Question

Hydroboration of the following bicycloalkene followed by oxidation in alkaline hydroperoxide is both stereoselective and regioselective. The product is a single alcohol in better than \(95 \%\) yield. Propose a structural formula for this alcohol and account for the stereo- and regioselectivity of its formation. Hint: Examine a molecular model of this alkene and see if you can determine which face of the double bond is more accessible to hydroboration.

Short answer

Question: Propose a structural formula for the alcohol produced from the hydroboration-oxidation of a bicycloalkene and explain the stereo- and regioselectivity of its formation. Answer: The alcohol's structural formula can be predicted by applying the regio- and stereoselectivity rules of hydroboration-oxidation to the given bicycloalkene. In this reaction, the boron atom preferentially attaches to the less hindered carbon due to steric hindrance within the bicyclic structure. This results in regioselective formation of one alcohol, following the Anti-Markovnikov rule. Meanwhile, the stereochemistry arises from syn-addition in the hydroboration step, which ensures the cis orientation of the newly formed bond. Thus, the product alcohol is produced in better than 95% yield, following Anti-Markovnikov regioselectivity and cis stereoselectivity.

Step-by-step solution

Illustrate the general hydroboration-oxidation reaction mechanism

Hydroboration-oxidation is a two-step process. First, the alkene undergoes hydroboration, where a borane (BH3) adds across the double bond to form an alkylborane. This addition follows the so-called "Anti-Markovnikov" rule, meaning the hydrogen atom attaches to the carbon with more hydrogen substituents, while the boron atom attaches to the carbon with more alkyl substituents. Moreover, the hydroboration step occurs with syn-addition, leading to cis stereochemistry in the product. In the second oxidation step, the alkylborane is treated with alkaline hydrogen peroxide (H2O2). The boron atom is replaced with a hydroxyl (OH) group, resulting in the formation of the product alcohol.

Predict the product alcohol's structural formula

To determine the product alcohol's structure, apply the regio- and stereoselectivity rules mentioned above to the given bicycloalkene. Since the double bond is within the bicyclic structure, the bulkier group at the bridgehead carbon determines regioselectivity: the boron atom will preferentially attach to this carbon. Additionally, the syn-addition in the hydroboration step ensures the product's cis stereochemistry.

Explain the stereo- and regioselectivity of the reaction

The regioselectivity arises from the steric hindrance around the alkene due to the bicyclic structure. The boron prefers to avoid such steric hindrance and, thus, bonds to the less hindered carbon. As a result, the regioselective formation of one alcohol is observed. The stereoselectivity is governed by the syn-addition of the borane in the hydroboration step. Since boranes are sterically hindered and would largely prefer to approach the alkene from the less sterically hindered side, syn addition of the borane and hydrogen ensures the newly formed bond's cis orientation. Considering the stereo- and regioselective nature of this hydroboration-oxidation reaction on the given bicycloalkene, a single alcohol is produced in better than 95% yield, following the Anti-Markovnikov rule and with cis stereochemistry.

Key concepts

Stereochemistry in Organic Reactions

Stereochemistry considers the three-dimensional arrangement of atoms within molecules, especially when it concerns reactions that can form different stereoisomers—molecules with the same connectivity but different spatial arrangements. In organic reactions, understanding stereochemistry is crucial as it can affect both the physical properties and the reactivity of the resulting compounds.

For instance, in hydroboration-oxidation reactions, the addition of borane to the double bond occurs in a syn-fashion, meaning that both the boron and hydrogen add to the same side of the double bond. This is different from other addition reactions where anti-addition can occur, leading to trans products. The syn-addition is a stereochemical outcome that profoundly influences the final structure of the product, as observed in the formation of alcohols from alkenes with high stereochemical fidelity.

Understanding the stereochemistry of organic reactions also becomes pivotal when considering the biological activity of molecules, as enzymes and receptors often 'recognize' only one particular stereoisomer.

Regioselective Hydroboration

Regioselectivity refers to the preference of a chemical reaction to occur at one direction or position over another, producing a predominantly or exclusively one isomer when various structural possibilities are present. In the arena of hydroboration, the bulky nature of boron-containing reagents often governs the regioselective outcome of the reaction.

The preference of the boron atom to add to the less substituted carbon of the alkene is a hallmark of hydroboration and aligns with the Anti-Markovnikov rule. In the case of complex substrates like bicycloalkenes, the spatial arrangement around the double bond dramatically influences regioselectivity. The boron reagent will generally attach to the more accessible side of the double bond, which is less hindered, overriding typical electronic preferences seen in other addition reactions.

By predicting and controlling these regioselective outcomes, chemists can synthesize highly specific products, making hydroboration a powerful tool in the synthesis of alcohols and other functionalized molecules.

Anti-Markovnikov Rule

The Anti-Markovnikov rule is an empirical guideline indicating that in certain addition reactions, the addendum (usually a hydride or nucleophile) will add to the less substituted carbon atom of a double bond. This rule is opposite to Markovnikov's rule which states that in addition reactions of hydrogen halides to alkenes, the hydrogen atom attaches to the more substituted carbon.

In the context of hydroboration-oxidation, this rule is particularly relevant as it helps predict the regiochemistry of the reaction. Borane additions to alkenes are quintessential examples of Anti-Markovnikov behavior. The boron atom bonds with the more substituted carbon, while the hydrogen attaches to the less substituted carbon, ultimately leading to the formation of alcohols where the OH group is located at the more substituted carbon after the oxidation step. This regiochemical outcome, predicted by the Anti-Markovnikov rule, is invaluable for synthesizing molecules with complex structural requirements.