Synthesis with Perfect Atom Economy: Generation of Furan Derivatives by 1,3-Dipolar Cycloaddition of Acetylenedicarboxylates at Cyclooctynes

Abstract

Cyclooctyne and cycloocten-5-yne undergo, at room temperature, a 1,3-dipolar cycloaddition with dialkyl acetylenedicarboxylates 1a,b to generate furan-derived short-lived intermediates 2, which can be trapped by two additional equivalents of 1a,b or alternatively by methanol, phenol, water or aldehydes to yield polycyclic products 3b–d, orthoesters 4a–c, ketones 5 or epoxides 6a,b, respectively. Treatment of bis(trimethylsilyl) acetylenedicarboxylate (1c) with cyclooctyne leads to the ketone 7 via retro-Brook rearrangement of the dipolar intermediate 2c. In all cases, the products are formed with perfect atom economy.

Keywords

• cascade reactions
• cyclopropenes
• Diels-Alder reactions
• dipolar intermediates
• epoxides
• orthoesters
• oxygen heterocycles
• reaction mechanisms
• retro-Brook reactions
• strained compounds