1,2-Ethanedithiol reduction

AHylestrenol (37) is prepared from (32), an intermediate in the synthesis of norethindrone. Treatment of (32) with ethanedithiol and catalytic boron trifluoride provides a thioketal. Reduction with sodium in Hquid ammonia results in the desired reductive elimination of the thioketal along with reduction of the 17-keto group. Oxidation of this alcohol with chromic acid in acetone followed by addition of aHyl magnesium bromide, completes the synthesis... 

Spirapril (37) is a clinically active antihypertensive agent closely related structurally and mechanistically to enalapril. Various syntheses are reported with the synthesis of the substituted proline portion being the key to the methods. This is prepared fkim l-carbobenzyloxy-4-oxopro-line methyl ester (33) by reaction with ethanedithiol and catalytic tosic acid. The product (34) is deprotected with 20% HBr to methyl l,4-dithia-7-azospiro[4.4 nonane-8-carboxylate (35), Condensation of this with N-carbobenzyloxy-L-alanyl-N-hydroxysuccinate leads to the dipeptide ester which is deblocked to 36 by hydrolysis with NaOH and then treatment with 20% HBr. The conclusion of the synthesis of spirapril (37) follows with the standard reductive alkylation [11]. 

Scheme 5. Reaction conditions i, reductive amination ii, protection of amino group iii, Collins reagent iv, Ph3F CHCioH2i" v, hydrolysis vi, Hg(OAc>2 vii, NaBH4 viii, l-decen-3-one ix, ethanedithiol x, Raney Ni xi, HCl-EtOH.

Cyclization by amidomercuration has been reported (391). Reaction of N-methoxycarbonyl-6-aminohept-l-ene (211) with mercuric acetate gave the organomercurial (212). Reductive coupling of 212 with l-decen-3-one in the usual way gave the cis and trans isomers (213). Successive treatment of 213 with ethanedithiol, Raney nickel, and ethanolic hydrogen chloride afforded ( )-sole-nopsin A (Id, 2 parts) and its isomer (Ic, 3 parts), which were separable by preparative gas chromatography (GC) (Scheme 5) (391). 

Cyclization of enone (9) in hexane with boron trifluorideetherate in presence of 1,2-ethanedithiol, followed by hydrolysis with mercury (II) chloride in acetonitrile, yielded the cis-isomer (10) (16%) and transisomer (11) (28%). Reduction of (10) with lithium aluminium hydride in tetrahydrofuran followed by acetylation with acetic anhydride and pyridine gave two epimeric acetates (12) (32%) and (13) (52%) whose configuration was determined by NMR spectroscopy. Oxidation of (12) with Jones reagent afforded ketone (14) which was converted to the a, 3-unsaturated ketone (15) by bromination with pyridinium tribromide in dichloromethane followed by dehydrobromination with lithium carbonate and lithium bromide in dimethylformamide. Ketone (15), on catalytic hydrogenation with Pd-C in the presence of perchloric acid, produced compound (16) (72%) and (14) (17%). The compound (16) was converted to alcohol (17) by reduction with lithium aluminium hydride. 

Attempts to transesterify diorgano tellurium dialkoxides with 1,2-ethanedithiol or 1,3-propanedithiol caused formation of disulfides and reduction of the diorgano tellurium dialkoxides to diorgano telluriums1. 

Moreover, a-cyano-a-epoxy esters are easily reduced to a-cyano-a-epoxy alcohols by NaBH4 in aqueous THF [MR4]. Ethanedithiol can also be an additive for the reduction of esters by NaBH4, except r-butyl esters. Nitrile groups remain unperturbed under these conditions [GEl]. Methyl benzoate is reduced to benzylalcohol by NaBH4-ZrCl4 in THF [ISl],... 

The synthesis of verazine [(25S)-22,26-epiminocholesta-5,22(iV)-dien-3/3-ol)] (95) from tomatid-5-en-3/S-ol was described [64-66). Reduction of 86 with sodium borohydride in methanol afforded diol 87 which, when acetylated, furnished the iV,0,C>-fn-acetate (88). Alkaline hydrolysis of 88 yielded the diol 89. Through partial oxidation with one equivalent of chromium trioxide, the A-acetyldiol (89) gave the ketone 90. Treatment of this ketone with ethanedithiol—hydrochloric acid, followed by desulfurization of the resulting thioketal 91 with Raney nickel, yielded 92. 

