Ability of a chemical reaction to produce an unequal mixture of stereoisomers
In chemistry, stereoselectivity[1] is the property of a chemical reaction in which a single reactant forms an unequal mixture of stereoisomers during a non-stereospecific creation of a new stereocenter or during a non-stereospecific transformation of a pre-existing one.[2] The selectivity arises from differences in steric 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: both products are at least possible and merely differ in amount. 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,[3] 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 stereospecificity, 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.
Stereomutation is a general term for the conversion of one stereoisomer into another. For example, racemization (as in SN1 reactions), epimerization (as in interconversion of D-glucose and D-mannose in Lobry de Bruyn–Van Ekenstein transformation), or asymmetric transformation (conversion of a racemate into a pure enantiomer or into a mixture in which one enantiomer is present in excess, or of a diastereoisomeric mixture into a single diastereoisomer or into a mixture in which one diastereoisomer predominates).[4]
Examples
An example of modest stereoselectivity is the dehydrohalogenation of 2-iodobutane which yields 60% trans-2-butene and 20% cis-2-butene.[5] Since alkene geometric isomers are also classified as diastereomers, this reaction would also be called diastereoselective.
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:[6]
The Sharpless epoxidation is an example of an enantioselective process, in which an achiralallylic 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 the possible 4 stereoisomers.[7]
With a stereogenic center next to the carbocation the substitution can be stereoselective in inter- [8] and intramolecular [9][10] 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:
↑ (a)"Overlap Control of Carbanionoid Reactions. I. Stereoselectivity in Alkaline Epoxidation," Zimmerman, H. E.; Singer, L.; Thyagarajan, B. S. J. Am. Chem. Soc., 1959, 81, 108-116. (b)Eliel, E., "Stereochemistry of Carbon Compound", McGraw-Hill, 1962 pp 434-436.
↑ For instance, the SN1 reaction destroys a pre-existing stereocenter, and then creates a new one.
↑ Or fewer than all possible relative stereochemistries are obtained.
↑ Eliel, E.L. & Willen S.H., "Stereochemistry of Organic Compounds", John Wiley & Sons, 2008 pp 1209.
↑ Effects of base strength and size upon in base-promoted elimination reactions. Richard A. Bartsch, Gerald M. Pruss, Bruce A. Bushaw, Karl E. Wiegers J. Am. Chem. Soc.; 1973; 95(10); 3405-3407. doi:10.1021/ja00791a067
↑ Diastereoselective Friedel-Crafts Cyclization Reactions to 2-Substituted 1-Phenyl-1,2,3,4-tetrahydronaphthalenes Friedrich Mühlthau, Thorsten Bach Synthesis 2005: 3428-3436 doi:10.1055/s-2005-918482
↑ High Facial Diastereoselectivity in Intra- and Intermolecular Reactions of Chiral Benzylic Cations Friedrich Mühlthau, Oliver Schuster, and Thorsten Bach J. Am. Chem. Soc., 2005, 127 (26), pp 9348–9349 doi:10.1021/ja050626v
↑ Davin LB, Wang HB, Crowell AL, etal. (1997). "Stereoselective bimolecular phenoxy radical coupling by an auxiliary (dirigent) protein without an active center". Science. 275 (5298): 362–6. doi:10.1126/science.275.5298.362. PMID8994027. S2CID41957412.
In organic chemistry, the Cahn–Ingold–Prelog (CIP) sequence rules are a standard process to completely and unequivocally name a stereoisomer of a molecule. The purpose of the CIP system is to assign an R or S descriptor to each stereocenter and an E or Z descriptor to each double bond so that the configuration of the entire molecule can be specified uniquely by including the descriptors in its systematic name. A molecule may contain any number of stereocenters and any number of double bonds, and each usually gives rise to two possible isomers. A molecule with an integer n describing the number of stereocenters will usually have 2n stereoisomers, and 2n−1 diastereomers each having an associated pair of enantiomers. The CIP sequence rules contribute to the precise naming of every stereoisomer of every organic molecule with all atoms of ligancy of fewer than 4.
In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ 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 or their order differs. By definition, molecules that are stereoisomers of each other represent the same structural isomer.
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoisomers, which by definition have the same molecular formula and sequence of bonded atoms (constitution), but differ in the geometric positioning of the atoms in space. For this reason, it is also known as 3D chemistry—the prefix "stereo-" means "three-dimensionality".
In chemistry, an enantiomer – also called optical isomer, antipode, or optical antipode – is one of two stereoisomers that are non-superposable onto their own mirror image. Enantiomers are much like one's right and left hands; without mirroring one of them, hands cannot be superposed onto each other. No amount of reorientation in three spatial dimensions will allow the four unique groups on the chiral carbon to line up exactly. The number of stereoisomers a molecule has can be determined by the number of chiral carbons it has. Stereoisomers include both enantiomers and diastereomers.
