Organocatalytic stereoselective [8+2] and [6+4] cycloadditions
Rasmus Mose1, Gert Preegel1, Jesper Larsen1
1Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Nature Chemistry
|April 22, 2017
Summary
This study revives stereocontrolled higher-order cycloadditions, specifically [8+2] and [6+4] reactions, using novel dienamine intermediates derived from cyclic enones and heptafulvenes. This work unlocks efficient synthesis of complex polycyclic molecules with potential applications in drug discovery.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Catalysis
Background:
- Higher-order cycloadditions (involving >6 π electrons) are valuable for constructing polycyclic scaffolds with medium-sized rings.
- Stereocontrolled [8+2] and [6+4] cycloadditions have been underutilized in synthetic chemistry for decades.
- These reactions offer potential for discovering new bioactive molecules and synthesizing natural products.
Purpose of the Study:
- To develop novel methods for stereocontrolled higher-order cycloadditions, specifically [8+2] and [6+4] reactions.
- To explore the use of dienamine intermediates derived from cyclic enones and heptafulvenes.
- To provide access to complex, all-carbon polycyclic scaffolds.
Main Methods:
- Development of cross-dienamine activation of 2-cyclopentenone.
- Development of endocyclic linear-dienamine activation of 2-cyclohexenones and 2-cycloheptenones.
- Aminocatalytic stereoselective cycloadditions of these dienamines with various heptafulvenes.
Main Results:
- Successful demonstration of aminocatalytic stereoselective [8+2], [6+4], and formal [4+2] cycloadditions.
- Control over periselectivity based on the ring size of 2-cycloalkenones and heptafulvene substitution.
- Generation of chiral polycyclic products amenable to further chemical and photochemical transformations.
Conclusions:
- This work establishes a powerful and stereoselective platform for higher-order cycloadditions, reviving neglected reaction classes.
- The developed methods provide efficient access to diverse and complex all-carbon polycyclic structures.
- The methodology holds significant promise for natural product synthesis and the discovery of novel bioactive compounds.
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