CBS catalyst
Encyclopedia
The CBS catalyst or Corey-Bakshi-Shibata catalyst is an asymmetric catalyst
derived from proline
. It finds many uses in organic reaction
s such as the CBS reduction
, Diels-Alder reaction
s and [3+2] cycloaddition
s. Proline, a naturally occurring chiral compound, is readily and cheaply available. It transfers its stereocenter
to the catalyst which in turn is able to drive an organic reaction enantioselectively to one of two possible enantiomer
s. This selectivity is due to steric strain in the transition state
that develops for one enantiomer but not for the other.
of a CBS catalyst is shown below. The first leg of the reaction sequence starts from the azeotropic
dehydration
of a boronic acid
(1) such as one based on toluene
to a boroxine (2). This boroxine
reacts with the proline derivative (3d) to form the basic
oxazaborolidine CBS catalyst (4). The oxazaborolidine was first developed as a ketone reducing agent by the laboratory of Itsuno, and thus is more properly called the Itsuno-Corey oxazaborolidine. Proline derivative 3d is prepared in a separate leg from a Grignard reaction
with Grignard reagent 3c and proline ester 3b. A lewis acid
superacid salt (6) can be obtained with the aid of triflic acid (5). Many other such catalysts exist with different derivatives of these reactants.
Chiral synthesis
Enantioselective synthesis, also called chiral synthesis, asymmetric synthesis or stereoselective synthesis, is organic synthesis that introduces one or more new and desired elements of chirality...
derived from proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
. It finds many uses in organic reaction
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
s such as the CBS reduction
CBS reduction
The Corey-Itsuno Reduction, also known as the Corey-Bakshi-Shibata reduction, is a chemical reaction in which an achiral ketone is enantioselectively reduced to produce the corresponding chiral, non-racemic alcohol...
, Diels-Alder reaction
Diels-Alder reaction
The Diels–Alder reaction is an organic chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can proceed even if some of the atoms in the newly formed ring are not carbon...
s and [3+2] cycloaddition
Cycloaddition
A cycloaddition is a pericyclic chemical reaction, in which "two or more unsaturated molecules combine with the formation of a cyclic adduct in which there is a net reduction of the bond multiplicity." The resulting reaction is a cyclization reaction.Cycloadditions are usually described by the...
s. Proline, a naturally occurring chiral compound, is readily and cheaply available. It transfers its stereocenter
Stereocenter
A stereocenter or stereogenic center is an atom, bearing groups such that an interchanging of any two groups leads to a stereoisomer.A chirality center is a stereocenter consisting of an atom holding a set of ligands in a spatial arrangement which is not superposable on its mirror image...
to the catalyst which in turn is able to drive an organic reaction enantioselectively to one of two possible enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
s. This selectivity is due to steric strain in the transition state
Transition state
The transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate. At this point, assuming a perfectly irreversible reaction, colliding reactant molecules will always...
that develops for one enantiomer but not for the other.
Organic synthesis
The general outline for the organic synthesisOrganic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
of a CBS catalyst is shown below. The first leg of the reaction sequence starts from the azeotropic
Azeotropic distillation
In chemistry, azeotropic distillation is any of a range of techniques used to break an azeotrope in distillation. In chemical engineering, azeotropic distillation usually refers to the specific technique of adding another component to generate a new, lower-boiling azeotrope that is heterogeneous...
dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
of 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...
(1) such as one based on toluene
Toluene
Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...
to a boroxine (2). This boroxine
Boroxine
Boroxine is a 6-membered, heterocyclic compound composed of alternating oxygen and singly-hydrated boron atoms. Boroxine derivatives such as trimethylboroxine and triphenylboroxine also make up a broader class of compounds called boroxines. These compounds are solids that are usually in...
reacts with the proline derivative (3d) to form the basic
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
oxazaborolidine CBS catalyst (4). The oxazaborolidine was first developed as a ketone reducing agent by the laboratory of Itsuno, and thus is more properly called the Itsuno-Corey oxazaborolidine. Proline derivative 3d is prepared in a separate leg from a Grignard reaction
Grignard reaction
The Grignard reaction is an organometallic chemical reaction in which alkyl- or aryl-magnesium halides add to a carbonyl group in an aldehyde or ketone. This reaction is an important tool for the formation of carbon–carbon bonds...
with Grignard reagent 3c and proline ester 3b. A lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
superacid salt (6) can be obtained with the aid of triflic acid (5). Many other such catalysts exist with different derivatives of these reactants.