Enantioselective Addition of Boronates to o-Quinone Methides Catalyzed by Chiral Biphenols

Abstract

Chiral biphenols were found to catalyze the enantioselective asymmetric addition of aryl- or alkenyl-boronates to ortho-quinone methides. Substituted 2-styryl phenols were obtained in good yields (up to 95%) and high enantiomeric ratios (up to 98:2) in presence of 10 mol % of 3,3′-Br2-BINOL. A two step synthesis of (S)-4-Methoxy-dalbergione is achieved in good yield and selectivity.

Brønsted‐Säure‐katalysierte konjugierte Addition von β‐Dicarbonylverbindungen an in situ erzeugte ortho‐Chinomethide – enantioselektive Synthese von 4‐Aryl‐4H‐chromenen

“…[4] Schaus und Mitarbeiter nutzten ein chirales Binaphthol als Katalysator für die unter sehr milden Bedingungen ablaufende enantioselektive Addition von Aryl-und Vinylboronaten an in situ erzeugte orthoChinomethide. [5] Schließlich berichteten kürzlich unabhängig voneinander die Gruppen um Ye und Scheidt über NHCkatalysierte enantioselektive [4+3]-Cycloadditionen von a,bungesättigten Aldehyden und ortho-Chinomethiden zur Synthese von Benzoxopinonen. [6] Das Chromangerüst gehçrt zu den privilegierten Strukturelementen sowohl im Bereich der Naturstoffe als auch vieler pharmakologisch aktiver Substanzen mit cytotoxischer, antibakterieller, antiviraler, entzündungshemmender und antioxidativer Wirkung.…”

Enantioselective Multicomponent Condensation Reactions of Phenols, Aldehydes, and Boronates Catalyzed by Chiral Biphenols

“…Comparison of ( 4f ) to the previously reported compound confirmed the absolute stereochemistry of the product and is consistent with the reported o QM mechanistic model of enantioselectiv-ity. 7 2-Naphthaldehyde was tolerated in the reaction, however, sterics limited the reactivity of 1-naphthaldehyde (4g, 4h ). Notably, ortho -substitution improved the selectivity in the case of 2-bromobenzaldehyde ( 4i ).…”

“…Enantioselective additions of boronates to o QMs catalyzed by chiral biphenols provide access to chiral motifs that appear in natural products and drugs. 7 For instance, myristinin A is a potent inhibitor of DNA polymerase β and contains a chiral diaryl methane within its chroman core. 8 Other notable examples include myristicyclin A, dracoflavans C and D, and cochinchinenins B and C. 9–11 Methods to form o QMs typically require oxidation, acid/base chemistry, photolysis, or thermolysis.…”

“…In agreement with our previous studies, ( R )-3,3′-Br 2 -BINOL was identified as the catalyst for further evaluation giving the best combination of yield and enantioselectivity. 7 Higher concentrations improved the yield but resulted in lower enantioselectivity (Table 1, entries 7–9). A temperature of 80 °C was found to be ideal for promoting the condensation while maintaining enantioselectivity.…”

“…This is consistent with our earlier studies in which enantioselective additions of boronates to o QMs occur at low temperatures. 7 The facile nature of this dissociation-ligand-transfer also explains why there is no observation of a dioxaborin intermediate during the reaction. 20 The cyclization is initiated by protonation of the electron rich olefin.…”