Sulphonate esters reduction

Base-catalyzed condensation of cyanothioacetamide with ethyl / -(ethoxy-methylene)acetoacetate furnished (127), which was quantitatively 5-methylated to yield (128). Ester reduction and alcohol protection generated (129), which was oxidized to the corresponding sulphone with mcpba. Guanidine cycli-zation to (130) and deprotection then afforded (131), identical in all respects with material prepared by the previously described ring-transformation reaction. 

II. ELECTROREDUCTION OF SULPHONIC ESTERS A. Direct and Indirect Reductions... 

While the available literature only describes the electronic activity of organic arenesulphinates, it should be assumed that esters 1 can undergo cathodic reduction only when R and/or R possess a rather low energy level of their LUMO. In other words, when R and R are fully saturated, it is rather foreseeable that 1 is totally inactive in terms of cathodic reactivity. To the best of our knowledge, all papers devoted to sulphonic esters deal only with the behaviour of arenesulphonates4 and nearly all of them focus their interest on the reduction of tosylates 2 (R" = p-CH3). 

Super-hydride (LlBEt H) has been shown to be more effective than other reagents (e.g.. LAH) for reductive cleavage of epoxides and sulphonate esters. Thus methyl a-abequioslde (3) was obtained in 94 yield on reduction of the epoxy-sugar sulphonate (4), while... 

Reactions.—New systems for the reduction of alkyl halides to alkanes include mixtures of lithium aluminium hydride with transition-metal chlorides (such as Ni or Co" chlorides) and some complex metal hydrides of copper, especially the THF-soluble Li4CuHs. Details of the application of sodium cyanoborohydride to the reduction of halides (and sulphonate esters) in dipolar aprotic solvents have been published. Virtually all other functional groups are inert to this convenient, mild, and efficient system, which has been used to develop a one-pot deoxygenation of primary alcohols (Scheme 39) via the iodides. The alternative cyanoborohydride reagents (55) and the polymeric (56) are also discussed. ... 

Ring cgntractions have been recorded in reductions and displacements of sulphonate esters. Treatment of the 6-deoxy-ditosylate (57) with lithium triethylborohydride gave the furanose (58), as well as the 3-reduced pyranoses (59) and (60), which arose via the mechanisms in Scheme 7. Substantial amounts of the DL-digino-furanoside (61) and the DL-rhodinofuranoside (62) were obtained by reaction of sodium benzoate in DiMF with the 4.-0-fflesylates of DL-... 

In the preparation of various unsaturated amides, the dianion of -phenyl-2-(phenyIsulphonylmethyl)propenamide (49) proved to be a versatile synthon. Borohydride reduction of alkylation products of the dianion occurred in high yield to afford moderate overall yields of ,B-unsaturated amides.The dianion of the corresponding phenyl sulphide alkylated poorly giving small amounts of oth a- and y-alkylation products, whereas the sulphone-ester corresponding to (49) was found to be labile under the deprotonation conditions. Compound (49) was also employed in the development of a general strategy for the synthesis of 3,4-epoxy-2-methylene-alkanoic acid amides (Scheme 29). ... 

Methods reported this year for the reduction of alkyl halides to alkanes include the potassium-dicyclohexyl-18-crown-6 reduction of alkyl fluorides, sodium borohydride reduction of alkyl chlorides, bromides, and iodides (or sulphonate esters) under liquid-liquid phase-transfer conditions, and the selective reduction of tertiary alkyl, benzyl, and allyl halides with the borate (61). Continuing... 

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

Fig. 3.93. The HPLC analysis on metabolites resulting from decolourization of reactive red 22 by Pseudomonas luteola (a) at the beginning of static incubation (IA = 3 639 667, /B = 130 140, Ic 116 243), (b) after static incubation for 4.7 h (/A = 2 231 542, /B = 230 559, Ic = 120 563), (c) after static incubation for 23.4 h (/A = 1 892 854, /B = 428 414, Ic = 205 169), (d) 3-amino t-methoxyphenyl /1-hydroxyl sulphone sulphonic acid ester (AMHSSAE), 90 per cent pure, 52 mg/1, and (e) products resulting from decolourization of Reactive red 22 by chemical reduction with SnCl2, (/A, /B, and 7C represent intensities of peaks A, B, and C, respectively). Reprinted with permission from J.-S. Chang et al. [154].

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... 

Polyhydroxy- phenols. amino acids, di- and polyamino compounds, amino alcohols. Sulphonic acids. Sulphinic acids. Salts. sulphinic acids, aminosulphonic acids and sulphonamides. Some diketones and /3-keto esters. Ethers and acetals. Lactones. Acyl halides. Diaryl ethers. intermediate reduction products of nitro compounds. Sulphones, sulphonamides of secondary amines, sulphides, sulphates and other sulphur compounds. 

Indanyl)-phenol 16 was obtained by reacting p-methoxy-phenyl-acetic acid ethyl ester with benzylchloride to form a-benzyl-p-methoxyphenyl ethyl acetate, saponification into the acid, conversion of the acid with thionylchloride into the chloride, cyclization to 2-p-methoxy-phenyl-l-indanone, NaBH4 reduction to 2-p-methoxyphenyl-l-indanole, dehydration with p-toluene-sulphonic acid in toluene to 2-p-methoxyphenyl-indene, catalytic hydrogenation to 2-p-methoxyphenyl-indene, and treating the ether with HBr [Eq. (5)]. 

The third synthesis, by Crombie et al., utilizes the base-catalysed condensation of the trans,trans-phenyl farnesyl sulphone (10) with trans,trans-Qthy farneso-ate to give the ester (11) as a major product via the intermediate (12). Lithium aluminium hydride reduction again yielded presqualene alcohol (1). In each case the labelled synthetic alcohol, as its pyrophosphate, was incorporated by yeast subcellular particles into squalene in ca. 68 % yield. The minor synthetic isomers were not incorporated. 

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. ... 

This conclusion has been confirmed by a total synthesis of macronecine (7), which involves successive reductions of the racemic pyrrolizidine ester (8) by zinc and acetic acid, followed by lithium aluminium hydride. Resolution was achieved via the a-bromo-D-camphor-n-sulphonate salts. The conclusion concerning the relative stereochemistry in macronecine was substantiated by the preparation of the other three racemates having the same gross structure as macronecine, and a detailed comparison of their n.m.r. spectra. In consequence of this work, the complete structure of macrophylline is as given in (9). ... 

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). 

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