Eschenmoser cleavage

Eschenmoser a,p-epoxy ketone cleavage (2,419-422 3,293). In the synthesis of a prostanoid, Corey and Sachdev encountered a case where the Eschenmoser cleavage reaction with p-toluenesulfonylhydrazine gave a very complex mixture from which none of the desired acetylenic aldehyde could be isolated. They then found that cleavage could be effected with 2,4-dinitrobenzenesulfonyl-hydrazine in CH2CI2 or THF at 0-25°. Pyridine, sodium carbonate, or sodium bicarbonate can be used as catalysts. The yield can sometimes be improved by addition of ethyl isocyanate to scavenge the sulfinic acid formed in the fragmentation. This modified procedure was shown to be effective in five cases. 

A -Ergostadiene-Sll-ol, 502 A -5a-Ergostene-3 -ol, 502 Ergosterol, 502 Ergosteryl acetate, 100, 595 Ergosteryl acetate tricarbonyliron, 39 Erythionolide B, 215 Eschenmoser cleavage, 232-233 Eschenmoser s reagent, 106 Esterification, 106, 138, 246, 269, 274,... 

Birch reduction of the bisketal of 54 to the enone 55, followed by Eschenmoser cleavage of the derived epoxyketone with aminodiphenylaziridine, yielded the acetylide 56. Ring B was formed by aldol condensation, hydrolysis of the acetylene to the methyl ketone, and selective ketalization to give 57. The extensive manipulation of protecting groups resulted in a somewhat unsatisfactory overall yield of 14%. 

Selective reduction to 128 was achieved in much improved yield (56%). The A ring modification to 129 was then accomplished by Eschenmoser cleavage of the derived epoxide, addition of methyllithium, and trifluoracetic acid mediated cyclization to 130. 

Dinitrobenzenesulfonylhydrazine (19) has been found to be a useful reagent in the Eschenmoser cleavage of a,/3-epoxy ketones (20), especially in instances where the product is an acetylenic aldehyde such as compound 21 (eq 10). ... 

Equations 1-10 illustrate some mild methods that can be used to cleave amides. Equations 1 and 2 indicate the conditions that were used by Woodward and Eschenmoser, respectively, in their synthesis of vitamin B12. Butyl nitrite, nitrosyl chloride, and nitrosonium tetrafluoroborate (NO BF4 ) have also been used to cleave amides. Since only tertiary amides are cleaved by potassium -butoxide (eq. 3), this method can be used to effect selective cleavage of tertiary amides in the presence of primary or secondary amides.(Esters, however, are cleaved by similar conditions.) Photolytic cleavage of nitro amides (eq. 4) is discussed in a review. 

Schemes 15 and 16 summarize the syntheses of intermediates that represent rings A and D of vitamin Bi2 by the Eschenmoser group. Treatment of lactam/lactone 51, the precursor to B-ring intermediate 8 (whose synthesis has already been described, see Scheme 8), with potassium cyanide in methanol induces cleavage of the y-lac-tone ring and furnishes intermediate 76 after esterification of the newly formed acetic acid chain with diazomethane. Intermediate 76 is produced as a mixture of diastereomers, epimeric at the newly formed stereocenter, in a yield exceeding 95%. Selective conversion of the lactam carbonyl in 76 into the corresponding thiolactam...

Only two operations remain. Reaction of the enolic form of aldehyde 162 with Eschenmoser s reagent (H2C=NMe2+I-)62 in the presence of triethylamine provides the desired enal after a simple / -elimination. Finally, cleavage of the remaining tcrt-butyldi-methylsilyl ether with HF pyridine completes the total synthesis of (+)-brevetoxin B (1). 

Fragmentation of a.fJ-Epoxy Hydrazones Eschenmoser-Tanabe ring cleavage... 

Eschenmoser Fragmentation (Eschenmoser-Tanabe Fragmentation / Ring Cleavage)... 

Eschenmoser, A., Frey, A. Cleavage of methanesulfonyl esters of 2-methyl-2-(hydroxymethyl)cyclopentanone with bases. Helv. Chim. Acta 1952, 35, 1660-1666. 

Acid conditions ensure enolisation on the more substituted side (Chapter 20) and thermodynamic control gives the -isomer of (17)—the one we want. Eschenmoser found that oxidative cleavage of (16) under acidic conditions led to spontaneous lactone formation without the isolation of (15). 

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