Atropisomer
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Atropisomers are stereoisomers resulting from hindered rotation about single bonds where the steric strain barrier to rotation is high enough to allow for the isolation of the conformers [1]. The word atropisomer is derived from the Greek a which means not and tropos which translates as turn. The name was coined by Kuhn in 1933, but atropisomerism was first detected in 6,6’-dinitro-2,2’-diphenic acid by Cristie in 1922.
Oki defined atropisomers as conformers that interconvert with a half-life of more than 1000 seconds at a given temperature.[2] Atropisomers are an important class of compounds because they display axial chirality. They differ from other chiral compounds in that they can be equilibrated thermally whereas in the other forms of chirality isomerization is usually only possible chemically.
The most important class of atropisomers are biaryls such as the aforementioned diphenic acid which is a derivative of biphenyl with a complete set of ortho substituents. Others are dimers of naphthalene derivatives such as 1,1'-bi-2-naphthol. In a similar way aliphatic ring systems like cyclohexanes linked through a single bond may display atropisomerism provided that bulky substituents are present.
Examples of naturally occurring atropisomers include vancomycin and knipholone which is found in the roots of Kniphofia Foliosa of the family Asphodelaceae.
Separation of atropisomers is possibly by chiral resolution methods such as selective crystallization. In an atropo-enantioselective or atropselective synthesis one atropisomer is formed at the expense of the other. Atroposelective synthesis may be carried out by use of chiral auxiliaries like a CBS catalyst in the total synthesis of knipholone or by approaches based on thermodynamic equilibration when an isomerization reaction favors one atropisomer over the other.
[edit] Scope
In one application the asymmetry in an atropisomer is transferred in a chemical reaction to a new stereocenter [3]. The atropisomer is an iodoaryl compound synthesised starting from (S)-valine and exists as the (M,S) isomer and the (P,S) isomer. The interconversion barrier between the two is 24.3 kcal/mol (101.7 kJ/mol). The (M,S) isomer can be obtained exclusively from this mixture by recrystallisation from hexanes. The iodine group is homolytically removed to form an aryl radical by a tributyltin hydride/triethylboron/oxygen mixture as in the Barton-McCombie reaction. Although the hindered rotation is now removed in the aryl radical the intermolecular reaction with the alkene is so much faster than rotation of the carbon-nitrogen bond that the stereochemistry is preserved. In this way the (M,S) isomer yields the (S,S) dihydroindolone.
An axial chirality switch is reported [4] for a diol prepared from intramolecular pinacol coupling of the corresponding di-aldehyde with samarium(II) iodide. In methanol this compound has the two alcohol groups in equatorial positions but in hexane helicity is reversed with both groups in axial positions.
[edit] External links
- Selective atropisomer preparation in natural product synthesis reported by Kevin M. Peese 2002 Website
[edit] References
- ^ Atroposelective Synthesis of Axially Chiral Biaryl Compounds Gerhard Bringmann, Anne J. Price Mortimer, Paul A. Keller, Mary J. Gresser, James Garner, Matthias Breuning Angewandte Chemie International Edition Volume 44, Issue 34 , Pages 5384 - 5427 2005 Abstract
- ^ Oki, M; Topics in Stereochemistry 1983, 1
- ^ Relaying Asymmetry of Transient Atropisomers of o-Iodoanilides by Radical Cyclizations Marc Petit, Andre J. B. Lapierre, and Dennis P. Curran J. Am. Chem. Soc.; 2005; 127(43) pp 14994 - 14995; (Communication) DOI: 10.1021/ja055666d Abstract
- ^ Development of an Axial Chirality Switch Stefan Reichert and Bernhard Breit Org. Lett.; 2007; 9(5) pp 899 - 902; (Letter) doi:10.1021/ol0700660
