Development of the Enantioselective Oxidation of Secondary Alcohols and Natural Products Total Synthesis

catalysis;enantioselective;oxidation;palladium

Bagdanoff, Jeffrey Thomas ; Stoltz, Brian M.

University:California Institute of Technology

Department:Chemistry and Chemical Engineering

关键词: catalysis;    enantioselective;    oxidation;    palladium;   

Others  :  https://thesis.library.caltech.edu/5248/15/Thesis.pdf

美国|英语

来源: Caltech THESIS

【 摘 要 】

Oxidation is a fundamental process in chemistry and biology.In synthetic chemistry, there are several methods for the asymmetric oxidation of organic substrates.Classically, these methods have focused on the delivery of a heteroatom from a reagent or catalyst to a prochiral substrate.What have historically been underdeveloped are enantioselective oxidation methods that do not involve the transfer of a heteroatom, but rather are defined by the enantioselective dehydrogenation of an organic substrate.This type of oxidative transformation was investigated using a palladium(II) catalyst system.

A palladium-catalyzed oxidative kinetic resolution of secondary alcohols was developed.Key features of the catalytic system include the use of (–)-sparteine as the source of chiral relay, and molecular oxygen as the sole stoicheometric oxidant.Under the described catalytic system, a number of benzylic and allylic alcohols have been oxidized in an enantioselective manner, to provide a ketone and residual alcohol in high enantiomeric excess and excellent yield.

Subsequent to the original system, the systematic investigation of a number of mechanistic hypotheses involving the role of exogenous bases and H-bonding additives prompted the discovery of new reaction conditions displaying greatly enhanced reactivity, selectivity, atom economy, and generality.The net result of these improvements was a catalytic system effective in oxidative desymmetrization of a number of complex meso-diols.Ultimately, these advances have permitted our method to be applied towards a number of synthetic endeavors, including the key step in the total synthesis of the natural product alkaloid (–)-lobeline.