Torquoselectivity

Last updated March 15, 2019

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."^[1] 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 (i.e. the direction of torque on the substituents). The concept was originally developed by Kendall N. Houk.

In chemistry, stereoselectivity 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. 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. 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.

In organic chemistry, an electrocyclic reaction is a type of pericyclic rearrangement where the net result is one pi bond being converted into one sigma bond or vice versa. These reactions are usually categorized by the following criteria:

Organic chemistry subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

Organic chemistry is the chemistry subdiscipline for the scientific study of structure, properties, and reactions of organic compounds and organic materials. Study of structure determines their chemical composition and formula. Study of properties includes physical and chemical properties, and evaluation of chemical reactivity to understand their behavior. The study of organic reactions includes the chemical synthesis of natural products, drugs, and polymers, and study of individual organic molecules in the laboratory and via theoretical study.

For ring closing reactions, it is an example of enantioselectivity, wherein a single enantiomer of a cyclization product is formed from the selective ring closure of the starting material. In a typical electrocyclic ring closing, selection for either conrotatory or disrotatory reactions modes still produces two enantiomers. Torquoselectivity is a discrimination between these possible enantiomers that requires asymmetric induction.

In chemistry, an enantiomer, also known as an optical isomer, 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 being reversed along one axis. A single chiral atom or similar structural feature in a compound causes that compound to have two possible structures which are non-superposable, each a mirror image of the other. Each member of the pair is termed an enantiomorph ; the structural property is termed enantiomerism. The presence of multiple chiral features in a given compound increases the number of geometric forms possible, though there may be some perfect-mirror-image pairs.

Asymmetric induction in stereochemistry 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.

Conrotatory and disrotatory modes of rotation each showing two possible directions of rotation that result in pairs of enantiomers for a generic hexatriene system. Note: in the case shown, there is no reason for the reaction to be torquoselective and both products would be expected for any particular set of conditions. Torquo.png — Conrotatory and disrotatory modes of rotation each showing two possible directions of rotation that result in pairs of enantiomers for a generic hexatriene system. **Note:** in the case shown, there is no reason for the reaction to be torquoselective and both products would be expected for any particular set of conditions.

Torquoselectivity is also used to describe selective electrocyclic ring openings, in which different directions of rotation produce distinct structural isomers. In these cases, steric strain is often the driving force for the selectivity. Studies have shown that the selectivity can also be changed by the presence of electron donating and electron withdrawing groups.^[2]

Other mechanisms by which torquoselectivity can operate include chiral Lewis acid catalysts, induction via neighboring stereocenters (in which case the torquoselectivity is a case of diastereoselectivity), and axial-to-tetrahedral chirality transfer. An example of the latter case is shown below for the torquoselective Nazarov cyclization reaction of a chiral allenyl vinyl ketone.^[3]

Chirality is a geometric property of some molecules and ions. A chiral molecule/ion is non-superposable on its mirror image. The presence of an asymmetric carbon center is one of several structural features that induce chirality in organic and inorganic molecules. The term chirality is derived from the Ancient Greek word for hand, χεῖρ (kheir).

In a molecule, a stereocenter is a particular instance of a stereogenic element that is geometrically a point. A stereocenter or stereogenic center is any point in a molecule, though not necessarily an atom, bearing groups, such that an interchanging of any two groups leads to a stereoisomer. The term stereocenter was introduced in 1984 by Kurt Mislow and Jay Siegel. A chiral center is a stereocenter consisting of an atom holding a set of ligands in a spatial arrangement which is not superimposable on its mirror image. The concept of a chiral center generalizes the concept of an asymmetric carbon atom such that an interchanging of any two groups gives rise to an enantiomer. In organic chemistry, a chiral center usually refers to a carbon, phosphorus, or sulfur atom, though it is also possible for other atoms to be chiral centers, especially in areas of organometallic and inorganic chemistry.

