1-Methylcyclopentene hydroboration-oxidation

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... 

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti—with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an -OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration. 

Figure 11.1 The hydroboration-oxidation of 1-methylcyclopentene. The first reaction is a syn addition of borane. (In this illustration we have shown the boron and hydrogen both entering from the bottom side of 1-methylcyclopentene. The reaction also takes place from the top side at an equal rate to produce the enantiomer.) In the second reaction the boron atom is replaced by a hydroxyl group with retention of configuration. The product is a trans compound (trans-2-methyl-cyclopentanol), and the overall result is the syn addition of -H and -OH.

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. 

Working backward, use hydroboration-oxidation to form 2-methyl-cyclopentanol from 1-methylcyclopentene. The use of (1) and (2) above and below the reaction arrow indicates individual steps in a two-step sequence. 

The stereochemistry of the hydroboration-oxidation of 1-methylcyclopentene is shown next. Boron and hydrogen add to the same face of the double bond (syn) to form a trialkylborane. Oxidation of the trialkylborane replaces boron with a hydroxyl group in the same stereochemical position. The product is frracemic mixture is expected because a chiral product is formed from achiral reagents. 

As can be seen in Figure 4, the hydroboration-oxidation of 1-methylcyclopentene produces only the trans-2-methyl-cyclopentanol with a yield of 86%.45 This result implies that the boron atom and the hydrogen atom are added to the double bond simultaneously on a syn mechanism.46 A concerted mechanism is invoked for these additions - it is shown in Figure 5.1... 

Problem 7.9 What product will result from hydroboration/oxidation of l-methylcyclopentene with deuterated borane, BD3 Show both the stereochemistry /spatial arrangement) and the regiochemistry (orientation of the product. 

Methylcyclohexanol, dehydration of, 183 1-Methylcyclopentene addition of hydrogen chloride, 215 hydroboration-oxidation, 230-233 Methylenecyclohexane, 677 Methylene group, 57 prefix, 170... 

In this problem, 1-methylcyclopentene, an alkene, is the starting product. This must be converted into the alcohol so that it may be then transformed into the sodium alkoxide for use in the Williamson synthesis. (One does not want to convert 1-methylcyclo-pentene into an alkyl halide because a secondary or tertiary structure would result, and this is not very efficient, as mentioned previously.) Now, there exist a number of ways to synthesize an alcohol from an alkene. The method of choice, however, is the one that provides us with the required stereochemistry. Recall that the final product must be a trans isomer. If hydroboration-oxidation of the alkene is used, addition occurs in a cis fashion and the trans isomer will be the net result. That is, the -H and -OH add trans to the methyl group. 

The addition of boron and hydrogen across the carbon-carbon double bond appears to occur by stereospecific syn addition. The replacement of the C—B bond by a C—OH bond in the oxidation step is also stereospecific. The mechanism proposed for the oxidation of one of the carbon-boron bonds is shown in equations 9.47 through 9.51, so the configuration of the carbon-boron bond is retained in the product. As an example, hydroboration-oxidation of 1-methylcyclopentene (50, equation 9.52) followed by oxidation of the organoborane (51) gave only the trans-2-methylcyclohexanol (52). 

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. 

Acid-Catalyzed Hydration of 2-Methylpropene 227 Hydroboration of 1-Methylcyclopentene 233 Oxidation of an Organoborane 235 Bromine Addition to Cyclopentene 237 Epoxidation of Bicyclo[2.2.1]-2-heptene 240 Free-Radical Addition of Hydrogen Bromide to 1-Butene 243... 

Either material when used for hydroboration of 1-methylcyclopentene gives, after oxidation, frans-2-methylcyclopentanol in 70-75% optical purify. 

Hydroboration of 1-methylcyclopentene (1) with diborane gives tris-(frans-2-methyl-cyclopentyl)borane (2), which on oxidation gives tra/is-2-methylcyclopentanol (3).1 Addition of sodium cyanide to a solution of (2), followed by treatment with trifluoro-acetic anhydride (TFAA) and then by oxidation with alkaline hydrogen peroxide, gives... 

In Chapter 5, the cis addition inherent to hydroboration is the result of a four-center transition state (sec. 5.2.A.ii), which delivered boron and hydrogen from the same face. Subsequent transformations that involve boron lead to a new group on the same face as boron. Reaction of methylcyclopentene with 9-BBN, for example, gave exclusively the trans borane (96), and that was converted to aldehyde 97 by carbonylation. The addition of the boron dictated the stereochemical relationship of the methyl group and the 9-BBN moiety. The carbonylation and oxidation reactions proceeded with net retention of configuration, maintaining the trans geometry in the isolated product. 

Scheme 6.25. A representation of the oxidative hydroboration of 1-methylcyclopentene (as a typical alkene). The addition of boron and hydride (H ) is suprafacial with the double bond attacking the boron so as to build up charge on that carbon of the double bond that would be the most stable carbocation it is to this carbon of the double bond that the hydride (H") adds. In the oxidation step, the anion of hydrogen peroxide (H02 ) attacks the boron. Subsequent rearrangement of carbon to oxygen with oxygen-oxygen bond cleavage produces the alcohol. Only one ligand to boron is shown to emphasize the oxidation process.

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