Enantioselective C-H Amination of Alkenes and Carbonyl Compounds and Novel Application Thereof

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Project Summary: The general aim of the project is to develop synthetic methods of broad utility and function that will ultimately provide new chemical tools for the diverse range of synthetic chemists and biomedical researchers that utilize chiral amines and chiral N- heterocycles. The main objective is to invent new catalytic asymmetric amination methods that allow enantioselective access to chiral allyl amines and α-amino carbonyls. As a consequence, this core research will prove valuable to a number of wide-ranging industrial areas. During the project period, the PIs plan to demonstrate the value of this new chemical strategy in the context of first examples of catalytic enantioselective aminations and their application to access valuable chiral molecules. Individual goals of the proposed research include: (i) Developing a novel approach for the synthesis of chiral allyl amines, (ii) Synthesis of important chiral N-aryl β-alkyl Aza Baylis-Hillman (ABH) adducts which were not yet reported because of substrate scope limitation of classical ABH reactions; (ii) As metal-nitroso intermediates are moderately thermally stable, it will be possible to elaborate the mechanisms of asymmetric allylic amination, to learn the best ways to design and synthesize practical efficient catalysts; thus, shedding light on the mechanism of these asymmetric nitrogenation reactions; (iii) Total synthesis of a hydroxymethyl docetaxel fragment, (iv) Asymmetric synthesis of β-aminoacids and β-lactams, (v) Synthesis of the cholesterol absorption inhibitor Ezetimibe, (vi) Antiepileptic drug Vigabatrin, (vii) Asymmetric α C-H amination of carbonyl compounds, and (viii) Asymmetric α C-H amination of oxindoles. These new strategies provide a practical solution to access novel synthetic targets and should allow for future advances in the fields of asymmetric amination and group transfer reactions.