Robinson annulation 2
These two processes together in one reaction creates two new carbon-carbon bonds and also creates a ring.
Key Terms Robinson annulation reaction Study Notes The building of an alicyclic compound from acyclic starting materials can present an interesting challenge to the synthetic organic chemist.
In the Michael reaction, the ketone is deprotonated by a base to form an enolate nucleophile which attacks the electron acceptor in red.
In a paperRobert Robinson and collaborator William Rapson reported that a substituted methyl vinyl ketone and cyclohexanone gave a product with a new six membered ring containing an alpha,beta unsaturated ketone: This has become known as the Robinson Annulation, and it still finds use today.
Subsequent aldol type ring closure leads to the keto alcohol, which is then followed by dehydration to produce the annulation product.
Robinson annulation mechanism
This intramolecular amine-catalyzed aldol condensation was actually a key sharpening stone in the development of one of the most important areas of modern chemical research. The figure below shows the three possible stereochemical pathways, assuming a chair transition state. These two processes together in one reaction creates two new carbon-carbon bonds and also creates a ring. Scope and variations[ edit ] Reaction conditions[ edit ] Although the Robinson annulation is generally conducted under basic conditions, reactions have been conducted under a variety of conditions. The trans compound is favored due to antiperiplanar effects of the final aldol condensation in kinetically controlled reactions. The 1,3-dichloro-cisbutene is employed to avoid undesirable polymerization or condensation during the Michael addition. Notes Even within the past few years, new variations of the Robinson Annulation have been developed. Wichterle reaction[ edit ] The Wichterle reaction is a variant of the Robinson annulation that replaces methyl vinyl ketone with 1,3-dichloro-cisbutene. As in some of the other syntheses that you have studied, when you are simply given the structure of a compound and asked how it could have been prepared, it can be difficult to recognize which reactions might have been used. The Michael Reaction segment involves three steps: formation of the enolate conjugate addition, and protonation of the new enolate. The Hauser acceptor is a Michael acceptor.
Initial synthesis gave a racemic form of the compound using an intramolecular etherification reaction of the alcohol motifs and the double bond.
But for the keen, I present two applications of this reaction in synthesis, particularly applied to steroids.
Robinson annulation mcat
However, the C-3 enolate is a dead-end; formation of the strained 4-membered ring is reversible, and equilibrium will eventually drive the reaction toward formation of the six-membered aldol condensation product] Formation of the enolate on C-1 is followed by attack at the ketone five carbons away, giving the six-membered ring. Related Posts:. The 1,5-diketone produced by the Michael reaction then becomes the starting material for the next segment of the Robinson annulation, the intramolecular aldol condensation. The reaction conditions can be seen below. An enantioselective example from the Toste lab is highlighted here. Heathcock and Ellis report similar results to the base-catalyzed method using sulfuric acid. The first step is to recognize the key pattern in the product of a Robinson: a six-membered ring containing a double bond adjacent to a ketone an alpha, beta unsaturated ketone. This suggests that the presence of protic or aprotic solvents gives rise to different transition states. Initial synthesis gave a racemic form of the compound using an intramolecular etherification reaction of the alcohol motifs and the double bond. At this point I will confess that the example above, as written, is a bit of a cheat.
Thus, when asked how such a compound might be prepared, you should keep the possibility of using a Robinson annulation reaction in mind.
based on 43 review