Atropisomerism

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The two atropisomers of 6,6'-dinitro-2,2'-diphenic acid - the free rotation around the single bond between the phenyl rings is limited.

Atropisomerism is a special case of axial chirality . In atropisomers is rotamers in which the rotation of a covalent single bond is constrained by bulky substituents such that conformers can be isolated. According to a definition by M. Oki, the half-life of isomerization (conversion of one rotamer into the other) at a given temperature must be longer than 1000 seconds.

The phenomenon “atropisomerism” was first described in 1922 by Christie and Kenner, who were able to separate the isomers of 6,6'-dinitro-2,2'-diphenic acid. Atropisomerism can also be observed in sterically demanding α-substituted styrenes. If such atropisomers contain an additional center of chirality, then diastereomeric atropisomers can easily be detected by NMR spectroscopy.

Stereochemistry and nomenclature

Atropisomers are enantiomers that can be separated and - like other enantiomers - usually have the same chemical and physical properties, with the exception of the rotation value . In a chiral environment, i.e. H. when chemically reacting with an enantiomer of another chiral compound, atropisomers - like other enantiomers - show different properties and effects. The physiological properties of atropisomers are usually different. With regard to the nomenclature , the rules of the Cahn-Ingold-Prelog system are applied and the configuration of the chiral axis is described as R a or S a , or the stereochemistry according to the helix nomenclature with the descriptors P (plus) or M (minus) described.

Examples

The four stereoisomers of metolachlor

One field of application for atropisomerism is asymmetric synthesis . Chiral auxiliaries such as BINAP or BINOL are used in stereoselective reactions.

Atropisomeric products can be found in individual drugs , natural substances and the herbicide metolachlor .

The drug telenzepine contains a C – N bond that is stereogenic due to the blocked rotation. In a neutral aqueous solution, the half-life for racemization is about 1000 years. After separation of the enantiomers, it was found that the (+) - isomer has an inhibitory effect on the muscarinic receptor M1 that is about 500 times stronger than the (-) - isomer.

Web links

Individual evidence

  1. ↑ M. Oki: Recent Advances in Atropisomerism. in "Topics in Stereochemistry", 1983, Vol. 14, pp. 1-81.
  2. ↑ Christian Wolf: Dynamic stereochemistry of chiral compounds: principles and applications. The Royal Society of Chemistry, Cambridge 2008 ( limited preview in Google Book Search), p. 84.
  3. Jump up ↑ HU Blaser: The Chiral Switch of ( S ) -Metolachlor: A Personal Account of an Industrial Odyssey in Asymmetric Catalysis , Advanced Synthesis & Catalysis 2002, 344 , 17-31. doi : 10.1002 / 1615-4169 (200201) 344: 1 <17 :: AID-ADSC17> 3.0.CO; 2-8 .
  4. ^ J. Clayden, WJ Moran, PJ Edwards, SR LaPante: The Challenge of Atropisomerism in Drug Discovery , Angew. Chem. Int. Ed. 2009 , 48 , 6398-6401.