Hydroboration-oxidation reactions stereochemistry

Hydroboration-oxidation reactions are steteospecific the net addition of —H and —OH is syn, and if chirality centers are formed, their configuration depends on the stereochemistry of the starting alkene. 

Note that other textbooks will refer to the regioselectivity of the hydroboration-oxidation reaction as anti-Markovnikov, while we prefer the term non-Markovnikov. We do not favor the use of anti-Markovnikov because it can be confusing to students due to the syn, not anti, stereochemistry of addition observed with this reaction. 

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... 

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. 

The hydroboration-oxidation of a-pinene gives the product shown. Carefully explain the regiochemistry and the stereochemistry of this reaction. 

Yields refer to chromatographically homogeneous material. bYields are for three steps methylenation, RCM (35-40 mol% of 7) and hydroboration-oxidative work-up. Stereochemistry at C-l and C-2 determined by acetylation and analysis of //-2 coupling constant in H NMR. dA fair amount of unreacted mono-1,6-ester was isolated from the reaction mixture. cIn this case, the RCM reaction was stopped early, the (bis)C-glycal was isolated and purified (48%, unoptimized) and then subjected to hydroboration (66%, unoptimized). 

The reaction of 1,2-dimethylcyclopentene illustrates the stereochemistry of the synthesis hydroboration-oxidation involves overall syn addition. 

A partial synthesis of villalstonine (322) has been achieved by Cook, following the biomimetic method of LeQuesne (223), by condensation of synthetic (-i-)-macroline (338), or the more stable macroline equivalent (341), with natural pleiocarpamine (342) in ().2N HCl, to furnish villalstonine (Scheme 22). The (+)-macroline was prepared starting from the optically active tetracyclic ketone 343, prepared from D-(-i-)-tryptophan by an en-antiospecific Pictet Spengler reaction and stereocontrolled Dieckmann cyclization. The synthesis (Scheme 23) features the use of a stereoselective Claisen rearrangement, followed by stereospecific hydroboration-oxidation of the exocyclic methylene function at C(16), to install the required C(15) and C(16) stereochemistry (225-227). 

In designing a multistep synthesis, one must consider aspects of stereochemistry as well as functionality. In the chapters dealing with individual reactions, many examples were given in which the aspects of stereochemistry were a direct consequence of the reaction mechanism. For example, hydroboration-oxidation involves a syn addition followed by oxidation with retention of configuration. The generalization, widely but not universally correct, that reagents attack molecules from the sterically less hindered side was also illustrated on numerous occasions. 

The reaction in equation 9.52 does not provide a convincing demonstration of the stereochemistry of hydroboration-oxidation, since 52 is thermodynamically more stable than the corresponding cis isomer. Therefore, Brown and Zweifel also carried out the procedure on 1,2-dimethylcyclopentene (53, equation 9.53). The product of that reaction was the less stable stereoisomer... 

While the four-center transition structure for BH3 addition is a widely used model, other reaction pathways have also been considered. In a synthesis of optically active (-)-l-butanol-l-d, Streitwieser and co-workers used the optically active borane formed from diborane and (-l- )-a-pinene (R2BH) to carry out the hydroboration-oxidation of (Z)-l-butene-l-d. To explain the observed stereochemistry of the reduction, they proposed that hydroboration involves a n complex between R2BH and the alkene (Figure 9.41). Note the close resemblance of such a complex to the cyclic structures... 

Devise an experimental procedure for hydroboration/oxidation of 1-methylcyclopen-tene, the results of which will test the net anti-Markovnikov orientation of the overall reaction and its stereochemistry. Be certain the spectral data are available in the literature for the possible isomers that could be formed, so that you can analyze the product(s) you obtain. Check with your instructor before undertaking the procedure. 

Why does hydroboration/oxidation take place with syn, non-Markovnikov regiochemistry to yield the less highly substituted alcohol Hydroboration differs from many other alkene addition reactions in that it occurs in a single step without a carbocation intermediate. Because both C-H and C-B bonds form at the same time and from the same face of the alkene, syn stereochemistry results. Non-Markovnikov regiochemistry is found because attachment of boron is favored at the less sterically crowded carbon atom of the alkene rather than at the more crowded carbon (Figure 8.4). 

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— hydroboratlon-oxidation and oxymercuration-demercuration—give complementary products. Hydroboration-oxidation occurs with syn stereochemistry and gives the non-Markovnikov addition product oxymercuration-demercuration gives the Markovnikov product. 

The hydroboration-oxidation of olefins is one example of this approach. The process involves a stereospecific ty -addition of H and OH across the olefin r-bond. This reaction sequence is regioselective with unsymmetri-cal olefins. The diastereoselective conversion of E-olefin 177 to 178, and the isomeric Z-olefin 179 to 180, illustrates this process. Note that this discussion applies to relative control of stereochemistry. Whereas use of an enantioselective hydroborating agent might afford 178 and 180 as single enantiomers (or enriched in one enantiomer), 177 would still provide 178 and the diastereomeric olefin (179) would provide the diastereomeric alcohol (180).20... 

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