Copper-catalyzed conjugate reduction

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Jurkauskas, Valdas, 1966-

Advisor dc:contributor.advisor

• Stephen L. Buchwald.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/17742

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/17742