Stereoselectivity
Encyclopedia
In chemistry
, stereoselectivity is the property of a chemical reaction
in which a single reactant forms an unequal mixture of stereoisomers
during the non-stereospecific
creation of a new stereocenter
or during the non-stereospecific
transformation of a pre-existing one. The selectivity arises from differences in steric effects and electronic effects in the mechanistic pathways leading to the different products. Stereoselectivity can vary in degree but it can never be total since the activation energy difference between the two pathways is finite. However, in favorable cases, the minor stereoisomer may not be detectable by the analytic methods used.
An enantioselective reaction is one in which one enantiomer
is formed in preference to the other, in a reaction that creates an optically active product from an achiral starting material, using either a chiral catalyst, an enzyme
or a chiral reagent. The degree of selectivity is measured by the enantiomeric excess
. An important variant is kinetic resolution
, in which a pre-existing chiral center undergoes reaction with a chiral catalyst, an enzyme or a chiral reagent such that one enantiomer reacts faster than the other and leaves behind the less reactive enantiomer, or in which a pre-existing chiral center influences the reactivity of a reaction center elsewhere in the same molecule.
A diastereoselective reaction is one in which one diastereomer
is formed in preference to another (or in which a subset of all possible diastereomers dominates the product mixture), establishing a preferred relative stereochemistry. In this case, either two or more chiral centers are formed at once such that one relative stereochemistry is favored, or a pre-existing chiral center (which needs not be optically pure) biases the stereochemical outcome during the creation of another. The degree of relative selectivity is measured by the diastereomeric excess.
Stereoconvergence can be considered an opposite of stereoselectivity, when the reaction of two different stereoisomers yield a single product stereoisomer.
The quality of stereoselectivity is concerned solely with the products, and their stereochemistry. Of a number of possible stereoisomeric products, the reaction selects one or two to be formed.
of 2-iodo-butane which yields 60% trans-2-butene and 20% cis-2-butene. Since alkene geometric isomers are also classified as diastereomer
s, this reaction would also be called diastereoselective.
The addition of formic acid
to norbornene
is also stereospecific because the exo isomer is formed exclusively without any of the endo isomer :
Cram's rule predicts the major diastereomer
resulting from the diastereoselective nucleophilic addition to a carbonyl group next to a chiral center. The chiral center need not be optically pure, as the relative stereochemistry will be the same for both enantiomers. In the example below the (S)-aldehyde reacts with a thiazole to form the (S,S) diastereomer but only a small amount of the (S,R) diastereomer :
The Sharpless epoxidation
is an example of an enantioselective process, in which an achiral
allylic alcohol substrate is transformed into an optically active epoxyalcohol. In the case of chiral allylic alcohols, kinetic resolution results. Another example is Sharpless asymmetric dihydroxylation
. In the example below the achiral alkene yields only one of possible 4 stereoisomers.
With a stereogenic center next to the carbocation the substitution can be stereoselective in intra and intramolecular reactions. In the reaction depicted below the nucleophile (furan) can approach the carbocation formed from the least shielded side away from the bulky t-butyl group resulting in high facial diastereoselectivity:
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
, stereoselectivity is the property of a chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
in which a single reactant forms an unequal mixture of stereoisomers
Stereoisomerism
Stereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms , but that differ only in the three-dimensional orientations of their atoms in space. This contrasts with structural isomers, which share the same molecular formula, but the bond connections...
during the non-stereospecific
Stereospecificity
In chemistry, stereospecificity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one of the stereoisomers."Overlap Control of Carbanionoid Reactions. I. Stereoselectivity in Alkaline...
creation of a new 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...
or during the non-stereospecific
Stereospecificity
In chemistry, stereospecificity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one of the stereoisomers."Overlap Control of Carbanionoid Reactions. I. Stereoselectivity in Alkaline...
transformation of a pre-existing one. The selectivity arises from differences in steric effects and electronic effects in the mechanistic pathways leading to the different products. Stereoselectivity can vary in degree but it can never be total since the activation energy difference between the two pathways is finite. However, in favorable cases, the minor stereoisomer may not be detectable by the analytic methods used.
