A Stereoselective Synthesis of (−)-Tetrodotoxin

An asymmetric synthesis of the fugu fish poison, (−)-tetrodotoxin, is described. The route to this extraordinary target employs a number of unique transformations, foremost of which are two stereospecific C−H bond functionalization reactions. Accordingly, Rh-catalyzed carbene and nitrene C−H insertions facilitate rapid entry to the cyclohexane core of the natural product and make possible the late-stage installation of the tetrasubstituted carbinolamine center.