Tosylhydrazones hydrocarbons

Two techniques, electrochemical reduction (section IIl-C) and Clem-mensen reduction (section ITI-D), have previously been recommended for the direct reduction of isolated ketones to hydrocarbons. Since the applicability of these methods is limited to compounds which can withstand strongly acidic reaction conditions or to cases where isotope scrambling is not a problem, it is desirable to provide milder alternative procedures. Two of the methods discussed in this section, desulfurization of mercaptal derivatives with deuterated Raney nickel (section IV-A) and metal deuteride reduction of tosylhydrazone derivatives (section IV-B), permit the replacement of a carbonyl oxygen by deuterium under neutral or alkaline conditions. 

The reduction of tosylhydrazones by complex metal hydrides has been used very effectively to prepare saturated steroid hydrocarbons in high yields. ... 

Thus, the 1,2-C pathway dominates when 84 is generated by the thermolysis of a tosylhydrazone salt, but a 1,2-H shift to cyclopropylethene is the major pathway when 84 is generated from either a hydrocarbon precursor or via the atomic carbon abstraction of oxygen from cyclopropylmethylketone at —196°C.U1... 

Homofulvenes 8 (4-alkylidenebicyclo[3.1.0]hex-2-enes <25%), in addition to several hydrocarbon products (10-35%), are formed in the thermal decomposition of sodium salts of bicyclo[3.2.0]hept-2-en-6-one tosylhydrazones 5 at 130-150°C in both protic and aprotic solvents.8 The formation of homofulvenes 8 may be explained by the initial conventional ring contraction of the cyclobutylidenes 6 to the methylenecyclopropanes 7, the strain of which is released in a thermal rebonding to give homofulvenes 8.8... 

The reduction of tosylhydrazones by complex metal hydrides has been used very effectively to prepare saturated steroid hydrocarbons in high yields.317 In certain cases this reduction (with lithium aluminum hydride) takes a different course, and olefins are formed.318 The effect is dependent on both the reagent concentration and the steric environment of the hydrazone.319 Dilute reagent and hindered hydrazone favor olefins borohydride gives the saturated hydrocarbon. The hydrogen picked up in olefin formation comes from solvent, and in full reduction one comes from hydride and the other from solvent. This was shown by deuteriation experiments with the hydrazone (150) 319... 

Fig. 17.71. Reduction of a conjugated tosylhydrazone. Since the diazene intermediate D cannot decompose via a diazene anion (cf. Figure 17.67-17.69) for lack of base and the radical decomposition mechanism of Figure 17.70 is not employed either, the third of a total of three mechanisms of the diazene —> hydrocarbon transformation is presented here.

Conjugated tosylhydrazoncs also can be reduced to hydrocarbons with the method depicted in Figure 14.60, that is, with NaBH(OMe)3.The C=C double bond is retained but it is shifted. Figure 14.61 exemplifies this situation for tosylhydrazone A. The sequence of initial steps A —> B —> D resembles the one shown in Figure 14.60. However, the diazo compound D undergoes a different reaction, namely, a retro-ene reaction. A retro-ene reaction is a one-step fragmentation reaction of... 

A new selective and very mild method for the reduction of ketone tosylhydrazones to hydrocarbons offers promise for steroid chemistry reduction with catechol-borane and buffered hydrolysis gives the hydrocarbon in good yield.193 2,4-Dinitrobenzenesulphonylhydrazine is superior to toluene-p-sulphonylhydrazine for... 

In the second, aprotic decomposition of tosylhydrazone 101 was shown to proceed with conventional cyclopropane ring formation.148 On catalytic hydrogenation, one of the two products (102) was converted to tricyclo[3.3.0.03, 7]-octane (103) (Scheme 20). This hydrocarbon is not only a dehydrobicyclo[3.3.01-octane but is also of interest because of its bisnor relationship to adamantane. 

The pyrolysis of tetramethylenediazirine in the gas phase is a first-order reaction yielding only cyclopentene and nitrogen. Similarly, the treatment of the tosylhydrazone of cyclopentanone with base under aprotic conditions yields cyclopentene as the only hydrocarbon product. Photolysis of this diazirine yields cyclopentene as the principal hydrocarbon product (99.2%), but very small quantities of bicyclo[2,1,0]-pentane (0.3%) and methylenecyclobutane (0.1%) are also formed. In addition, about 0.5% of another hydrocarbon was detected but not identified. Its early position of the chromatogram indicates that it may be a fragmentation product. 

The transition metal complex bis(triphenylphosphine)copper(I) borohydride, (Ph3P)2CuBH4, has also been shown to be effective for the reduction of tosylhydrazones to hydrocarbons under mild conditions (refluxing chloroform). Yields from unhindered aliphatic aldehyde and ketone tosylhydrazones are generally in the range 48-84%. Reductions of hindered ketones (e.g. camphor) and aromatic aldehydes were less successful giving 0-20% of reduced products. ... 