The Nazarov cyclization reaction is a chemical reaction used in organic chemistry for the synthesis of cyclopentenones. The reaction is typically divided into classical and modern variants, depending on the reagents and substrates employed. It was originally discovered by Ivan Nikolaevich Nazarov (1906–1957) in 1941 while studying the rearrangements of allyl vinyl ketones.

Related Research Articles

The Sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols.

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.

The aldol reaction is a means of forming carbon–carbon bonds in organic chemistry. Discovered independently by the Russian chemist Alexander Borodin in 1869 and by the French chemist Charles-Adolphe Wurtz in 1872, the reaction combines two carbonyl compounds to form a new β-hydroxy carbonyl compound. These products are known as aldols, from the aldehyde + alcohol, a structural motif seen in many of the products. Aldol structural units are found in many important molecules, whether naturally occurring or synthetic. For example, the aldol reaction has been used in the large-scale production of the commodity chemical pentaerythritol and the synthesis of the heart disease drug Lipitor.

The ene reaction is a chemical reaction between an alkene with an allylic hydrogen and a compound containing a multiple bond, in order to form a new σ-bond with migration of the ene double bond and 1,5 hydrogen shift. The product is a substituted alkene with the double bond shifted to the allylic position.

The 1,3-dipolar cycloaddition is a chemical reaction between a 1,3-dipole and a dipolarophile to form a five-membered ring. The earliest 1,3-dipolar cycloadditions were described in the late 19th century to the early 20th century, following the discovery of 1,3-dipoles. Mechanistic investigation and synthetic application were established in the 1960s, primarily through the work of Rolf Huisgen. Hence, the reaction is sometimes referred to as the Huisgen cycloaddition. 1,3-dipolar cycloaddition is an important route to the regio- and stereoselective synthesis of five-membered heterocycles and their ring-opened acyclic derivatives.

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.

Azomethine ylides are nitrogen-based 1,3-dipoles, consisting of an iminium ion next to a carbanion. They are used in 1,3-dipolar cycloaddition reactions to form 5-membered heterocycles, including pyrrolidines and pyrrolines. These reactions are highly stereo- and regioselective, and have the potential to form four new contiguous stereocenters. Azomethine ylides thus have high utility in total synthesis, and formation of chiral ligands and pharmaceuticals. Azomethine ylides can be generated from many sources, including aziridines, imines, and iminiums. They are often generated in situ, and immediately reacted with dipolarophiles.

The Woodward–Hoffmann rules, devised by Robert Burns Woodward and Roald Hoffmann, are a set of rules used to rationalize or predict certain aspects of the stereochemistry and activation energy of pericyclic reactions, an important class of reactions in organic chemistry. The Woodward–Hoffmann rules are a consequence of the changes in electronic structure that occur during a pericyclic reaction and are predicated on the phasing of the interacting molecular orbitals. They are applicable to all classes of pericyclic reactions, including (1) electrocyclizations, (2) cycloadditions, (3) sigmatropic reactions, (4) group transfer reactions, (5) ene reactions, (6) cheletropic reactions, and (7) dyotropic reactions. Due to their elegance, simplicity, and generality, the Woodward–Hoffmann rules are credited with first exemplifying the power of molecular orbital theory to experimental chemists.

Danishefsky’s diene is an organosilicon compound and a diene with the formal name trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene named after Samuel J. Danishefsky. Because the diene is very electron-rich it is a very reactive reagent in Diels-Alder reactions. This diene reacts rapidly with electrophilic alkenes, such as maleic anhydride. The methoxy group promotes highly regioselective additions. The diene is known to react with amines, aldehydes, alkenes and alkynes. Reactions with imines and nitro-olefins have been reported.

Allylic strain in organic chemistry is a type of strain energy resulting from the interaction between a substituent on one end of an olefin with an allylic substituent on the other end. If the substituents are large enough in size, they can sterically interfere with each other such that one conformer is greatly favored over the other. Allyic strain was first recognized in the literature in 1965 by Johnson and Malhotra. The authors were investigating cyclohexane conformations including endocyclic and exocylic double bonds when they noticed certain conformations were disfavored due to the geometry constraints caused by the double bond. Organic chemists capitalize on the rigidity resulting from allylic strain for use in asymmetric reactions.

