Alkenes from hydrazones

Vinyl halides represent yet another important class of intermediates in the conversion of ketones to alkenes. The most widely applied conditions for the conversion of ketones into vinyl halides are those developed by Barton et a/. ° for the conversion of 3p-acetoxyandrost-5-ene-17-one into 3P-hydroxyandrosta-5,16-diene (Scheme 44). These conditions of vinyl halide formation and subsequent reduction have been useful in a number of steroid systems for the introduction of a A -carbon-carbon double bond and have been shown to be compatible with such functional groups as alcohols, isolated double bonds and acetals. The scope of vinyl iodide formation from hydrazones has been studied by Pross and Stemhell, and recently the original reaction conditions were improved by using sterically hindered guanidine bases rather than triethylamine. Haloalkenes have also been prepared from the corresponding ketones by treatment with iodoform and chromium chloride or with phosphorous penta-halides. ... 

The original Shapiro reaction involves the preparation of unfiinctionalized alkenes from ketone tosyl-hydrazones by quenching of the in situ generated alkenyllithium reagents with water. Recent applications of this reaction in natural product synthesis include the synthesis of 9(0)-methanoprostacyclin (Scheme 12), the in vitro conversion of humulene to A ( -capnellene (Scheme 13), the synthesis of die basic skeleton of isoadsirene (equation S2) ° and the total synthesis of the eudesmanolides rothin A and rothin B (equation 53). ... 

Fig, 8 Synthesis of alkenes through coupling of heterocyclic tosylhydrazones with aryl halides, (a) reaction from hydrazone (b) reaction from ketone... 

The mechanism of the Leighton silane promoted acylhy-drazone-alkene cycloaddition is assumed by the authors to be stepwise. The approach of the alkene from the re face of the hydrazone-silane should be controlled by the chiral silane. The exact conformation 66 of the hydrazone-silane... 

Hydroperoxides have been obtained from the autoxidation of alkanes, aralkanes, alkenes, ketones, enols, hydrazones, aromatic amines, amides, ethers, acetals, alcohols, and organomineral compounds, eg, Grignard reagents (10,45). In autoxidations involving hydrazones, double-bond migration occurs with the formation of hydroperoxy—azo compounds via free-radical chain processes (10,59) (eq. 20). 

Isoxazolidinoindolizines and pyrazolidinoindolizines, 268, can be prepared from the oximes or hydrazones 267. 1,3-Dipolar cycloadditions of oxime or hydrazone on to the adjacent alkene occur cleanly by heating the substrate in acetonitrile, or in the case of the basic aliphatic hydrazones, under acidic conditions <1987JOC226> (Equation 40). 

Alkyl- and aryl-hydrazones of aldehydes and ketones readily peroxidise in solution and rearrange to azo hydroperoxides [1], some of which are explosively unstable [2], Dry samples of the p-bromo- and p-fluoro-hydroperoxybenzylazobenzenes, prepared by oxygenation of benzene solutions of the phenylhydrazones, exploded while on filter paper in the dark, initiated by vibration of the table or tapping the paper. Samples were later stored moist with benzene at —60°C to prevent explosion [3], A series of a-phenylazo hydroperoxides derived from the phenyl-or p-bromophcnyl-hydrazones of acetone, acetophenone or cyclohexanone, and useful for epoxidation of alkenes, are all explosive [4], The stability of several substituted phenylazo hydroperoxides was found to be strongly controlled by novel substituent effects [5],... 

Other papers of interest in this section report transamination of camphor-3-carbothioamides with secondary cyclic amines, reaction of camphorquinone with dimethyl /S-ketoglutarate, the use of fenchone (212 X=0) in alkene formation from Grignard reagents, bromination of 2-e/itfo-6-endo-dibromobornane to yield 2,3,6-endo-tribromoborn-2-ene, and camphor-enol trimethylsilyl ether formation by quenching the reaction mixture of butyl-lithium and camphor tosyl-hydrazone with trimethylsilyl chloride. ... 

CHEC(1984) <1984CHEC(2)1> and CHEC-II(1996) <1996CHEC-II(6)1> covered examples of the cycloaddition reaction of diazoalkenes with alkenes yielding 2,3,4,5-tetrahydropyridazines. The diazadiene is normally generated in situ from an a-halogenated hydrazone with the assistance of base. 

Besides the activation of the olefinic partner by a metal, the unfavorable thermodynamics associated with the addition of an enolate to a carbon—carbon multiple bond could be overwhelmed by using a strained alkene such as a cyclopropene derivative286. Indeed, Nakamura and workers demonstrated that the butylzinc enolate derived from A-methyl-5-valerolactam (447) smoothly reacted with the cyclopropenone ketal 78 and subsequent deuterolysis led to the -substituted cyclopropanone ketal 448, indicating that the carbometallation involved a syn addition process. Moreover, a high level of diastereoselectivity at the newly formed carbon—carbon bond was observed (de = 97%) (equation 191). The butylzinc enolates derived from other amides, lactams, esters and hydrazones also add successfully to the strained cyclopropenone ketal 78. Moreover, the cyclopropylzincs generated are stable and no rearrangements to the more stable zinc enolates occur after the addition. 

By contrast with the above examples which involve activated olefins, the addition of zinc enolates to unactivated alkenes is much more difficult to achieve. Although ethylene seems to be an acceptable partner for such additions, the reactions have to be carried out under pressure and require relatively long reaction times. Thus, the butylzinc aza-enolate generated from the SAMP hydrazone of cyclohexanone 452 reacted slowly with ethylene... 

In combination with the range of standard transformations of alcohols, alkenes, and vinylsulfides, these silicon-tethered additions of functionalized radicals offer a versatile and stereoselective approach to amino alcohol synthesis. Whereas vinyl and 2-oxoethyl radicals have not yet been demonstrated as competent participants in the various intermolecular additions reported in the literature, the temporary tether approach allows such functionalized fragments to be installed in an efficient and stereoselective manner. Synthesis of the aminosugar daunosamine from achiral precursors shows how this concept, employing hydrazone radical acceptors, can be merged with asymmetric catalysis to achieve practical synthetic advances. 

Oxadiazoline (59), on irradiation in benzene, forms an equilibrium mixture with its synthetic precursors diphenylketene and diphenyldiazomethane. Ring opening occurs on irradiation in the presence of alcohols (66AHC(7)183). Photolysis of oxadiazolinones (60a) proceeds similarly to thermolysis and a ketone R COR2 is produced concurrently with loss of nitrogen and carbon dioxide. In the presence of cyclohexene the major product is the hydrazone (63) which is believed to arise from a bimolecular photoreaction of the alkene with the oxadiazolinone. Similar photoreactions occur with 2-phenylpropene and diethyl ether (78S535). 

Cycloaddition reaction of diazadienes (generated in situ from an -halogenated hydrazone) with alkenes yielding 2,3,4,5-tetrahydropyridazines followed by aromatization is a general synthetic approach to substituted pyridazines (e.g., 131) a representative example is shown in Scheme 67 <1995TL5703>. 

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