Sodium borohydride enones

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

All that remains before the final destination is reached is the introduction of the C-l3 oxygen and attachment of the side chain. A simple oxidation of compound 4 with pyridinium chlorochro-mate (PCC) provides the desired A-ring enone in 75 % yield via a regioselective allylic oxidation. Sodium borohydride reduction of the latter compound then leads to the desired 13a-hydroxy compound 2 (83% yield). Sequential treatment of 2 with sodium bis(trimethylsilyl)amide and /(-lactam 3 according to the Ojima-Holton method36 provides taxol bis(triethylsilyl ether) (86 % yield, based on 89% conversion) from which taxol (1) can be liberated, in 80 % yield, by exposure to HF pyridine in THF at room temperature. Thus the total synthesis of (-)-taxol (1) was accomplished. 

Chemo- and stereoselective reduction of (56) to (55) is achieved In highest yield by sodium borohydride in ethanol. The isolated ketone is reduced more rapidly than the enone and (55) is the equatorial alcohol. Protection moves the double bond out of conjugation and even the distant OH group in (54) successfully controls the stereochemistry of the Simmons-Smith reaction. No cyclopropanation occurred unless the OH group was there. Synthesis ... 

The reaction of the aldehyde 174, prepared from D-glucose diethyl dithio-acetal by way of compounds 172 and 173, with lithium dimethyl methyl-phosphonate gave the adduct 175. Conversion of 175 into compound 176, followed by oxidation with dimethyl sulfoxide-oxalyl chloride, provided diketone 177. Cyclization of 177 with ethyldiisopropylamine gave the enone 178, which furnished compounds 179 and 180 on sodium borohydride reduction. 0-Desilylation, catalytic hydrogenation, 0-debenzyIation, and acetylation converted 179 into the pentaacetate 93 and 5a-carba-a-L-ido-pyranose pentaacetate (181). 

This procedure describes the preparation of 3-nitropropanai, 1, employing the rarely encountered 1,4-addition of ambident nitrite ion with its "softer N-atom,2 and further transformations of 1, as reported earlier.3 A similar preparation of 3-nitrobutanal from crotonaldehyde (3-butenal) is known,4 as well as analogous additions to a, 3-enones.2 The reduction of 1 to the alcohol 2, originally carried out with borane-dimethyl sulfide (BMS),3 is now more conveniently and economically done with sodium borohydride. The acetalization of 1 to yield the dimethyl acetal 3 is based on our earlier report.3... 

The synthesis of ( )-D-homotestosterone and ( )-progesterone has been accomplished via a now classical procedure involving the use of an isoxazole as an annelating agent (67JA5464). The enolate (424), prepared from 10-methyl-A1,9-octalin-2,5-dione, was alkylated by the 4-chloromethylisoxazole (425). The octalindione (426) was treated sequentially with one equivalent of sodium borohydride, hydrogenated, hydrogenolyzed and refluxed with sodium methoxide and then with sodium hydroxide to afford the crystalline enone (427). 

Compound 403 is readily reduced with sodium borohydride at -78°C and yields the monoalcohol 405 (115). It also reacts with potassium t -butyl hydroperoxide at -20°C and gives the cis-enone-perester carbonate 406 in high yield (116). This last transformation can be explained by retro-Claisen fragmentation of intermediate 407 followed by the elimination of methoxide ion from 408. It is also possible that 407 undergoes a direct stereoelectronically controlled Grob type fragmentation to compound 406. 

In order to transform the spirocyclic enone 445 to ( )-elwesine (439) and ( )-epielwesine (449), it was treated with boron trifluoride and dimethylsulfide to cleave the Al-carbobenzyloxy protecting group, and cyclization of the resulting amino enone spontaneously ensued to produce ( )-dihydrooxocrinine (447). Reduction of carbonyl function of 447 with sodium borohydride afforded ( )-3-epielwesine (449), which was converted to ( )-elwesine (439) by inversion of the hydroxyl function at C-3 via a Mitsunobu protocol using diethyl azodicarboxylate, triphenylphosphine, and formic acid. Attempted reduction of 447 directly to 439 by a Meerwein-Ponndorf-Verley reduction or with bulky hydride reagents gave only mixtures of 449 and 439 that were difficult to separate. 

The selective 1,2-reduction of enones with sodium borohydride is achieved in combination with CeCl3. 

Reductions. This hydride is a strong reducing agent comparable to other lithium trialkylhydrides. It is superior to DIBAH for selective 1,2-reduction of enones. Reduction of ketones, esters, acid chlorides, and anhydrides proceeds at -78°. However, ketones can be reduced selectively in the presence of an ester. Esters are reduced to a mixture of an alcohol and an aldehyde. Complete reduction to an alcohol can be effected by reduction at -78° with 2 equiv. of 1 and then with excess sodium borohydride. Tertiary amides are reduced by 1 equiv. of the reagent to aldehydes in generally high yield. Selective reduction of primary halides in the presence of secondary halides is possible. 

Correct reagent selection allowed reduction of steroidal enone (74) to either diastereoisomeric allylic alcohol, uncontaminated by its isomer. Sodium borohydride/cerium chloride in methanol-THF gave the equatorial alcohol (73), while L-selectride produced the axial isomer (75) via equatorial attack (Scheme 12). Unexpected axial attack on diketone (76) to give equatorial alcohol (77 equation 19) led to the proposition that for hydride additions to decalones two 1,3-diaxial interactions override one peri interaction which in turn takes precedence over a single 1,3-diaxial interaction. ... 

In spite of substantial evidence, the tendency for sodium borohydride to reduce enones in a conjugate sense is often ignored, but the need for reduction to the corresponding allylic alcohols has led to the development of several new specific reagent combinations. The most widely accepted of these involves sodium borohydride in the presence of cerium chloride, which has been optimized to give excellent... 

Sodium borohydride in methanol/dichloromethane (1 1) at-78 °C reduced ketones in the presence of conjugated enones with excellent selectivity. Competition experiments were complemented by reductions of diones to illustrate the synthetic value of the method. The Wieland-Miescher ketone was reduced to the 1-p-alcohol contaminated by less than 3% diol in quantitative yield. The same reagent in acetic acid was shown to be effective at reducing aromatic ketones with ortho hydroxy or ortho amino substituents rapidly.Other aromatic ketones were relatively inert under the same conditions. Presumably the success of this procedure relies on activation and intramolecular delivery of the acetoxyborohy-dride by the ortho substituent. 

Stereoselective reduction of an enone lactone was a key step in the construction of the 20-hydroxyec-dysone side chain. Totally different mixtures of products were obtained when the reduction was carried out with sodium borohydride or by catalytic hydrogenation (Scheme 30). In all cases, the 1,4-reduction mode is preferred. With borohydride, however, this process is followed by a subsequent reduction of the saturated ketone and base-catalyzed rearrangement of the 5-lactone into a y-lactone. 

Thermolysis of these yields the diketones (95) which are useful compounds for the synthesis of the perhydroazulenes This specific example (95) was converted into the natural product daucene (96). Others have also described the photocycloaddition of the enone (92) to the cyclobutene (93) to afford the (2+2)-adduct (94) in 24 % yield. The adduct was transformed into the natural product balanitol (97). The triplet state of conjugated enones can be photochemically reduced by sodium borohydride. ... 

Gemal, A. L., Luche, J. L. Lanthanoids in organic synthesis. 6. Reduction of a-enones by sodium borohydride in the presence of lanthanoid chlorides synthetic and mechanistic aspects. J. Am. Chem. Soc. 1981, 103, 5454-5459. 

Reduction of the enone 147 with sodium borohydride-cerium(Ill) chloride in methanol gave a 2 1 mixture of the unsaturated alcohols. 

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