Elimination, direction methylene groups

The same workers42 obtained an optically inactive racemate, 2,4 3,5-dimethylene-D,L-xylitol, by the direct methylenation of the pentitol in the presence of concentrated hydrochloric acid. Acetolysis of the racemate and treatment of the resulting diacetyl-acetoxymethyl-methylene-xylitol (XV) with sodium methoxide afforded 2,4-methylene-xylitol which was identified by its failure to react with periodate (see page 146).42 The labile methylene group may have occupied either the 1,3(3,5)- or the 1,5-position, but the latter possibility was eliminated on the grounds that the p-toluenesulfonate of the dimethylene-xylitol could be converted, by exchange with sodium iodide, into an iodo-desoxy-dimethylene-xylitol, and thence, by reduction, into a desoxy-dimethylene-xylitol, identical with that obtained when the known l-desoxy-2,3,4,5-diisopropylidene-D,L-xylitol was treated with formaldehyde and hydrochloric acid.42... 

S.J. Danishefsky and co-workers identified an exo-methylene hydroazulenone as a versatile intermediate in efforts directed toward the total synthesis of guanacastepene. The exo-methylene group was introduced on the hydroazulene by the two-step Eschenmoser methenylation procedure. The substrate was deprotonated with LiHMDS followed by the addition of 3 equivalents of Eschenmoser s salt. The resulting a-(dimethylamino)methyl ketone was treated with mCPBA to form the A/-oxide, which spontaneously underwent a Cope elimination to afford the desired exo-methylene hydroazulenone. 

Occasionally it is unnecessary to isolate the hydrazone since this is itself accessible by a coupling reaction. Numerous formazans can be obtained by treating compounds containing active methylene groups directly with 2 molar proportions of a diazonium salt. For example, pyruvic acid is converted into 3-oxalo-l,5-diphenylformazan (fi4formazylglyoxalic acid ) in 94% yield by benzenediazonium chloride in potassium hydroxide solution.351 Acyl groups (CH3CO or COOH) are often eliminated in such reactions 343,344,352 thus acetoacetic ester yields ethyl l,5-diphenylformazan-3-carboxylate almost... 

Two cis-structures of homotropilidine are interconvertable 1000 times per second at 180°C. This interconvertabity can be enhanced by eliminating possibility of formation of frans-isomer which can be achieved by connecting 1 and 5-positions either directly or through a methylene group. Ethylene bridge solves the same problem. As a result of these operations we get semibullvalene, barbaralene and bullvalene, respectively. 

Active methylene and methine compounds bearing a leaving group (X) on the y-carbon atom can afford cyclopropyl derivatives via 1,3-elimination of HX. 1,2-Elimination to give alkenes and direct nucleophilic substitution by base may compete with the 1,3-elimination, particularly in the preparation of excessively strained cyclopropyl derivatives. The preferred reaction course is, however, highly dependent on reaction conditions, especially on the nature of the base and solvent employed, as exemplified by the reactions of 4 (equation 7) 4. 

The combination of the chromatographic separation of enan-tiopure p-hydroxysulfoximine diastereomers and reductive elimination results in a method of ketone methylenation with optical resolution. The technique is illustrated in the synthesis of the ginseng sesquiterpene (—)-p-panasinsene and its enantiomer (eq 5). The addition of the enantiopure lithiosulfoximine to prochiral enones or the diastereoface selective addition to racemic enones results in the formation of two diastereomeric adducts. The hydroxy group in these adducts can be used to direct the Simmons-Smith cyclopropanation (eq 6 and eq 7). Catalytic osmylation of such adducts is directed by the anti effect of the hydroxy augmented by chelation by the methylimino group (eq 7). ... 

Nothing is known about the biological conversion of the proposed methylcyclopropane species to the methylene cyclopropyl group found in the hypoglycine (7) skeleton. This can be effected chemically by phenylselenoxide elimination from the cyclopropylcarbinol but this is unlikely to be directly analogous to the biosynthetic route. 

In addition to the examples in Table 1, the Peterson methylenation has been used in several interesting natural product syntheses, as the examples in equation (2)-(6) indicate. Danishefsky and coworkers used the Peterson reaction in an approach to mitomycins (4 equation 2). This tq>plication demonstrated the use of unique elimination conditions. The hydroxysilane intermediate was stable to direct Peterson elimination. Therefore, the removal of the silyl protecting group and the elimination of the silyloxy group were carried out with DDQ in quantitative yield. 

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