Acetylenic acids, reduction

The cis-fagaramide (J) was synthesized as outlined below. The required acetylenic acid (c) was prepared from piperonal (a) by the Corey s procedure.Treatment of piperonal with carbon tetrabromide, triphenylphosphine and zinc gave the bromo olefin (b) as an oil in 71% yield. The bromo olefin (b) was treated with 2 equivalents of n-butyl lithium followed by quenching with dry ice to give acetylenic acid (c) in 54% yield. Treatment of (c) with excess thionyl chloride without solvent at 50 followed by addition of isobutyl amine in benzene gave the acetylenic amide (d) as a viscous oil in 96% yield. Partial reduction of (d) gave cis-fagarmide (7 ) in 89% yield. 

The synthesis shown above can be modified for preparation of 4-alkylbutenolides (8) by reduction of the acetylenic acid with quinoline-poisoned catalyst (equation II). The optically active bulenolides have been used for a synthesis of optically pure enantiomers of threo- and Aro-4-methy 1-3-heptanols.2... 

The second method of preparation (shown in Scheme 2) depends on treating dehydroepiandrosterone (prepared from cholestrol or sitosterol) with acetylene to form the 17a-ethnyl-17p-hydroxy derivative, which is carbonated to the 17a-propionic acid. Reduction of the unsaturated acid in alkaline solution yields the saturated acid, which cyclizes to the lactone on acidification. Bromination to the 5,6-dibromo-compound, followed by oxidation of the hydroxyl group to the ketone, and then dehydro-bromination to the 7a-hydroxyl derivative, produces spironolactone when esterified with thiolacetic acid. 

Radical Addition. Free-radical addition of toluene-/>-sulphonyl iodide or methanesulphonyl iodide to acetylenes proceeds readily and stereoselectively when the two are mixed in ether and illuminated. The high yields of crystalline products (102) obtained imply that in the mechanism (Scheme 7), chain transfer by the sulphonyl iodide ( 3) is much faster than isomerization of the intermediate vinyl radical (k. The /ra 5-addition was confirmed by zinc-acetic acid reduction to the sulphone, and by Z-ray analysis of one of the adducts. 

Penicillin>derived sulphenic acids have been intercepted intramolecularIy, as in the case of (lOOjt), or intermolecularly, by esterification or by addition to acetylenic esters. Reduction of the sulphenic acid [P(OMe)s, AcjO] gave azetidinone thioacetate (102 v, R = Ac), from which the mercapto-azetidinone (102 v,R = H) was obtained by silver- or mercury-catalysed cleavage. ... 

Electrochemical reduction of 2,3-diphenylthiirene 1-oxide yields acetylene (80%) and benzil (10%). Electrolysis of 2,3-diphenylthiirene 1,1-dioxide in DMF gives trans-stilbene (30%) but in the presence of acetic acid, 1,2-diphenylvinylmethyl sulfone (27%) is obtained in addition to the stilbene (40%) (81CC120). 

Silver fluoborate, reaction with ethyl bromide in ether, 46, 114 Silver nitrate, complexing with phenyl-acetylene, 46, 40 Silver oxide, 46, 83 Silver thiocyanate, 45, 71 Sodium amide, in alkylation of ethyl phenylacetate w ith (2-bromo-ethyl)benzene, 47, 72 in condensation of 2,4-pentanedione and 1 bromobutane to give 2,4-nonanedione, 47, 92 Sodium 2 ammobenzenesulfinate, from reduction of 2 mtrobenzenesul-finic acid, 47, 5... 

Dihydro-2f/-pyran-2-one has been prepared by reductive cycliza-tion of 5-hydroxy-2-pentynoic acid [2-Pentynoic acid, 5-hydroxy-], which is obtained in two steps from acetylene [Ethyne] and ethylene oxide [Oxirane] 3 and by the reaction of dihydropyran [277-Pyran, 3,4-dihydro-] with singlet oxygen [Oxygen, singlet].4,5 2ff-Pyran-2-one has been prepared by pyrolysis of heavy metal salts of coumalic acid [2//-Pyran-5-carboxylic acid, 2-oxo-],8 by pyrolysis of a-pyrone-6-carboxylic acid [211 - Pyran-6-carboxyl ic acid, 2-oxo-] over copper,7 and by pyrolysis of coumalic acid over copper (66-70% yield).8... 

The classification is unaffected by allylic, vinylic, or acetylenic unsaturation appearing in both starting material and product, or by increases or decreases in the length of carbon chains for example, the reactions f-BuOH f-BuCOOH, PhCHgOH - PhCOOH, and PhCH=CHCH20H -PhCH=CHCOOH would all be considered as preparations of carboxylic acids from alcohols. Conjugate reduction and alkylation of unsaturated... 

As corroborated by deuterium labeling studies, the catalytic mechanism likely involves oxidative dimerization of acetylene to form a rhodacyclopen-tadiene [113] followed by carbonyl insertion [114,115]. Protonolytic cleavage of the resulting oxarhodacycloheptadiene by the Bronsted acid co-catalyst gives rise to a vinyl rhodium carboxylate, which upon hydrogenolysis through a six-centered transition structure and subsequent C - H reductive elimina-... 

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