High Rotational Barrier Atropisomers.

ABSTRACT

Atropisomers have attracted a great deal of attention lately due to their numerous applications in organic synthesis and to their employment in drug discovery. However, the synthetic arsenal at our disposal with which to access them remains limited. The research described herein is two-pronged; we both demonstrate the use of MCR chemistry as a synthetic strategy for the de novo synthesis of a class of atropisomers having high barriers to rotation with the simultaneous insertion of multiple chiral elements and we study these unprecedented molecular systems by employing a combination of crystallography, NMR and DFT calculations. By fully exploiting the synthetic capabilities of our chemistry, we have been able to monitor a range of different types of interaction, i. e. π-π, CH-π, heteroatom-π and CD-π, in order to conduct structure-property studies. The results could be applied both to atroposelective synthesis and in drug discovery.