Reduction with calcium borohydride

11 (x-Dihydroxy-5 -pregnan-20-one from 11 x-Hydroxy-5 -pregnane-3,20-dione  

A solution of 0.25 g sodium borohydride in 140 ml of ethanol is added to a stirred solution of 0.56 g of calcium chloride in 60 ml of ethanol at —25°. The vigorously stirred mixture is treated dropwise at —25° over 5 min with 4.87 g of 1 la-hydroxy-5/S-pregnane-3,20-dione in 100 ml of ethanol. After a further 3 hr at —20°, 10 ml of 40% aqueous acetic acid is added and the mixture is evaporated to dryness under vacuum. The residue is dissolved in 150 ml of ether and the ethereal solution is washed with 30 ml of 2 A hydrochloric acid and twice with 30 ml of water and dried over Na2S04. Removal of the solvent gives 4.6 g of crystals, which are recrystallized from 20 ml of ether to yield 2.9 g (60%) of the dihydroxy ketone, mp 182-184° [aj 110° (ethanol). 

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Irradiation of the 5,7-diene gave the previtamin, which was isomerized and saponified to give la-hydroxy-vitamin D3. For the last synthesis of la-hydroxy-7-dehydrocholesterol recorded here, cholesta-l,4,6-triene-3-one was again used as starting steroid.122 Deconjugation of this trienone with strong base followed by immediate reduction with calcium borohydride led to the unstable 3/3-hydroxycholesta-l,5,7-triene which, without isolation, was converted into the 1,4-addition product (265) upon reaction with 4-phenyl-l,2,4-triazoline-3,5-dione. 

The reduction of ketones containing nitro groups to nitro alcohols is best carried out by borohydrides. 5-Nitro-2-pentanone was converted to 5-nitro-2-pentanol in 86.6% yield by reduction with sodium borohydride at 20-25°. Other nitro ketones gave 48.5-98.7% yields, usually higher than were obtained by Meerwein-Ponruiorf reduction [907]. 2-Acetamido-3-(p-nitrophenyl)-l-hydroxypropan-3-one was reduced with calcium borohydride at — 30° to 70% of threo- and 10% of er7tAro-2-acetamido-3-(p-nitrophenyl)propane-l,3-diol while sodium borohydride afforded a mixture of the above isomers in 25% and 47% yields, respectively [902]. 

Lactitol is a disaccharide sugar alcohol prepared by reduction of the glucose residue to a sorbitol group. It is prepared by hydrogenation of a lactose solution hydrogenation at 100°C for 6 hr and 8825 kPa with a Raney nickel catalyst produces lactitol in nearly quantitative yield (van Velthuijsen 1979 Linko et al. 1980). Hydrogenation of lactose with sodium or calcium amalgam catalysts and reduction with sodium borohydride (Scholnick et al 1975) have also been successful. 

Reductions of cis- and /ran -oxadiazine-5-carboxylates (154 R = C02Me) (Section 6.17.7.2.3.1) with calcium borohydride in THF-ethanol proceed in high yields (90%) without epimerization. Swern oxidation of the resulting alcohols (154 R = CH20H) yields the stereoisomeric aldehydes (154 R = CHO) <89TL5507>. 

Good yields of phenylarsine [822-65-17, C H As, have been obtained by the reaction of phenylarsenic tetrachloride [29181-03-17, C H AsCl, or phenyldichloroarsine [696-28-6], C3H3ASCI25 with lithium aluminum hydride or lithium borohydride (41). Electrolytic reduction has also been used to convert arsonic acids to primary arsines (42). Another method for preparing primary arsines involves the reaction of arsine with calcium and subsequent addition of an alkyl haUde. Thus methylarsine [593-52-2], CH As, is obtained in 80% yield (43) ... 

Palladium catalysts resemble closely the platinum catalysts. Palladium oxide (PdO) is prepared from palladium chloride and sodium nitrate by fusion at 575-600° [29,30]. Elemental palladium is obtained by reduction of palladium chloride with sodium borohydride [27, 31], Supported palladium catalysts are prepared with the contents of 5% or 10% of palladium on charcoal, calcium carbonate and barium sulfate [32], Sometimes a special support can increase the selectivity of palladium. Palladium on strontium carbonate (2%) was successfully used for reduction of just y, (5-double bond in a system of oc, / , y, (5-unsaturated ketone [ii]. 

Palladium catalysts are more often modified for special selectivities than platinum catalysts. Palladium prepared by reduction of palladium chloride with sodium borohydride Procedure 4, p. 205) is suitable for the reduction of unsaturated aldehydes to saturated aldehydes [i7]. Palladimn on barium sulfate deactivated with sulfur compounds, most frequently the so-called quinoline-5 obtained by boiling quinoline with sulfur [34], is suitable for the Rosenmund reduction [i5] (p. 144). Palladium on calcium carbonate deactivated by lead acetate Lindlar s catalyst) is used for partial hydrogenation of acetylenes to cw-alkenes [36] (p. 44). 

More reliable therefore is reduction with lithium aluminum hydride, lithium borohydride or calcium borohydride, which do not hydrogenolyze hydroxy groups [92]. 

S-Benzyl-y-butyrolactones (44) for which convenient preparative procedures are available, and improved techniques for their a-alkylation and a-hydroxyalkylation, provide the most common synthetic route for these lignan sub-classes (39). The Stobbe condensation (40) of aryl aldehyde with dimethyl succinate (Scheme 9) leads to the half-ester (42) which can be catalytically hydrogenated at atmospheric pressure to give the dihydro half-ester (43). Selective reduction of the potassium salt of the latter can be effectively achieved by calcium borohydride (41)... 

Methoxy-a-(phenylthio) ketones, e.g., 3-methoxy-l-phenyl-2-phenylthiopropanone and 5-methoxy-l-phenyl-4-phenylthio-l-penten-3-onc (Table 6), can also be reduced with syn selectivity by zinc borohydride. calcium borohydride and lithium triethylborohydride82. For zinc and calcium borohydride, at least, it is reasonable to suppose that the transition state 4 (where R3 = MOM) is reinforced by /1-chclation. These reagents are actually more successful than L-Selectride in the reduction of 3-methoxy-1-phenyl-2-phenylthiopropanone, where the L-Se-lectridc result is anomalously poor. A /5-hydroxy substrate, 3-hydroxy-2-mcthylthio-l-phenyI-propanone, could be reduced to 2-methylthio-l-phenyl-l,2-propanediol with good syn selectivity using zinc borohydride (yield 65% d.r. 93 7)81. 

Reduction of Carbonyl Groups. Rapid reduction of salts of carboxylic acids to alcohols with 2 molar equivalents of borane in tetrahydrofuran (THF) has been reported. Full details have appeared of the improved procedure for reduction of esters to primary alcohols, using borane dimethyl sulphide (6,157) in THF at reflux, which allows the dimethyl sulphide that is liberated to distil off during the reaction. Further suggested procedures for the reduction of esters to primary alcohols use lithium borohydride in diethyl ether or THF, calcium borohydride in THF, and sodium borohydride in a t-butyl alcohol-methanol mixed solvent. The reactions using lithium borohydride-diethyl ether can be catalysed by lithium 9-boratobicyclo[3.3.1]nonane (1), lithium triethylboro-hydride, or the Lewis acid 9-methoxy-9-borabicyclo[3.3.1]nonane (2). ... 

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