White catalyst
Encyclopedia
The White catalyst is a transition metal
coordination complex named after the chemist by whom it was first synthesized, M. Christina White, a professor at the University of Illinois. The catalyst has been used in a variety of allylic C-H functionalization reactions of α-olefins
. In addition, it has been shown to catalyze oxidative Heck reaction
s.
, followed by reaction with palladium acetate.
of allylic C-H acetoxylation has been studied. The first step in the catalytic cycle
is cleavage of the allylic C-H bond. The sulfoxide
ligand
is thought to promote this step by generating a highly electrophilic, possibly cationic palladium species in situ. This species coordinates to the alkene and acidifies the adjacent C-H bond, which allows acetate
to abstract the proton
and forms a π-allyl palladium complex (II). Subsequently, a π-acid such as benzoquinone coordinates to the palladium, activating the π-allyl complex to nucleophilic attack (III). A nucleophile
, in this case acetate, attacks to reductively eliminate palladium, generating the product and palladium(0) (IV). The palladium(0) is reoxidized to palladium(II) by benzoquinone and the sulfoxide ligand reassociates, closing the catalytic cycle.
fluoride as a chiral cocatalyst. A macrolactonization reaction based on the branched allylic esterification was developed for the preparation of 14- to 19-membered macrolides. This method was applied to the total synthesis of 6-deoxyerythronolide B. In addition to acetate, a wide variety of carboxylic acids may be employed as nucleophiles in the branch allylic esterification reaction. As the first step in an esterification/Heck sequence, aliphatic and aromatic carboxylates were demonstrated, including amino acids.
close to acetic acid
, as more basic nucleophiles divert reactivity to aminopalladation. The intermolecular version of the allylic C-H amination is also known. Using methyl N-tosyl carbamate nucleophile, the linear E-allylic amine products are obtained from α-olefin substrates. It has been shown that functionalization of the π-allyl intermediate may be promoted by chromium(III) salen chloride activation of the electrophile
, or Hunig's base activation of the nucleophile
.
. Rather than performing allylic C-H cleavage—a relatively slow process—the catalyst quickly transmetallates
with a boronic acid
. This aryl palladium intermediate undergoes a 1,2-addition across the alkene double bond. β-Hydride elimination
releases the product. The oxidative Heck was originally reported as a sequential process following allylic C-H esterification. It was subsequently demonstrated as a stand-alone method for a broad range of α-olefin
substrates. The regioselectivity
of the reaction is controlled by directing groups such as carbonyl
s, alcohols and amines.
Transition metal
The term transition metal has two possible meanings:*The IUPAC definition states that a transition metal is "an element whose atom has an incomplete d sub-shell, or which can give rise to cations with an incomplete d sub-shell." Group 12 elements are not transition metals in this definition.*Some...
coordination complex named after the chemist by whom it was first synthesized, M. Christina White, a professor at the University of Illinois. The catalyst has been used in a variety of allylic C-H functionalization reactions of α-olefins
Alpha-olefin
Alpha-olefins are a family of organic compounds which are olefins or alkenes with a chemical formula CxH2x, distinguished by having a double bond at the primary or alpha position...
. In addition, it has been shown to catalyze oxidative Heck reaction
Heck reaction
The Heck reaction is the chemical reaction of an unsaturated halide with an alkene and a base and palladium catalyst to form a substituted alkene. Together with the other palladium-catalyzed cross-coupling reactions, this reaction is of great importance, as it allows one to do substitution...
s.
Preparation
This compound is commercially available. It may be prepared by oxidation of 1,2-bis(phenylthio)ethane to the sulfoxideSulfoxide
A sulfoxide is a chemical compound containing a sulfinyl functional group attached to two carbon atoms. Sulfoxides can be considered as oxidized sulfides...
, followed by reaction with palladium acetate.
Mechanism of allylic C-H acetoxylation
The reaction mechanismReaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
of allylic C-H acetoxylation has been studied. The first step in the catalytic cycle
Catalytic cycle
A catalytic cycle in chemistry is a term for a multistep reaction mechanism that involves a catalyst . The catalytic cycle is the main method for describing the role of catalysts in biochemistry, organometallic chemistry, materials science, etc. Often such cycles show the conversion of a...
is cleavage of the allylic C-H bond. The sulfoxide
Sulfoxide
A sulfoxide is a chemical compound containing a sulfinyl functional group attached to two carbon atoms. Sulfoxides can be considered as oxidized sulfides...
ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
is thought to promote this step by generating a highly electrophilic, possibly cationic palladium species in situ. This species coordinates to the alkene and acidifies the adjacent C-H bond, which allows acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...
to abstract the proton
Proton
The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....
and forms a π-allyl palladium complex (II). Subsequently, a π-acid such as benzoquinone coordinates to the palladium, activating the π-allyl complex to nucleophilic attack (III). A nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...
