Chemical reaction From Wikipedia, the free encyclopedia
The Catellani reaction was discovered by Marta Catellani (Università degli Studi di Parma, Italy) and co-workers in 1997.[1][2] The reaction uses aryl iodides to perform bi- or tri-functionalization, including C-H functionalization of the unsubstituted ortho position(s), followed a terminating cross-coupling reaction at the ipso position. This cross-coupling cascade reaction depends on the ortho-directing transient mediator, norbornene.
The Catellani reaction is catalyzed by palladium and norbornene, although in most cases superstoichiometric amounts of norbornene are used to allow the reaction to proceed at a reasonable rate.[4] The generally accepted reaction mechanism, as outlined below, is intricate and believed to proceed via a series of Pd(0), Pd(II), and Pd(IV) intermediates, although an alternative bimetallic mechanism that avoids the formation of Pd(IV) has also been suggested.[5]
Initially, Pd(0) oxidatively adds into the C–X bond of the aryl halide. Subsequently, the arylpalladium(II) species undergoes carbopalladation with the norbornene. The structure of the norbornylpalladium intermediate does not allow for β-hydride elimination at either of the β-positions due to Bredt's Rule for the bridgehead β-hydrogen and the trans-configuration between palladium and other β-hydrogen.[6] Thereafter, the Pd(II) species undergoes electrophilic cyclopalladation at the ortho position of the aryl group. Subsequently, the palladacyclic intermediate undergoes a second oxidation addition with the alkyl halide coupling partner to form a Pd(IV) intermediate, which undergoes reductive elimination to forge the first C–C bond of the product. After β-carbon elimination of norbornene, the resultant Pd(II) species then undergoes a second C–C bond forming step via a Heck reaction or cross coupling with an organoboron reagent to afford the final organic product and close the catalytic cycle.[7]
Steps of the Catellani reaction:
The Catellani reaction facilitates a variety of C—C and C—N bond-forming reactions at the ortho position. These include alkylation from alkyl halides,[1] arylation from aryl bromides,[8] amination from benzyloxyamines,[9][10][11][12] acylation from anhydrides.[13][14] Likewise in the case of terminating ipso coupling partners with Heck-type termination with olefins,[1] Suzuki-type reaction with boronic esters,[9] borylation with bis(pinacolato)diboron,[10][15] protonation with i-PrOH,[11] decarboxylative alkynylation with alkynyl carboxylic acids.[12]
With tethered cross-coupling partners, Lautens, Malacria, and Catellani used this reaction to construct a variety of fused ring systems since 2000.[7] The Catellani reaction has been used as a key step for the total synthesis (+)-linoxepin,[16] rhazinal,[17] aspidospermidine,[18] and (±)-goniomitine.[18]
Seamless Wikipedia browsing. On steroids.