Selenoxide elimination
Selenoxide elimination (also called α-selenation)
Mechanism and stereochemistry
After the development of
selenoxide elimination has grown into a general method for the preparation of α,β-unsaturated carbonyl compounds.(1)
Mechanism
Elimination of selenoxides takes place through an intramolecular syn elimination pathway. The carbon–hydrogen and carbon–selenium bonds are co-planar in the transition state.[5]
(2)
The reaction is highly
(3)
Kinetic isotope effect studies have found a ratio of pre-exponential factors of AH/AD of 0.092 for sulfoxide elimination reactions, indicating that quantum tunneling plays an important role in the hydrogen transfer process.[7][8]
Scope and limitations
Selanylating and oxidizing reagents
α-Selanylation of carbonyl compounds can be accomplished with
- Diphenyl diselenide
- Benzeneselanyl chloride
- Benzeneselanyl bromide
- Benzeneselinyl chloride
- Sodium benzeneselenolate
- Trimethylsilyl phenyl selenide
The most common
(4)
For substrates whose product
(5)
(6)
Substrates
α-Phenylseleno aldehydes, which are usually prepared from the corresponding enol ethers, are usually oxidized with mCPBA or ozone, as hydrogen peroxide causes over-oxidation. α-Phenylseleno ketones can be prepared by kinetically controlled enolate formation and trapping with an electrophilic selanylating reagent such as benzeneselenyl chloride. A second deprotonation, forming a selenium-substituted enolate, allows alkylation or hydroxyalkylation of these substrates.[13]
(7)
Base-sensitive substrates may be selanylated under acid-catalyzed conditions (as enols) using benzeneselenyl chloride.
(8)
The seleno-
(9)
A second significant side reaction in reactions of ketones and aldehydes is selanylation of the intermediate selenoxide. This process leads to elimination products retaining a carbon-selenium bond,[16] and is more difficult to prevent than the seleno-Pummerer reaction. Tertiary selenoxides, which are unable to undergo enolization, do not react further with selenium electrophiles.
(10)
Comparison with other methods
Analogous sulfoxide eliminations are generally harder to implement than selenoxide eliminations. Formation of the carbon–sulfur bond is usually accomplished with highly reactive sulfenyl chlorides, which must be prepared for immediate use. However, sulfoxides are more stable than the corresponding selenoxides, and elimination is usually carried out as a distinct operation. This allows thermolysis conditions to be optimized (although the high temperatures required may cause other thermal processes). In addition, sulfoxides may be carried through multiple synthetic steps before elimination is carried out.[17]
(11)
The combination of
(12)
For β-dicarbonyl compounds, DDQ can be used as an oxidizing agent in the synthesis of enediones. Additionally, some specialized systems give better yields upon DDQ oxidation.[20]
(13)
See also
References
- ISBN 978-0-470-16982-7.
- ISBN 978-0-471-26418-7.
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- ISSN 0002-7863.
- ISSN 0001-4842.
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- doi:10.3987/R-1986-02-0309 (inactive 2024-03-07).)
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