, in this case acetate, attacks to reductively eliminate palladium, generating the product and palladium(0) (IV). The palladium(0) is reoxidized to palladium(II) by benzoquinone and the sulfoxide ligand reassociates, closing the catalytic cycle.
Allylic esterification
The White catalyst was originally developed for use in a branched allylic acetoxylation reaction. An enantioselective version of this reaction was subsequently reported, using chromium(III) salenSalen ligand
Salen is the abbreviation for a popular chelating ligand used in coordination chemistry and homogeneous catalysis. The name salen is a contraction for salicylaldehyde and ethylenediamine. The ligand is a bright yellow micaceous solid that is soluble in polar organic solvents.-Nomenclature:The...
fluoride as a chiral cocatalyst. A macrolactonization reaction based on the branched allylic esterification was developed for the preparation of 14- to 19-membered macrolides. This method was applied to the total synthesis of 6-deoxyerythronolide B. In addition to acetate, a wide variety of carboxylic acids may be employed as nucleophiles in the branch allylic esterification reaction. As the first step in an esterification/Heck sequence, aliphatic and aromatic carboxylates were demonstrated, including amino acids.
Allylic amination
The White catalyst can effect both branched and linear regioselective allylic C-H aminations. In order to promote nucleophilic attack at the internal terminus of the π-allyl to generate branched product, a tethered N-sulfonyl carbamate nucleophile is used. This strategy has been applied to the synthesis of 1,2 and 1,3-amino alcohols. The amination proceeds with high yields and good diastereoselectivity, and the products may be readily elaborated to amino acids and other synthetic intermediates and natural products. Key to the development of the reaction was identification of a very acidic nitrogen nucleophile with a pKaPKA
PKA, pKa, or other similar variations may stand for:* pKa, the symbol for the acid dissociation constant at logarithmic scale* Protein kinase A, a class of cAMP-dependent enzymes* Pi Kappa Alpha, the North-American social fraternity...
close to acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
, as more basic nucleophiles divert reactivity to aminopalladation. The intermolecular version of the allylic C-H amination is also known. Using methyl N-tosyl carbamate nucleophile, the linear E-allylic amine products are obtained from α-olefin substrates. It has been shown that functionalization of the π-allyl intermediate may be promoted by chromium(III) salen chloride activation of the electrophile
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...
, or Hunig's base activation of the nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...
.
Allylic alkylation
In 2008, simultaneous publications described the allylic C-H alkylation of allylarene substrates. These reactions were catalyzed by the White catalyst or by an earlier version of the complex bearing benzyl substituents on the sulfoxide in place of phenyl. It was demonstrated that an additional sulfoxide ligand, dimethylsulfoxide (DMSO), was essential for promoting functionalization of the π-allyl intermediate; the bis-sulfoxide ligand alone was unable to complete the catalytic cycle.Heck reaction
The White catalyst has been found to be an effective catalyst for an oxidative version of the classic Heck reactionHeck reaction
The Heck reaction is the chemical reaction of an unsaturated halide with an alkene and a base and palladium catalyst to form a substituted alkene. Together with the other palladium-catalyzed cross-coupling reactions, this reaction is of great importance, as it allows one to do substitution...
. Rather than performing allylic C-H cleavage—a relatively slow process—the catalyst quickly transmetallates
Transmetalation
Transmetalation is a general chemical reaction type in organometallic chemistry describing the exchange of ligands between two metal centers....
with a boronic acid
Boronic acid
A boronic acid is an alkyl or aryl substituted boric acid containing a carbon–boron bond belonging to the larger class of organoboranes. Boronic acids act as Lewis acids. Their unique feature is that they are capable of forming reversible covalent complexes with sugars, amino acids, hydroxamic...
. This aryl palladium intermediate undergoes a 1,2-addition across the alkene double bond. β-Hydride elimination
Beta-hydride elimination
Beta-hydride elimination is a reaction in which an alkyl group bonded to a metal centre is converted into the corresponding metal-bonded hydride and an alkene. The alkyl must have hydrogens on the beta carbon. For instance butyl groups can undergo this reaction but methyl groups cannot...
releases the product. The oxidative Heck was originally reported as a sequential process following allylic C-H esterification. It was subsequently demonstrated as a stand-alone method for a broad range of α-olefin
Alpha-olefin
Alpha-olefins are a family of organic compounds which are olefins or alkenes with a chemical formula CxH2x, distinguished by having a double bond at the primary or alpha position...
substrates. The regioselectivity
Regioselectivity
In chemistry, regioselectivity is the preference of one direction of chemical bond making or breaking over all other possible directions. It can often apply to which of many possible positions a reagent will affect, such as which proton a strong base will abstract from an organic molecule, or where...
of the reaction is controlled by directing groups such as carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
s, alcohols and amines.