Robinson Annulation: Videos & Practice Problems

In organic chemistry, the formation of 15 dicarbonyl compounds through intramolecular self-condensation leads to the creation of 6-membered enones. This process is enhanced by the Michael reaction, where an enone reacts with an enolate to generate a 15 dicarbonyl compound. The subsequent cyclization of this compound is known as the Robinson annulation, which can be conceptualized as a series of aldol reactions.

The Robinson annulation involves three key steps: first, an aldol reaction produces the initial enone, which is an α,β-unsaturated carbonyl compound. Next, a second aldol reaction occurs when the enolate attacks the enone via conjugate addition, resulting in the formation of the 15 dicarbonyl. Finally, this 15 dicarbonyl undergoes cyclization to yield a new 6-membered enone, completing the process.

When drawing the product of a Robinson annulation, it is crucial to determine the correct position for the enolate attack. For instance, if the enolate is placed in a position that does not allow for the formation of a 6-membered ring, the reaction will yield a 4-membered ring instead. Therefore, careful consideration of the molecular structure is necessary to ensure the desired product is achieved.

To illustrate this, consider a scenario where you start with a Michael reaction involving an enone and an enolate. After forming the Michael product, you would then proceed to perform the Robinson annulation. The final product typically features a cyclic enone, which may undergo dehydration to yield a more stable structure, often represented as a methyl-substituted double bond within the ring.

In summary, the Robinson annulation is a powerful synthetic strategy in organic chemistry that combines the principles of aldol reactions and conjugate addition to create complex cyclic structures from simpler precursors. Understanding the sequence of reactions and the importance of molecular positioning is essential for successful synthesis.

The Michael product is a key concept in organic chemistry, particularly in the context of Michael reactions, which involve the formation of enolates. To visualize the process, one can start by drawing the enol in its original form and then overlaying the enolate. The goal is to determine the optimal site for enolate formation that will lead to the creation of a six-membered ring.

In this scenario, there are several potential sites for enolate formation, but not all are suitable for forming a stable six-membered ring. For instance, sites that are only four carbons away from the carbonyl group can be eliminated, as they will not yield the desired ring structure. This leaves two viable options: one that is six carbons away and another that also spans six carbons but includes atoms that are already part of a ring structure.

Choosing the first option, where only two of the atoms are part of the ring, is preferable. This minimizes the complexity of the resulting structure and avoids the formation of a bicyclic compound, which can complicate the reaction. By rearranging the molecule to resemble the enone that will form later, one can visualize the reaction more clearly.

After the enolate attacks the carbonyl, a six-membered ring is formed, resulting in a new cyclic structure. The ketone remains intact during this process, and the negatively charged oxygen will eventually be protonated to form an alcohol. Following this, dehydration occurs, leading to the formation of an α,β-unsaturated carbonyl compound, or enone, as the final product.

This reaction, known as the Robinson annulation, is often considered challenging due to its complexity and the need for careful visualization of the molecular transformations involved. Mastery of this reaction requires practice in drawing and understanding the mechanisms at play, making it an essential topic in organic chemistry studies.