Hydrazones from ketones

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

A considerable number of examples will be found in the text in which halo-genated and other substituted olefins are produced. Their modes of fonnation do not usually differ in principle from the corresponding unsubstituted case. However, some special methods have been used, for example, the direct preparation of halo olefins from ketones with phosphorous hahdes, or via hydrazones. 

In the case of alkylated SAMP-hydrazones derived from aldehydes, only two stereoisomers are observed, i.e., the (S,R)-(E)- and the (S,S)-( )-isomers. During H-NMR measurements of alkylated SAMP-hydrazones derived from ketones, a slow isomerization of the (S,R)-(Z)- and (5,S)-(Z)-isomers, generated during metalation, to the thermodynamically more stable (SJi)-(E)- and (S,5)-( )-isomers occurs3. 

SAMP-Hydrazones derived from ketones may also be cleaved by treatment with three equivalents of sodium perborate tetrahydrate at pH 7 in water/rert-butyl alcohol at 60 °C. Hydrolysis of aliphatic derivatives is effected in 4-24 hours and reactions yielding aromatic ketones proceed within 2- 3 days. This cleavage reaction furnishes the desired ketones chemoselectively in the presence of olefinic double bonds in 85-95% yield (cyclopentanone 70% yield)30. 

Regiospecific and enantioselective aldol reactions 168) were also performed with SAMP (137). Lithiated hydrazones obtained from ketones (154) as described above were alkylated with carbonyl compounds and the adducts then treated with chloro-trimethylsilane. The resulting trimethylsilylethers (155) were finally oxidatively hydrolyzed to yield the chiral (3-hydroxyketones (156) (e.e. = 31-62%)168),... 

ElectrophiHc substitutions with carbon and hetero electrophiles a to the carbonyl group of aldehydes and ketones are among the most important synthetic operations. Such regio-, diastereo-, and enantioselective substitutions can be carried out efficiently with the SAMP/RAMP hydrazone methodology [3]. For cases where virtually complete asymmetric inductions could not be attained, an alternative approach based on a-silylated ketones 2 was developed [4]. They can be prepared easily from ketones 1 in high enantiomeric purity (ee > 98%) by asymmetric carbon silylation employing the SAMP/RAMP hydrazone method (Fig. 1.1.1). After the introduction of various electrophiles via classical enolate chemistry with excellent asymmetric inductions, the desired product ketones 3... 

In the meanwhile, a new method for preparing various sec-alkane-phosphonates (103) from ketones by way of the hydrazone 101 and then the substituted tolylhydrazines 102, had been developed.57 By using this... 

R2C—0 - R2CF2. This reaction has been carried out directly with diethyl-aminosulfur trifluoride (DAST, 6, 183-184). It can also be effected by reaction of hydrazones of aldehydes or ketones with bromine fluoride, BrF, generated in situ from NBS and Py(HF)n. Yields from reactions of hydrazones of ketone are in the range 30-95% the yield from reaction of the hydrazone of an aldehyde was 28%. 

Tosylhydrazones can be silylated with (fert-bufyldimethylsilyl)trifluoromethanesulfonate (Me2teriBuSi03SCF3) on the sulfonamide nitrogen. This is how the starting material for a broadly applicable alkane synthesis is produced ( Figure 1.49). Due to their ability to undergo reductive cyanization (Figure 17.69) mesitylene sulfonyl hydrazones allow for a two-step synthesis of nitriles from ketones. 

Fig. 13.35. Enders RAMP method for the generation of enantiomerically pure a-alky-lated carbonyl compounds RAMP, (/ )-aminoprolinol methyl ether or R-l-amino-2-(methoxymethyl)pyrrolidine. While hydrazones derived from ketones, such as compound E, are methylated at the doubly bound nitrogen, the methyla-tion of the corresponding aldehyde-derived hydrazones preferentially occurs at the nitrogen atom of the heterocycle.

Aza-enolates also react cleanly at carbon with acid chlorides. Good examples come from dimethyl-hydrazones of ketones. When the ketone is unsymmetrical, the aza-enolate forms on the less substituted side, even when the distinction is between primary and secondary carbons. The best of our previous regioselective acylations have distinguished only methyl from more highly substituted carbon atoms. 

Hydrogenation of hydrazones and azines is a useful way to prepare hydrazine derivatives. The hydrogenation may proceed further to amines depending on the structure of compound, catalyst, and reaction conditions. Unsubstituted hydrazones (I) are liable to hydrolysis, especially with the hydrazones derived from ketones in acidic media and slow hydrogenation. The ketones thus formed may afford azines (II) by condensation with the parent hydrazones. Hydrogenation of azines affords symmetrically... 

