Umpolung

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 [cite journal | author = Seebach D. | title = Methods of Reactivity Umpolung | journal = Angewandte Chemie International Edition in English | volume = 18 | issue = 4 | pages = 239–258 | publisher = | year = 1979 | url = | doi = 10.1002/anie.197902393 | id = | accessdate = ] [cite journal | author = Gröbel B. T., Seebach D. | title = Reactivity of Carbonyl-Compounds Through Sulfur-Containing Reagents | journal = Synthesis-Stuttgart | volume = 6 | issue = | pages = 357–402 | publisher = | year = 1977 | url = | doi = 10.1055/s-1977-24412 | id = | accessdate = ] . This modification allows secondary reactions of this functional group that would otherwise not be possible [cite journal | author = Seebach D., Corey E. J. | title = Generation and synthetic applications of 2-lithio-1,3-dithianes | journal = Journal of Organic Chemistry | volume = 40 | issue = 2 | pages = 231–237 | publisher = | year = 1975 | url = http://pubs.acs.org/cgi-bin/abstract.cgi/joceah/1975/40/i02/f_jo00890a018.pdf | doi = 10.1021/jo00890a018 | id = | accessdate = ] . 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 phenyl-epoxyethane, shown below. 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 [cite journal | author = Smith A. B. , III, Xian M. | title = Anion Relay Chemistry: An Effective Tactic for Diversity Oriented Synthesis | journal = Journal of the American Chemical Society | volume = 128 | issue = 1 | pages = 66–67 | publisher = | year = 2006 | url = http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ja057059w | doi = 10.1021/ja057059w | id = | accessdate = ] . 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 [cite journal | author = Fischer C., Smith S. W., Powell D. A., Fu G. C. | title = Umpolung of Michael Acceptors Catalyzed by N-Heterocyclic Carbenes | journal = Journal of the American Chemical Society | volume = 128 | issue = 5 | pages = 1472–1473 | publisher = | year = 2006 | url = | doi = 10.1021/ja058222q | id = | accessdate =