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To generate rings in organic compounds, the chemical process known as Robinson annulation is employed. By creating three new C–C bonds, Robert Robinson came up with the idea of creating six-membered rings in 1935. To synthesise a -unsaturated ketone in a cyclohexane ring, a methyl vinyl ketone, and a ketone is employed in a Michael addition followed by aldol condensation. Creating fused ring structures is one of the most significant methods.
Example
Cyclohexenone and its derivatives are necessary for the production of various natural compounds and other interesting chemical molecules, such as steroids and antibiotics. To synthesise cortisone, the Robinson annulation is employed.
Cyclohexanone can be synthesised by reacting with an unsaturated ketone in the year 1935, according to Rapson and Robinson. For six-membered ring compounds, this is one of the most important methods for making it happen. Many aspects of the reaction, such as substrate modifications and reaction conditions, have been researched because of the reaction’s widespread use.
Important details
First, a nucleophilic attack on an unsaturated vinyl ketone is carried out using the Robinson annulation method. As a result, the Michael adduct was formed as an intermediary step. Aldol type ring closure, followed by dehydration to produce annulation products, produces keto alcohol.
In the Michael reaction, it targets the electron acceptor. The most common acceptor is an,-unsaturated ketone, but aldehydes, acid derivatives, and other related compounds can also be employed. The thermodynamic enolate governs the outline’s regioselectivity.
Because of the intramolecular aldol condensation, the six-member ring is installed. Carbon atoms form the unsaturated system and the by-carbonyl product’s group combines to form the newly installed ring’s four-carbon bridge.
It is a common practice to first separate the Michael adduct, then cyclize it to produce the desired octalone, to avoid a reaction with the original product. In stereochemistry, the Robinson annulation reaction scheme has been researched for its ability to produce hydroxy ketones. Due to the antiperiplanar effects of the final aldol condensation, the trans-molecule is favoured in kinetically regulated processes. However, cyclization can also occur in a synclinal orientation, as was discovered recently.
Mechanics-based classification
Tandem Michael-aldol reactions, such as the Robinson annulation, are a well-known type of chemical transformation. Aldol reaction and Michael addition are carried out simultaneously. First, the two reactants are bound together via Michael addition. Afterward, the aldol reaction takes place intra-molecularly to generate the ring system as a consequence, as in the case of the Robinson annulation.
The Michael acceptor, product Michael adduct, and nucleophile-Michael donor are the alpha beta-unsaturated molecules that undergo Michael’s addition. Resonance-stabilised 1,4-addition reactions of nitriles and carbon nucleophiles are involved in Michael addition.
Mechanism of annulation
Michael’s addition and aldol condensation are key components of the Robinson annulation reaction.
First, the Michael reaction happens after the aldol condensation occurs in the Robinson annulation mechanism.
In the Robinson annulation reaction, the ketone undergoing Michael’s addition is the following step.
There is enolate production as a result of a process known as Tautomerization.
Cyclization is the next stage. Aldol condensation produces a six-membered cyclic product.
After hydrolysis, the unsaturated cyclic ketones are finally produced.
Constraints on reactivity
Despite the fact that the Robinson annulation is most often performed in the most basic of conditions, several reactions have been carried out. Results from the sulfuric acid-catalysed and base-catalysed methods are comparable. Under neutral conditions, the Michael reaction can occur in the presence of an enamine. When a Mannich base is heated in the presence of a ketone, the Michael adduct is formed. To successfully produce compounds, Robinson annulation processes were employed.
Applications
The Robinson annulation reaction mechanism is used to synthesise spirocyclic molecules. The Robinson annulation’s advantage is that it may be used to synthesise complicated compounds, such as steroids, terpenoids, and alkaloids, easily. Formal 4+2 reactions invariably result in six-membered rings being produced, which are then condensed. 3+3 annulations are now part of the process concept. The intramolecular aldol reaction and the Michael addition, as in the Robinson annulation mechanism, are often part of all ring-formation cascades. The Robinson annulation is used in a significant number of synthesises. In particular, those who employ the method to construct an internal ring are of great importance. Synthesis of the 6-member ring requires the Robinson annulation, a key step. The Platensimycin Enantioselective method is a more complicated use of the procedure.
Conclusion
Robinson annulation is an organic chemistry process that is necessary for the production of ring structures. In 1935, Sir Robert Robison made the discovery that led to the process’s current name. By forming a six-membered ring, three new carbon-carbon bonds are created in the Robinson annulation process. This procedure makes use of methyl vinyl and ketone to produce an aldol condensation after a -unsaturated ketone is synthesised via Michael addition. Polycyclic compounds with six-membered rings, such as steroids, can be made using this chemical. Annulations, which means “building ring,” is an extremely complicated system.
