Question

Propose two syntheses of 4-phenyl-2-pentanone, each involving conjugate addition of a lithium diorganocopper reagent.

Short answer

Question: Provide two different syntheses of 4-phenyl-2-pentanone using conjugate addition of a lithium diorganocopper reagent. Answer: 1) In the first synthesis, the conjugate addition reaction between 4-phenyl-3-penten-2-one and 1-lithium ethyl copper (EtCuLi) can be performed. This reaction results in the formation of 4-phenyl-2-pentanone. 2) In the second synthesis, 4-phenyl-3-penten-2-one with a different protecting group can be used as the starting material. The conjugate addition reaction between this modified starting material and 1-lithium propyl copper (PrCuLi) can be performed. After the reaction is complete and the protecting group is removed, the desired product, 4-phenyl-2-pentanone, can be obtained again.

Step-by-step solution

Synthesis 1: Identifying the starting materials and lithium diorganocopper reagent

In this first synthesis, we will use the conjugate addition of a lithium diorganocopper reagent, which will result in the addition of a new carbon-carbon bond to the starting material. We need to identify the starting materials which will give us the desired product when reacted with the lithium diorganocopper reagent. For the starting material, we could use an α,β-unsaturated ketone, like 4-phenyl-3-penten-2-one. For the lithium diorganocopper reagent, we could use 1-lithium ethyl copper (EtCuLi) which will be added to the β-position during conjugate addition.

Synthesis 1: Conjugate addition reaction

To complete the synthesis, we perform the conjugate addition reaction between the starting material (4-phenyl-3-penten-2-one) and the lithium diorganocopper reagent (EtCuLi). The reagent adds in a 1,4-fashion to the starting material, resulting in the formation of a new carbon-carbon bond. On completing the reaction, we obtain the desired product, 4-phenyl-2-pentanone.

Synthesis 2: Identifying the starting materials and lithium diorganocopper reagent

In this second synthesis, we will use a different lithium diorganocopper reagent for the conjugate addition reaction. For the starting material, we could still use an α,β-unsaturated ketone, like 4-phenyl-3-penten-2-one, as we did in synthesis 1. For the lithium diorganocopper reagent, we could use 1-lithium propyl copper (PrCuLi), and use a different protecting group on the carbonyl group of 4-phenyl-3-penten-2-one to differentiate the two synthesis.

Synthesis 2: Conjugate addition reaction

Perform the conjugate addition reaction between the starting material (4-phenyl-3-penten-2-one with a different protecting group) and the lithium diorganocopper reagent (PrCuLi). The reagent adds in a 1,4-fashion to the starting material, resulting in the formation of a new carbon-carbon bond. After the reaction is complete, we can remove the carbonyl protecting group to obtain the desired product, 4-phenyl-2-pentanone once again. In both syntheses, 4-phenyl-2-pentanone is produced by conjugate addition of different lithium diorganocopper reagents with the same starting material, 4-phenyl-3-penten-2-one. The key difference between these two syntheses is the choice of lithium diorganocopper reagent used for the conjugate addition reaction.

Key concepts

Lithium Diorganocopper Reagents

Lithium diorganocopper reagents, or organocopper compounds, are essential tools in organic synthesis, particularly in carbon-carbon bond formation. These reagents typically consist of a lithium salt paired with an organocopper moiety.

They are known for their ability to add across unsaturated systems, especially in conjugate 1,4-addition reactions. In these reactions, the copper species acts as a nucleophile, attacking the electrophilic β-carbon atom. This is particularly beneficial when you aim to form a new carbon-carbon bond in organic molecules.

A significant advantage of using lithium diorganocopper reagents is their chemoselectivity. They preferentially add to less hindered sites, providing a controlled way to synthesize specific structural formations in complex molecules. Additionally, these reagents possess a mild reaction profile, which allows for functional group compatibility, preventing unwanted side reactions.

Organic Synthesis

Organic synthesis involves constructing complex chemical compounds from simpler ones. It is a central endeavor in the chemistry field, as it allows us to create useful compounds, including drugs, polymers, and many other materials.

In the context of our exercise, organic synthesis takes advantage of the unique properties of reagents like lithium diorganocopper compounds to perform conjugate additions. This kind of reaction is pivotal for forming new bonds and adding functionalities to organic molecules while maintaining or modifying their structural complexity.

Organic synthesis is not just about creating chemical bonds; it's about carefully planning a sequence of reactions that ultimately leads to the target molecule in the most efficient and practical manner. This often involves selecting appropriate starting materials, choosing suitable reagents, and optimizing reaction conditions to maximize yield and purity.

α,β-Unsaturated Ketones

α,β-Unsaturated ketones are characterized by having a carbonyl group (C=O) with a double bond in the alpha-beta position. Typically, this configuration is denoted as a conjugated system, where the double bonds are separated by a single sigma bond.

These compounds are highly reactive due to the electrophilic nature of the β-carbon. This makes them excellent candidates for conjugate addition reactions, such as with lithium diorganocopper reagents, where a new bond can form at the β-carbon.

The utility of α,β-unsaturated ketones in synthesis lies in their ability to undergo various transformations, not just conjugate additions. They can participate in cycloaddition reactions, serve as intermediates in the synthesis of aromatics, and even act as precursors for enolates, which further broadens their use in diverse chemical pathways.