Transannular [4+3] Cycloadditions of Macrocyclic Epoxy Ketones
Diana Chan1, Yu Chen1, Kam-Hung Low1
1Department of Chemistry, State Key Laboratory of, Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|January 10, 2018
Summary
Macrocyclic epoxy ketones undergo transannular [4+3] cycloadditions to create fused ring systems with central cycloheptane cores. This method efficiently generates enantiomerically enriched tricyclic compounds from optically pure starting materials.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Macrocyclic compounds present unique structural challenges in synthesis.
- Cycloaddition reactions are powerful tools for constructing complex ring systems.
Purpose of the Study:
- To develop a novel synthetic route to fused ring systems containing cycloheptane subunits.
- To explore the utility of macrocyclic epoxy ketones in transannular cycloaddition reactions.
- To achieve enantioselective synthesis of complex polycyclic structures.
Main Methods:
- Transannular [4+3] cycloaddition reactions utilizing dienophiles derived from macrocyclic epoxy ketones.
- Direct base-induced cycloisomerization of epoxy ketones.
- Conversion of epoxy ketones to enolsilanes prior to cycloaddition.
- Use of optically pure epoxy ketones for enantioselective synthesis.
Main Results:
- Successfully synthesized fused ring systems incorporating central cycloheptane units.
- Demonstrated two pathways: direct cycloisomerization and cycloaddition via enolsilanes.
- Achieved enantiomerically enriched tricyclic arrays using chiral epoxy ketones.
Conclusions:
- Transannular [4+3] cycloadditions of macrocyclic epoxy ketone derivatives provide an effective strategy for constructing complex fused ring systems.
- The methodology allows for control over stereochemistry, yielding enantiomerically enriched products.
- This approach expands the synthetic toolkit for accessing novel polycyclic architectures.
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01:16[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
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The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
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01:16Cycloaddition Reactions: Overview
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Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
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01:12Cycloaddition Reactions: MO Requirements for Photochemical Activation
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Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
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01:16Cycloaddition Reactions: MO Requirements for Thermal Activation
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Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
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01:04Structures of Aldehydes and Ketones
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Vanillin—a flavoring agent in vanilla, cinnamaldehyde—a molecule responsible for the distinct smell of cinnamon, and acetone—a strong-smelling ingredient in nail polish removers, all belong to a class of carbonyl compounds called aldehydes and ketones (Figure 1). Although both aldehydes and ketones contain the characteristic carbonyl (C=O) bond, their chemical structures vary with respect to the groups directly attached to the carbonyl carbon.
In aldehydes (Figures 1a and 1b), the...
In aldehydes (Figures 1a and 1b), the...
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01:09IUPAC Nomenclature of Ketones
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Like aldehydes, ketones are named using IUPAC rules; in this case, by replacing “e” in the name of the longest hydrocarbon chain with “one.” In acyclic ketones, the ketonic carbon is given the lowest locant value. For instance, as shown below, a simple five-carbon ketone is named pentan-2-one, instead of pentan-4-one. IUPAC rules also allow the placing of the locant value before the parent name to give an alternate name, 2-pentanone.
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