Chiral Lewis acids (CLAs) are a type of Lewis acid catalyst that effects the chirality of the substrate as it reacts with it. In such reactions the synthesis favors the formation of a specific enantiomer or diastereomer. The method then 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 an 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 most often have multiple Lewis basic sites that allow the formation of a ring structure involving the metal atom.

The Staudinger Synthesis, also called the Staudinger Ketene-Imine Cycloaddition, is a chemical synthesis in which an imine 1 reacts with a ketene 2 through a non-photochemical 2+2 cycloaddition to produce a β-lactam3. The reaction carries particular importance in the synthesis of β-Lactam antibiotics. The Staudinger Synthesis should not be confused with the Staudinger Reaction, a phosphine or phosphite reaction used to reduce azides to amines.

The Birch reduction is an organic reaction which is particularly useful in synthetic organic chemistry. The reaction was reported in 1944 by the Australian chemist Arthur Birch (1915–1995) working in the Dyson Perrins Laboratory at the University of Oxford, building on earlier work by Wooster and Godfrey published in 1937. It converts aromatic compounds having a benzenoid ring into a product, 1,4-cyclohexadienes, in which two hydrogen atoms have been attached on opposite ends of the molecule. It is the organic reduction of aromatic rings in liquid ammonia with sodium, lithium or potassium and an alcohol, such as ethanol and tert-butanol. This reaction is quite unlike catalytic hydrogenation, which usually reduces the aromatic ring all the way to a cyclohexane.

The [2,3]-Wittig rearrangement is the transformation of an allylic ether into a homoallylic alcohol via a concerted, pericyclic process. Because the reaction is concerted, it exhibits a high degree of stereocontrol, and can be employed early in a synthetic route to establish stereochemistry. The Wittig rearrangement requires strongly basic conditions, however, as a carbanion intermediate is essential. [1,2]-Wittig rearrangement is a competitive process.

The imine Diels-Alder reaction involves the transformation of all-carbon dienes and imine dienophiles into tetrahydropyridines.

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 stereo selective methods for benzylic and homobenzylic fictionalization have been developed based on this property.

References

↑ Jefford, C.W.; Bernardinelli, G.; Wang, Y.; Spellmeyer, D.C.; Buda, A.; Houk, K.N. (1992), "Torquoselectivity in the Electrocyclic Conversion of Benzocyclobutenes to o-Xylylenes", J. Am. Chem. Soc. , 114: 1157–1165, doi:10.1021/ja00030a005
↑ Kirmse, W.; Rondan, N.G.; Houk, K.N. (1984), "Stereoselective Substituent Effects on Conrotatory Electrocyclic Reactions of Cyclobutenes", J. Am. Chem. Soc. , 106: 7989–7991, doi:10.1021/ja00337a067
↑ Frontier, A. J.; Collison, C. (2005), "The Nazarov cyclization in organic synthesis. Recent advances.", Tetrahedron , 61: 7577, doi:10.1016/j.tet.2005.05.019

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[Definition-1] Jefford, C.W.; Bernardinelli, G.; Wang, Y.; Spellmeyer, D.C.; Buda, A.; Houk, K.N. (1992), "Torquoselectivity in the Electrocyclic Conversion of Benzocyclobutenes to o-Xylylenes", J. Am. Chem. Soc. , 114: 1157–1165, doi:10.1021/ja00030a005

[Houk_electronics-2] Kirmse, W.; Rondan, N.G.; Houk, K.N. (1984), "Stereoselective Substituent Effects on Conrotatory Electrocyclic Reactions of Cyclobutenes", J. Am. Chem. Soc. , 106: 7989–7991, doi:10.1021/ja00337a067

[Frontier-3] Frontier, A. J.; Collison, C. (2005), "The Nazarov cyclization in organic synthesis. Recent advances.", Tetrahedron , 61: 7577, doi:10.1016/j.tet.2005.05.019