Narasaka, Chiba and Kitamura. JACS, 2006, ASAP, DOI: 10.1021/ja060408h
Tot. Syn. loves oxidative radical cyclisations, so Narasaka’s synthesis of Sodarin was a welcome read this week. Also containing a ÃŸ(1,2-cis)-selective glycosidation and a Tsuji-Trost allylation to construct the bicyclic system, this is a particularly ambitious route. First to the radical chemistry:
Using diethylzinc and diiodomethane to generate the cyclopropane, exposure to catalytic quantities of silver nitrate opened the cyclopropane homolytically, oxidising the hydroxyl and leaving a beta radical. This then closed onto the terminal olefin in a 5-exo-trig manner to leave the fused 7,5 system in 85%. Of course, a stoichiometric oxidant was needed, and in this case, was (NH4)2S2O8.
To construct the bicycle they used an impressive Tsuji-Trost allylation:
With the end now in sight, they screened conditions for the glycosidation using neopentyl alcohol as a model for their system, and settled upon Mukaiyama conditions (SnCl2, AgClO4 in Et2O), which gave them a 79% yield of the ÃŸ-anomer when coupling with their fluoro-sugar (made in 15 steps from D-mannose).
Phew! What an effort – and a fine read too!