Nonbiaryl atropisomers are molecules defined by a stereogenic axis featuring at least one nonarene moiety. Among these, scaffolds bearing a conformationally stable C(sp2)–C(sp3) stereogenic axis have been observed in natural compounds; however, their enantioselective synthesis remains almost completely unexplored. Herein we disclose a new class of chiral C(sp2)–C(sp3) atropisomers obtained with high levels of stereoselectivity (up to 99% ee) by means of an organocatalytic asymmetric methodology. Multiple molecular motifs could be embedded in this class of C(sp2)–C(sp3) atropisomers, showing a broad and general protocol. Experimental data provide strong evidence of the conformational stability of the C(sp2)–C(sp3) stereogenic axis (up to t1/225 °C >1000 y) in the obtained compounds and show kinetic control over this rare stereogenic element. This, coupled with density functional theory calculations, suggests that the observed stereoselectivity arises from a Curtin–Hammett scenario establishing an equilibrium of intermediates. Furthermore, the experimental investigation led to evidence of the operating principle of central-to-axial chirality conversions.

Organocatalytic Enantioselective Construction of Conformationally Stable C(sp2)–C(sp3) Atropisomers

Bertuzzi, Giulio;Corti, Vasco;
2022

Abstract

Nonbiaryl atropisomers are molecules defined by a stereogenic axis featuring at least one nonarene moiety. Among these, scaffolds bearing a conformationally stable C(sp2)–C(sp3) stereogenic axis have been observed in natural compounds; however, their enantioselective synthesis remains almost completely unexplored. Herein we disclose a new class of chiral C(sp2)–C(sp3) atropisomers obtained with high levels of stereoselectivity (up to 99% ee) by means of an organocatalytic asymmetric methodology. Multiple molecular motifs could be embedded in this class of C(sp2)–C(sp3) atropisomers, showing a broad and general protocol. Experimental data provide strong evidence of the conformational stability of the C(sp2)–C(sp3) stereogenic axis (up to t1/225 °C >1000 y) in the obtained compounds and show kinetic control over this rare stereogenic element. This, coupled with density functional theory calculations, suggests that the observed stereoselectivity arises from a Curtin–Hammett scenario establishing an equilibrium of intermediates. Furthermore, the experimental investigation led to evidence of the operating principle of central-to-axial chirality conversions.
Bertuzzi, Giulio; Corti, Vasco; Izzo, Joseph A.; Ričko, Sebastijan; Jessen, Nicolaj Inunnguaq; Jørgensen, Karl Anker
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/863328
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