Eschenmoser ring cleavage

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

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

Improved conditions have been found for the synthesis of cycloalkynones by Eschenmoser fragmentation of bicyclic epoxy-ketones. Various cyclodecene derivatives have been prepared from the Diels-Alder adduct of cyclo-octyne and furan-3,4-dicarboxylates, ° and some simple cyclodecanones have been obtained from 9-decalinols by radical-induced ring cleavage. ... 

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...

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%. 

The sequence developed by Eschenmoser et al. provided a means for cleavage of the A ring (97 — 103) without loss of carbon. Addition of meth-... 

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. 

Ring B pyrrole aldehyde (78) and ring C lactam (79) form under base induced condensation and subsequent introduction of sulfur the bicyclic BC thiolactam (80). This bicyclic lactam was coupled by a modification of Eschenmoser s sulfide contraction method 58) with the monocyclic chiral D building block (81) to yield after ester cleavage and complexation with nickel (II) the tricyclic intermediate (82). After hydrogenolytic cleavage of the benzylester in (82) the crude carboxylic acid formed with the ring A pyrrole aldehyde (83) the linear tetrapyrrole... 

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