Enders and coworicers have shown that deprotonation of chiral SAMP/RAMP hydrazones (or their substituted analogs) derived from ketones or aldehydes, followed by reaction with Davis oxaziridine reagent provides the a-hydroxy hydrazones in moderate yield but with high diastereoselectivity. Direct unmasking or protection followed by unmasking provides the corresponding a-hydroxy ketones or aldehydes respectively (Scheme 24). Both antipodes of the hydroxylated compounds are available by appropriate choice of (5)- or (R)-proline-deiived auxiliaries. The direction of induction is predictable, if not wholly uniform (R substitution alters the a-stereochemistry for aldehyde hydrazones). The process clearly provides a valuable approach to both systems. 

Both hydrazones formed from ketones (Table 3, entries 1-6) and aldehydes (entry 7) react with bromine monofluoride, although the latter yield is low (28 %). Adamantanone azine (entry 8) reacts with bromine monofluoride afl ording the corresponding em-difluoride in high yield (77%). 

Primary and secondary aUcyltetrasulfanes may be prepared from ketones via hydrazones by reaction with H2S (equations 70 and 71). The mechanism and stoichiometry of equation (71) are unknown, but MeC02H and 2NH4+ are probably formed as by-products, in which case four equivalents of H2S are needed, resulting in a tetrasulfane. 

Derivatives of hydrazine (R NH NH2) react with ketones to form substituted hydrazones of general formula (i). These compounds cannot suffer elimination of nitrogen because the intermediate diimides would be disubstituted, and therefore could not give anions. The effect of forming a substituted hydrazone from an a -substituted ketone is to promote... 

A final method of alkene formation from a-derivatized ketones entails formation of unsaturated tosyl-hydrazones from a,P-unsaturated ketones followed by conjugate reduction with sodium cyanoborohy-diide in acid media. This transformation, which proceeds with regioselective migration of the original double bond, has been applied to the synthesis of quassinoids by Ganem et al. (Scheme 22). A similar... 

The compounds formed with hydroxylamine are known as oximes those from aldehydes are called ald-oximes and those from ketones ket-oximes. The compounds resulting from the action of phenylhydra-zine on aldehydes or ketones are known as hydrazones. 

From Oximes and Hydrazones.—The oximes and hydrazones obtained from ketone acids yield amino acids on reduction with sodium amalgam and glacial acetic acid. 

The azaallyl oidates, Le. enolates derived from ketone imines or hydrazones are synthetic equivalents of the ketone endates and thus two examples of azaallyl enolates are included in th section. Lithiated cyclrdiexanonephenylimine (151) crystallizes out of hydrocarbon solution as the dimeric diisopropylamine solvate (152). Significant disorder between the cyclohexyl and the phoiyl moieties is obse ed in this crystal structure however, it is clear that there are no V-az yl carbm contacts in this structure. This lithiated imine structure can be compared with the lithittted dimethylhydrazone of cyclohexanone... 

Carbanions (c/. Chapter 2, Chapter 3.4) derived from ketones, hydrazones or phosphonates react with 0-alkyl chlorothioformates or thiocarbonates, resulting in 0-alkyl P-oxo- (59), p-hydrazono- (60) or a,P-unsaturated-carbothioates (equation 56). ... 

Methods for the preparation of hydrazones and oximes differ little from those used for the synthesis of imines from ketones and aldehydes in that the appropriate nitrogen species and the ketone are mixed. However, the equilibrium for the majority of reactions of ketones and aldehydes with hydrazines and hy-droxylamine favor the product hydr nes and oximes and removal of the water formed by the condensation is not required. 8(> Acid catalysis is complicated by the basicity of the reagent and, for example, the maximum rate of oxime formation is at approximately pH 4. Complicating reactions can occur such as the 1 2 combination of hydrazine with two ketones or aldehydes to form azines but this is not a problem with the substituted hydrazines that are used for asymmetric induction. 

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). ... 

Eelix, D., Schreiber, J., Piers, K., Horn, U., Eschenmoser, A. New version of epoxy ketone-> alkynone fragmentation. Thermal decomposition of hydrazones from a,P-epoxycarbonyl compounds and W-aminoaziridines. Helv. Chim. Acta 1968, 51, 1461-1465. 

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