Two-fold extrusion reactions
Twofold extrusion reactions involve the loss of two small, typically inorganic fragments bridging two atoms with the formation of a double bond between the atoms (most commonly, an alkene or imine). These reactions are particularly useful for the introduction of hindered double bonds, as extrusion can often be initiated thermally without the need for added reagents.
- 1 Introduction
- 2 Mechanism and Stereochemistry
- 3 Scope and Limitations
- 4 Synthetic Applications
- 5 Comparison to Other Methods
- 6 Experimental Conditions and Procedure
- 7 References
Twofold extrusion reactions involve the loss of small, inorganic fragments from a heterocyclic ring system with the formation of a double bond between carbons in the ring (Eq. 1). This suite of reactions has been applied for the synthesis of hindered alkenes, for which other methods such as the Wittig reaction are not successful. Synthetic routes to molecular machines have also involved twofold extrusion reactions. The scopes of these reactions are limited primarily by the availability of precursors to the required cyclic starting materials. At high temperatures or in the presence of a reductant such as a phosphine, extrusion is commonly spontaneous.(1)
Precursors to the ring systems that undergo twofold extrusion include thiones, hydrogen sulfide, selones, diazo compounds, and azines. Thia- and selenadiazoline ring systems and their oxidized analogues are the most common starting materials for the extrusion step itself; however, several different methods exist for the preparation of these substrates.
Mechanism and Stereochemistry
Alkene Formation from Thia- and Selenadiazolines
The mechanism of thermal extrusion reactions of thiadiazolines has been studied in detail. Initial loss of nitrogen from thiadiazoline 1 produces a thiocarbonyl ylide, which may be represented as a diradical, dipole, or tetravalent sulfur structure. This intermediate can be captured through 1,3-dipolar cycloaddition with alkynes or treatment with acid. 4π-electron, conrotatory ring closure of the thiocarbonyl ylide affords thiirane 2. It is often possible to isolate the thiirane at this stage; however, subsequent treatment with tertiary phosphines, phenyllithium, or copper bronze leads to the extrusion of sulfur and alkene formation.(2)
Alkene Formation from Sulfenes and Diazo Compounds
Sulfenes and diazo compounds react to afford alkenes, but unlike extrusion reactions employing thiones and diazo compounds (for which thiadiazolines are intermediates; see above), the mechanism of this reaction does not directly involve thiadiazoline-1,1-dioxides. Solvent effect studies and independent investigation of isolated thiadiazoline-1,1-dioxides support a polar mechanism involving addition of the diazo compound to the sulfene followed by ring closure. Related thiadiazoline-1,1-dioxides lose sulfur dioxide upon heating to afford the corresponding azines, not alkenes.(3)
Imine Formation from Thiatriazolines
Azides are nitrogen-containing analogues of diazo compounds, and react with thiones to afford imines after twofold extrusion. Trapping experiments support the intermediacy of a thiocarbonyl-S-imide 3 in this mechanism, most likely generated via cycloaddition of the azide and thione followed by extrusion of nitrogen.(4)
Scope and Limitations
Comparison to Other Methods
Experimental Conditions and Procedure
- ↑ a b Guziec, L. J.; Guziec, Jr., F. S. Org. React. 2012, 78, 1.
- ↑ Kellogg, R. M.; Wassenaar, S. Tetrahedron Lett. 1970, 11, 1987.
- ↑ Kellogg, R. M. Tetrahedron Lett. 1976, 32, 2165.
- ↑ Mlostoń, G.; Heimgartner, H. Pol. J. Chem. 2000, 74, 1503.
- ↑ Barton, D. H. R.; Willis, B. J. J. Chem. Soc., Chem. Commun. 1970, 1225.
- ↑ Kellogg, R. M.; Wassenaar, S.; Buter, J. Tetrahedron Lett. 1970, 11, 4689.
- ↑ Quast, H.; Kees, F. Chem. Ber. 1981, 114, 787.
- ↑ Quast, H.; Kees, F. Chem. Ber. 1981, 114, 802.
- ↑ Mlostoń, G.; Romański, J.; Linden, A.; Heimgartner, H. Pol. J. Chem. 1996, 70, 880.
- ↑ Bee, L.; Beeby, J.; Everett, J.; Garratt, P. J. Org. Chem. 1975, 40, 2212.