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New Approaches Towards the Asymmetric Allylation of the Formyl and Imino Groups via Strained Silane Lewis Acids
This dissertation presents new approaches towards the asymmetric allylation of the imino and formyl functionalities by using strained silanes as Lewis acids. Here in the Laboratory of Professor James L. Leighton, chiral homoallylic alcohols and amines are considered privileged products given their important role as building blocks in natural product synthesis. The new approaches reported herein are focused on expanding the scope of imine allylation reactions and gaining full synthetic utility of the corresponding homoallylic amine products by means of economic and user-friendly protocols. In addition, the discovery of a novel catalytic and mild approach to the asymmetric allylation of aldehydes will be the focus of discussion at the end of this works. Chapter 1 will give a brief introduction about general concepts in asymmetric allylation of aldehydes and imines as well as in applications of strained silane Lewis acids in these reactions. Chapter 2 will discuss the development of a novel asymmetric allylation method for N-heteroaryl hydrazones and the N-heteroaryl cleavage from the product to unmask the corresponding free amines. Chapter 3 will carry on these studies into different imine activating groups in search for a more general and user-friendly approach towards both allylation and cleavage protocols. Finally, Chapter 3 will discuss the development of a new methodology in which chiral bismuth (III) complexes can catalyze the asymmetric allylation of aldehydes with achiral strained allylsilanes
Streamlining bioactive molecular discovery through integration and automation
The discovery of bioactive small molecules is generally driven via iterative design–make–purify–test cycles. Automation is routinely harnessed at individual stages of these cycles to increase the productivity of drug discovery. Here, we describe recent progress to automate and integrate two or more adjacent stages within discovery workflows. Examples of such technologies include microfluidics, liquid-handling robotics and affinity-selection mass spectrometry. The value of integrated technologies is illustrated in the context of specific case studies in which modulators of targets, such as protein kinases, nuclear hormone receptors and protein–protein interactions, were discovered. We note that to maximize impact on the productivity of discovery, each of the integrated stages would need to have both high and matched throughput. We also consider the longer-term goal of realizing the fully autonomous discovery of bioactive small molecules through the integration and automation of all stages of discovery
P<sub>2</sub>Et Phosphazene: A Mild, Functional Group Tolerant Base for Soluble, Room Temperature Pd-Catalyzed C–N, C–O, and C–C Cross-Coupling Reactions
The non-nucleophilic organic superbase
P<sub>2</sub>Et phosphazene
can enable a broad range of palladium-catalyzed cross-coupling reactions,
including C–C, C–N, and C–O couplings of aryl
chlorides, bromides, and iodides at room temperature. The mildness
and substrate compatibility of this chemistry can deliver immediate
synthetic utility for the preparation of complex molecules