Hydration hydroboration-oxidation reactions with

When predicting the product of a reaction, you have to recall what you know about the kind of reaction being carried out and then apply that knowledge to the specific case you re dealing with. In the present instance, recall that the two methods of hydration—hydroboration/oxidation and oxymercura-tion—give complementary products. Hydroboration/oxidation occurs with syn stereochemi. itiy and gives the non-Markovnikov addition product oxymercuration gives the Markovnikov product. 

The mechanistic complexity of hydroboration-oxidation stands m contrast to the simplicity with which these reactions are carried out experimentally Both the hydrobo ration and oxidation steps are extremely rapid reactions and are performed at room tern perature with conventional laboratory equipment Ease of operation along with the fact that hydroboration-oxidation leads to syn hydration of alkenes and occurs with a regio selectivity opposite to Markovmkov s rule makes this procedure one of great value to the synthetic chemist... 

Oxidation. The oxidation reactions of organoboranes have been reviewed (5,7,215). Hydroboration—oxidation is an anti-Markovnikov cis-hydration of carbon—carbon multiple bonds. The standard oxidation procedure employs 30% hydrogen peroxide and 3 M sodium hydroxide. The reaction proceeds with retention of configuration (216). 

The hydroboration/oxidation sequence is complementary to the direct, mercury(ll)-catalyzed hydration reaction of a terminal alkyne because different products result. Direct hydration with aqueous acid and mercury(IJ) sulfate leads to a methyl ketone, whereas hydroboration/oxidation of the same terminal alkyne leads to an aldehyde. 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

Formal hydration of the double bond appeared by the hydroboration-oxidation sequence. Desymmetrization reactions with catalytic asymmetric hydroboration are not restricted to norbornene or nonfunctionalized substrates and can be successfully applied to meso bicyclic hydrazines. In the case of 157, hydroxy derivative 158 is formed with only moderate enantioselectivity both using Rh or Ir precatalysts. Interestingly, a reversal of enantioselectivity is observed for the catalytic desymmetrization reaction by exchanging these two transition metals. Rh-catalyzed hydroboration involves a metal-H insertion, and a boryl migration is involved when using an Ir precatalyst (Equation 17) <2002JA12098, 2002JOC3522>. 

Some other catalytic events prompted by rhodium or ruthenium porphyrins are the following 1. Activation and catalytic aldol condensation of ketones with Rh(OEP)C104 under neutral and mild conditions [372], 2. Anti-Markovnikov hydration of olefins with NaBH4 and 02 in THF, a catalytic modification of hydroboration-oxidation of olefins, as exemplified by the one-pot conversion of 1-methylcyclohexene to ( )-2-methylcycIohexanol with 100% regioselectivity and up to 90% stereoselectivity [373]. 3. Photocatalytic liquid-phase dehydrogenation of cyclohexanol in the presence of RhCl(TPP) [374]. 4. Catalysis of the water gas shift reaction in water at 100 °C and 1 atm CO by [RuCO(TPPS4)H20]4 [375]. 5. Oxygen reduction catalyzed by carbon supported iridium chelates [376]. - Certainly these notes can only be hints of what can be expected from new noble metal porphyrin catalysts in the near future. 

Because the C=C double bond of the cyclohexene used in Figure 3.22 is labeled with deuterium, it is possible to follow the stereochemistry of the whole reaction sequence. First there is a c -selective hydroboration. Two diastereomeric, racemic trialkylboranes are produced. Without isolation, these are oxidized/hydrolyzed with sodium hydroxide solution/ H202. The reaction product is the sterically homogeneous but, of course, racemic di-deuteriocyclohexanol. The stereochemistry of the product proves the cw-selectivity of this hydration. 

In general, the acetylenic triple bond is highly reactive toward hydrogenation, hydroboration, and hydration in the presence of acid catalyst. Protection of a triple bond in disubstituted acetylenic compounds is possible by complex formation with octacarbonyl dicobalt [Co2(CO)g Eq. (64) 163]. The cobalt complex that forms at ordinary temperatures is stable to reduction reactions (diborane, diimides, Grignards) and to high-temperature catalytic reactions with carbon dioxide. Regeneration of the triple bond is accomplished with ferric nitrate [164], ammonium ceric nitrate [165] or trimethylamine oxide [166]. 

