Back to Table of Contents

42754-G1
Asymmetric Morita-Baylis-Hillman Reaction: A Novel Tethered Bifunctional Lewis Acid-Lewis Base Catalysis Strategy

Yun-Ming Lin, University of Toledo

The Lewis base catalyzed asymmetric Morita-Baylis-Hillman (MBH) reaction between an aldehyde and a Michael acceptor is an important carbon-carbon bond forming reaction that produces a highly functionalized vinyl alcohol. However, the synthetic applications of this atom economical reaction are hampered by its current limitations (slow reaction rates, etc.) and the lack of a generally applicable catalyst for asymmetric catalysis. We had proposed a Lewis acid-Lewis base (LA-LB) bifunctional catalysis strategy as a new approach for improving its reaction rate as well as for inducing enantioselectivity. The tethered LA-LB bifunctional catalysts (i.e., intramolecular bifunctional catalysis) would activate both the electrophile and the latent nucleophile in the MBH reaction intramolecularly, thus resulting in reaction rate acceleration and chiral induction. Since our first annual progress report, we have re-designed our catalytic systems and synthesized novel tridentate ligands as well as novel pentadentate ligands. Subsequent bifunctional catalytic activity screening uncovered an active LA*-LB* bifunctional catalyst derived from Zn(II) and the tridentate ligand [see Tetrahderon Lett. 2007, 48, 5561-5564]. During our catalytic activity studies employing the asymmetric Wynberg reaction as a proof-of-principle reaction, a remarkably active LA*-LB* bifunctional catalyst (1 mol% catalyst loading leading to >99% ee) was also discovered for the asymmetric Wynberg reaction that converts aldehydes and ketenes to beta-lactones in unprecedented enantioselectivity [see Org. Lett. 2007, 9, 567-570]. We have also developed a predictive model that foretells the R/S absolute configuration in the LB*-dependent asymmetric bifunctional catalysis (ABC) [see Tetrahedron Lett. 2007, 48, 5275-5278]. During our catalytic activity screening, we have also discovered a new catalytic, highly stereoselective olefination reaction that converts aldehydes and acetyl chloride into trans-enone exclusively, using only 5 mol% of a Cu(II) derived LA*-LB* bifunctional catalyst [see Tetrahedron Lett. 2007, 48, 5531-5534]. Supported by this PRF grant, our initial success in the area of asymmetric bifunctional catalysis (ABC) and new catalytic reaction discovery has had a positive impact on PI's independent career as well as students participated in these projects. Developing new catalytic methods for challenging organic reactions and discovering new reactions are ongoing research effort in PI's laboratory.

Back to top