My watch list  


Umpolung or polarity inversion in organic chemistry is the chemical modification of a functional group with the aim of the reversal of polarity of that group [1] [2] . This modification allows secondary reactions of this functional group that would otherwise not be possible [3]. The concept was introduced by D. Seebach (hence the German word umpolung for reversed polarity) and E.J. Corey. Classic umpolung applications can be found in Grignard reagents and in the Benzoin condensation.

Carbonyl umpolung

A classic example of polarity inversion is observed in dithiane chemistry.

Ordinarily the oxygen atom in the carbonyl group is more electronegative than the carbon atom and therefore the carbonyl group reacts as an electrophile at carbon. This polarity can be reversed when the carbonyl group is converted into a dithiane or a thioacetal. In synthon terminology the ordinary carbonyl group is an acyl cation and the dithiane is a masked acyl anion.

When the dithiane is derived from an aldehyde such as acetaldehyde the acyl proton can be abstracted by n-butyllithium in THF at low temperatures. The thus generated 2-lithio-1,3-dithiane reacts as a nucleophile in nucleophilic displacement with alkyl halides such as benzyl bromide, with other carbonyl compounds such as cyclohexanone or oxiranes such as styrene oxide. After hydrolysis of the dithiane group the final reaction products are α-alkyl-ketones or α-hydroxy-ketones. A common reagent for dithiane hydrolysis is (bis(trifluoroacetoxy)iodo)benzene.

Dithiane chemistry opens the way to many new chemical transformations. One example is found in so-called anion relay chemistry in which an anionic functional group resulting from one organic reaction is transferred to a different location within the same carbon framework and available for secondary reactions [4]. In this example of a multi-component reaction both formaldehyde (1) and isopropylaldehyde (8) are converted into dithianes 3 and 9 with 1,3-propanedithiol. Sulfide 3 is first silylated by reaction with tert-butyllithium and then trimethylsilyl chloride 4 and then the second acyl proton is removed and reacted with optically active (-)-epichlorohydrin 6 replacing chlorine. This compound serves as the substrate for reaction with the other dithiane 9 to the oxirane ring opening product 10. Under influence of the string base HMPA, 10 rearranges in a 1,4-Brook rearrangement to the silyl ether 11 reactivating the formaldehyde dithiane group as an anion (hence the anion relay concept). This dithiane group reacts with oxirane 12 to the alcohol 13 and in the final step the sulfide groups are removed with (bis(trifluoroacetoxy)iodo)benzene.

Enone umpolung

In ordinary nucleophilic conjugate additions the β-carbon atom acts as an electrophile. In special cases this position can be modified to react as a nucleophile [5]. The reaction depicted in scheme 3 is a Heck reaction equivalent. The active catalyst is not palladium compound but a triazole derived persistent carbene.

This carbene reacts with the α,β-unsaturated ester 1 at the β-position forming the intermediate enolate 2. Through tautomerization 2b can displace the terminal bromine atom to 3. An elimination reaction regenerates the carbene and releases the product 4.

For comparison: in the Baylis-Hillman reaction the same electrophilic β-carbon atom is attacked by a reagent but resulting in the activation of the α-position of the enone as the nucleophile.


  1. ^ Seebach D. (1979). "Methods of Reactivity Umpolung". Angewandte Chemie International Edition in English 18 (4): 239-258. doi:10.1002/anie.197902393.
  2. ^ Gröbel B. T., Seebach D. (1977). "Methods of Reactivity Umpolung Reactivity of Carbonyl-Compounds Through Sulfur-Containing Reagents". Sythesis-Stuttgart 6: 357-402. doi:10.1055/s-1977-24412.
  3. ^ Seebach D., Corey E. J. (1975). "Generation and synthetic applications of 2-lithio-1,3-dithianes". Journal of Organic Chemistry 40 (2): 231-237. doi:10.1021/jo00890a018.
  4. ^ Smith A. B. , III, Xian M. (2006). "Anion Relay Chemistry: An Effective Tactic for Diversity Oriented Synthesis". Journal of the American Chemical Society 128 (1): 66 - 67. doi:10.1021/ja057059w.
  5. ^ Fischer C., Smith S. W., Powell D. A., Fu G. C. (2006). "Umpolung of Michael Acceptors Catalyzed by N-Heterocyclic Carbenes". Journal of the American Chemical Society 128 (5): 1472 - 1473. doi:10.1021/ja058222q.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Umpolung". A list of authors is available in Wikipedia.
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE