Preparation of Alcohols via Reduction

For a review of the factors that affect substitution vs. elimination, see Section 8.14. 

With a secondary substrate, neither 5 2 nor SnI are particularly effective for preparing a secondary alcohol. Under S l conditions, the reaction is generally too slow, while 5 2 conditions (use of hydroxide as the nucleophile) will generally favor elimination over substitution. 

In Chapter 9, we learned several addition reactions that produce alcohols. 

Acid-catalyzed hydration proceeds with Markovnikov addition (Section 9.4). That is, the hydroxyl group is positioned at the more substituted carbon. It is a useful method if the substrate is not susceptible to carbocation rearrangements (Section 6.11). In a case where the substrate can possibly rearrange, oxymercuration-demercuration can be employed. This approach also proceeds via Markovnikov addition, but it does not involve carbocation rearrangements. Hydroboration-oxidation is used to achieve an r ft Markovnikov addition of water. 

7 Identify the reagents that you would use to accomplish each of the following transformations -Br OH 

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Preparation of Alcohols via Reduction Preparation of Diols Preparation of Alcohols via Grignard Reagents... 

Oxymercuration-reduction of alkenes preparation of alcohols Addition of water to alkenes by oxymercuration-reduction produces alcohols via Markovnikov addition. This addition is similar to the acid-catalysed addition of water. Oxymercuration is regiospecific and auft -stereospecific. In the addition reaction, Hg(OAc) bonds to the less substituted carbon, and the OH to the more substituted carbon of the double bond. For example, propene reacts with mercuric acetate in the presence of an aqueous THF to give a hydroxy-mercurial compound, followed by reduction with sodium borohydride (NaBH4) to yield 2-propanol. 

Phosphorinanones have been utilized as substrates for the preparation of alkenes,11 amines,12 indoles,5,13 and in the synthesis of a series of secondary and tertiary alcohols via reduction,10 and by reaction with Grignard6,11 and Refor-matsky11,14 reagents. Phosphorinanones have also been used as precursors to a series of 1,4-disubstituted phosphorins.15 The use of 4-amino-l,2,5,6-tetrahydro-l-phenylphosphorin-3-carbonitrile for the direct formation of phosphorino-[4,3-d] pyrimidines has been reported.16... 

Midland, M. M., Tramontane, A., Zderic, S. A. Preparation of optically active benzyl-a-d alcohol via reduction by B-3a-pinanyl-9-borabicyclo[3.3.1]nonane. A new highly effective chiral reducing agent. J. Am. Chem. Soc. 1977, 99, 5211-5213. 

Purpose. The oxidation of an alkene to an alcohol is investigated via the in situ formation of the corresponding trialkylborane, followed by the oxidation of the carbon-boron bond with hydrogen peroxide. The conditions required for hydroboration (a reduction) of unsaturated hydrocarbons are explored. Alkylboranes are particularly useful synthetic intermediates for the preparation of alcohols. The example used in this experiment is the conversion of 1-octene to 1-octanol in which an anti-Markovrukov addition to the double bond is required to yield the intermediate, trioctylborane. Since it is this alkyl borane that subsequently undergoes oxidation to the alcohol, hydroboration offers a synthetic pathway for introducing substituents at centers of unsaturation that are not normally available to the anti-Markovnikov addition reactions that are based on radical intermediates. 

For a long time, kinetic resolution of alcohols via enantioselective oxidation or via acyl transfer employing, for example, lipases along with dynamic kinetic resolution have been the biocatalytic methods of choice for the preparation of chiral alcohols. In recent years, however, impressive progress has been made in the use of alcohol dehydrogenases (ADHs) and ketor-eductases (KREDs) for the asymmetric synthesis of alcohols by stereoselective reduction of the corresponding ketones. Furthermore, recent remarkable multienzymatic systems have been successfully applied to the deracemisation of alcohols via stereoinversion based on an enantioselective oxidation followed by an asymmetric reduction. 

The reduction of allylic systems is frequently used to generate isolated double bonds. Suitable systems are obtained from oe,jS-unsaturated ketones via allylic alcohols (ref. 185, p. 256 ref. 283, 284) for example, the preparation of A" -cholestene (135). 

The Rosenmund reduction is usually applied for the conversion of a carboxylic acid into the corresponding aldehyde via the acyl chloride. Alternatively a carboxylic acid may be reduced with lithium aluminum hydride to the alcohol, which in turn may then be oxidized to the aldehyde. Both routes require the preparation of an intermediate product and each route may have its advantages over the other, depending on substrate structure. 

An interesting appetite suppressant very distantly related to hexahydroamphetamines is somanta-dine (24). The reported synthesis starts with conversion of 1-adamantanecarboxylic acid (20) via the usual steps to the ester, reduction to the alcohol, transformation to the bromide (21), conversion of the latter to a Grignard reagent with magnesium metal, and transformation to tertiary alcohol 22 by reaction with acetone. Displacement to the fomiamide (23) and hydrolysis to the tertiary amine (24) completes the preparation of somantadine [6]. 

Traynelis et al. described the preparation of 4-chlorobenzo[6]thiepin (24) via the key intermediate, 7a-chlorocyclopropa[6]benzo[6]thiapyran-7-one (25fK The ketone 25 underwent reduction with sodium borohydride to give the corresponding alcohol, which was ring opened with hydrochloric acid to yield the precursor 26 of... 

Hydroboration and oxidation of 160 yields an alcohol that is subsequently oxidized with PDC to give ketone compound 161. Enolization and triflation converts this compound to enol triflate 162, which can be further converted to x,/i-unsaturated ester 163 upon palladium-mediated carbonylation methox-ylation. The desired alcohol 164 can then be readily prepared from 163 via DIBAL reduction. Scheme 7 50 shows these conversions. 

Access to P-mannosides [209] is illustrated by the preparation of 179 from P-glucoside 178 by oxidation of the equatorial 2-OH followed by stereoselective reduction to give the axial alcohol an efficient indirect route to the a-mannosides [206] utilizes the P-thioglucoside 182, readily obtained from epoxide 173, proceeding via an oxidation-reduction protection sequence to give P-thiomannoside glycosyl donor 184, from which a-mannoside 185 can be stereoselectively prepared. 

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