Synthesis with Perfect Atom Economy: Generation of Furan Derivatives by 13-Dipolar Cycloaddition of Acetylenedicarboxylates at Cyclooctynes

摘要

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.