Chiral phosphoric acid-catalyzed enantioselective phosphinylation of 3,4-dihydroisoquinolines with diarylphosphine oxides

Catalytic enantioselective phosphinylation of imines with diarylphosphine oxides is a powerful approach to access chiral alpha-amino diarylphosphine oxides. Here, the authors report the asymmetric phosphinylation of 3,4-dihydroisoquinolines at the C1 position using diarylphosphine oxides, catalyzed by chiral phosphoric acids. Chiral phosphorous-containing compounds are playing a more and more significant role in several different research fields. Here, we show a chiral phosphoric acid-catalyzed enantioselective phosphinylation of 3,4-dihydroisoquinolines with diarylphosphine oxides for the efficient and practical construction of a family of chiral alpha-amino diarylphosphine oxides with a diverse range of functional groups. The phosphine products are suitable for transforming to several kinds of chiral (thio)ureas, which might be employed as chiral ligands or catalysts with potential applications in asymmetric catalysis. Control and NMR tracking experiments show that the reaction proceeds via the tert-butyl 1-(tert-butoxy)-3,4-dihydroiso-quinoline-2(1H)-carboxylate intermediate, followed by C-P bond formation. Furthermore, computational studies elucidated that the hydrogen bonding strength between the phosphonate and isoquinolinium determines the stereoselectivity of the phosphinylation reaction.