| Autor: |
Bertuzzi G; Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark., Corti V; Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark., Izzo JA; Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark., Ričko S; Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.; Aarhus Institute of Advanced Studies (AIAS), Aarhus University, Høegh-Guldbergs Gade 6B, DK-8000 Aarhus C, Denmark., Jessen NI; Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark., Jørgensen KA; Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark. |
| Abstrakt: |
Nonbiaryl atropisomers are molecules defined by a stereogenic axis featuring at least one nonarene moiety. Among these, scaffolds bearing a conformationally stable C(sp 2 )-C(sp 3 ) 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(sp 2 )-C(sp 3 ) 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(sp 2 )-C(sp 3 ) atropisomers, showing a broad and general protocol. Experimental data provide strong evidence of the conformational stability of the C(sp 2 )-C(sp 3 ) stereogenic axis (up to t 1/2 25 ° 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. |
