Ethynyl compounds, oxidation

The orally active progestational agent 17a-ethynyltestosterone (56) was subsequently obtained by Oppenauer Oxidation. Similarly ethynyla-tion of 3-ethoxyandrosta-3,5-dien-17-one followed by acid hydrolysis afforded the 17a-ethynyl compound (56). ... 

Oppenauer oxidation of the enol ether (34) affords the corresponding 17 ketone (37) (the enol ether is stable to the basic oxidation conditions). This ketone affords the corresponding 17a-ethynyl compound on reaction with metal acetylides. Hydrolysis of the enol ether under mild conditions leads directly... 

Analogous reactions were postulated to occur for 17a-ethynylestradiol and, on the basis of experiments with model compounds, oxidation of the ethynyl group to -COCHO (Huber et al. 2004). 

Oppenauer oxidation of the enol ether (34) affords the corresponding 17 ketone (37) (the enol ether is stable to the basic oxidation conditions). This ketone affords the corresponding 17a-ethynyl compound on reaction with metal acetylides. Hydrolysis of the enol ether under mild conditions leads directly to ethynodrel (39), an orally active progestin. This is the progestational component of the first oral contraceptive to be offered for sale. Treatment of the ethynyl enol ether with strong acid leads to yet another oral progestin employed as a contraceptive, norethindrone (40). ° In practice these and all other so-called combination contraceptives are mixtures of 1-2% mestranol... 

The bromination with alkali hypobromite in aqueous solution gives good results with (hetero)arylacetylenes, enynes (RCH=CHOCH) and diynes (RC=CC=CH) all acetylenes that are more acidic than those acetylenes in the aliphadc or cycloaliphatic series with an isolated triple bond. For the conjugated systems the hypobromite method is superior to the reaction of metallated acetylenes with bromine. Various acetylenic alcohols are also brominated smoothly, which can be explained in part by their better solubility in water. Since in the case of primary and secondary ethynyl alcohols, oxidation of the alcohol can occur, the use of an excess of hypobromite should be avoided. The best procedure is drop wise additon of a small shot measure of hypobromite ro a mixture of alcohol and water. If the bromoalkynes to be prepared are not too volatile, small amounts of THF or dioxane may be added to effect a better solubility of the alkyne in the aqueous phase. Addition of a co-solvent may also be desired when the starting compound is a solid (e.g. ethynylcyclohexanol). 

Formation of diphenyldiacetylene by the oxidation of the copper(i) salt of phenylacetylene was observed by Glaser over a century ago . The modern refinement of the reaction involves shaking an ethynyl compound with an aqueous... 

Ethyne may be condensed first with the alkyl halide to give H3C [CH2]a C=CH or with the difunctional entity to give Hcic(CH2)yY. The carboxyl group can be generated by oxidation of an alcohol or by reaction of halide with cyanide and then with acidic methanol to give a methyl ester. Condensation with acetylene or an ethynyl compound requires the sodium or lithium derivative and is usually conducted in liquid ammonia. Modification of this approach is necessary when the unsaturated centre is close to either end of the molecule. 

Rhodium(lll)-catalyzed redox—neutral coupling of N-phenoxyacet-amides and alkynes led to benzo[l)]furan derivatives (13AGE6033). Furo[2,3-l)]pyran-6-one derivatives were prepared via rhodium(II)-catalyzed reactions of diazo compounds and ethynyl compounds (13T9294). Copper-mediated oxidative annulation of phenols and unactivated internal alkynes afforded benzo[l ]furan derivatives (13CS3706). E t-kaurane maoecrystalV was produced via C-H functionalization (13JA14552). Rhodium-catalyzed intramolecular C-H... 

In a similar way, upon oxidation the lithium stabilized carbanion of an ethynyl compound or the ethynyl compound itself (E 1.4 V/SCE for Fc-C H) leads to a radical that reacts with the surface of carbon as shown in Fignre 3.69. The presence of the Fc group on the surface is ascertained by cyclic voltanunetry and the surface coverage F = 8.1 x 10 mol cm- is equivalent to about 1.8 monolayers [419]. 

Clinical trials of these orally active progestins showed that they were effective as contraceptives with a success rate that exceeded 99%. These compounds were then marketed as obtained from the reaction sequence after appropriate purification. As the analytical methodology improved it became apparent that a small amount of an impurity was present in all active samples. An examination of the reaction scheme allowed ready identification of that by-product. Any unreduced estradiol methyl ether (13-1) will go to estrone methyl ether on oxidation this will then afford the potent orally active estrogen mestranol (9-1) on ethynylation. Subsequent... 

Furan has served as a starting material for the synthesis of methyl rt-tetradeca-frans-2,4,5-trienoate (177), a compound presumed to be a sex attractant of the male dried bean beetle (72TL3777). Conversion of furan to 4,4-dimethoxy-frans-but-2-en-l-al (174) was accomplished in two steps by a previously reported procedure. Intermediate (174) was then ethynylated, acetylated and reacted with lithium dioctylcuprate to yield allene (176). Hydrolysis of the acetal and Mn02-NaCN oxidation of the aldehyde afforded the methyl ester (177 Scheme 37). 

Oxidation of ethynylcarbinols dihydroxyacetonyl compounds.1 This hyperva-lent iodine reagent oxidizes ethynyl carbinols to dihydroxy acetones. 

Oxidative homocoupling Glaser-Hay polymerization of compound 1 [5] - ,poly[trans-bis (Z)-4-ethynyl-6-(triisopropylsilyl)-3-[(triisopropyl-silyl)ethynyl]-hex-3-ene-l,5-diynyl bis(triethylphosphane)platinum(ll)] (2)... 

A neat hydroformylation - allylboration - hydroformylation reaction sequence reported by Hoffmann el al. afforded the pyrano-fused oxepanes 135 and 136 (48% total yield ca 1 1 ratio) from the precursor 134 the compound 134 required a number of steps for synthesis from the alcohol 130, the ethynyl ether 131, and the boronate 133 (by addition of 132) in moderate overall yield. Dess-Martin oxidation of 135 and 136 then afforded the final lactones 137 and 138 [01NJC102],... 

Vinyl and ethynyl groups attached to an imidazole ring can be catalytically reduced to the saturated (or less unsaturated) species and cleaved by oxidation. The corresponding 4-carbaldehyde is formed in 71% yield when l-methyl-2,5-diphenyl-4-styrylimidazole is oxidized with osmium tetroxide. However, they may not react like aliphatic alkenes and alkynes not all addition reactions occur normally, Michael additions are known, and the compounds can act as dienophiles in DielsAlder reactions (e.g., Scheme 132). 

Ethynyl carbinols (propargylic alcohols) such as 134 (Scheme 2.58) represent another important group of oxidation level 3 compounds. Their preparation involves nucleophilic addition of acetylides to the carbonyl group, a reaction that is nearly universal in its scope. Elimination of water from 134 followed by hydration of the triple bond is used as a convenient protocol for the preparation of various conjugated enones 135. Easily prepared O-acylated derivatives are extremely useful electrophiles in reactions with organocuprates, which proceed with propargyl-allenyl rearrangements to furnish allene derivatives 136. 

A number of the condensation reactions of 2-ethynyl-l-methylbenzimidazole are summarized in Scheme 114. The oxidative self-condensation of the compound can take two courses depending on the reaction solvent (74CHE1491). Under Favorskii reaction conditions (KOH in ether) the expected product (212) with acetone is not formed. Instead, further... 

Oxidative coupling of compounds having two terminal ethynyl groups per molecule has been used for the preparation of polymers, as illustrated by equation (9)... 

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

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