Copper-catalyzed conjugate reduction

• Main Author: Jurkauskas, Valdas, 1966-
• Other Authors: Stephen L. Buchwald.
• Format: Others
• Language: English
• Published: Massachusetts Institute of Technology 2005
• Subjects: Chemistry.
• Online Access: http://hdl.handle.net/1721.1/17742

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004. === Includes bibliographical references. === Chapter 1. A highly enantioselective catalyst for the asymmetric conjugate reduction of a,- unsaturated cyclic ketones was generated upon combination of catalytic amounts of CuCl, NaOt-Bu, and a chiral bis-phosphine with poly(methylhydrosiloxane) (PMHS) as the stoichiometric reductant. In this process, chiral 3-alkylcyclopentanones were isolated in high enantiomeric excess (ee =/> 92%) and in moderate to excellent yields (42-91%). Chapter 2. Kinetic resolution, with good selectivity factors (25-52), was achieved by conjugate reduction with catalytic CuCl/NaOt-Bu/(S)-p-tol-BINAP and stoichiometric quantities of PMHS. When stoichiometric amounts of NaOt-Bu and t-BuOH were included in the reaction mixture, rapid racemization of the starting material occurred allowing for the dynamic kinetic resolution of the cyclopentenone substrates. In this process, chiral 2,4-dialkylcyclopentanones were isolated with high stereoselectivity (ee =/> 91%, dr=/>90:10) and in high yield (=/> 89%). Chapter 3. An N-heterocyclic carbene-copper chloride complex was prepared and used to catalyze the conjugate reduction of [alpha], [beta]-unsaturated carbonyl compounds. The combination of catalytic amounts of N-heterocyclic carbene-copper chloride complex and NaOt-Bu with PMHS as the stoichiometric reductant generates an active catalyst for the 1,4-reduction of tri- and tetrasubstituted a,f3-unsaturated esters and cyclic enones. The active catalytic species can also be generated in situ from 1,3-bis(2,6-di-isopropylphenyl)-imidazolium chloride and CuCl2.2H20 in the presence of NaOt-Bu and PMHS. === by Valdas Jurkauskas. === Ph.D.