Enantioselective Total Synthesis of (+)-Psiguadial B

The first enantioselective total synthesis of the cytotoxic natural product (+)-psiguadial B is reported. Key features of the synthesis include (1) the enantioselective preparation of a key cyclobutane intermediate by a tandem Wolff rearrangement/asymmetric ketene addition, (2) a directed C­(sp3)–H alkenylation reaction to strategically forge the C1–C2 bond, and (3) a ring-closing metathesis to build the bridging bicyclo[4.3.1]­decane terpene framework.