Catellani Reaction
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The Catellani reaction was discovered by Marta Catellani (
Università degli Studi di Parma The University of Parma () is a public university located in Parma, Emilia-Romagna, Italy. Organized into nine departments, it is one of the oldest universities in the world. As of 2016, it had approximately 26,000 students. History During the ...
, Italy) and co-workers in 1997. 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 Position often refers to: * Position (geometry), the spatial location (rather than orientation) of an entity * Position, a job or occupation Position may also refer to: Games and recreation * Position (poker), location relative to the dealer * ...
. This
cross-coupling In organic chemistry, a cross-coupling reaction is a reaction where two different fragments are joined. Cross-couplings are a subset of the more general coupling reactions. Often cross-coupling reactions require metal catalysts. One important reac ...
cascade reaction A cascade reaction, also known as a domino reaction or tandem reaction, is a chemical process that comprises at least two consecutive reactions such that each subsequent reaction occurs only in virtue of the chemical functionality formed in the p ...
depends on the '' ortho''-directing transient mediator,
norbornene Norbornene or norbornylene or norcamphene is a highly strained bridged cyclic hydrocarbon. It is a white solid with a pungent sour odor. The molecule consists of a cyclohexene ring with a methylene bridge between carbons 1 and 4. The molecule carr ...
.


Reaction mechanism

The Catellani reaction is catalyzed by
palladium Palladium is a chemical element; it has symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1802 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas (formally 2 Pallas), ...
and
norbornene Norbornene or norbornylene or norcamphene is a highly strained bridged cyclic hydrocarbon. It is a white solid with a pungent sour odor. The molecule consists of a cyclohexene ring with a methylene bridge between carbons 1 and 4. The molecule carr ...
, although in most cases superstoichiometric amounts of norbornene are used to allow the reaction to proceed at a reasonable rate. 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. 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 In organic chemistry, an anti-Bredt molecule is a Bridged compound, bridged molecule with a double bond at the Bicyclic molecule, bridgehead. Bredt's rule is the empirical observation that such molecules only form in large ring systems. For exam ...
for the bridgehead β-hydrogen and the ''trans-''configuration between palladium and other β-hydrogen. 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 Norbornene or norbornylene or norcamphene is a highly strained bridged cyclic hydrocarbon. It is a white solid with a pungent sour odor. The molecule consists of a cyclohexene ring with a methylene bridge between carbons 1 and 4. The molecule carr ...
, the resultant Pd(II) species then undergoes a second C–C bond forming step via a
Heck reaction The Heck reaction (also called the Mizoroki–Heck reaction) is the chemical reaction of an unsaturated halide (or triflate) with an alkene in the presence of a base and a palladium catalyst to form a substituted alkene. It is named after T ...
or cross coupling with an organoboron reagent to afford the final organic product and close the catalytic cycle. Steps of the Catellani reaction: #
Oxidative addition Oxidative addition and reductive elimination are two important and related classes of reactions in organometallic chemistry. Oxidative addition is a process that increases both the oxidation state and coordination number of a metal centre. Oxidat ...
# Carbopalladation of
norbornene Norbornene or norbornylene or norcamphene is a highly strained bridged cyclic hydrocarbon. It is a white solid with a pungent sour odor. The molecule consists of a cyclohexene ring with a methylene bridge between carbons 1 and 4. The molecule carr ...
# Palladacycle formation #
Oxidative addition Oxidative addition and reductive elimination are two important and related classes of reactions in organometallic chemistry. Oxidative addition is a process that increases both the oxidation state and coordination number of a metal centre. Oxidat ...
to palladacycle #
Reductive elimination Reductive elimination is an elementary step in organometallic chemistry in which the oxidation state of the metal center decreases while forming a new covalent bond between two ligands. It is the microscopic reverse of oxidative addition, and is ...
from palladacycle #
Norbornene Norbornene or norbornylene or norcamphene is a highly strained bridged cyclic hydrocarbon. It is a white solid with a pungent sour odor. The molecule consists of a cyclohexene ring with a methylene bridge between carbons 1 and 4. The molecule carr ...
extrusion # Termination via
Heck reaction The Heck reaction (also called the Mizoroki–Heck reaction) is the chemical reaction of an unsaturated halide (or triflate) with an alkene in the presence of a base and a palladium catalyst to form a substituted alkene. It is named after T ...
,
Suzuki reaction The Suzuki reaction or Suzuki coupling is an organic reaction that uses a palladium complex catalyst to cross-couple a boronic acid to an organohalide. It was first published in 1979 by Akira Suzuki, and he shared the 2010 Nobel Prize in Chemi ...
, etc.


''Ortho'' and ''ipso'' cross-coupling partners

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, arylation from aryl bromides, amination from benzyloxyamines, acylation from anhydrides. Likewise in the case of terminating ''ipso'' coupling partners with Heck-type termination with
olefins In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as α-olefins. The International Union of P ...
,
Suzuki is a Japanese multinational mobility manufacturer headquartered in Hamamatsu, Shizuoka Prefecture, Shizuoka. It manufactures automobiles, motorcycles, all-terrain vehicles (ATVs), outboard motor, outboard marine engines, wheelchairs and a va ...
-type reaction with
boronic ester A boronic acid is an organic compound related to boric acid () in which one of the three hydroxyl groups () is replaced by an alkyl or aryl group (represented by R in the general formula ). As a compound containing a carbon–boron bond, memb ...
s,
borylation Metal-catalyzed C–H borylation reactions are transition metal catalyzed organic reactions that produce an organoboron compound through functionalization of aliphatic and aromatic C–H bonds and are therefore useful reactions for carbon–hydroge ...
with
bis(pinacolato)diboron Bis(pinacolato)diboron is a covalent compound containing two boron atoms and two pinacolato ligands. It has the formula CH3)4C2O2Bsub>2; the pinacol groups are sometimes abbreviated as "pin", so the structure is sometimes represented as B2pin2. I ...
, protonation with ''i''-PrOH, decarboxylative
alkynylation In organic chemistry, alkynylation is an addition reaction in which a terminal alkyne () is added to a carbonyl group () to form an α-alkynyl alcohol (). When the acetylide is formed from acetylene (), the reaction gives an α-ethynyl alcohol. ...
with alkynyl carboxylic acids.


Uses

With tethered cross-coupling partners, Lautens, Malacria, and Catellani used this reaction to construct a variety of fused ring systems since 2000. The Catellani reaction has been used as a key step for the
total synthesis Total synthesis, a specialized area within organic chemistry, focuses on constructing complex organic compounds, especially those found in nature, using laboratory methods. It often involves synthesizing natural products from basic, commercially ...
(+)- linoxepin, rhazinal, aspidospermidine, and (±)- goniomitine.


References


External links


Total Synthesis of (+)-Linoxepin by Utilizing the Catellani Reaction
{{Organic reactions Chemical reactions Name reactions