Deprotonations tosylhydrazones

Scheme 5.15 shows some examples of the Shapiro reaction. Entry 1 is an example of the standard procedure, as documented in Organic Syntheses. Entry 2 illustrates the preference for the formation of the less-substituted double bond. Entries 3, 4, and 5 involve tosylhydrazone of a, (3-unsaturated ketones. The reactions proceed by a -deprotonation. Entry 6 illustrates the applicability of the reaction to a highly strained system. 

Figure 10.2 illustrates selected examples of these epoxide products. Aromatic and heteroaromatic aldehydes proved to be excellent substrates, regardless of steric or electronic effects, with the exception of pyridine carboxaldehydes. Yields of aliphatic and a,/ -unsaturated aldehydes were more varied, though the enantio-selectivities were always excellent. The scope of tosylhydrazone salts that could be reacted with benzaldehyde was also tested (Fig. 10.3) [29]. Electron-rich aromatic tosylhydrazones gave epoxides in excellent selectivity and good yield, except for the mesitaldehyde-derived hydrazone. Heteroaromatic, electron-poor aromatic and a,/ -unsaturated-derived hydrazones gave more varied results, and some substrates were not compatible with the catalytic conditions described. The use of stoichiometric amounts of preformed sulfonium salt derived from 4 has been shown to be suitable for a wider range of substrates, including those that are incompatible with the catalytic cycle, and the sulfide can be recovered quantitatively afterwards [31]. Overall, the demonstrated scope of this in situ protocol is wider than that of the alkylation/deprotonation protocol, and the extensive substrate...

The reaction of alkyllithium reagents with acyclic and cyclic tosylhydrazones can lead to mixtures of elimination (route A) and addition (route B) products (Scheme 22). The predominant formation of the less-substituted alkene product in the former reaction (Shapiro Reaction) is a result of the strong preference for deprotonation syn to the N-tosyl group. Nucleophilic addition to the carbon-nitrogen tosyl-hydrazone double bond competes effectively wiA a-deprotonation (and alkene formation) if abstraction of the a-hydrogens is slow and excess organolithium reagent is employed. Nucleophilic substitution is consistent with an Su2 addition of alkyllithium followed by electrophilic capture of the resultant carbanion. 

Salts such as 7 are readily prepared by deprotonation of the p-tosylhydrazone (using freshly generated sodium methoxide) and are isolable materials which can be stored for long periods of time without decomposition and weighed and transferred in air Creary X (1985) Org Synth 64 207... 

Studies of deprotonation regioselectivity in mono-A-substituted ketone hydrazones have mainly dealt with the regiochemistry of ketone tosylhydrazone deprdtonations. Deprotonation of these tosylhydra-zones, as well as deprotonation of mono-A-alkyl- or mono-A-aryl-hydrazones, proceeds predominantly syn to the starting —NHR group. This regioselectivity is plausibly similar to that reported for oxime and imine deprotonations. ... 

Dithioles and Related Systems. - Base-catalysed condensation of the 1,2-dithiolium salt (195) with ethylidenemalononitrile yields the dithiole (196). The action of potassium borohydride on the enamine (197) results in the rearranged thiopyranthione (199), presumably via compound (198). Deprotonation of the bisulphate (200) or heating the tosylhydrazone (201) produces the thienothiophen (202). It has been reported that the dihydrodithiolone (203) is desulphurized by hexaethylphosphoric triamide to yield the thietanone (204). 1,2-Dithiole-3-thiones (205 X = S =... 

The mechanism of the Shapiro reaction is believed to involve initial deprotonation of the NH proton from tosylhydrazone 5 to generate 6, which undergoes a second deprotonation adjacent to the hydrazone group to afford dianion 7. Elimination of lithium p-toluene-... 

As mentioned above, one significant problem with the use of phenyl- or tosylhydrazones in the Shapiro reaction is competing deprotonation of an orfAo-position on the aromatic ring. This side reaction often leads to diminished yields and/or the requirement for >3 equivalents of the alkyllithium base. This problem has been addressed through the use of trisylhydrazones (trisyl = 2,4,6-triisopropylphenyl), which do not contain aromatic protons that are easily metalated.11 For example, trisylhydrazone 15c... 

The a-alkylation of sulfonylhydrazone dianions with disulfides followed by Shapiro reaction has been used to effect the 1,2-transposition of carbonyl groups.19,20 As shown below, treatment of tosylhydrazone 31 with n-BuLi/TMEDA followed by addition of dimethyl disulfide and deprotonation with an additional equivalent of w-BuLi provided vinylsulfide 32.19 Exposure of this compound to mercuric chloride in hot aqueous acetonitrile provided ketone 33 in 75% overall yield. 

Deprotonation of Tosylhydrazones. The deprotonation of tosylhydrazones with NaHMDS provides the corresponding sodium salts very efficiently. The formation of aUyUc alcohols from sugar hydrazones was accompUshed when NaHMDS was combined with LiAlH4 (eq 27). ... 

Initially, the decomposition of tosylhydrazones with base (and variations thereof) was used as a preparative procedure to synthesize a series of aryldiazomethanes and is still a standard method for their generation. This procedure initially involves deprotonation of the tosylhydrazone 1 to form the corresponding anion. When the reaction is performed cold, the tosylhydrazone salt 2 can sometimes be isolated. Upon heating (generally 60 °C or higher), the tosylate anion will dissociate, generating the diazo compound 3. It has been found that this reaction must be performed in either a polar media such as pyridine or methanol, or in a basic aqueous two-phase system. 

Deprotonation of TosyIhyd razones. The deprotonation of to-sylhydrazones with LHMDS provides the corresponding lithium salts, which can be further decomposed into the diazo intermediates. The addition of late transition metal complexes leads to the formation of metal carbenoid species which undergo various reactions, such as cyclopropanation, aziridination, epoxidation, and C-H insertion. For instance, the lithium salt of tosylhydrazone 2, prepared from LHMDS, is reacted with an imine or an alkene in the presence of rhodium(II) acetate and a chiral sulfide to give respectively, the corresponding aziridine or cyclopropane derivatives (eqs 36 and 37). Under similar reaction conditions, the sodium salt prepared from NHMDS works equally well. 

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