Pummer reaction

Rearrangement

1. BY Dr . Gurumeet.C.Wadhawa DEPARTMENT OF CHEMISTRY K. B. P . College,Vashi,Navimumbai Lossen Rearrangement

2. PUMMERER REARRANGEMENT In 1909, R. Pummerer observed that by heating phenylsulfinylacetic acid with mineral acids (e.g., HCl , H2SO4 ), thiophenol and glyoxylic acid were formed.1 Later this transformation was shown to be general, and today the formation of α-substituted sulfides from the corresponding sulfoxides is referred to as the Pummerer rearrangement .

3. The general features of the reaction are: the sulfoxide substrates must have at least one hydrogen atom at their α-position; 2 ) acetic anhydride (Ac2O) is the most widely used activating reagent for the rearrangement, and it is often applied as the solvent in combination with other solvents such as benzene or ethyl acetate ; 3 ) the use of acid co-catalysts (e.g., TsOH , AcOH , TFAA) is common to minimize side reactions and increase the product yields; 4 ) Ac2O can be replaced with TFAA, which is a stronger reagent and allows for milder reaction conditions; 5 ) the most common product of the reaction is an α- acetoxy sulfide; 6 ) upon acidic hydrolysis, the α- acetoxy sulfide affords a thiol and a carbonyl compound that can be easily separated; 7 ) upon treatment with base , vinyl sulfides are formed via a β-elimination ; 8) the rearrangement is regioselective when the sulfoxide has hydrogens at both the α- and α'-positions and the more acidic position will get preferentially substituted; 9 ) The regioselectivity can be altered by steric factors especially in cyclic systems: isomeric sulfoxides often give rise to different products; and 10 ) the rearrangement can take place both inter- and intramolecularly .

4. Drawbacks of the reaction are: 1) substrates with unprotected hydroxyl or amino groups result in side rections with the activating reagent ; 2 ) unreactive substrates may undergo undesired sulfenic acid elimination if harsh conditions are necessary; 3) fragmentation products are observed when stable carbocations (e.g., allylic , benzylic ) can be formed by the heterolytic cleavage of the C-S bond; 4) when the nucleophile is a primary or secondary alcohol, reduction of the sulfoxide to the sulfide may occur along with the oxidation of the alcohol (see Swern oxidation).

5. There are several variants of the rearrangement: 1) when selenoxides are the substrates, the seleno-Pummerer rearrangement takes place ; 2 ) sila-Pummerer rearrangement occurs with sulfoxides bearing a TMS group on the α-carbon, which spontaneously rearrange to α- silyloxy sulfides, and no activating reagents are needed; 3 ) vinyl sulfoxide substrates may undergo the additive- and vinylogous Pummerer rearrangement; 4 ) chirality transfer from enantiopure sulfoxides to the α-carbon is possible, and it constitutes the asymmetric Pummerer rearrangement, but this process is limited in scope

6. References 1. Pummerer, R. Ber. 1910, 43, 140-1412 . Rudolf Pummerer, born in Austria in 1882, studied under von Baeyer, Willstätter , and Wieland. He worked for BASF for a few years and in 1921 he was appointed head of the organic division of the Munich Laboratory, fulfilling his long-desired ambition. 2. Katsuki, T.; Lee, A. W. M.; Ma, P.; Martin, V. S.; Masamune, S.; Sharpless, K. B.; Tuddenham , D.; Walker, F. J. J. Org. Chem. 1982, 47, 1373-1378 . 3. De Lucchi, O.; Miotti, U.; Modena, G. Org. React. 1991, 40, 15-406 . (Review). 4. Padwa , A.; Gunn, D. E., Jr.; Osterhout , M. H. Synthesis 1997, 135-1378 . (Review). 5. Padwa , A.; Waterson , A. G. Curr . Org. Chem. 2000, 4, 17-203 . (Review). 6. Padwa , A.; Bur, S. K.; Danca , D. M.; Ginn , J. D.; Lynch, S. M. Synlett 2002, 851-862 . (Review). 7. Gámez Montaño , R.; Zhu, J. Chem. Commun . 2002, 2448-2449 . 8. Padwa , A.; Danca , M. D.; Hardcastle , K.; McClure, M. J. Org. Chem. 2003, 68, 929-941 . 9. Suzuki, T.; Honda, Y.; Izawa, K.; Williams, R. M. J. Org. Chem. 2005, 70, 7317-7323 . 10. Nagao, Y.; Miyamoto, S.; Miyamoto, M.; Takeshige , H.; Hayashi, K.; Sano, S.; Shiro , M.; Yamaguchi, K.; Sei, Y. J. Am. Chem. Soc. 2006, 128, 9722-9729 . 11. Ahmad, N. M. Pummerer Rearrangement. In Name Reactions for Homologations-Part II; Li, J. J., Ed.; Wiley: Hoboken, NJ, 2009, pp 334-352 . (Review). 12. Patil, M.; Loerbroks , C.; Thiel , W. Org. Lett . 2013, 15, 1682-1685 .