Amine-Tethered Phenylboronic Acid-Enabling Ring-Opening Strategy for Carbon Chain Elongation from Double Aldol Cyclic Hemiacetals

The addition of carbon nucleophiles to cyclic hemiacetal forms of double aldols is a promising approach toward the synthesis of structurally attractive 1,3-polyol derivatives. Cyclic hemiacetals are generally unreactive to carbon nucleophiles under neutral conditions, however, because the electrophilic aldehyde function is masked. Here we developed an amine-tethered phenylboronic acid 7g, which transforms double aldol cyclic hemiacetals to ring-opened linear aldehydes. Combined with the previously-developed copper-catalysed asymmetric double aldol reaction, this method produced synthetically useful chiral building blocks containing a 1,3-di- or tri-ol moiety.