Transition Metal Catalyzed Approaches to the Asymmetric Construction of All-Carbon Quaternary Centers

Author: Moghadam, Farbod Arya

Year: 2026

Degree: Dissertation (Ph.D.)

Advisor: Stoltz, Brian M.

Committee Members: Nelson, Hosea M.; Demirer, Gozde S.; Peters, Jonas C.; Stoltz, Brian M.

Option: Chemistry

DOI: 10.7907/11d1-9b20

Abstract

In the Stoltz group, chemical research leverages the interplay between methods development and total synthesis, wherein new synthetic technologies enable the pursuit of novel target compounds and challenges encountered during synthetic campaigns inspire the invention of methodologies. Given the stereochemical complexity of natural products and emerging pharmaceuticals, methods development in our group has focused in particular on the asymmetric construction of all-carbon quaternary centers. Herein is described the development of transition metal catalyzed approaches to the formation of such centers with high levels of stereocontrol. Chapter 1 describes the discovery of an Ir-catalyzed asymmetric allylic alkylation reaction efficiently merging linear, trisubstituted allylic electrophiles with prototypical malonate nucleophiles to generate enantioenriched β-quaternary carbonyl products. The reaction proceeds with low catalyst loadings of iridium and at ambient temperature, marking the first reaction of its kind to be performed under such mild conditions. Appendix 2 highlights recent efforts to develop an Ir-catalyzed process for the doubly stereoselective formation of vicinal quaternary stereocenters. Chapter 2 discloses a more sustainable, Mo-catalyzed alternative to the Ir-catalyzed process in Chapter 1, unveiling thus far unknown reactivity with molybdenum and generating the desired products with outstanding enantioselectivity. This advance was enabled by exhaustive investigation of suitable ligand scaffolds, ultimately leading to the creation of the novel, C1-symmetric ShabyDACH ligand. Chapter 3 discusses the elaboration of a Pd-catalyzed a-vinylation of lactam nucleophiles to forge a-quaternary carbonyls. These products could further be diversified to a range of elusive scaffolds, highlighting their synthetic utility.

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