User:Alderdiels/sandbox
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The Alder–Diels reaction (not to be confused with the Diels-Alder reaction, is an organic chemical reaction (specifically, a [4+2] cycloaddition) between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene derivative. It is a variant of the Diels-Alder reaction first described by Kurt Alder and Otto Diels in 1928, for which work they were awarded the Nobel Prize in Chemistry in 1950. In contrast to the Diels–Alder reaction, the Alder-Diels proceeds with opposite regiochemical preferences. It is particularly useful in synthetic organic chemistry as a reliable method for forming 6-membered systems with good control over regio- and stereochemical properties, due to its concerted nature.[1][2][3] The underlying concept has also been applied to other π-systems, such as carbonyls and imines, to furnish the corresponding heterocycles, known as the hetero-Alder–Diels reaction.
Selectivity
[edit]The Alder-Diels reaction proceeds with the opposite regioselectivity and diastereoselectivity of the Diels-Alder reaction. The cause of this effect is not known, as the mechanism itself is not understood, in contrast to the extensively studied Diels-Alder reaction. It has been proposed that the reaction proceeds through radical intermediates, where stereospecifity is conferred by the fact that the radicals remain in the solvent cage to complete the reaction before diffusing apart. The solvent has been suggested to impart selectivity due to the asynchronous nature of the collisions. However, spectroscopic studies have been unable to elucidate the dynamics of the solvent during the course of the reaction.
Examples
[edit]The Alder-Diels reaction has been extensively utilized in synthesis. For instance, researchers have used it to synthesize a bicyclic frame that is highly congested with stereocenters. They noted that the order of addition was critical for determining the reaction outcome, as opposite enantiomers were obtained depending on the experimental procedure. This is a testament to the stereospecific nature of the reaction.
Variants
[edit]Lewis base activation
[edit]Lewis bases such as tertiary alkylamines, phosphines, and nucleophilic catalysts such as 4-(dimethylamino)pyridine, can act as catalysts of normal-demand Diels–Alder reactions by coordination to the dienophile. The complexed dienophile becomes more nucleophilic and more reactive toward the diene, increasing the reaction rate and often improving the regio- and stereoselectivity as well. Note that this is the opposite of the Diels-Alder reaction, where Lewis acid catalysis is often used in place of Lewis base catalysis. The use of Lewis base activation also enables Alder–Diels reactions to proceed at low temperatures, i.e. without thermal activation.[4]
Asymmetric Alder–Diels
[edit]In contrast to other synthetic methods, little effort has been put into development of the Alder-Diels reaction, due to the control over enantioselectivity offered by order of addition.
See also
[edit]- Diels-Alder reaction
- Inverse electron-demand Alder–Diels reaction
- Intramolecular Alder–Diels cycloaddition
- Imine Alder–Diels reaction
References
[edit]- ^ Kloetzel, M. C. (1948). "The Diels–Alder Reaction with Maleic Anhydride". Organic Reactions. 4: 1–59. doi:10.1002/0471264180.or004.01. ISBN 0471264180.
- ^ Holmes, H. L. (1948). "The Diels-Alder Reaction Ethylenic and Acetylenic Dienophiles". Organic Reactions. 4: 60–173. doi:10.1002/0471264180.or004.02. ISBN 0471264180.
- ^ Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G. (2002). "The Diels-Alder Reaction in Total Synthesis". Angewandte Chemie International Edition. 41 (10): 1668–1698. doi:10.1002/1521-3773(20020517)41:10<1668::AID-ANIE1668>3.0.CO;2-Z.
- ^ Carey, Part B., pp. 474–526
Bibliography
[edit]- Carey, Francis A.; Sundberg, Richard J. (2007). Advanced Organic Chemistry: Part B: Reactions and Synthesis (5th ed.). New York: Springer. ISBN 0387683542.
External links
[edit]- Asymmetric Hetero-Alder–Diels Reactions
- Semi-empirical calculations of the Alder–Diels reaction.
- Exo Addition Rule
- Recent Advances in Asymmetric Alder–Diels Reactions
- [1] English Translation of Diels and Alder's seminal 1928 German article that won them the Nobel prize. English title: 'Syntheses of the hydroaromatic series'; German title "Synthesen in der hydroaromatischen Reihe".