Development and Applications of New Catalytic Reactions

Despite great progress in organic reaction development, there remains a great need for new organic reactions for the stereo- and enantioselective synthesis of functionally rich molecules under operationally and environmentally friendly reaction conditions.

See the highlight of our novel catalytic reaction in Angew. Chemie!

Our interests in this area include:

(1) Catalytic Generation of Activated Carboxylates

We have recently developed a method for the truly catalytic generation of activated carboxylates. Widely available, non-toxic organic heterocycles promote the intramolecular redox reaction of alpha-heteroatomic aldehydes. This leads to catalytic generation of a catalyst-bound activated carboxylates, which reacts with nucleophiles to afford esters, thioesters, or amides.

• J. Am. Chem. Soc. 2004, 126, 8126–8127. Link

We are currently exploiting the broad substrate scope of these reaction to develop catalytic, asymmetric routes to a variety of highly prized molecules including alpha-chiral esters, beta-amino acids, anti-aldol adducts, and chiral ketones. We have also developed a new, highly active organocatalyst for the redox esterification of enals.

• Org. Lett. 2005, 7, 3873–3876. Link

(2) New Catalytic, Asymmetric Carbon-Carbon Bond Forming Reactions

With insights gained from our development of catalytically generated activated carboxylates, we are have developed the first truly catalytic method for the generation and reaction of homoenolates from readily availalbe starting materials. These reaction proceed under mild, convenient reaction conditions and do not require stoichiometric reagents. The transient homoenolates react with a variety of electrophiles, or can be protonated to give activated carboxylates. We have applied this methodology to the direct annulation of enals and aldehydes, leading to the stereoselective synthesis of gamma-butyrolactones and gamma-lactams. Currently, we are developing catalytic homoenolate approaches to other hetero- and carbocyclic structures, exploring catalytic, asymmetric methods, and applying these reactions to the total synthesis of biologically active pharmacueticals and natural products.

• J. Am. Chem. Soc. 2004, 126, 14370–14371. Link

• Org. Lett. 2005, 7, 3131–3134. Link