Robinson Annulation

The Robinson annulation is a significant chemical reaction in organic chemistry, named after the British chemist Sir Robert Robinson, who discovered it in 1935. This reaction is pivotal for constructing six-membered rings through the formation of three new carbon-carbon bonds. It involves the use of a ketone and a methyl vinyl ketone to form an α,β-unsaturated ketone within a cyclohexane ring through a Michael addition followed by an aldol condensation[1][4].

The Robinson annulation is not just a standalone reaction but a combination of two key reactions: the Michael Addition and the Aldol Condensation. The process begins with the Michael addition of a ketone to an α,β-unsaturated ketone, leading to the formation of an enolate. This enolate then undergoes tautomerization, setting the stage for the subsequent intramolecular aldol condensation. This series of reactions culminates in the formation of a six-membered cyclic product, specifically an α,β-unsaturated cyclic ketone[4].

This reaction has broad applications in the synthesis of complex organic molecules, including the construction of polycyclic compounds, steroids, alkaloids, and terpenoids. Its versatility and efficiency in forming six-membered rings make it a cornerstone in the synthesis of naturally occurring compounds. For instance, the synthesis of cortisone, a significant achievement in organic chemistry, utilizes the Robinson annulation[1].

The reaction mechanism involves the nucleophilic attack of a ketone in a Michael reaction on an α,β-unsaturated ketone, followed by an aldol-type ring closure to produce a keto alcohol. This intermediate then undergoes dehydration to yield the final annulation product. The Michael reaction component of this process involves the deprotonation of the ketone to form an enolate nucleophile, which attacks the electron-deficient α,β-unsaturated ketone[1].

Robinson's contribution to organic chemistry through the development of this reaction was recognized with the Nobel Prize in Chemistry in 1947. The Robinson annulation remains a fundamental method for constructing six-membered ring compounds and has been extensively studied and applied in various synthetic strategies for the synthesis of complex organic molecules[1].

Citations:

[1] https://en.wikipedia.org/wiki/Robinson_annulation

[2] https://www.youtube.com/watch?v=_wio-EENoW0

[3] https://www.sciencedirect.com/topics/chemistry/robinson-annulation

[4] https://byjus.com/chemistry/robinson-annulation/

[5] https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_%28OpenStax%29/23:_Carbonyl_Condensation_Reactions/23.13:_The_Robinson_Annulation_Reaction

[6] https://onlinelibrary.wiley.com/doi/10.1002/ajoc.202200668?af=R

[7] https://www.organic-chemistry.org/namedreactions/robinson-annulation.shtm

[8] https://testbook.com/chemistry/robinson-annulation

[9] https://www.masterorganicchemistry.com/2018/12/10/the-robinson-annulation/

[10] https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_%28Morsch_et_al.%29/23:_Carbonyl_Condensation_Reactions/23.12:_The_Robinson_Annulation_Reaction

[11] https://openstax.org/books/organic-chemistry/pages/23-12-the-robinson-annulation-reaction

[12] https://www.vedantu.com/chemistry/robinson-annulation