The aldol reaction is a reaction that combines two carbonyl compounds to form a new β-hydroxy carbonyl compound.
In chemistry, racemization is a conversion, by heat or by chemical reaction, of an optically active compound into a racemic form. This creates a 1:1 molar ratio of enantiomers and is referred to as a racemic mixture. Plus and minus forms are called Dextrorotation and levorotation. The D and L enantiomers are present in equal quantities, the resulting sample is described as a racemic mixture or a racemate. Racemization can proceed through a number of different mechanisms, and it has particular significance in pharmacology as different enantiomers may have different pharmaceutical effects.
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 creates a new stereoisomer. Stereocenters are also referred to as stereogenic centers.
In stereochemistry, diastereomers are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have different configurations at one or more of the equivalent (related) stereocenters and are not mirror images of each other. When two diastereoisomers differ from each other at only one stereocenter, they are epimers. Each stereocenter gives rise to two different configurations and thus typically increases the number of stereoisomers by a factor of two.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes. This geometric property is called chirality. The terms are derived from Ancient Greek χείρ (cheir) 'hand'; which is the canonical example of an object with this property.
Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction in which one or more new elements of chirality are formed in a substrate molecule and which produces the stereoisomeric products in unequal amounts."
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.
In stereochemistry, enantiomeric excess (ee) is a measurement of purity used for chiral substances. It reflects the degree to which a sample contains one enantiomer in greater amounts than the other. A racemic mixture has an ee of 0%, while a single completely pure enantiomer has an ee of 100%. A sample with 70% of one enantiomer and 30% of the other has an ee of 40%.
Atropisomers are stereoisomers arising because of hindered rotation about a single bond, where energy differences due to steric strain or other contributors create a barrier to rotation that is high enough to allow for isolation of individual conformers. They occur naturally and are important in pharmaceutical design. When the substituents are achiral, these conformers are enantiomers (atropoenantiomers), showing axial chirality; otherwise they are diastereomers (atropodiastereomers).
In stereochemistry, a chiral auxiliary is a stereogenic group or unit that is temporarily incorporated into an organic compound in order to control the stereochemical outcome of the synthesis. The chirality present in the auxiliary can bias the stereoselectivity of one or more subsequent reactions. The auxiliary can then be typically recovered for future use.
Dirigent proteins are members of a class of proteins which dictate the stereochemistry of a compound synthesized by other enzymes. The first dirigent protein was discovered in Forsythia intermedia. This protein has been found to direct the stereoselective biosynthesis of (+)-pinoresinol from coniferyl alcohol monomers:
Asymmetric induction describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment. Asymmetric induction is a key element in asymmetric synthesis.
Chiral Lewis acids (CLAs) are a type of Lewis acid catalyst. These acids affect the chirality of the substrate as they react with it. In such reactions, synthesis favors the formation of a specific enantiomer or diastereomer. The method is an enantioselective asymmetric synthesis reaction. Since they affect chirality, they produce optically active products from optically inactive or mixed starting materials. This type of preferential formation of one enantiomer or diastereomer over the other is formally known as asymmetric induction. In this kind of Lewis acid, the electron-accepting atom is typically a metal, such as indium, zinc, lithium, aluminium, titanium, or boron. The chiral-altering ligands employed for synthesizing these acids often have multiple Lewis basic sites that allow the formation of a ring structure involving the metal atom.
Organostannane addition reactions comprise the nucleophilic addition of an allyl-, allenyl-, or propargylstannane to an aldehyde, imine, or, in rare cases, a ketone. The reaction is widely used for carbonyl allylation.
Benzylic activation and stereocontrol in tricarbonyl(arene)chromium complexes refers to the enhanced rates and stereoselectivities of reactions at the benzylic position of aromatic rings complexed to chromium(0) relative to uncomplexed arenes. Complexation of an aromatic ring to chromium stabilizes both anions and cations at the benzylic position and provides a steric blocking element for diastereoselective functionalization of the benzylic position. A large number of stereoselective methods for benzylic and homobenzylic functionalization have been developed based on this property.
Torquoselectivity is a special kind of stereoselectivity observed in electrocyclic reactions in organic chemistry, defined as "the preference for inward or outward rotation of substituents in conrotatory or disrotatory electrocyclic reactions." Torquoselectivity is not to be confused with the normal diastereoselectivity seen in pericyclic reactions, as it represents a further level of selectivity beyond the Woodward-Hoffman rules. The name derives from the idea that the substituents in an electrocyclization appear to rotate over the course of the reaction, and thus selection of a single product is equivalent to selection of one direction of rotation. The concept was originally developed by Kendall N. Houk.
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