One successful application of cyanoborohydride reductions is the reduction of tosylhydrazones to hydrocarbons which, since its introduction in 1971, has been employed extensively for such conversions. The reductions are most often conducted in 1 1 DMFrsulfolane containing a small amount of acid at... 

The related borane bis(benzoyloxy)borane has also been found to be effective for tosylhydrazone reductions, examples of which are presented in Table 10 (entries 7 and 8). The latter case required the use of NaOD/D20 for efficient deuterium incorporation (instead of NaOAc/ThO). A pyridine-bo-rane complex likewise reduces tosylhydrazones in acidic ethanol/dioxane to tosylhydrazines (91-98% yields), which may be converted to hydrocarbons by treatment with KOH/MeOH or Na0Ac-3H20/CHCl3. ... 

Tosylhydrazones (260) of 3-oxo-steroids (and presumably of other suitable carbonyl derivatives) are reduced to saturated hydrocarbons (261) by sodium cyanoborohydride and toluene-p-sulphonic acid in dimethylformamide-sulpho-... 

In situ reduction of tosylhydrazones by NaBHjCN provides an efficient method for the deoxygenation of carbonyl compounds to furnish the corresponding hydrocarbons (see also Section 3.4). In the case of tosylhydrazones derived from a,P-unsaturated carbonyl compounds, the reduction leads to a stereoselective migration of the double bond to give the corresponding tran -alkene. 

Mechanistic information on the photolytic Bamford-Stevens reaction is provided by the successful isolation of a diazo hydrocarbon as a reaction intermediate from the direct photolysis of a tosylhydrazone sodium salt (90 Scheme 10). This study also clarifies that the carbene derived thermally and that derived photolytically behave differently with respect to the stereoselectivity of the 1,2-hydrogen shift that produces the alkene. 

Cleavage of tosylhydrazones, arylhydrazones, and oximes to their parent ketones simply by exchange in acetone is said to offer a mild and convenient method under non-acidic conditions. Hexadeuterioacetone affords a-deuteriated ketones. Although tosylhydrazones of saturated ketones are reduced by borohydride in methanol to give hydrocarbons, similar treatment of the tosylhydrazone of cholest-4-en-3-one gave a mixture of 3a- and 3/S-methoxycholest-4-enes, apparently through a diazonium alkoxide ion pair. The reduction of tosylhydrazones of... 

Selective reduction of aliphatic ketones and aldehydes to hydrocarbons,6 Aliphatic ketones and aldehydes can be reduced selectively in high yields to hydrocarbons with sodium cyanoborohydride and p-toluenesulfonylhydrazine in DMF-sulfolane containing p-toluenesulfonic acid at 100-105°. The prior preparation of tosylhydrazones is not necessary because carbonyl groups are reduced slowly by sodium cyanoborohydride. Maximum yields are obtained with a fourfold molar excess of NaBH3CN. Yields are in the range 62-98%. Ester groups, if present, are not affected. Aromatic ketones are not reduced. 

Synthesis and subsequent thermal decomposition of aryldiazomethanes under standard Bam-ford-Stevens conditions has also been utilized to prepare aryl-substituted cyclopropanes. When benzaldehyde tosylhydrazone is mixed with solid sodium methoxide in naphthalene, phenan-threne, and anthracene and heated above 130°C, phenylcarbene is generated. All the three aromatic hydrocarbons are attacked at the site of highest double-bond character to give, albeit in low yield, norcaradienes. The best results were obtained with naphthalene, which gave 1-phenyl-la,7b-dihydro-l//-cyclopropa[a]naphthalene (7) in 9% yield. ... 

In organic acid media, NaCNBHj is converted to acyloxycyanoborohydrides whose reactivity is comparable to that of NaBH4 in CF3COOH, especially concerning the reduction of imines to amines, tosylhydrazones to saturated hydrocarbons, oximes to hydroxylamines, or reductive amination. Depending on the substrate, NaBH4 or NaCNBHj is recommended (Sections 3.3.1, 3.3.4) [GNl]. 

In ether media (diethylether or THF), the nature of the reagent is ill defined. It reduces aldehydes, ketones, and acid chlorides, but leaves esters, anhydrides, and amides unchanged. In methanol, the reduction of enamines and imines to amines may be effected in the same way as the reduction of tosylhydrazones to hydrocarbons (Section 3.3.4). 

In neutral media, they leave carbonyl derivatives intact but reduce tosylhydrazones to the corresponding hydrocarbons under reflux of CHCI3 (Section 3.3.4). This reduction is compatible with a-enone, epoxide, or lactone groups present in the molecule [GL3]. In cold acetone, these reagents reduce acid chlorides to aldehydes [FHl] (Section 3.2.7). In the presence of Lewis acids or gaseous HCl in CHjClj, they reduce aldehydes and ketones. The selective reduction of aldehydes in the presence of ketones can also be realized (Section 3.2.1). These reagents also reduce aromatic azides to amines (Section 5.2). 

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