Oxymercuration oxidative demercuration

In the area of pheromone synthesis, oxymercuration-oxidative demercuration has also proven valuable. For example, all four stereoisomers (rf tetrahydro-2,2,6-trimethyi-2//-pyran-3-ol, from the eim bark beetle Pteleobius vittatus have been acquired by a sequence from (/ )- and (S)-sulcatol, which incorporates this mercury chemistry. The epimeric alcohols (47) and (48 Scheme 37) were separable (MPLC)... 

Oxymercuration-oxidative demercuration (OM-OD) has considerably broadened the utility of organo-mercurial applications in synthesis. Typically, a solution of the mercurial in DMF (room temperature) was added to a DMF solution of NaBH, through which oxygen was rapidly passed. Generally 1.2-1.3 mol of borohydride was required to effect complete demercuration. In addition to the expected alcohols and hydrocarbons, other products presumed to be alkoxyboron compounds were also formed, but these could be hydrolyzed to alcohols. A typical result is shown in equation (17), with yields after the hydrolysis step. 

Step 1 Hydroboration-oxidation of sterically less hindered terminal alkene. Step 2 Oxymercuration-demercuration of the internal alkene yields the diol G. 

Hydroboration-oxidation, then, converts alkenes into alcohols. Addition is highly regiospecific the preferred product here, however, is exactly opposite to the one formed by oxymercuration-demercuration or by direct acid-catalyzed hydration. For example ... 

Alternatively, the mesylate 77 was treated with sodium iodide in refluxing 2-butanone to produce the olefin 90 (Scheme 3). " Oxymercuration-demercuration reaction of 90 using mercnric acetate-sodinm borohydride afforded a 1 1 mixture of 91 and 92. Compound 92 was mesylated, rednced and cyclized in boiling ethanol, in the presence of sodium acetate, to give 93. This was converted by standard steps into 94, and subsequent hydrolysis of 94 followed by oxidation with pyridinium chlorochromate afforded the lactone 95 (28% overall yield from 92), which was nsed in the synthesis of retronecine (22). " ... 

Another reaction that is relevant to the mechanism of the formation of the alkaloid erysodienone in vitro is the K3[Fe(CN)6]-induced para-para oxidative coupling of the phenol (13) to the azoninone derivative (14). ° Oxymercuration-demercuration [by Hg(OAc)2 and then NaBH4] of the cyclic lactam (15) resulted in the regio- and stereo-specific transannular formation of (16). The conformation of (15) is represented by (17), in which there is no steric crowding by the methyl group. The ring is believed to be responsible for the course of the reaction. 

The anfi-Markownikoff-hydration of carbon-carbon double bonds hydroboration-oxidation has been supplemented by a remarkably simple and likewise stereospecific Markownikoff-hydration achieved by a one-step oxymercuration-demercuration p-Nitrophenyl chloroformate has been recommended for the protection of hydroxyl groups in nucleosides... 

As a consequence, hydroboration-oxidation gives us a method for the preparation of alcohols that cannot normally be obtained through the acid-catalyzed hydration of alkenes or by oxymercuration—demercuration. 

Oxymercuration-demercuration and hydroboration-oxidation have complementary regioselectivity. 

In the first step, boron and hydrogen undergo syn addition to the alkene in the second step, treatment with hydrogen peroxide and base replaces the boron with — OH with retention of configuration. The net addition of —H and —OH occurs with autl-Markovnikov regioselectivity and syn stereoselectivity. Hydroboration-oxidation, therefore, serves as a useful regiochemical complement to oxymercuration-demercuration. 

Oxymercuration-demercuration is commonly used for the Markovnikov hydration of olefins. In order to improve the selectivity of the reaction with dienes, the use of various mercuric salts was envisaged, but the choice of commercially available compounds is limited. A simple sonochemical preparation was found (p. 164), and the in situ formation from mercuric oxide and a carboxylic acid in the presence of a diene provided increased selectivities. The case of the hydration of limonene is illustrative (Eq. 8). 

The synthesis is simply the reverse of the disconnection process, so alkene 139 is converted to alcohol 140 via oxymercuration-demercuration (Chapter 10, Section 10.4.5), and oxidation with pyridinium chlorochromate (PCC Chapter 17, Section 17.2.3) leads to the requisite ketone. Treatment of the ketone with LDA to form the kinetic enolate (note the kinetic control conditions) is followed by addition of propanal and hydrolysis to give the final target, 138. 

Alcohols can be prepared from a variety of other functional groups, including by reduction of a carbonyl, hydration of an alkene, or substitution of a leaving group. Remember, regiochemistry is a concern when starting with an alkene, and water can be added with either Markovnikov (oxymercuration-demercuration) or anti-Markovnikov (hydroboration-oxidation) orientation. 

The previous sections covered two different methods for achieving a Markovnikov addition of water across a it bond (1) acid-catalyzed hydration and (2) oxymercuration-demercuration. In this section, we will explore a method for achieving an ij wri-Markovnikov addition of water. This process, called hydroboration-oxidation, places the OH group at the less substituted carbon ... 

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 Markovnikov addition of water. 

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