In addition, Bergmann et al. In order to avoid a reaction between the original enolate and the cyclohexenone product, the initial Michael adduct, labeled C, is often isolated first and then cyclized to give the desired octalone, labeled F, in a separate step.
Usually five- or six-membered rings are generated. This suggests that the presence of protic or aprotic solvents gives rise to different transition states. Yamamoto reports the use of an alternative intramolecular Robinson annulation to provide a straightforward enantioselective synthesis of tetracyclic core of platensimycin.
A Mannich base can be heated in the presence of the ketone to produce the Michael adduct. It has also been found though that the cyclization can proceed in synclinal orientation.
Heathcock and Ellis report similar results to the base-catalyzed method using sulfuric acid. Studies report the use of L-proline as well as several other chiral amines for use as catalysts during both steps of the Robinson annulation reaction.
Applications to synthesis[ edit ] The Wieland—Miescher ketone is the Robinson annulation product of 2-methyl-1,3-cyclohexanedione and methyl vinyl ketone.
Subsequent aldol type ring closure leads to the keto alcohol, which is then followed by dehydration to produce the annulation product.
The reaction conditions can be seen below. The trans compound is favored due to antiperiplanar effects of the final aldol condensation in kinetically controlled reactions.
As is the case with Robinson annulation, Michael addition usually happens first to tether the two reactants together, then aldol reaction proceeds intramolecularly to generate the ring system in the product. This compound is used in the syntheses of many steroids possessing important biological properties and can be made enantiopure using proline catalysis.
Reaction mechanism[ edit ] The original procedure of the Robinson annulation begins with the nucleophilic attack of a ketone in a Michael reaction on a vinyl ketone to produce the intermediate Michael adduct. In the Michael reactionthe ketonelabeled A in the diagram below, is deprotonated by a base to form an enolate nucleophile which attacks the electron acceptor as we can see in step B.
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.
Enantioselective route to platensimycin[ edit ] Scientists at Merck have recently discovered a novel antibiotic lead compound with potential medicinal applications called platensimycin as seen in the adjacent picture.
The Hauser acceptor is a Michael acceptor. Scanio found that changing the solvent of the reaction from dioxane to DMSO gives different stereochemistry in step D above.
The Hauser donor is an aromatic sulfone or methylene sulfoxide with a carboxylic ester group in the ortho position. The aldol condensation is an intramolecular process that creates the namesake ring of the Robinson annulation product going from step C through to step F.
Wichterle reaction[ edit ] The Wichterle reaction is a variant of the Robinson annulation that replaces methyl vinyl ketone with 1,3-dichloro-cisbutene.This work (Chem Advanced Organic Chemistry.
Diels-Alder; Robinson Annulation by Nowick, James) is licensed under a Creative Commons Attribution United States License. Organic Synthesis and Carbon-Carbon Bond Forming Reactions. 1. To introduce basic concepts of organic synthesis: Retrosynthesis In An Aliphatic Molecule – A Guide To Alternative Disconnections.
The Robinson Annulation Reaction: Intramolecular Claisen Condensations – The Dieckmann Cyclisation. The Robinson Annulation reaction. Reaction type: Conjugate addition, then intramolecular Aldol and finally an Elimination (!) Summary. A complex sequence that can be used to form bicyclic systems containing a substituted cyclohexenone system.
Exam 4 Study Guide 1: Review of C-C bond forming reactions CHEM In an effort to summarize everything we have covered, this “survey” has been prepared.
Use it to guide your studying for the next exam. Robinson ring annulation reactions). To do the retro-synthesis, remember to reverse the dehydration first, placing. Robinson Annulation. Many times the product of a Michael addition produces a dicarbonyl which can then undergo an intramolecular aldol reaction.
The Robinson annulation is a chemical reaction used in organic chemistry for ring formation. It was discovered by Robert Robinson in as a method to create a six membered ring by forming three new carbon–carbon bonds.Download