TheIvanov reaction is a carbon–carbon bond-formingchemical reaction involving the addition of dianions (endiolates) ofarylacetic acids (Ivanov reagents) with electrophilic substrates such asaldehydes,ketones,isocyanates, oralkyl halides, resulting in β‑hydroxy acids. The reaction was named after the Bulgarianorganic chemist, AcademicianDimitar Ivanov, who discovered it. Mechanistically, the Ivanov reaction proceeds via a Zimmerman–Traxler six-membered chair-like transition state, coordinating metalcations to both enolate oxygens and the electrophile, which explains its high anti‑stereoselectivity.
The reaction was first reported by Bulgarianorganic chemist, AcademicianDimitar Ivanov Popov in 1931 in Bulletin Société Chimique de France,[1][1] with follow-up studies in 1932 and significant reviews in 1970 and 1975.[2][3][4]
The reaction involvesmagnesium-enediolate dianions ofarylacetic acids (Ivanov reagents) attacking electrophilic substrates such asaldehydes,ketones,isocyanates, oralkyl halides, resulting in β‑hydroxy acids.[5] The product does not usually spontaneously decarboxylate, but it is possible with some reagents. Use of the dianion ofphenylacetic acid withformaldehyde givestropic acid, an intermediate used in the synthesis ofatropine andhyoscyamine.[6]
The conformation follows the Zimmerman–Traxler cyclic transition state, coordinating metalcations to both enolate oxygens and the electrophile.[1][7] It exhibits strong anti‑stereoselectivity, typically forming anti‑β‑hydroxy acids due to favorable chair transition state and steric interactions.[1] In 1985, Toullec measured reaction rates and determined the energy profile using phenylacetic acid magnesium enediolate reacting with aldehydes/ketones.[8] Some Ivanov adducts may undergo decarboxylation under harsh conditions. The process is sensitive to moisture and temperature; requires low temps and anhydrous environment to maintain enediolate stability.[1]
Synthesis of β-hydroxy esters → useful intermediates in medicinal chemistry.
Aldol-type reactions, but with stabilized enolates.
Precursor for β-diketones, lactones, and heterocycles.
Used in natural product synthesis for building complex skeletons.