Epoxy ketones, fragmentation

Reagent for characterisation of alcohols and sugars, dehydrations and epoxy ketone fragmentations. Mp 108-110°. 

For other methods of fragmentation of an a,p-epoxy ketone derivatives, see Mac Alpine, G.A. Warkentin, J. Can. J. Chem., 1978, 56, 308, and references cited therein. 

The fragmentation is stereospecifically anti as shown by complementary geometry obtained in the cleavage of the epimeric pair of epoxycyclobutanones 91 and 92 (Eq. 110). The fragmentation product 93 of cyclobutanone 91 is transformable into the dimethyl ester of the pheromone of the Monarch butterfly. Considering the availability of the starting epoxy ketones from enones, the oxasecoalkylation serves to reorient the oxidation pattern with chain extension as summarized in Eq. 111. 

The reaction starts with formation of the tosylhydrazone from the epoxy-ketone. The tosylhydra-zone is unstable with respect to opening of the epoxide in an elimination reaction, and it is this elimination that sets up the familiar 1, 2, 3, 4 system ready for fragmentation. The push comes from the newly created hydroxyl group, and the pull from the irresistible concerted loss of a good leaving group (Ts ) and an even better one (N2). Notice how all the (green) bonds that break are parallel to one another, held anti-periplanar by two double bonds. Perfect ... 

Pyrolysis, photolysis, and electronolysis of ethylene oxide (128) yielded similar products (P. Brown et al., 1966). Electron impact-induced fragmentation (129) of the epoxide (51) (P. Brown et al., 1966) was similar to the photochemical behaviour (130) of the epoxide (52) (Kristinsson and Griffin, 1966). Rearrangement of the a,/3-epoxy-ketone to the diketone after ionization (131) has been suggested to account for... 

Epoxides will fragment if carbanions are formed adjacent to the epoxide ring. Decomposition of the hydrazone of an epoxy ketone in the presence of base may lead to an allylic alcohol (Scheme 2.24). Since the epoxy ketone may be prepared from an unsaturated ketone, this can form part of a sequence for the 1- 3 transposition of an oxygen function. 

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. 

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. 

The first examples to demonstrate the synthetic power of this method were the preparations of exal-tone (118) and muscone (119), starting from the a,p-unsaturated ketones (135) and proceeding via the epoxy ketones (136), the tosylhydrazones of which are cleaved to the cycloalkynones (137 Scheme 44). A little later, Tanabe described the same reaction type starting from epoxydecalones, using this fragmentation for the synthesis of secosteroid alkynic ketones. ... 

The formation of epoxy ketones from sterically crowded enones is often difficult. Avoiding the epoxi-dation step, fragmentation to give the alkynone (137 Scheme 47) occurs on treatment of the unsaturated hydrazones (145) (from 135) with an excess of NBS in methanol. Ohloff and Buchi used this sequence for a further synAesis of exaJtone (118) and muscone (119). 

During modei studies for the synthesis of botrydiane sesquiterpene antibiotics, B.M. Trost and co-workers prepared a compiex 1,6-enyne precursor for transition metal catalyzed enyne metathesis reactions. The 1,6-enyne was prepared from a heavily substituted alkynal, which was synthesized via the Eschenmoser-Tanabe fragmentation of an epoxy ketone. The resulting alkynal was unstable, so it was immediately subjected to a Wittig oiefination to afford the desired 1,6-enyne. 

Eschenmoser-Tanabe fragmentation Formation of alkynals or alkynones from epoxy ketone hydrazones. 158... 

Schreiber, J., et al. Synthesis of acetylenic carbonyl compounds by fragmentation of a,P-epoxy ketones with p-tolylsulfonylhydrazine. Helv. Chim. Acta 1967, 50, 2101-2108. 

Eelix, D., Schreiber, J., Ohioff, G., Eschenmoser, A. Synthetic methods. 3. a,P-Epoxy ketone->alkynone fragmentation. I. Synthesis of exaltone and ( )-muscone from cyclododecanone. Helv. Chim. Acta 1971, 54, 2896-2912. 

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