderate to good yield <2006OL3283>. 

S02. There is much evidence for this mechanism,311 including the isolation of the episulfone intermediate,312 and the preparation of episulfones in other ways and the demonstration that they give olefins under the reaction conditions faster than the corresponding a-halo sulfones.313 Episulfones synthesized in other ways (e.g., 6-62) are reasonably stable compounds but eliminate S02 to give olefins when heated or treated with base. 

Table 4.1 gives the chemoselectivity of E2 eliminations from representative bromides of the type Rprim—Br, Rsec—Br, and Rten—Br. The fraction of E2 product increases in this sequence from 1 to 79 and to 100% and allows for the following generalization E2 eliminations with sterically unhindered bases can be carried out chemoselectively (i.e., without a competing SN2 reaction) only starting from tertiary alkyl halides and sulfonates. To obtain an E2 product from primary alkyl halides and sulfonates at all or to obtain an E2 product from secondary alkyl halides and sulfonates exclusively, one must change the base (see Section 4.4.2). 

Julia-Lythgoe olefmation is probably the most important method for synthesizing acceptor-free, -configured alkenes, starting from an aldehyde and a primary alkylphenyl sulfone. In this two-step procedure, first the sulfone reacts with the aldehyde to form an acetyl-protected alcoholate and second this species undergoes Elcb elimination to afford the desired alkene. (Sylvestre) Julia olefination is a one-step procedure. It also affords -configured olefins from an aldehyde and an alkylsulfone as substrates, but is limited to base-resistant aldehydes. The most advanced variant is (Sylvestre) Julia-Kocienski olefination, which is also a one-step procedure and is applicable to all kinds of aldehydes. The mechanism is shown below. 

Most recently, the immunosuppressive agent FK-S06 (416) has been the target of total synthesis. To date several approaches to the trisubstituted alkene region at C-19 and C-20 have appeared. These preliminary studies allow the comparison between the Warren phosphine oxide approach and the Julia coupling. In the first total synthesis of FK-S06, Jones and coworkers at Merck formed the the alkene deprotonadon of the phosphine oxide (418) and condensation with the aldehyde (417). The hydroxy-phosphine oxides were formed in a ratio of 1 1 in 77% yield. The less polar diastereomer was treat with base to obtain the ( )-alkene (419) in 32% overall yield from the aldehyde (equation 96). Danishefsky utilized the Julia coupling for the formation of the trisubstituted alkene region. The sulfone anion (420) was treated with isobu raldehyde as a model, followed by acetylation and reductive elimination to... 

Direct a-alkylation of anions of allylic sulfones 179 gives products 180 from which PhSOj can be eliminated with mild base (MeONa) to give fi-dienes 181. The more usual condensation of sulfones with aldehydes is not necessary and those adducts 169 may eliminate to give vinyl sulfones instead of alkenes.47... 

The Julia olefin synthesis is rather like the Wittig reaction with a sulfone instead of a phosphonium salt but with one other important difference the elimination step is stereoselective and both dia-stereoisomers of the intermediate can give the same isomer of the alkene. Treatment of the sulfone 147 with a strong base gives the anion 148 (or a metal derivative) that combines with an aldehyde to give a diastereomeric mixture of adducts 149. Elimination by various methods gives, in open chain compounds, mostly -150 but, in cyclic compounds, mostly the Z-alkene.29... 

Conversion of dialkyl sulfones to alkenes either by rearrangement of a-halosulfones with base (via S02 elimination from thiaranedioxides) (Ramberg-Backlund) or by desulfonation of sulfones with BuLi-LAH(Paquette) (see 1st edition). 

Piperine (25) [56] and trichonine (13) [57] have been prepared by reaction of the corresponding a-sulfonyl organolithium compound with N-(4-oxobutanoyl)piperidine and pyrrolidine, respectively, followed by acetylation of the resulting (3-hydroxy sulfone and final base-promoted double elimination (Scheme 13). Using 4-oxobutanoic ethyl ester, this methodology has been applied to the synthesis of dodecatetraeneamide (19) [23],... 

The tosylation of carbon can be accomplished using electron transfer conditions. Treatment of styrene and analogs with Copper(II) Chloride and tosyl chloride or Benzenesulfonyl Chloride results in a formal replacement of the vinyl proton by the sulfonyl moiety (eq 35). The intermediacy of a trans-(S-chloro sulfone has been demonstrated by H NMR. Treatment with base induced the elimination of HCl. A variety of other sulfonyl transfer reagents can be ertployed in the synthesis of isolated /3-chloro sulfones, with good results (60-97% yield) for a variety of alkenes (ethylene, 1-butene, 2-butene, 1-octene, acrylonitrile, methyl acrylate, and 1,3-butadiene). ... 

The radical addition of sulfinates to unsaturated compounds via the iodosulfonylation-dehydroiodination reaction sequence constitutes a general method for the preparation of vinyl sulfones the latter may be rearranged to aUyUc sulfones by treatment with base. The radical addition may be carried out on a, -unsaturated carbonyl compounds as well as alkenes. In the case of unsaturated carbonyl compounds the elimination process can be quite stereoselective, ( )-alkenes being normally formed. For the addition to nonconjugated alkenes, conditions have been described for the preparation of either ( )- or (. -alkenes. ... 

Q -monoamon is more reactive and more basic 12.5). When fully substituted at a the deprotonation of phenylsulfonyl methyl sulfones at a also initiates the Ramberg-Backlund rearrangement with loss of phenylsulfinate ion. When no a -CH is available for deprotonation, treatment with base serves to eliminate triflinate, as in eq 6, and is also used to create cyclic vinyl sulfones when the a-dialkylation is done with a,ffii-dihalides. ... 

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