Dithioacetals Raney nickel

Enzymic syntheses are considered next. Xylitol is a substrate for sheep-liver L-iditol dehydrogenase, a NAD-linked enzyme. 1-Deoxy-D-xylitol, prepared by Raney nickel reduction of D-xylose diethyl dithioacetal in a 27% overall yield from D-xylose, was also reported31 to be a substrate, although with a higher Km and lower Vmax. The product was assumed to be l-deoxy-D-f/ireo-pentulose because of the appearance of a yellowish fluorescent spot when a chromatogram was sprayed with acidic 3,5-aminobenzoic acid, resembling that formed from 1 -deoxyfructose. There was no more-rigorous characterization. 

D-Galactose was converted by ethanethiol and hydrochloric acid into crystalline D-galactose diethyl dithioacetal, which was acetonated with acetone-zinc chloride. The product (15) was reduced to the L-fu-citol derivative (16) with Raney nickel. The overall yield of 16 was 29%, and it was characterized as the crystalline 6-p-toluenesulfonate 17. Oxidation of 16 by the Pfitzner-Moffatt reagent55 proceeded readily and, after O-deacetonation, and purification of the product by chromatography on a column of silica gel, L-fucose (18 13% overall yield from D-galactose) and L-fucitol (19 1% yield) were isolated (see Scheme 3). 

The dithiane derivative 60 (Scheme 14) is such a compound, it being made from 2,3 5,6-di-0-isopropylidene-D-mannose by treatment with 2-lithio-l,3-dithiane to give a heptose dithioacetal that was refunctionalized at C-2-C-3 by way of the C-l anion and then converted to the 6,7-epoxide following selective acid-catalyzed cleavage of the 6,7-acetal ring. Treated with n-butyllithium it gives, in 70% yield, the cyclized 61, which is efficiently convertible into validatol 62, a component of validamycin A, by desulfurization with Raney nickel and de-O-protection by use of boron tribromide in dichloromethane [31]. 

We have discussed previously (see Section 2.4) some aspects of the dithioacetalization step involved in this strategy. The presence of the sulfur atoms offers another possibility as a methylene unit results from desulfurization by Raney nickel, dissolved metal or LiAlH4/ZnCl2 reduction [281]. 

All types of electrophiles have been used with 2-lithio-l,3-dithiane derivatives, including alkyl halides, sulfonates, sulfates, allylic alcohols, arene-metal complexes, epoxides, aziridines, carbonyl compounds, imines, Michael-acceptors, carbon dioxide, acyl chlorides, esters and lactones, amides, nitriles, isocyanates, disulfides and chlorotrialkylsilanes or stannanes. The final deprotection of the dithioacetal moiety can be carried out by means of different types of reagents in order to regenerate the carbonyl group by heavy metal coordination, alkylation and oxidation184 or it can be reduced to a methylene group with Raney-nickel, sodium or LiAIII4. 

Hydrogenolysis of the C-S bond can be achieved both by dissolving metal systems (sodium in liquid ammonia) or by catalytic methods, particularly with a finely divided reactive form of nickel known as Raney nickel. When the latter is combined with dithioacetal formation, using either ethanedithiol or propane-1,3-dithiol, the result is a mild method for reducing a carbonyl group to a methylene group. 

A corresponding equilibrium between the pyrrolidine form, the Schiff base, and the dimer exists in aqueous solutions of 4-amino-4,5-dideoxy-L-xylose. Its synthesis proceeds from D-arabinose to 5-O-p-tolylsulfonyl-D-arabinose diediyl dithioacetal, which is reduced to 5-deoxy-D-arabinose diethyl dithioacetal. This compound, in the form of its 2,3-0-isopropylidene acetal, is transformed into 5-deoxy-2,3-O-isopropylidene-D-arabinose diethyl acetal. p-Toluenesulfonyl-ation followed by treatment with sodium azide gives 4-azido-4,5-dideoxy-2,3-0-isopropylidene-L-xylose diethyl acetal, which is reduced in the presence of Raney nickel catalyst to 4-amino-4,5-dideoxy-2,3-0-isopropylidene-L-xylose diethyl acetal (104). 

Another indirect method is conversion of the aldehyde or ketone to a dithioacetal or ketal, and desulfurization of using Raney nickel or another reagent (14-27). 

The reactivity of 120 is much less than that of either a normal alkene or a dithioacetal. Attempts to hydrogenolyze (see Section IV,3) or reduce 120 with Raney nickel, to hydrolyze the dithioacetal (see Section IV,1) with mercury(II) chloride (even in the presence of an overwhelming excess of the reagent), and to ozonize the double bond at —78°, produce only the starting material an analytical sample was prepared by extended treatment of the crude product with a concentrated, aqueous, alkaline solution of potassium permanganate at the reflux temperature.20 Acetolysis, ozonolysis, or brominolysis of 120 at room temperature affords diphenyl disulfide, and extended oxidation with hydrogen peroxide in acetone, with peroxypropionic acid, and with peroxyacetic acid, produces benzene-sulfonic acid, methyl phenyl sulfone, and an uncharacterized explosive, respectively the products occur as intractable mixtures, and the yields are invariably low. 

Raney nickel in aqueous ethanol normally acts to substitute hydrogen atoms in place of all of the alkyl-(or aryl- or other)thio groups present in a dithioacetal, without disturbing other substituents thus, the 2-S-ethyl-2-thio-D-pentose diethyl dithioacetal137 156, 5-S-ethyl-5-thio-D-arabinose diethyl dithioacetal145 (157), and 2,3,4,5-tetra-0-acetyl-6-S-acetyl-6-thio-D-galactose diethyl dithioacetal or its 6-thiocyanato analogue346 (158) react with Raney nickel to... 

Treatment of D-galactose diethyl dithioacetal (112) with an aged preparation of Raney nickel or with a limited amount of the fresh reductant affords348 the corresponding 1-S-ethyl-l-thioalditol (163) as the major product the same process occurs for D-gluco, c-arabino, D-manno, and 6-deoxy-L-manno analogues, and complete reduction of 163 to the deoxyalditol 164 was accomplished by further hydrogenolysis. The stepwise conversion of a methanolic solution of 112 into 163 (isolable in 60% yield), and thence into 164 (isolable in fair... 

Acetolysis of 19-mesyloxy-4-androstene-3,17-dione-3-thioketal under buffered conditions yields the steroidal 3-eno[3,4-b]dithiane 18 in 73% yield. In the absence of buffer, acetolysis leads exclusively to 19-acetoxy-4-androstene-3,17-dione 3-dithioacetal in 65% yield. Subsequent desulfurization of 18 with Raney nickel affords 5f ,19-cycloandrost-3-en-17-one in 81 % yield.The rearrangement of 3-eno[3,4-6]dithiane constitutes a homoallylic cyclopropanation accompanied by sulfur migration. 

Desulfurization with Raney nickel replaces the dithioacetal group by a methyl group. 

Two examples of desulfurization reactions of sugar dithioacetals, in which episulfonium ion formation is postulated, are pertinent here. Treatment of the 3-amino-3,6-dideoxy-D-mannose derivative (324) with Raney nickel gave some of the 1,2,6-trideoxy alditol (326), along with the... 

As in the 19-nor series, reaction of 17-hydroxy-6a-methylprogesterone (10-1) with ethylene dithioglycol proceeds to form the dithioacetal 16-1 (Scheme 6.16). Desulfurization by means of Raney nickel then yields the derivative with a methylene group instead of a ketone at C3 (16-2). Treatment of that intermediate with acetic anhydride in the presence of /1-toluenesulfonic acid gives the progestin angesterone (16-3). 

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