Epoxy tosylhydrazones

Cyclic a,p-unsaturated ketones can be cleaved by treatment with base of their epoxy tosylhydrazone derivatives to give acetylenic ketones. The reaction can be applied to the formation of acetylenic aldehydes (R=H) by using the corresponding, 2,4-dinitrotosylhydrazone derivatives.Hydrazones (e.g., 47) prepared from... 

Eschenmoser and collaborators (28) have reported the base induced fragmentation of a.B-epoxy-tosylhydrazones to produce acetylenic ketones (e.g. 69 71). Interestingly, in this fragmentation, both the triple-bond and molecular nitrogen are produced from the key intermediate 70 via an anti mode. The decarboxylation of nitrobenzisoxazole carboxylate (72) into 2-cyano-5-nitrophenol (73) can also be viewed as a trans-elimination (29, 30). 

Still other epoxide cleavage processes can be nucleophile induced, but without direct attack at a heterocyclic carbon. A good illustration of this phenomenon is seen in the alkylative elimination of epoxy tosylhydrazones (62). Optically pure allyl alcohols have been prepared... 

The cleavage of an a.jS-epoxy-tosylhydrazone to give an acetylenic ketone has been employed to generate the 5(10)-seco-compound (386) best yields resulted from epoxidation of the tosylhydrazone of the 5(10)-en-6-one (385), rather than from first forming the epoxy-ketone. Aldol condensation of the derived saturated seco-3,10-dione (387) afforded the A-nor-B-homo-enone (388). The hydrazones derived from a, -epoxy-ketones and 2-phenyl- (389) or trans-23-diphenyl-l-aminoaziridines (390) undergo thermal fission (e.g. in refluxing DMF), also giving acetylenic aldehydes or ketones. ... 

A new type of arenesulphonylhydrazone fragmentation to alkynones has been reported. With N-bromosuccinimide in alcohols, the tosylhydrazone (86) yielded the cyclic alkynone (87), which was subsequently reduced to ( )-muscone [equation (56)]. The method may offer advantages over the Eschenmoser fragmentation of epoxy-tosylhydrazones in cases where epoxidation of crowded enones is difficult. 

A 2-cyclohexenone derivative can be transformed into the corresponding epoxy tosyl-hydrazone by sequential treatment with peracid and tosylhydrazine. The elimination of nitrogen and p-toluenesulfinate and fragmentation after rearrangement to the 3-tosylazo allylic alcohol may occur under mild conditions. Carbonyl compounds with 5,6-triple bonds are formed in high yields (J. Schreiber, 1967 M. Tanabe, 1967). If one applies this reaction to a 9,10-epoxy-1-decalone, a ten-membered 5-cyclodecyn-l-one ring is formed (D. Felix, 1971). This product is an important intermediate in the perfume industry and has been used on a large scale. For this purpose Eschenmoser developed a synthesis in which the readily removed styrene was split off instead of a sulfmic acid. Thus a l-amino-2-phenylaziridine hydrazone was used instead of a tosylhydrazone (D. Felix, 1968). ... 

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 ... 

C(6) [14] and C(7) tosylhydrazones [2y] in contrast gave the A - and A -olefins respectively. A i4a-hydroxy-i7-tosyl-hydrazone (5) reacted with C(i8>"methyl migration and participation by the hydroxyl group to form the i3a,i4a-epoxy derivative (6) [28]. All these reactions can be accommodated by a carbonium-ion mechanism (see below). 

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. 

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. ... 

P-Hydroxy tosylhydrazones, which are the products of a conventional aldol reaction between a dilithi-ated tosylhydrazone reagent and an aldehyde, can also be prepared by alternative routes. For example, Stork and Ponaras have described a procedure whereby an epoxy ketone is converted into an epoxy hydrazone. Subsequent addition of an alkyl- or aryl-magnesium bromide followed by hydrolysis yields either an a-alkyiated- or a-arylated-p-hydroxy ketone or an a,p-unsaturated ketone. Since the attack of the Grignard reagent on the epoxide occurs with inversion at the a-carbon, this reaction can be used to... 

A stirred mixture of 2a,5-epoxy-5a-diolestan-3-one tosylhydrazone and powdered LiH in toluene-xylene refluxed 24 hrs. l), 3) -cyclo-2a,5-epoxy-5a-diolestane. Y 80.7%. F.e. s. T.Komeno and H.Itani, Chem. Pharm. Bull. 19, 1123 (1971). 

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