Reduction of carboxylic acid esters. Esters are not reduced by sodium borohydride. However, if ethanedithiol is added (excess), most benzoate esters are reduced to benzyl alcohols in high yield. Thiophenol and ethylmercaptan do not share this property. Several aliphatic esters are also reduced by NaBH4 activated by HSCHjCHjSH. ... 

Treatment of 649 with ethanedithiol in the presence of boron trifluoride etherate results in acetal—thioacetal interchange at C-6 and subsequent lactonization of the 4)5-hydroxyl group with the r/-butyl ester, thus furnishing 651 in 83% yield. Reduction of the lactone to a lactol, protection with a MOM group, hydrolysis of the thioacetal, and reduction of the ketone with lithium aluminum hydride gives 653 as a single product. After benzoylation of the alcohol, conversion of the OMOM derivative to carboxamide (OMOM —> OAc CN — CONH2) affords 140 as a 10 1 mixture of isomers. 

Cyclic voltammetry (CV) is useful to probe the electronic effect of pterin and quinoxaline groups on the Mo reduction potential and this method was applied to a series of I MoO(dithiolene) complexes. The results are graphically summarized in Figure 2.16. Within a series of T MoO(dithio-lenes), it is clear that pterin (or quinoxaline) substitution causes a significant shift in the Mo redox potential to more positive values compared to simpler dithiolenes like benzenedithiolate (bdt) or ethanedithiolate (edt). This conclusion seems to contradict the results from EPR and MCD studies of Tp MoO(pterin-dithiolene vs. T MoO(bdt), which, as noted above, failed to reveal any differences among the dithiolene complexes. 

A more promising approach to 4-deoxo derivatives of eucomol appeared to be reduction of a suitable thioketal derivative. Eucomol (10) itself did not react with ethanedithiol and boron-trifluoridediethyl ether complex as catalyst. The negative result is probably due to chelate formation. 5,7-Di-O-methyleucomol (24), however, was smoothly transformed to the thioketal (70) which gave 4-deoxo-5,7-di-0-methyleucomol (71) and the racemic chromane (73) on treatment with Raney nickel in ethanol. An attempt to interrelate these compounds via an elimination of water from (71) in boiling acetic anhydride yielded only the 3-O-acetyl derivative (72) (64). 

Reduction of l,3-dithiole-2-thione and its benzo-derivative with lithium aluminium hydride gives ethanedithiol and thiocatechol respectively, but similar reduction of the cyclohexene compound (59) replaces the thio-carbonyl group by a methylene group. ... 

The nitroketone 118 (see Section IV,B,1) was treated with hydrogen chloride in ethanedithiol to afford the thioketal 119. Reduction of 119 with zinc and acetic acid and further treatment with Raney nickel in ethanol furnished lactam 120. Hydrolysis of 120 in aqueous methanol containing K2C03 gave 121, which on LAH reduction horded the amine 122. On treatment with sodium methoxide, the iV-chloro derivative of 122 gave verazine (123) (215). 

Scheme 8.106. The reaction of 1,2-ethanedithiol with cyclohexanone to produce the corresponding dithioketal and reduction of the latter with Raney nickel to cyclohexane.

Dithioketals and dithioacetals can be induced to undergo reductive desulfurization on heating alcoholic solutions of those dithio-derivatives in the presence of moist Raney nickel (see, e.g., page 746). These sulfur compounds are prepared by treating the aldehyde or ketone with 1,2-ethanedithiol (CAUTION STENCH) in the presence of an add catalyst (an addition to the carbon of the carbonyl with loss of water, a process that will be discussed at length, vide infra) (Scheme 9.13). 

Finally, in this vein, as pointed out earlier (Chapter 8), thiols behave much the same as alcohols and thus 1,2-ethanedithiol reacts with cyclohexanone to produce the corresponding dithioketal (via the corresponding thiohemiketal) as shown in Scheme 9.63. Reductive desulfurization of the dithioketal with, for example, Raney nickel, in the presence of hydrogen (Ft2), yields the alkane (Chapter 8, Scheme 8.106). 

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