Novel Catalytic Methods

Fundamental research in catalytic method development is crucial for the discovery of synthetically useful carbon-carbon and carbon-heteroatom bond forming reactions. In recent years, our research in this area has focused on organocatalysis and homogeneous silver catalysis.

Our research in organocatalysis has revealed methods for constructing enantiomerically pure four membered and six membered rings with up to four stereocenteres in one step, via iminium activation of enals using proline derived catalysts. The novel [3+3] methodology has proven efficacious as the key reaction in the total synthesis of various Amaryllidacea alkaloids. We are currently exploring the development of new catalysts, and new methodologies for the construction of four, five and six membered rings.

Our work in the field of transition metal chemistry led to the development of stable silver complexes with hemilabile 2-phosphinobenzamide ligands. These catalysts were used in the discovery of the first azide-alkyne cycloadditions using homogenous, as opposed to heterogenous, transition metal catalysts. These complexes also catalyse the intramolecular hydroamination reactions of 2-ethynylanilines, for the synthesis of indole derivatives. Given their relatively low cost compared to other transition metals, such as palladium, we are currently exploring further applications for these catalysts.

Relevant Articles

Organocatalyis

Total Synthesis of the Natural Product (+)-trans-Dihydronarciclasine via an Asymmetric Organocatalytic [3+3]-Cycloaddition discovery of its potent anti-Zika Virus (ZIKV) Activity. O. Revu, C. Zepeda-Velazquez, A. Nielsen, J. McNulty*, R. H. Yolken, L. Jones-Brando, ChemistrySelect, 1, 5895-5899 (2016).

Asymmetric Organocatalytic Stepwise [2+2] Entry to Tetrasubstituted Heterodimeric and Homochiral Cyclobutanes. A. J. Nielsen, H. A, Jenkins, J. McNulty,Chem. Eur. J. 22, 9111-9115 (2016).

Enantioselective Organocatalytic Michael-aldol Sequence to the Anticancer Natural Product (+)-trans-dihydrolycoricidine. J. McNulty*, C. Zepeda-Velazquez, Angew. Chem. Int. Ed. 53, 8450-8454 (2014). See also:  Short Synthesis of a Wildflower Alkaloid, Chem. & Eng. News, July 7th, 2014, p. 28-29.  See also: Synfacts, 10, 982 (2014).

Homogenous Silver Catalysis

High Yielding Synthesis of Carboranes Under Mild Conditions Using a Homogeneous Silver(I) Catalyst. Direct Evidence of a Bimetallic Intermediate. M. E. El-Zaria, K. Keskar, A. R. Genady, J. A. Ioppolo, J. McNulty, J. F. Valliant*, Angew. Chem. Int. Ed. 53, 5156-5160 (2014).   See also: Synfacts, 10, 585 (2014).

A robust, well defined homogeneous silver(I) catalyst for mild intramolecular hydroamination of 2-ethynylanilines leading to indoles. J. McNulty*, K. Keskar, Eur. J. Org. Chem. 1622-1629 (2014).

Discovery of a robust and efficient homogeneous silver(I) catalyst for the cycloaddition of azides onto terminal alkynes. J. McNulty*, K. Keskar, Eur. J. Org. Chem. 5462-5470 (2012).

The first well-defined silver(I)-complex catalyzed cycloaddition of azides onto terminal alkynes at room temperature. J. McNulty*, K. Keskar, R. Vemula, Chem. Eur. J. 17, 14727-14730 (2011).