Fragmentation, Eschenmoser

Ring opening by intramolecular attack by an electron source located on a /3-carbon is represented by the Wharton reaction (Scheme 62) (8UCS(P1)2363) and the Eschenmoser fragmentation (Scheme 63) (81S276). 

Treatment of 210 under traditional Eschenmoser fragmentation conditions gave only low yields of the desired alkynyl ketone 211, but this result was improved significantly by use of p-nitrobenzenesulfonylhydrazine in place of the commonly used p- lolueriesul fonylhydrazine. Compound 211 was transformed into the bis-oxime 212, reductive cyclization of which by treatment with ZrCU and NaBH4 and subsequent acylation afforded the polycyclic compound 213 with the desired all-cis... 

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

A simple, high yielding (65-90%) procedure has been described for the preparation of medium ring and macrocyclic acetylenic lactones which is mechanistically related to the well known Eschenmoser fragmentation reaction, and the following example is representative. Bromination of the tosylhydrazone of 1 was carried out with NBS at -10°C in a water/t-butanol/acetone mixture. The reaction mixture was then treated with aqueous NaHSC>3 solution and the resulting mixture heated at 50-60°C for one hour, which gave the acetylenic lactone 2. 

There is much current interest in the design and development of the "double functional group transformation" concept, an excellent illustration of which is the now well known and widely exploited Eschenmoser fragmentation reaction. A recent example of the "double functional group transformation" is the one-flask conversion of 1-nitrocycloalkenes into terminally unsaturated nitriles by treatment first with trimethylsilylmethylmagnesium chloride (1.8 eq.) in THF at -20°C and then, in situ, with PCI3 (2.5 eq.) at 67°C. 2-Nitrobicyclo[2.2.1]hept-2-ene, for example, gave cis-1 -cyano-3-vinylcyclopentane in 33% yield, and similar yields of ene-nitriles were obtained from a variety of monocyclic and bicyclic 1-nitrocycloalkenes. 

The a,/1-epoxyketone — alkynone fragmentation is called Eschenmoser fragmentation [43]. 

The Eschenmoser fragmentation does not have to be a ring expansion, and it is a useful synthetic method for making keto-alkynes. The following reaction, which we will use to discuss the fragmentation s mechanism, was used to make an intermediate in the synthesis of an insect pheromone, exo-brevicoinin. 

What steps wo uld be necessaiy to carry out an Eschenmoser fragmentation on this ketone and what products would be formed ... 

ERLENMEYER PLGCHL - BERGMANN Amnoacid synthesis 109 ESCHENMOSER Fragmentation 110 Esehenmoser 241... 

A cyclopentane aldehyde (297) is obtained when verbenone epoxide (298) is treated with zinc bromide. The presence of pinene in the products is difficult to explain, and the difference in products obtained with aluminium chloride (Vol. 1, p. 45) is remarkable. When the toluene-p-sulphonylhydrazone of the epoxide (298) is treated with potassium t-butoxide, both isomers of the cyclobutyl-acetylene (299) are obtained in an Eschenmoser fragmentation. ... 

The compound is an alkyne formed by the Eschenmoser fragmentation (Chapter 38). It is no possible to assign all the NMR with certainty but the alkyne Cs come in the region 70-85 p.p.m... 

The Eschenmoser fragmentation uses a tosyl hydrazone of an cr,/S-epoxy-ketone (p. 1008). epoxide can be made with alkaline hydrogen peroxide and the tosylhydrazone needs tosylhydrazine to form what is simply an imine. Then the fiin can begin. The stereochem y doesn t matter for once. 

Kredible as it may seem, this ylid with an extra three-membered ring, still does the epoxide This method was called nation mentioned in the chapter (pp. 1258-60). The very strained intermediate rearranges in secoalkylation by its inventors and finally fragments in a way quite like the Eschenmoser fragmentation (p. 1008). Chem so 1972 m"477 ... 

Mesitylene-2-sulfonylhydrazone is found to be particularly effective in the Eschenmoser fragmentation reaction. For example, reaction of the epoxy ketone of type (97) gives rise to the corresponding cy-cloalkynone in reasonable yield (equation 51). The same reaction with tosylhydrazone failed, however. 

A special reaction type involves the a,p-epoxy ketone to alkynone fragmentation, often cited as the Eschenmoser fragmentation . First published by Eschenmoser, and a little later and independently by Tanabe, the utility of this fragmentation for the synthesis of open-chained or cyclic alkynones (Scheme 3) is obvious. 

Some examples of the synthetic value of the Eschenmoser fragmentation should be given. Kocienski s economical and highly stereoselective synthesis of both endo- and exo-brevicomin (140) uses the alky-none (139) as an intermediate, easily accessible by fragmentation of the keto epoxide (138 Scheme 45). Stevens used this fragmentation during the course of studies on the synthesis of vitamin B12 precursors. 

Treatment of the steroid (146 Scheme 48) with LTA and TMS-N3 gives the 5,6-seco-5-oxo-7-carboni-trile steroid (147) useful for the synthesis of ring b homoazasteroids. ZbiraF explains the mechanism as an aza analog of the Eschenmoser fragmentation via formation of the azido epoxide. 

Occasionally, the fragmentation is unexpected and unwanted. For the synthesis of sesquicarene (152), Coates heated the sodium salt of tosylhydrazone (150). However, the main reaction was the carbon analog of the Eschenmoser fragmentation leading to the alkyne (151 Scheme SO). 

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