Reductive desulphonylation

Solanesol and other prenyl alcohols are important as metabolites in mulberry and tobacco leaves and in the synthesis of isoprenoid quinones. Hence, Sato and collaborators107 have developed a stereoselective synthesis of all-trans-polyprenol alcohols up to C50. Construction of the requisite skeletons was accomplished by the alkylation of a p-toluenesulphonyl-stabilized carbanion, followed by reductive desulphonylation of the resulting allylic sulphonyl group. This was achieved most efficiently by the use of a large excess of lithium metal in ethylamine (equation (43)), although all reaction conditions led to mixtures. The minor product results from double bond rearrangement. 

Examples of a desulphonylation procedure on complex molecules are provided by Fuchs and coworkers199 who reported on a triply convergent synthesis of L-( —)-prostaglandin E2. The molecules can be classified as homoallylic sulphones and reductive desulphonylation was best achieved with a mixture of sodium methoxide and sodium borohydride in methanol, with yields being better than 90%, despite the complexity of the molecules involved (equation 87). 

In all the desulphonylation reactions discussed in Sections III.B and III.C the sulphur is lost from the starting sulphone and is reduced in the process simultaneously, the former carbon-sulphur bond is either reduced to a C—H bond or is converted into a C=C bond. The reactions described in this section have the common thread that the sulphur atom is lost with reduction at sulphur, but the carbon atom is converted directly into a carbonyl group. Formally, these reactions offer a route from alkyl halides to aldehydes or ketones. 

Perhaps of more significance is a detailed study132 into the reductive desulphonylation of 7-methyl-7-phenylsulphonylestratrienes. The goal was stereoselective removal of the sulphonyl group, and hydride reductions, alkali-metal-amalgam reductions and electrochemical reductions were explored. The latter proved to be the most effective and the best results are illustrated in Scheme 3. 

Details of the conditions used in these reductions are discussed, especially the fact that this is apparently the first example in which the stereochemical aspects of an electrochemical desulphonylation reaction on a complex molecule have been examined. It is likely that further work will be profitable, given suitable substituents on a molecule, since sulphones (especially vinyl and aryl sulphones) should be good candidates for this type of reduction. 

This synthetic sequence for an olefin synthesis has been further developed by Kocienski who has shown that eliminative desulphonylations carried out on / -acyloxysulphones are remarkably stereoselective for the synthesis of trans-disubstituted-olefins. The method has wide applicability in that a-lithio phenyl sulphones are readily generated, and are readily coupled to aldehydes or ketones, to give j8-hydroxysulphones. The hydroxyl function of these is then esterified and the synthesis is completed by the reductive elimination with sodium amalgam. Kocienski has prepared two reviews that summarize his syntheses of a range of natural products - one of which is diumycinoP obtained... 

The above-described desulphonylation, combined with the previously described selective reduction of a, -unsaturated carbonyl compounds, can be applied to a-alkylidene... 

It has been reported that the reaction of 102 with (TMS)3SiH affords the cyclic sulphone 103 (equation 58) 11. The authors have proposed an unusual mechanistic scheme for this reaction, equivalent to a reductive desulphonylation process. However, a simple chain reaction process cannot account for the large amount of (TMS)3SiH and AIBN used and the prolonged reaction time (>20 h) required. 

Transformation of the ester moiety into the ketone 32 (Arisawa et al. 1997) and reductive desulphonylation (Trost et al. 1976 Somfai and Ahman 1992) generated ( )-anatoxin-a in 88% ee. The natural (+)-enantiomer would be equally accessible simply by switching the chirality of the ligand. 

Reductive desulphonylation of a-alkylidene fi-oxosulphones (typical procedure) To a solntion of NaTeH, prepared from tellurium (0.65 g, 5 mmol) and NaBH (0.45 g, 12 mmol) in EtOH (20 mL) under Nj, is added, while stirring, a solution of a-(p-bromoben-zylidene) )3-ketosulphone (0.73 g, 2 mmol) in DMF (15 mL). The solution, which immediately turns red-black, is stirred at room temperature for 3 h, and after addition of HjO (30 mL) is exposed to air for 30 min, to precipitate tellurium. The mixture is fdtered, the filtrate extracted with EtjO (3x40 mL) and the combined ether extracts dried (MgS04) and concentrated in vacuo to give the crude product, which is purified by SiOj chromatography (elution with benzene/EtOAc, 10 1), giving pure 2-(p-bromophenyl)ethyl phenyl ketone (0.46 g (80%) m.p. 65-66°C). 

Anions from the Schiffs base (78) can be C- or A -alkylated with ethyl iodide or diethyl sulphate. The ratio of the products depends both on the solvent and on the presence of 18-crown-6. In non-polar solvents, the crown ether increases the solubility of the base, and C-alkylation is the major pathway. In dipolar aprotic solvents, the 18-crown-6 breaks up ion pairs by solvation of the Na" cation, and favours A -alkylation. A nerylsulphonamide, formed from (79), undergoes regiospecific reductive desulphonylation to give nerol (80), which implies that (79) is an effective synthon for cisoid iso-prenoids. Chiral complexes of crown ethers, e.g. (81), catalyse the Michael addition reaction of j3-keto-esters and methyl vinyl ketone to give adducts in high optical yields. ... 

A recent synthesis of 11-deoxyanthracyclinones makes use of the ability of bromosulphones such as 75 to undergo annulation reactions with cycloalkan-ones which lack additional activating groups. Reductive desulphonylation and dehydration of the condensation product 77 gave 78 which was converted to ( )-7,ll-dideoxydaunomycinone 79 [65]. 

Base-promoted desulphonylation of this compound provides methyl retinoate (19) (aIl- 13Z=5 l). The Cio-sulphone 28 also works as a coupling partner of 25 (Scheme 9) [11]. The Cio-disulphone 29 thus obtained is converted into 30 by successive oxidation, Pummerer reaction, NaBH4-reduction, Jones oxidation and methylation with diazomethane. Treatment of 30 with NaOMe in MeOH furnishes methyl retinoate (18) (all- 13Z=6 4). 

In the area of non-reducing disaccharides various 2-deoxy, 3-deoxy and 2,3-dideoxy derivatives of a,o-trehalose have been made by reductive desulphonylation of tosylates with lithium tri-ethylborohydride, and a bis-allo-2,3-epoxlde has afforded a route to 3-amino-3-deoxy-a-D-mannopyranosyl 3-amino-3-deoxy-a-D-... 

It has now been reported that magnesium in methanol is an effective alternative reagent for reductive desulphonylation. ... 

Colloidal potassium was also used to desulphonylate cyclic sulphones [106]. This reaction is only synthetically useful under these conditions and is extremely slow in the absence of ultrasound. Furthermore, the reaction is highly regioselective and reductive cleavage occurs preferentially at the more substituted centre giving the product shown (13). This contrasts with the low degree of regioselectivity of literature methods (Scheme 43). 

Several methods for the reduction of allylic functional groups have been reported. Although some of these are derivative of earlier procedures, useful improvements and modifications are noteworthy. For example, combination of [Pd(PhaP)4] with lithium triethylborohydride provides an effective system for the reductive removal of allylic ethers, sulphides, sulphones, selenides, and t-butyl-dimethylsilyl ethers. Many of these functional groups, of course, are not readily removed by other methods. Furthermore, this combination gives good to excellent maintenance of the regio- and stereo-integrity of the allylic double bonds. In a similar fashion, 2-tosyl homoallyl alcohols can be easily desulphonylated to... 

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