Synthesis of (+)-Saxitoxin Facilitated by a Chiral Auxiliary for Photocycloadditions Involving Alkenylboronate Esters

Abstract

(+)-Saxitoxin, a potent neurotoxin and Na_V blocker, poses significant synthetic challenges due to its compact tricyclic framework and guanidinium moieties. We report a concise and asymmetric total synthesis featuring an intramolecular [2 + 2] photocycloaddition of an alkenylboronate ester equipped with a new chiral auxiliary. This auxiliary, compatible with UV light and easily exchangeable on B(pin) derivatives, enabled high stereocontrol through hydrogen-bond-mediated transition-state stabilization. Our approach not only introduces an innovative surrogate for intramolecular Michael addition, particularly addressing transformations with contra-thermodynamic barriers, but also highlights the potential of boron-enabled photochemistry for synthesizing complex molecules.