Thioacetals, desulfurization

In much the same vein as above, hydrolysis of the enol ether (13-2) with a weak acid gives the unconjugated 5,9 olefin (16-1). This is then successively converted to a thioacetal, desulfurized, oxidized, and ethynylated. There is thus obtained the orally active progestin tigestol (16-2) [18]. 

Deoxygenation of the carbonyl group of aldehydes and ketones via the intermediacy of their hydrazone derivatives, known as the Wolff-Kishner reduction,offers an alternative to the thioacetal desulfurization method. The Wolff-Kishner reduction in the presence of hydrazine and NaOH (or KOH) has been replaced largely by the Huang-Minlon method,where the deoxygenation is carried out with hydrazine in refluxing ethylene glycol. 

Aldehydes and ketones react with thiols to form thioacetals desulfurization replaces the C—bonds with C— H bonds. 

Wolff-Kishner reduction complements the Cletnmensen and thioacetal desulfurization methods of deoxygenating aldehydes and ketones. Thus, the Clemmensen reduction is unsuitable for compounds containing acid-sensitive groups, and hydrogenation of multiple bonds can accompany desulfurization with hydrogen and Raney nickel. Such functional groups are generally not affected by Wolff-Kishner conditions. 

In Summary The Wolff-Kishner reduction is the decomposition of a hydrazone by base, the second part of a method of deoxygenating aldehydes and ketones. It complements Clemmensen and thioacetal desulfurization procedures. 

Chrzanowska and Rozwadowska (60) performed a total synthesis of ( )-43, using amine 49 and the thioacetal of methoxycarbonylpiperonal (26) as substrates (Scheme 13). These two synthons were joined together under the influence of LDA, and the resulting addition product 50 was subjected to reductive desulfurization with Raney nickel to give racemic peshawarine (43). 

The keto function is frequently deoxygenated via Ra-Ni-mediated desulfurization of thioacetals 412 14 That is, the ketone group can be removed from compound (36) by thioketalization followed by desulfurization with Ra-Ni (81 mmol Ni/mmol) in MeOH for 20 minutes (Scheme 4.118).415... 

The organotitanium compounds produced by desulfurization of the diphenyl thioacetals of aldehydes 28 with the titanocene(II) species Cp2Ti[P(OEt)3]2 29 react with carbon—carbon double bonds to form the olefin metathesis-type products. Thioacetals 28 may be transformed into terminal olefins by desulfurization with 29 under an ethene atmosphere (Scheme 14.15) [27]. This reaction is believed to proceed through a titanacyclobutane intermediate, formed by cycloaddition of the titanocene-alkylidene with ethene. 

An unusual reductive elimination can ensue from titanacyclobutanes possessing an alkenyl group at the carbon a to the titanium atom. Thus, alkenylcarbene complexes 48, prepared by the desulfurization of (fy-unsaturated thioacetals 49 or l,3-bis(phe-nylthio)propene derivatives 50 with a titanocene(II) reagent, react with terminal olefins to produce alkenylcyclopropanes 51 (Scheme 14.22, Table 14.4) [37]. This facile reductive... 

The carbene complexes generated by desulfurization of thioacetals with the titanoce-ne(II) species react with internal alkynes to produce the conjugated dienes 79 with high stereoselectivity (Scheme 14.34) [77]. The process appears to involve syn-elimination of P-hydride from the alkyl substituent that originates from the carbene complex after the formation of titanacyclobutene 80. 

In order to ascertain whether sufficient nickel to complete a given reaction has been used, the liquid phase may be tested for starting material before an attempt is made to isolate a product. In general the sodium fusion test for sulfur is satisfactory for this purpose but in certain individual cases a specific test may be more convenient. Thus, in the desulfurization of thioacetals (mercaptals), unreacted material... 

That the desulfurizing action of Raney nickel is retained even in the absence of hydrogen has been demonstrated by Hauptmann, Wladislaw and Camargo16 who found that Raney nickel which had been deprived of its hydrogen through heating in vacuum at 200° converted, for example, benzaldehyde dibenzyl thioacetal into a mixture of stilbene and bibenzyl. That this type of reaction proceeds by a free-radical mechanism appears... 

A somewhat similar configurational correlation between (leva)-glyceraldehyde and (dexfro)-lactic acid has been made by Wolfrom, Lemieux, Olin and Weisblat.36 Reductive desulfurization of tetra-acetyl-2-methyl-D-glucose diethyl thioacetal (XXVII) and hydrolysis of the product gave 2-methyl-l-desoxy-D-glucitol (XXVIII) oxidation... 

In- the preceding section the reductive desulfurization of some substances which are both thioglycosides and thioacetals has been mentioned here the hydrogenolysis of the simple 1-thioglycosides will be discussed. 

In addition to the common methods of synthesis, it has been shown that the desulfurization of thioacetals yields organogermanes (Equations (7) and (8)) with excellent selectivity in some cases (Equation (9)).8 Ring-opening reactions of strained [l]ferrocenophanes furnish germanium-substituted ferrocenes9,10 (Equation (10)).9... 

The compound in which the 3-keto group is reduced to a hydrocarbon interestingly still acts as an orally active progestin. The preparation of this compound starts with the hydrolysis of dihydrobenzene (13-2) to afford 19-nortestosterone (15-1). Reaction with ethane-1,2-thiol in the presence of catalytic acid leads to the cyclic thioacetal (15-2). Treatment of this intermediate with Raney nickel in the presence of alcohol leads to the reduced desulfurized derivative (15-3). The alcohol at 17 is then oxidized by any of several methods, such as chromic acid in acetone (Jones reagent), and the resulting ketone (15-4) treated with hthium acetylide. There is thus obtained the progestin lynestrol (15-5) [18]. 

Desulfonylation Lithium-Ammonia, 158 Lithium triethylborohydride, 168 Magnesium-Methanol, 170 Sodium dithionite, 281 Sodium naphthalenide, 294 Desulfurization Lithium aluminum hydride-Bis(cyclopentadienyl)nickel, 158 Lithium l-(dimethylamino)naph-thalenide, 165 Lithium-Ethylamine, 158 Dethioacetalization (see Hydrolysis of thioacetals and -ketals)... 

In one report, the enantiomers of the racemic compound 73, whose structure resembles ketone 2a, were separated by fractional recrystallization of the optically active mandelic acid salts [43]. Although we tried to optically resolve the optically active mandelic acid salts of the racemic ketone ( )-2a, no satisfying results were obtained. After several trials, the (+)- or (-)-di-p-toluoyl tartrate salt prepared from ketone ( )-2a was effectively fractionally recrystallized and finally provided the optically active ketones (+)-2a and (-)-2a [42]. The chiral ketone (-)-2a was converted to compound 73 via compound 72 by thioacetalization followed by desulfurization using Raney nickel... 

Alkyl fluorides.1 a-Fluoro sulfides, available by reaction of mercury(II) fluoride with thioacetals, are convertible into alkyl fluorides by reductive desulfurization with sodium in ethanol. 

The substrate for metathesis leading to product 103 was prepared in situ prior to cyclization in the form of a titanium-carbene complex, by desulfurization of thioacetals with low-valent titanium catalysts, such as Cp2Ti[P(OEt)3]2 (Scheme 42 <2000H(52)147 . 

---