Cyclic sulphones reduction

At this stage, it is not possible to decide whether what little reduction that does occur on unstrained, acyclic or cyclic sulphones is occurring directly on the sulphone or whether reduction is indeed occurring on the a,a -dianion as was proposed by Weber70. Further work on the mechanisms of the LAH reactions with sulphones is thus needed to clarify the above proposals. 

It is intriguing to note that this reaction scheme for the reduction of a sulphone to a sulphide leads to the same reaction stoichiometry as proposed originally by Bordwell in 1951. Which of the three reaction pathways predominates will depend on the relative activation barriers for each process in any given molecule. All are known. Process (1) is preferred in somewhat strained cyclic sulphones (equations 22 and 24), process (2) occurs in the strained naphtho[l, 8-hc]thiete 1,1-dioxide, 2, cleavage of which leads to a reasonably stabilized aryl carbanion (equation 29) and process (3) occurs in unstrained sulphones, as outlined in equations (26) to (28). Examples of other nucleophiles attacking strained sulphones are in fact known. For instance, the very strained sulphone, 2, is cleaved by hydride from LAH, by methyllithium in ether at 20°, by sodium hydroxide in refluxing aqueous dioxane, and by lithium anilide in ether/THF at room temperature. In each case, the product resulted from a nucleophilic attack at the sulphonyl sulphur atom. Other examples of this process include the attack of hydroxide ion on highly strained thiirene S, S-dioxides , and an attack on norbornadienyl sulphone by methyllithium in ice-cold THF . ... 

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. 

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). 

The reductive desulphurization of a cyclic sulphonic ester plays a primary role in a stereospecific synthesis of /3-santalene (Scheme 164). 

Properties of Sulphones.—The extreme difficulty experienced in achieving the reduction of open-chain and six-membered cyclic sulphones with sodium bis-(2-methoxyethoxy)aluminium hydride does not apply to five-membered sulphones. Surprisingly, this reagent leads first to the a-monoanion or a,a-dianion, and LiAlH4 also gives sulphides with some exchange of a- H further details are to be elucidated. ... 

The polarographic reduction potentials of the sulphonic acids and derivatives (25 X = heteroatomic groups) and the carbocyclic (25 X = Ph) and heterocyclic sulphones could be well rationalized by HMO calculations. Mesomeric interaction between the conjugated v systems and the SOagroup in diaryl sulphones does not affect the S==0 bonds the case of cyclic sulphones derived from thiophens is different, a finding recently established by i.r. data. ... 

One of the more interesting reactions involving the reduction of a sulphone was recently described in a paper87 that reported on a synthetic approach to biotin. The molecule in question contains a sulphone as part of a thiolane ring that is fused to a cyclic urea. As outlined in equation (33), either functionality can be reduced depending on the selection of... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

Cyclic p-kcio esters and )9-diketones (596) smoothly effect ring-opening of 1,1-bis(benzenesulphonyl)cyclopropane (412) under basic conditions. Reductive cleavage of the resulting sulphones (597) by lithium arylides provides routes to 598 and 599 (equation 210) The bis-benzenesulphonyl compound appears to fulfil the requirements for a propylene 1,3-dipole. The fact that the sulphones can be sequentially removed permits selective introduction of from one to three electrophiles (E) (equation 211). In the case of )5-keto esters, such versatility created a novel three carbon insertion between the ester group and the ketone or a cyclopentane annulation. ... 

In contrast to the usual reaction of aromatic aldehydes with cyclic ketones o-nitrobenzaldehyde condenses with 17-ketones to produce good yields of seco-acids, a reaction which has been applied to the preparation of 16-oxa-steroids. Thus, 3 -hydroxy-5a-androstan-17-one or its acetate affords the seco-steroid (153), which can be oxidised either as the free acid by ozone and alkaline hydrogen peroxide to the diacid (155) or, as its methyl ester (154), with chromium trioxide to the monomethyl ester (156). Diborane reduction of the diacid (155) or lithium aluminium hydride reduction of the dimethyl ester (157) gave the trans-diol (158), cyclised with toluene-p-sulphonic acid to 16-oxa-androstan-3)5-ol (159) or, by oxidation with Jones reagent to the lactone (152) (as 3-ketone) in quantitative yield. This lactone could also be obtained by lithium borohydride reduction of the monomethyl ester (156), whilst diborane reduction of (156) and cyclisation of the resulting (151) afforded the isomeric lactone (150). The diacid (155) reacted with acetic anhydride to afford exclusively the cis-anhydride (161) which was reduced directly with lithium aluminium hydride to the cis-lactone (160) or, as its derived dimethyl ester (162) to the cis-diol (163) which cyclised to 16-oxa-14)5-androstan-3) -ol (164). 

Lactones have also been synthesized from the rearrangement of cyclic compounds. Thus (51) undergoes base-catalysed isomerization and reduction to form the phenylsulphonyl lactone. The sulphone group is reductively cleaved with sodium amalgam and Na2HP04 to form the lactone. ... 

A review of the preparation, structures, and stereochemistry of cyclic acetals of the aldoses and aldosides has appeared. Pyridinium toluene-p-sulphonate has been reported to be a mild catalyst for the formation and cleavage of dioxolane-type acetals, although no carbohydrate examples were quoted. Acetals and ketals of carbohydrates have been used as co-agents to introduce chirality into the products of sodium borohydride reduction of acetophenone, propiophenone, etc ... 

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