Anti-Markovnikov syn hydration

Hydroboration-oxidation converts 1-methylcyclopentene to the desired alcohol by anti-Markovnikov syn hydration of the double bond. The resulting alcohol is then converted to its p-toluenesulfonate ester and treated with acetate ion as in part (a) to give m-2-methyl-cyclopentyl acetate. 

Aicohols from Alkenes through Hydroboration-Oxidation Anti-Markovnikov Syn Hydration 352... 

ALCOHOLS FROM ALKENES THROUGH HYDROBORATION-OXIDATION ANTI-MARKOVNIKOV SYN HYDRATION... 

Hydroboration of an alkene is the starting point for a number of useful synthetic procedures, including the anti-Markovnikov syn hydration procedure we have just mentioned. Hydroboration was discovered by Herbert C. Brown (Purdue University), and it can be represented in its simplest terms as follows ... 

The stereochemical outcome is replacement of the C—B bond by a C—O bond with retention of configuration. In combination with stereospecific syn hydroboration, this allows the structure and stereochemistry of the alcohols to be predicted with confidence. The preference for hydroboration at the least-substituted carbon of a double bond results in the alcohol being formed with regiochemistry that is complementary to that observed by direct hydration or oxymercuration, that is, anti-Markovnikov. 

Hydrate to alcohol hydroborate/oxidize (THF/B2H5,H202/0H-) (syn, anti-Markovnikov)... 

Straightforward is the stereoselective introduction of two oxygen functionalities onto carbon-carbon double bonds, as represented by the Sharpless epoxidation4 or osmium tetroxide oxidation of allyl alcohols.5 An alternative route may be envisioned by anti-Markovnikov hydration of enol ether derivatives, as in the present method, but such an approach has so far been rarely studied. The only other reported method is hydroboration which affords syn/anti ratios in the range of 83/17 to 3/97 in essentially the same systems as those examined in this procedure. The method described here is a highly stereoselective route to 2,3-syn isomers of 1,2,3-triol skeletons from a-hydroxy enol ethers. 

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. 

In each case, the reaction proceeds with syn-addition (hydration) and anti-Markovnikov orientation. 

Mechanistic hypotheses play an important role in developing new catalytic and selective heterofunctionalizations of alkenes. Two basic reaction cycles for metal-catalyzed hydroalkoxylation (and hydration, for R = H) of alkenes can be postulated (Scheme 2). One pathway leads to Markovnikov products via activation of the nucleophile, oxy-metallation, and protonolysis (hydro-de-metallation) (Scheme 2a). Alternatively to the inner sphere syn-oxymetallation depicted in Scheme 2a, external anti-attack of the nucleophUe to coordinated olefin is plausible. The oxidation state of the metal remains constant in this cycle. The alternative hydrometallation pathway (Scheme 2b) proceeds via oxidative addition of the H-OR bond, hydrometallation of the olefin, and reductive elimination to the anti-Markovnikov addition product [3,4]. 

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. 

Because the oxidation step in the hydroboration-oxidation synthesis of alcohols takes place with retention of configuration, the hydroxyl group replaces the boron atom where it stands in the alkylboron compound. The net result of the two steps (hydroboration and oxidation) is the syn addition of —H and —OH. We can review the anti-Markovnikov and syn aspects of hydroboration-oxidation by considering the hydration of 1-methylcyclopentene, as shown in Fig. 8.3. 

Hydrobotation—oxidation results in anti-Markovnikov and syn hydration of an... 

In Summary Hydroboration-oxidation constitutes another method for hydrating alkenes. The initial addition is syn and regioselective, the boron shifting to the less hindered carbon. Oxidation of alkyl boranes with basic hydrogen peroxide gives anti-Markovnikov alcohols with retention of configuration of the alkyl group. 

In the oxymercuration step, water and mercuric acetate add to the double bond in the demercuration step, sodium borohydride reduces the acetoxymercury group and replaces it with hydrogen. The net addition of H— and —OH takes place with Markovnikov regioselectivity and generally takes place without the complication of rearrangements, as sometimes occurs with acid-catalyzed hydration of aUcenes. The overall alkene hydration is not stereoselective because even though the oxymercuration step occurs with anti addition, the demercuration step is not stereoselective (radicals are thought to be involved), and hence a mixture of syn and anti products results. 

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