Towards the synthesis of chiral benzofused cycloalkanes through iridium catalyzed asymmetric hydrogenation

Abstract

Enantioenriched chiral organic compounds, such as benzofused cycloalkanes, are key structures present in a large number of biologically active compounds, like natural products or pharmaceuticals. To answer this demand, asymmetric synthesis has gained a lot of interest in the last few years. So far, asymmetric hydrogenation has become one of the most relevant methodologies in the field, given its many benefits. However, it is still underdeveloped as a strategy for the synthesis of benzofused cycloheptanes. Motivated by this, our group has worked on developing a new methodology towards the synthesis of these chiral compounds, through an iridium catalyzed asymmetric hydrogenation. In this work, a benzofused methylene cycloheptane has been synthesized, and its asymmetric hydrogenation studied using different Ir-catalysts. Moreover, kinetic studies were conducted in order to analyze the effect of different catalysts in the isomerization process of the substrates. The results obtained led to the preparation of a new catalyst, Ir-NoaPHOX, that proved optimal by affording no isomerization process. Finally, Ir-NoaPHOX was tested on the asymmetric hydrogenation of benzofused methylene cycloheptanes, providing an enantiomeric excess of 89%. Additionally, derivate benzofused methylene cycloheptanes substrates were prepared, to broaden the scope of the methodology