Module 14 Practice Set: Synthesis

Synthesis Sample Question:

Draw a reasonable pathway for the synthesis of the product from the starting molecule. All carbons in the final molecule must come from the starting material. Include all isolated intermediates produced in each step of your synthetic scheme.

Answer Key:

Strategy Explained:

• The starting molecule is a 3-carbon chain, and it is the only carbon source we can use in the synthesis pathway. In the product, we see two different 3-carbon chains. They are highlighted in green and blue in the following image:
• The green and blue carbon chains shown above are bonded together through a carbon-carbon bond. This tells us we will most likely use an organocuprate or Grignard reaction. The carbon-carbon bond connecting these two groups together is highlighted orange in the following image:
• The oxygen group on the green carbon chain in the product is on the carbon adjacent to the orange carbon-carbon bond, which tells us an epoxide on the green carbon chain was likely used. The theoretical epoxide is shown in the following image:
• The opening of the epoxide shown above by the blue carbon chain nucleophile is illustrated in the following image with the bonds breaking and forming represented by dotted lines:
• Once the epoxide and nucleophile are reacted, the leftover alcohol from the epoxide will need to be oxidized. This will form the final product.

Steps Explained:

1. The first thing we need to do is turn the starting molecule into an epoxide, but the starting material is an alkane with no pi bonds, lone pairs, or leaving groups. Therefore, the only way we can start is by using radical halogenation to add a bromine. The bromine will be added to the middle carbon of the chain because it is the most substituted.
2. The bromine leaving group is then eliminated through an E2 reaction with KOtBu, a strong, bulky base. This is done to create an alkene which is the reactant necessary to create an epoxide.
3. The resulting alkene is then reacted with mCPBA and a benzene solvent to create an epoxide.
4. Now we need to synthesize the carbon nucleophile that will open the epoxide. Another version of the starting molecule has a bromine added to the middle carbon in the carbon chain via a radical halogenation reaction.
5. The bromine leaving group is then eliminated through an E2 reaction with KOtBu, a strong, bulky base. This is done to create an alkene which is the reactant necessary to create an epoxide.
6. The resulting alkene is then reacted with HBr and peroxide to add a bromine to the anti-Markovnikov carbon.
7. The 3-carbon chain with a terminal bromine undergoes the organolithium reaction because the organolithium product is a precursor to the organocuprate complex.
8. The organolithium product is reacted with CuCN to create an organocuprate complex. The organocuprate complex is the carbon nucleophile that will open the epoxide.
9. The epoxide created in step 3 is then reacted with the organocuprate complex created in step 8. This is followed by an acidic workup step to protonate the leftover oxygen from the epoxide. Because the acidic workup step is after the organocuprate has reacted with the epoxide, the epoxide opens at the least substituted carbon due to the organocuprate complex being a base.
10. The resulting alcohol is then oxidized with PCC to form a ketone. Note that because the alcohol is secondary any oxidizing agent can be used. This forms the final product.

Course Description:

Key Features:

• Synthesis Challenges: Engage with 30 synthesis questions that require you to plan and execute pathways from starting materials to target products.
• Comprehensive Answer Key: Access detailed answer keys for each synthesis question. Each answer key includes:
  • Pathway: Illustrated pathway showing the steps taken from the starting material to the product.
  • Strategy: Explanation of the strategic approach used to devise the synthesis pathway.
  • Step-by-Step Explanations: Detailed explanations for each synthetic step, clarifying why specific reactions were chosen and how they contribute to the synthesis goal.

Recommended Prerequisites:

Completion of instructional modules 1-14 and practice modules 1-13 is highly recommended. This module synthesizes knowledge and skills acquired throughout the first semester of organic chemistry, integrating concepts from foundational modules.

Who Should Take This Module:

This module is designed for students seeking to strengthen their synthetic organic chemistry skills. Ideal for those preparing for advanced coursework, exams, or seeking practical application of organic chemistry principles in synthesis planning.

Benefits:

• Practice planning and executing complex organic synthesis pathways.
• Gain proficiency in applying a wide range of organic reactions to achieve specific synthesis goals.
• Understand the strategic thinking behind synthesis planning and pathway selection.