Hydroboration—oxidation

Oxidation followed by hydroboration of alkenes results in alcohols. This reaction takes place in an anti-Markovnikov fashion. Notice that the hydrogen atom, instead of attaching to the carbon contained in the double bond with the highest number of hydrogen substituents, attaches to the carbon with the least number of hydrogen substituents. 

The addition of hydrogen and boron is simultaneous, and they must add to the same side of the double bond. Hence, this addition reaction involves syn addition or same-side addition. Study the next reaction. 

Hydroboration-oxidation of alkenes also requires two steps. The sequence of reactions adds the hydrogen and hydroxyl of water to a double bond to give a product that corresponds to anti-Markovnikov addition. 

In the first step, hydroboration, an alkene is treated with diborane (6113)2 or B2H1S. Di-borane acts as if it were the monomeric species called borane, (BH3). The boron reagent is usually prepared in an ether solvent such as diethyl ether or tetrahydrofuran. 

Borane adds to the carbon-carbon double bond of one alkene and then adds successively to two more alkenes, producing a trialkylborane, R3B. These steps are hydroboration reactions. 

In the oxidation step, the trialkylborane is treated with hydrogen peroxide and base to oxidize the 

The result of the hydroboration-oxidation of 1-methylcyclohexene reveals information about the stereochemistry of the reaction. The overall addition of water is t ft -Markovnikov. That is, the hydrogen atom adds to the more substituted carbon atom, and the hydroxyl group to the less substituted carbon atom. The hydrogen atom and hydroxyl group are introduced from the same side of the double bond. In the oxidation step, a hydroxyl group replaces the boron with retention of configuration. Therefore, the net addition of water is syn. 

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  

The stereochemical outcome of this reaction is also of particular interest. Specifically, when two new chirality centers are formed, the addition of water (H and OH) is observed to occur in a way that places the H and OH on the same face of the it bond  

This mode of addition is called a syn addition. The reaction is said to be stereospecific because only two of the four possible stereoisomers are formed. That is, the reaction does not produce the two stereoisomers that would result from adding H and OH to opposite sides of the it bond  

Any mechanism that we propose for hydroboration-oxidation must explain both the regioselec-tivity ( inri-Markovnikov addition) as well as the stereospecificity (ry addition). We will soon propose a mechanism that explains both observations. But first, we must explore the nature of the reagents used for hydroboration-oxidation. 

The stmcture of borane (BH3) is similar to that of a carbocation, but without the charge  

Regioseiectivity Markovnikov s ruie is foiiowed. X bonds to the iess substituted carbon. Stereochemistry Anti addition occurs. 

ProblEm 10.25 Draw the products of each reaction and indicate their stereochemistry. 

Problem 10.26 The eiements of Br and Ci are added to a doubie bond with Bra + NaCi. Draw the product formed when an unsymmetricai aikene such as 2-methyi-1 -propene is used as the starting material. 

Hydroboration-oxidation is a two-step reaction sequence that converts an aikene to an alcohol. 

Hydroboration is the addition of borane (BH3) to an aikene, forming an alkylborane. Oxidation converts the C - B bond of the alkylborane to a C - O bond. 

Another method for the addition of the elements of water, H and OH, to an alkene was developed by H. C. Brown, who shared the 1979 Nobel Prize in chemistry for this work. In this reaction the alkene is first allowed to react with a complex of borane (BH3) in tetrahydrofuran (THF). The initial product is then allowed to react with a basic solution of hydrogen peroxide. An example is shown in the following equation  

Although the hydroboration-oxidation reaction gives a product with a regiochemistry opposite to that predicted by Markovnikov s rule, the regiochemistry is in accord with the mechanistic version of this rule—that is, the electrophile adds to the less substituted carbon. Let s look at the mechanism of this reaction. 

Borane has the same structure as a carbocation. The boron is sjr hybridized, with trigonal planar geometry, and has an empty p orbital. Although neutral, it is electron deficient because there are only six electrons around the boron. It is a strong Lewis acid. An electron-deficient compound often employs unusual bonding to alleviate somewhat its instability. In the case of borane, two molecules combine to form one molecule of diborane  

Diborane has some very unusual bonds. The two B—H—B bonds are three-center, two-electron bonds that is, there are two electrons shared by all three of these atoms, one hydrogen and two borons. That is the only way for the borons to satisfy the octet 

However, it is easiest to understand the hydroboration reaction by considering the reactive species to be BH3 itself. 

