closo-Carboranyl Analogs of β-Arylethylamines: Direct Synthesis from Alkenes via EnT-Catalysis

Paulus, Fritz; Heusel, Corinna; Jaspers, Marc; Amrehn, Lilli M.; Schreiner, Florian; Rana, Debanjan; Daniliuc, Constantin G.; Hansen, Michael Ryan; Glorius, Frank

Abstract

closo-Carboranes are icosahedral carbon–boron clusters with unique properties and broad applicability. They particularly stand out in the context of drug development as privileged structural motifs for boron neutron capture therapy (BNCT) and as highly hydrophobic bioisosteres for the rotational volume of phenyl rings. Herein, we unveil the synthesis of N-protected carboranyl analogs of β-arylethylamines—widely found structural motifs in biologically active molecules—via a one-step alkene difunctionalization approach. Key for our success were the enabling mechanistic characteristics of energy transfer catalysis which we have used for the first time to generate closo-carboranyl radicals. Downstream modifications gave a series of analogs of amino acids and known N-methyl-d-aspartate receptor (NMDAR) antagonists.