Eschenmoser sulfide contraction explained

The Eschenmoser sulfide contraction is an organic reaction first described by Albert Eschenmoser for the synthesis of 1,3-dicarbonyl compounds from a thioester.^{[1] [2] [3]} The method requires a base and a tertiary phosphine. The method is of some relevance to organic chemistry and has been notably applied in the vitamin B₁₂ total synthesis.

A base abstracts the labile hydrogen atom in the thioester, a sulfide anion is formed through an episulfide intermediate which is removed by the phosphine.^[4]

Scope

The Eschenmoser sulfide contraction method has been employed in a number of total synthesis efforts, like that of fuligocandin A and B,^[5] cocaine,^[6] diplodialide A ^[7] and isoretronecanol ^[8]

An example of general synthetic utility is the synthesis of novel carbapenems ^[9]

Notes and References

1. Organic syntheses based on name reactions, Volume 22 2002 Alfred Hassner,C. Stumer
2. A New Type of Corrin Synthesis Angewandte Chemie International Edition in English Volume 8, Issue 5, Date: May 1969, Pages: 343-348 Yasuji Yamada, D. Miljkovic, P. Wehrli, B. Golding, P. Löliger, R. Keese, K. Müller, A. Eschenmoser
3. Sulfidkontraktion via alkylative Kupplung: Eine methode zur darstellung von -dicarbonylderivaten. Über synthetische methoden, 1. Mitteilung Helvetica Chimica Acta Volume 54, Issue 2, Date: 1971, Pages: 710-734 M. Roth, P. Dubs, E. Götschi, A. Eschenmoser
4. 10.15227/orgsyn.055.0127. Sulfide Contraction via Alkylative Coupling: 3-Methyl-2,4-Hepthanedione. P.. Loeliger. E.. Flückiger. Organic Syntheses. 1976. 55. 127.
5. One-Pot Eschenmoser Episulfide Contractions in DMSO: Applications to the Synthesis of Fuligocandins A and B and a Number of Vinylogous Amides Birgitta Pettersson, Vedran Hasimbegovic, Jan Bergman The Journal of Organic Chemistry 2011 76 (6), 1554-1561
6. Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid Ronghui Lin,, Josep Castells, and, Henry Rapoport The Journal of Organic Chemistry 1998 63 (12), 4069-4078
7. Macrocyclic lactone formation through sulfide contraction. Synthesis of (.+-.)-diplodialide A Robert E. Ireland, Frank R. Brown Jr. J. Org. Chem., 1980, 45 (10), pp 1868–1880
8. New approaches to the pyrrolizidine ring system: total synthesis of (.+-.)-isoretronecanol and (.+-.)-trachelanthamidine Harold W. Pinnick, Yeong-Ho Chang J. Org. Chem., 1978, 43 (24), pp 4662–4663
9. A new synthetic method of 1β-methylcarbapenems utilizing the eschenmoser sulfide contraction Tetrahedron Letters, Volume 35, Issue 14, 4 April 1994, Pages 2187-2190 Osamu Sakurai, Tsuyoshi Ogiku, Masami Takahashi, Hiroshi Horikawa, Tameo Iwasaki