A biomimetic synthesis of (−)-ascorbyl phloroglucinol and studies toward the construction of ascorbyl-modified catechin natural products and analogues

A method for appending the ascorbyl moiety onto the framework of phenolic natural products has been developed. This reaction proceeds in two steps from l-ascorbic acid and employs acetic acid catalysis. Excellent stereoselectivity is observed during C–C bond formation between the phenolic compound and dehydroascorbic acid, and the process is also chemoselective for phenol derivatives bearing electron-donating substituents in each of the 1, 3, and 5 positions. Further, good regioselectivity was also observed when phenols lacking an axis of C2 symmetry were employed. This method has led to the synthesis of (−)-ascorbyl phloroglucinol as well as the tetracyclic core of ascorbyl-modified catechin natural products.