The CBS catalyst or Corey–Bakshi–Shibata catalyst is an

asymmetric catalyst Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecul ...

derived from

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

. It finds many uses in

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, Mechanistic Organ ...

s such as the CBS reduction, Diels-Alder reactions and (3+2)

cycloaddition In organic chemistry, a cycloaddition is a chemical reaction in which "two or more Unsaturated hydrocarbon, unsaturated molecules (or parts of the same molecule) combine with the formation of a cyclic adduct in which there is a net reduction of th ...

s. Proline, a naturally occurring

chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...

compound, is readily and cheaply available. It transfers its

stereocenter In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups cr ...

to the

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

which in turn is able to drive an organic reaction selectively to one of two possible

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

s. This selectivity is due to

steric strain Van der Waals strain is strain resulting from Van der Waals repulsion when two substituents in a molecule approach each other with a distance less than the sum of their Van der Waals radii. Van der Waals strain is also called Van der Waals repuls ...

in the

transition state In chemistry, 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 potential energy along this reaction coordinate. It is often marked wi ...

that develops for one enantiomer but not for the other.

Synthesis

The CBS catalyst can be prepared from

diphenylprolinol Diphenylprolinol (D2PM), or (''R''/''S'')-(±)-diphenyl-2-pyrrolidinyl-methanol, is a norepinephrine-dopamine reuptake inhibitor which is used as a designer drug. Pharmacology The dextrorotary (''R'')-(+)-enantiomer is the more pharmacological ...

, condensed with a

phenylboronic acid Phenylboronic acid or benzeneboronic acid, abbreviated as PhB(OH)2 where Ph is the phenyl group C6H5-, is a boronic acid containing a phenyl substituent and two hydroxyl groups attached to boron. Phenylboronic acid is a white powder and is comm ...

, or with

borane Trihydridoboron, also known as borane or borine, is an unstable and highly reactive molecule with the chemical formula . The preparation of borane carbonyl, BH3(CO), played an important role in exploring the chemistry of boranes, as it indicated ...

(as shown below). The CBS catalyst then complexes ''in situ'' with

to give the active catalyst.

Use

The general outline for the

organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...

of a CBS catalyst is shown below. The first leg of the reaction sequence starts from the

azeotropic An azeotrope () or a constant heating point mixture is a mixture of two or more liquids whose proportions cannot be altered or changed by simple distillation.Moore, Walter J. ''Physical Chemistry'', 3rd e Prentice-Hall 1962, pp. 140–142 This ...

dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...

of a

boronic acid 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, membe ...

(1) such as one based on

toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) at ...

to a boroxine (2). This

boroxine Boroxine () is a 6-membered heterocyclic compound composed of alternating oxygen and singly-hydrogenated boron atoms. Boroxine Derivative (chemistry), derivatives (boronic anhydrides) such as trimethylboroxine and triphenylboroxine also make up a ...

reacts with the proline derivative (3d) to form the

basic BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of general-purpose, high-level programming languages designed for ease of use. The original version was created by John G. Kemeny and Thomas E. Kurtz at Dartmouth College ...

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 The Grignard reaction () is an organometallic chemical reaction in which alkyl, allyl, vinyl, or aryl-magnesium halides ( Grignard reagent) is added to a carbonyl group in an aldehyde or ketone. This reaction is important for the formation of ...

with

Grignard reagent A Grignard reagent or Grignard compound is a chemical compound with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromide ...

3c and proline ester 3b. A

Lewis acid A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any sp ...

superacid salt (6) can be obtained with the aid of

triflic acid Triflic acid, the short name for trifluoromethanesulfonic acid, TFMS, TFSA, HOTf or TfOH, is a sulfonic acid with the chemical formula CF3SO3H. It is one of the strongest known acids. Triflic acid is mainly used in research as a catalyst for este ...

(5). Many other such catalysts exist with different derivatives of these reactants.

References

* * * {{Organic reactions Reagents for organic chemistry Organoboron compounds Catalysts