Difference between revisions of "Two-fold extrusion reactions"

Brought to you by the Organic Reactions Wiki, the online collection of organic reactions
Jump to: navigation, search
Line 1: Line 1:
'''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.<ref>Guziec, L. J.; Guziec, Jr., F. S. ''Org. React.'' '''2012''', ''78'', 1.</ref>
+
'''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.<ref name=chapter>Guziec, L. J.; Guziec, Jr., F. S. ''Org. React.'' '''2012''', ''78'', 1.</ref>
  
 
==Introduction==
 
==Introduction==
Line 8: Line 8:
 
==Mechanism and Stereochemistry==
 
==Mechanism and Stereochemistry==
 
===Alkene Formation from Thia- and Selenadiazolines===
 
===Alkene Formation from Thia- and Selenadiazolines===
The mechanism of thermal extrusion reactions of thiadiazolines has been studied in detail.<ref>Kellogg, R. M.; Wassenaar, S. ''Tetrahedron Lett.'' '''1970''', ''11'', 1987.</ref> 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.<ref>Kellogg, R. M. ''Tetrahedron Lett.'' '''1976''', ''32'', 2165.</ref><ref>Mlostoń, G.; Heimgartner, H. ''Pol. J. Chem.'' '''2000''', ''74'', 1503.</ref> 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 phophine (or carrying out the reaction in the presence of phosphine) leads to the extrusion of sulfur and alkene formation.
+
The mechanism of thermal extrusion reactions of thiadiazolines has been studied in detail.<ref>Kellogg, R. M.; Wassenaar, S. ''Tetrahedron Lett.'' '''1970''', ''11'', 1987.</ref> 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.<ref>Kellogg, R. M. ''Tetrahedron Lett.'' '''1976''', ''32'', 2165.</ref><ref>Mlostoń, G.; Heimgartner, H. ''Pol. J. Chem.'' '''2000''', ''74'', 1503.</ref> 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,<ref>Barton, D. H. R.; Willis, B. J. ''J. Chem. Soc., Chem. Commun.'' '''1970''', 1225.</ref> phenyllithium,<ref>Kellogg, R. M.; Wassenaar, S.; Buter, J. ''Tetrahedron Lett.'' '''1970''', ''11'', 4689.</ref> or copper bronze<ref name=chapter></ref> leads to the extrusion of sulfur and alkene formation.
 
<span style="float:right;padding-right:50px;padding-top:30px;">'''''(2)'''''</span><center>[[File:Extrusion-Mech-1.png]]</center>
 
<span style="float:right;padding-right:50px;padding-top:30px;">'''''(2)'''''</span><center>[[File:Extrusion-Mech-1.png]]</center>
  
===The Staudinger-Pfenninger Reaction===
+
===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<ref>Quast, H.; Kees, F. ''Chem. Ber.'' '''1981''', ''114'', 787.</ref> and independent investigation of isolated thiadiazoline-1,1-dioxides<ref>Quast, H.; Kees, F. ''Chem. Ber.'' '''1981''', ''114'', 802.</ref> 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.
 
<span style="float:right;padding-right:50px;padding-top:30px;">'''''(3)'''''</span><center>[[File:Extrusion-Mech-2.png]]</center>
 
<span style="float:right;padding-right:50px;padding-top:30px;">'''''(3)'''''</span><center>[[File:Extrusion-Mech-2.png]]</center>
  
 
===Imine Formation from Thiatriazolines===
 
===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.<ref>Mlostoń, G.; Romański, J.; Linden, A.; Heimgartner, H. ''Pol. J. Chem.'' '''1996''', ''70'', 880.</ref>
 
<span style="float:right;padding-right:50px;padding-top:30px;">'''''(4)'''''</span><center>[[File:Extrusion-Mech-3.png]]</center>
 
<span style="float:right;padding-right:50px;padding-top:30px;">'''''(4)'''''</span><center>[[File:Extrusion-Mech-3.png]]</center>
  

Revision as of 22:54, 9 February 2012

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

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)
Extrusion-Gen.png

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.[2] 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.[3][4] 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,[5] phenyllithium,[6] or copper bronze[1] leads to the extrusion of sulfur and alkene formation.

(2)
Extrusion-Mech-1.png

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[7] and independent investigation of isolated thiadiazoline-1,1-dioxides[8] 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)
Extrusion-Mech-2.png

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.[9]

(4)
Extrusion-Mech-3.png

Scope and Limitations

Coming soon!

(5)
Extrusion-Scope-1.png
(6)
Extrusion-Scope-2.png
(7)
Extrusion-Scope-3.png
(8)
Extrusion-Scope-4.png
(9)
Extrusion-Scope-5.png
(10)
Extrusion-Scope-6.png
(11)
Extrusion-Scope-7.png

Synthetic Applications

(12)
Extrusion-Synth.png

Comparison to Other Methods

Coming soon!

(13)
Extrusion-Alt-1.png
(14)
Extrusion-Alt-2.png

Experimental Conditions and Procedure

Typical Conditions

Coming soon!

Example Procedure[10]

(15)
Extrusion-Ex.png

Coming soon!

References

  1. a b Guziec, L. J.; Guziec, Jr., F. S. Org. React. 2012, 78, 1.
  2. Kellogg, R. M.; Wassenaar, S. Tetrahedron Lett. 1970, 11, 1987.
  3. Kellogg, R. M. Tetrahedron Lett. 1976, 32, 2165.
  4. Mlostoń, G.; Heimgartner, H. Pol. J. Chem. 2000, 74, 1503.
  5. Barton, D. H. R.; Willis, B. J. J. Chem. Soc., Chem. Commun. 1970, 1225.
  6. Kellogg, R. M.; Wassenaar, S.; Buter, J. Tetrahedron Lett. 1970, 11, 4689.
  7. Quast, H.; Kees, F. Chem. Ber. 1981, 114, 787.
  8. Quast, H.; Kees, F. Chem. Ber. 1981, 114, 802.
  9. Mlostoń, G.; Romański, J.; Linden, A.; Heimgartner, H. Pol. J. Chem. 1996, 70, 880.
  10. Bee, L.; Beeby, J.; Everett, J.; Garratt, P. J. Org. Chem. 1975, 40, 2212.