Borane (BH3) is a reactive gas that exists mostly as the dimer, diborane (B2H6). Borane is a strong Lewis acid that reacts readily with Lewis bases. For ease in handling in the laboratory, it is commonly used as a complex with tetrahydrofuran (THF). 

Borane is sold for laboratory use as a complex with many other Lewis bases. Draw the Lewis acid-base complex that forms between BH3 and each compound, a. (CH3)2S b. (CHsCHslsN c. (CHiCHaCHaCHajaP 

The first step in hydroboration-oxidation is addition of the elements of H and BH2 to the Ji bond of the alkene, forming an intermediate alkylborane. 

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Carbocation intermediates are not involved m hydroboration-oxidation Hydration of double bonds takes place without rearrangement even m alkenes as highly branched as the following... 

A second aspect of hydroboration-oxidation concerns its stereochemistry As illustrated for the case of 1 methylcyclopentene H and OH add to the same face of the double bond... 

Hydroboration-oxidation of a pinene (page 235) like catalytic IS stereoselective Addition takes place at the less hindered face and a single alcohol is produced in high yield (89%) Sug... 

The regioselectivity and syn stereochemistry of hydroboration-oxidation coupled with a knowledge of the chemical properties of alkenes and boranes contribute to our under standing of the reaction mechanism... 

The electrophilic character of boron is again evident when we consider the oxida tion of organoboranes In the oxidation phase of the hydroboration-oxidation sequence as presented m Figure 6 11 the conjugate base of hydrogen peroxide attacks boron Hydroperoxide ion is formed m an acid-base reaction m step 1 and attacks boron m step 2 The empty 2p orbital of boron makes it electrophilic and permits nucleophilic reagents such as HOO to add to it... 

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... 

FIGURE 6 11 The oxidation phase in the hydroboration-oxidation of 1 methylcydo pentene... 

Hydroboration-oxidation (Sections 6 11-6 13) This two step sequence achieves hydration of alkenes in a ste reospecific syn manner with a regiose lectivity opposite to Markovnikov s rule An organoborane is formed by electro philic addition of diborane to an alkene Oxidation of the organoborane inter mediate with hydrogen peroxide com pletes the process Rearrangements do not occur... 

Hydroboration-oxidation of (E) 2 (p anisyl) 2 butene yielded an alcohol A mp 60°C in 72% yield When the same reaction was performed on the Z alkene an isomenc liquid alcohol B was obtained in 77% yield Suggest reasonable structures for A and B and describe the relation ship between them... 

Hydroboration-oxidation of alkenes (Section 6 11) H and OF add to the double bond with a regioselectivity opposite to that of Markovnikov s rule This is a very good synthetic method addition is syn and no rearrangements are observed... 

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). 

Asymmetric Hydroboration. Hydroboration—oxidation of (Z)-2-butene with diisopinocampheylborane was the first highly enantioselective asymmetric synthesis (496) the product was R(—)2-butanol in 87% ee. Since then several asymmetric hydroborating agents have been developed. Enantioselectivity in the hydroboration of significant classes of prochiral alkenes with representative asymmetric hydroborating agents is shown in Table 3. 

Constmction of multilayers requires that the monolayer surface be modified to a hydroxylated one. Such surfaces can be prepared by a chemical reaction and the conversion of a nonpolar terminal group to a hydroxyl group. Examples of such reactions are the LiAlH reduction of a surface ester group (165), the hydroboration—oxidation of a terminal vinyl group (127,163), and the conversion of a surface bromide using silver chemistry (200). Once a subsequent monolayer is adsorbed on the "activated" monolayer, multilayer films may be built by repetition of this process (Fig. 8). 

The synthetic method used to accomplish this is an indirect one known as hydroboration-oxidation. It was developed by Professor Herbert C. Brown and his coworkers at Purdue University in the 1950s as part of a broad progran designed to apply boron-containing reagents to organic chemical synthesis. The number of applications is so large (hydroboration-oxidation is just one of them) and the work so novel that Brown was a corecipient of the 1979 Nobel Prize in chemistry. 

With this as introduction, let us now look at the individual steps in more detail for the case of hydroboration-oxidation of 1-decene. A boron hydride that is often used is dibomne (B2H6). Diborane adds to 1-decene to give tridecylborane according to the balanced equation ... 

Hydroboration-oxidation of a-pinene (page 235), like catalytic... 

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