High-Efficiency Synthesis of Carbon-Bridged Dimers via Bioinspired Green Dimerization Involving Aldehydes

A simple, green, and efficient dimerization of nucleophiles possessing electron-rich p systems with diverse aldehydes was developed, which can be carried out in high yields in water at room temperature without any organic solvent or catalyst. This reaction was inspired by the nonenzymatic formation mechanism of some methylene-bridged dimeric natural products. We used this reaction to build a small library of carbon-bridged dimers for bioactivity screening. During this process, the decagramscale synthesis of the anticoagulant drug dicoumarol was achieved in 97% yield without column chromatographic separation. This green dimerization was also used in the syntheses of the natural products mindapyrrole A, dibohemamine A, and phaeochromycin F. Moreover, we developed the application of this reaction in the removal of formaldehyde in water.