Question

With organolithium and organomagnesium compounds, approach to the carbonyl carbon from the less hindered direction is generally preferred. Assuming this is the case, predict the structure of the major product formed by reaction of methylmagnesium bromide with 4-tertbutylcyclohexanone.

Short answer

Answer: The major product of the reaction between methylmagnesium bromide and 4-tertbutylcyclohexanone is 4-(tert-butyl)cyclohexanol with a methyl group on the less hindered side of the starting carbonyl group.

Step-by-step solution

Draw the Structure of 4-tertbutylcyclohexanone

Begin by drawing the structure of 4-tertbutylcyclohexanone. This molecule has a cyclohexanone ring with a carbonyl group (=O) and a tert-butyl group attached to the fourth carbon of the ring.

Identify the Less Hindered Side

We need to identify the less hindered side of the carbonyl group. Since the tert-butyl group contains three methyl groups, it creates significant steric hindrance on one face of the molecule. The carbonyl carbon thus will be less hindered on the opposite side, away from the tert-butyl group.

Draw the Structure of Methylmagnesium Bromide

Methylmagnesium bromide is an organomagnesium reagent, commonly known as a Grignard reagent, with the formula CH3MgBr. Draw its structure with a single bond between the carbon and magnesium atoms and a single bond between magnesium and the bromine atom.

Predict the Major Product

Knowing that organometallic reagents prefer to approach the carbonyl carbon from the less hindered direction, the methyl group from methylmagnesium bromide will attack the carbonyl carbon, and the carbonyl bond will shift to form a new O-MgBr bond. This results in an alkoxide intermediate, which, after quenching with an acidic workup, yields the corresponding alcohol as the major product. The final product will be 4-(tert-butyl)cyclohexanol with a methyl group on the less hindered side of the starting carbonyl group.

Key concepts

Organolithium Compounds

Organolithium compounds are powerful reagents in organic chemistry. They are characterized by a direct carbon-lithium bond, which makes them highly reactive. Typically, organolithium reagents are prepared by reacting lithium metal with suitable organic halides.

Organolithium compounds are known for their nucleophilic character, which means they can donate a pair of electrons to an electrophile, like a carbonyl carbon. The high polarity of the carbon-lithium bond makes organolithium compounds even more reactive than their magnesium counterparts, the Grignard reagents.

Applications of organolithium compounds in synthetic chemistry include the formation of new carbon-carbon bonds, crucial in building complex organic molecules. However, their high reactivity also requires careful handling as they can readily react with protic solvents such as water or alcohols.

Steric Hindrance

Steric hindrance refers to the prevention of reactions at a particular location within a molecule due to the size of atoms or groups near the reactive site. In our chemical reaction, steric hindrance is a key factor that influences the approach of nucleophiles to the carbonyl carbon.

In 4-tertbutylcyclohexanone, the presence of a bulky tert-butyl group generates significant steric hindrance on one side of the carbonyl. This hindrance steers the Grignard reagent, methylmagnesium bromide, to attack from the less hindered side, leading to the preferential formation of a specific product.

Key points about steric hindrance:

• It affects reaction rate and product distribution.
• Leads to formation of more stable isomers.
• Is an important consideration in designing synthetic pathways.

Understanding steric hindrance helps predict and control outcomes in chemical reactions.

Carbonyl Chemistry

Carbonyl chemistry is the study of the reactivity and transformations of carbonyl groups, which are characterized by a carbon double-bonded to oxygen ( C=O ). This function group is central to many chemical reactions, making it a key focal point in organic synthesis.

The carbonyl carbon is electrophilic due to the polar nature of the C=O bond, thus making it susceptible to nucleophilic attack. The reaction with methylmagnesium bromide, for example, involves this type of nucleophilic addition to the carbonyl group.

Essential aspects of carbonyl chemistry include:

• The carbonyl group participation in a range of reactions, such as acylation and hydration.
• Nucleophilic addition as a core transformation of carbonyl groups.
• The concept of reactivity based on the structure of carbonyl-containing molecules.

Mastering carbonyl chemistry is indispensable for predicting and synthesizing a wide array of organic compounds.

Organomagnesium Reagents

Organomagnesium reagents, commonly known as Grignard reagents, are fundamental tools in synthetic organic chemistry. Typical Grignard reagents include a carbon-magnesium bond, as exemplified by methylmagnesium bromide (CH₃MgBr).

These reagents are prepared by reacting an alkyl or aryl halide with magnesium metal in dry ether. The presence of magnesium imparts a strong nucleophilic character to the carbon, enabling it to form carbon-carbon bonds through reactions with electrophiles like carbonyls.

Noteworthy characteristics of Grignard reagents include:

• Versatility in forming carbon-carbon bonds.
• Sensitivity to moisture, requiring anhydrous conditions for reactions.
• Utilization in preparing alcohols, acids, and other functional groups by subsequent reactions.

Grignard reagents' ability to create complex molecules efficiently makes them invaluable in both laboratory and industrial chemistry settings.