Design and synthesis of novel chiral dirhodium(II) carboxylate complexes for asymmetric cyclopropanation reactions

Abstract

A novel approach for the design of dirhodium(II) tetracarboxylates derived from (S)- amino acid ligands is outlined. The new approach is founded on modifying the catalyst sterics through reducing the symmetry of the ligand’s N-heterocyclic tether. Investigations towards the new approach led to the preparation of Rh2(S-1, 2-NTTL)4 and analogues, Rh2(S-1-Ph-BPTTL)4, Rh2(S-tertPTTL)4, Rh2(S-BHTL)4, Rh2(SBOTL) 4 and Rh2(β-D-TAGA)4. The screening of the new complexes led to the uncovering of Rh2(S-tertPTTL)4 as a new member to the dirhodium(II) complexes family with an extraordinary selectivity. The stereoselectivity of Rh2(S-tertPTTL)4 was found to be comparable to Rh2(S-PTAD)4 (up to >99% ee), while being much more synthetically accessible catalyst. X-ray structure-based correlations justifying the observed enantioinduction enhancement are also discussed. The process of preparation and characterization of a Rh2(S-tertPTTL)4-catalyzed cyclopropanation capillary microreactor is also presented. The continuous flow Rh2(S-tertPTTL)4-catalyzed cyclopropanation microreaction is carried out to generate the cyclopropane product in moderate yield (44%) and excellent diastereoselectivity (>20:1 E:Z dr). The microreaction enantioselectivity, however, did not exceed 10% ee. Finally, the results are concluded and an outlook regarding the current field of research is outlined highlighting potential investigations that might be necessary for future development.

Date of Award	2015
Original language	English
Supervisor	Ashraf GHANEM (Supervisor) & Bill Maher (Supervisor)