Abstract
Benzocyclobutenones are an intriguing class of four-membered-ring ketones that have been used extensively as powerful synthetic intermediates in organic synthesis. Their high reactivity is primarily attributed to the unique high electrophilicity of the carbonyl unit and the ability to generate o-quinone dimethides, allowing a myriad of different transformations. However, the synthesis of benzocyclobutenones still represents a great challenge. This review provides an overview of the preparation, use and impact of benzocyclobutenones in organic synthesis. Selected applications in the synthesis of natural products are also described, in order to illustrate the utility of these compounds.
1 Introduction
2 Synthetic Methods for Preparing Benzocyclobutenones
2.1 [2+2]-Type Cycloadditions
2.2 Metal-Mediated Intramolecular Cyclizations
2.3 Metal-Catalyzed Cross-Coupling Reactions
2.3.1 Carbon–Hydrogen Bond-Functionalization Events
2.3.2 Stille Cross-Coupling Reactions
2.4 Other Synthetic Methods for Preparing Benzocyclobutenones
3 Synthetic Application of Benzocyclobutenones and Related Compounds
3.1 Synthesis of Polycyclic Compounds via o-Quinone Dimethides
3.1.1 Synthesis of α-Tetralones
3.1.2 Synthesis of Benzo[n]annulenes
3.1.3 Synthesis of Naphthalene Derivatives
3.1.4 Synthesis of Anthraquinones
3.1.5 Synthesis of Benzodiazepines
3.1.6 Synthesis of Tetrahydronaphthalenes
3.1.7 Synthesis of Isochromanones
3.2 Synthesis of Fused Rings via Non-Electrocyclization Techniques
3.2.1 Ring Expansions from Four- to Five-Membered Rings
3.2.2 Ring Expansions from Four- to Six-Membered Rings
3.3 Other Synthetic Applications
3.3.1 Tricarbonylchromium Complexes
3.3.2 Base-Induced Carbon–Carbon Bond Cleavage
3.4 Benzocyclobutenones and Their Derivatives in Natural Product Synthesis
4 Conclusions
Key words
benzocyclobutenones - cycloaddition - C–C bond cleavage -
o-quinone dimethides - fused π-aromatic systems - ring expansion