An enantioselective reaction is one in which one 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...
is formed in preference to the other, in a reaction that creates an optically active product from an achiral starting material, using either a chiral catalyst, an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
or a chiral reagent. The degree of selectivity is measured by the enantiomeric excess
Enantiomeric excess
The enantiomeric excess of a substance is a measure of how pure it is. In this case, the impurity is the undesired enantiomer .-Definition:...
. An important variant is kinetic resolution
Kinetic resolution
In kinetic resolution, two enantiomers show different reaction rates in a chemical reaction, thereby creating an excess of the less reactive enantiomer. This excess goes through a maximum and disappears on full completion of the reaction. Kinetic resolution is a very old concept in organic...
, in which a pre-existing chiral center undergoes reaction with a chiral catalyst, an enzyme or a chiral reagent such that one enantiomer reacts faster than the other and leaves behind the less reactive enantiomer, or in which a pre-existing chiral center influences the reactivity of a reaction center elsewhere in the same molecule.
A diastereoselective reaction is one in which one diastereomer
Diastereomer
Diastereomers are stereoisomers that are not enantiomers.Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more of the equivalent stereocenters and are not mirror images of each other.When two diastereoisomers differ from each other at...
is formed in preference to another (or in which a subset of all possible diastereomers dominates the product mixture), establishing a preferred relative stereochemistry. In this case, either two or more chiral centers are formed at once such that one relative stereochemistry is favored, or a pre-existing chiral center (which needs not be optically pure) biases the stereochemical outcome during the creation of another. The degree of relative selectivity is measured by the diastereomeric excess.
Stereoconvergence can be considered an opposite of stereoselectivity, when the reaction of two different stereoisomers yield a single product stereoisomer.
The quality of stereoselectivity is concerned solely with the products, and their stereochemistry. Of a number of possible stereoisomeric products, the reaction selects one or two to be formed.
Examples
An example of modest stereoselectivity is the dehydrohalogenationDehydrohalogenation
Dehydrohalogenation is an organic reaction from which an alkene is obtained from an alkyl halide . It is also called a β-Elimination reaction and is a type of elimination reaction....
of 2-iodo-butane which yields 60% trans-2-butene and 20% cis-2-butene. Since alkene geometric isomers are also classified as diastereomer
Diastereomer
Diastereomers are stereoisomers that are not enantiomers.Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more of the equivalent stereocenters and are not mirror images of each other.When two diastereoisomers differ from each other at...
s, this reaction would also be called diastereoselective.
The addition of formic acid
Formic acid
Formic acid is the simplest carboxylic acid. Its chemical formula is HCOOH or HCO2H. It is an important intermediate in chemical synthesis and occurs naturally, most notably in the venom of bee and ant stings. In fact, its name comes from the Latin word for ant, formica, referring to its early...
to norbornene
Norbornene
Norbornene or norbornylene or norcamphene is a bridged cyclic hydrocarbon. It is a white solid with a pungent sour odor. The molecule consists of a cyclohexene ring bridged with a methylene group in the para position...
is also stereospecific because the exo isomer is formed exclusively without any of the endo isomer :
Cram's rule predicts the major diastereomer
Diastereomer
Diastereomers are stereoisomers that are not enantiomers.Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more of the equivalent stereocenters and are not mirror images of each other.When two diastereoisomers differ from each other at...
resulting from the diastereoselective nucleophilic addition to a carbonyl group next to a chiral center. The chiral center need not be optically pure, as the relative stereochemistry will be the same for both enantiomers. In the example below the (S)-aldehyde reacts with a thiazole to form the (S,S) diastereomer but only a small amount of the (S,R) diastereomer :
The Sharpless epoxidation
Sharpless epoxidation
The Sharpless Epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols....
is an example of an enantioselective process, in which an achiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
allylic alcohol substrate is transformed into an optically active epoxyalcohol. In the case of chiral allylic alcohols, kinetic resolution results. Another example is Sharpless asymmetric dihydroxylation
Sharpless asymmetric dihydroxylation
Sharpless asymmetric dihydroxylation is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol....
. In the example below the achiral alkene yields only one of possible 4 stereoisomers.
With a stereogenic center next to the carbocation the substitution can be stereoselective in intra and intramolecular reactions. In the reaction depicted below the nucleophile (furan) can approach the carbocation formed from the least shielded side away from the bulky t-butyl group resulting in high facial diastereoselectivity: