Zinc Mediated Synthesis of Cyclopropylamines

The cyclopropylamine motif is often found in both natural and pharmaceutical compounds. Our group has recently developed a synthesis of trans-cyclopropylamines using electrophilic zinc homoenolate intermediates. This thesis describes the attempted extension of this concept to an intramolecular version of this transformation to yield cyclopropanated heterocycles. Despite the successful preparation of the linear precursor for the synthesis of 2,3-methanopyrrolidine, cyclization did not result in any desired product. The second part of this thesis describes a one-pot synthesis of trans-cyclopropylamines from readily available a-chloroaldehydes and amines. Zinc homoenolate intermediates have been reported in the synthesis of cyclopropanols from a-chloroaldehydes, as well as being the key intermediate in our synthesis of trans-cyclopropylamines. Hence, combining both processes would allow the development of a versatile synthetic method to access trans-cyclopropylamines. While products were obtained in excellent yields, diastereomeric ratios remained low, which led us to speculate that this reaction is under thermodynamic control.M.Sc.2019-11-03 00:00:0