Treatment of an alkene with mercuric acetate in aqueous THF results in the electrophilic addition of mercuric ion to the double bond to form an intermediate mercuri-um ion. Nucleophilic attack by H2O at the more substituted carbon yields a stable organomercury compound, which upon addition of NaBH4 undergoes reduction. Replacement of the caiton-mercury bond by a carbon-hydrogen bond during the reduction step proceeds via a radical process. The overall reaction represents Markovnikov hydration of a double bond, which contrasts with the hydroboration-oxidation process. 

Alcohols can be prepared by hydration of alkenes. Because the direct hydration of alkenes with aqueous acid is generally a poor reaction in the laboratory, two indirect methods are commonly used. Hydroboration/oxidation yields the product of syn, non-Markovnikov hydration (Section 7.5), whereas... 

The Diels-Alder reaction was utilized to construct bicyclo [2.2 1]heptane or bicyclo[2 2 l]heptene structures The reaction of isopropylidenecyclopentadiene with maleic anhydride produced the endo and exo configurational isomers of 8-isopropylidenebicyclo[2.2.1] hept-2-ene-5,6-dicarboxylic anhydride Similar reactions were applied to unsubstituted and l-(methoxycarbonyl)cyclopentadienes to give the corresponding anhydrides The anhydrides were reduced to alcohols, which were then allowed to react with thionyl chloride or tosyl chloride to give cyclic sulfites or tosylates Reaction of the tosylates with lithium chloride gave chlorinated compounds Hydration of the double bonds of the chlorinated compounds was accomplished by hydroboration-oxidation Diol 31 thus obtained was converted to 5,6-bis(chloromethyl)-7-isopropylidene-bicyclo[2 2 1] heptan-2-one [33] by chromium trioxide oxidation of the secondary hydroxyl group followed by dehydration at the C-7 substituent. 

Hydroboration-oxidation occurs by syn addition. The reagents are borane or an alkyl or dialkyl derivative, followed by oxidation, usually with HjOj and "OH. The oxidation occurs with retention of configuration of the alkyl group. The regioselectivity favors addition of the boron at the less-substituted carbon of the double bond. As a result, the reaction sequence provides a stereospecific syn, anti-Markovnikov hydration of alkenes. 

The hydroboration-oxidation procedure is a valuable method to hydrate an alkene with anti-Markovnikov orientation and with syn addition of the H and OH groups. ° Addition of BH3 (which may be added to the reaction mixture as diborane, B2Hg) to an alkene occurs readily in diethyl ether, THF, or similar solvent. The hydroboration is strongly exothermic, with a AH of -33kcal/mol per B-H bond that reacts. If stoichiometry and the steric requirements of the alkyl substituents on the boron atom permit, the reaction proceeds until three alkyl groups are attached to each boron atom. The trialkylborane can then be oxidized with hydrogen peroxide in aqueous base to produce the alcohol. 

The regiochemistry of acid-catalyzed hydration of alkenes to give alcohols is that predicted by Markovnikov s rule (Sec. 10.4) because the more stable intermediate carbocation is preferentially formed. Sometimes it is desirable to add the elements of water across a carbon-carbon Ti-bond in the opposite regiochemical sense to provide the anti-Markovnikov product (see the Historical Highlight at the end of this chapter). In order to accomplish this goal, a process termed hydroboration-oxidation was developed that involves the reaction of an alkene sequentially with diborane, B2H, and basic hydrogen peroxide (Eq. 10.26). 

Aldehydes and ketones have a central role in organic synthesis, and efficient procedures for their preparation are of great importance. Such compounds are synthesized in a number of ways, including hydration or hydroboration-oxidation of alkynes (Eqs. 16.10 and 16.11, respectively, and Chap. 11) and reaction of carboxylic acids or their derivatives with organometallic reagents or reducing agents... 

Like alkylboranes, dnylboranes can be converted into alcohols by treatment with basic peroxide (Fig. 10.75).The products are ends in this case, and they are in equilibrium with the corresponding carbonyl compounds. Here s an important point The regiochemistry of this reaction is the opposite of the regiochemistry of the hydration reaction of alkynes. This situation is exactly the same as the one that exists with the alkenes Hydration of an alkene gives overall Markovnikov addition, whereas the hydroboration/oxidation sequence gives the anti-Markovnikov product. 

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