The Acylative Kinetic Resolution of 1,2-Azaborine Naphthols

Abstract

The enantioselective synthesis of atropisomeric molecules containing stereogenic axes is becoming increasingly important due to their growing incorporation within medicinally relevant compounds. Organocatalytic routes to selectively prepare highly enantioenriched stereogenic axes containing a carbon(sp 2 )-boron(sp 2 ) bond remain underdeveloped due to the inherent challenge of the longer C-B bond length (1.58 Å) compared to its C(sp 2 )-C(sp 2 ) counterpart (1.49 Å). This manuscript showcases the development of an isothiourea catalysed acylative kinetic resolution of 1,2-azaborine frameworks to prepare configurationally stable carbon-boron stereogenic axes with good to excellent stereocontrol (24 examples, selectivity factors up to >200). The scope and limitations of this process have been investigated, with product derivatisation and racemisation studies providing insight into the configurational stability of these species and the association between boron hybridisation and atropisomeric stability. Building on insight gained from these studies preliminary proof of principle investigations concerning an acylative dynamic kinetic resolution in this system has been demonstrated.