Chemical Catalysis

Gary A. Molander

Photo: 
First Name: 
Gary A.
Last Name: 
Molander
Official Title: 
Hirschmann-Makineni Professor of Chemistry
Contact Information
Office Location: 
4001 IAST
Email: 
gmolandr@sas.upenn.edu
Phone: 
(215) 573-8604
Fax: 
(215) 573-7165
Twitter: 
@molandergroup
Admin Support: 
Research Interests: 

 

The central theme of the Molander group's research is the development of new synthetic methods and their application to the synthesis of organic molecules. The group's focus is to expand and improve the Suzuki coupling reaction for organoboron compounds. Robust, air- and water-stable potassium organotrifluoroborates (R-BF3K), are employed to carry out couplings under relatively mild conditions using non-toxic components.

Greener Routes to Standard Reagents

The preparation of aryl- and heteroaryl potassium trifluoroborate and trihydroxyborate salts has been modified to take advantage of atom-economical boron sources, such as bis-boronic acid (BBA) and tetrakis(dimethylamino)diboron, which allow low catalyst loading and relatively mild reaction conditions. Reactive boronic acid species are generated, and subsequent coupling reactions with these substrates allow greener access to biaryl products.

 

 

Improving Transformations with More Robust Reagents

 

Organotrifluoroborates allow installation of functional groups within a molecule in the place of an existing carbon-boron bond. This allows one to prepare or purchase a simple, functionalized organotrifluoroborate and to elaborate the structure, drawing on the reactivity of the boron species. Some of the transformations carried out to date in this way are outlined below, highlighting the ability to install a cyclopropyl, hydroxymethyl, or nitroso functional group using potassium trifluoroborates.

 

 

Novel Reagents and Transformations

Some methods have been developed for the synthesis of novel reagents containing alkyltrifluoroborates, namely potassium aminomethyl-, hydroxymethyl-, and a-alkoxyalkyltrifluoroborates. The synthesis of these structures is outlined below with their applications in cross coupling illustrated.

Marisa C. Kozlowski

Photo: 
First Name: 
Marisa C.
Last Name: 
Kozlowski
Official Title: 
Professor of Chemistry

Organic and Catalysis Chemistry

Contact Information
Office Location: 
4002 IAST, Lab: 4010, 4070 IAST
Email: 
marisa@sas.upenn.edu
Phone: 
(215) 898-3048
Admin Support: 
Research Interests: 

 

The central theme of research in my laboratory is the rational design of new methods and catalysts for use in organic synthesis. As well as using traditional screening and development approaches, we employ several novel computational tools for the discovery and optimization of new reagents and catalysts. These new synthetic methods comprise the key steps in our total synthesis strategies to a variety of important pharmaceutical agents and natural products.

 

Asymmetric Oxidative C-C Bond Forming Reactions: The development of chiral catalysts for oxidative C-C bond formation is a major focus in our laboratory. In addition to the substantial potential for developing biomimetic synthetic approaches to a variety of natural products, such transformations are appealing in that C-H bonds are directly transformed to C-C bonds with an inexpensive oxidant, molecular oxygen. 

 

To this end, we developed 1,5-diaza-cis-decalin copper complexes, the catalysts of choice for the oxidative asymmetric biaryl coupling of 2-naphthol derivatives. Study of the mechanism has allowed the development of new reaction methods as well as couplings of highly functionalized 2-naphthols. With this ability, we have completed the first asymmetric synthesis of the natural product nigerone. The first total syntheses of the complex natural products cercosporin and hypocrellin have also been accomplished. These structurally novel compounds display promising photodynamic therapy profiles in cancer treatment. Future goals include exploiting the oxidative biaryl coupling method in the synthesis of chiral bisanthraquinone and naphthodianthrone natural products.

 

Reactions of α-Ketoesters and Derivatives: We have described bifunctional salen-derived catalysts that contain electronically decoupled Lewis acid and Lewis base sites. This electronic decoupling permits generation of optimally active catalysts as both the Lewis acid and Lewis base can be maximized without quenching each other. These catalysts are particularly effective for the very difficult asymmetric alkylation of α-ketoesters and α-iminoesters to yield α-hydroxy and α-amino acid adducts in enantiomerically pure form. Further studies with α-iminoesters have revealed an umpolung addition pathway allowing addition of nucleophiles to imine nitrogens. We have exploited this reactivity pattern to develop a three-component coupling that generates highly functionalized α-amino acid derivatives.

 

Computer-Aided Design of Chiral Auxiliaries and Catalysts:Diastereo- and enantioselective chemical reactions are essential components for the efficient synthesis of complex chiral targets. We have generated several computational tools to assist researchers in designing and optimizing chiral catalysts including database searching and functionality mapping. In addition, we have developed semi-empirical quantum mechanical quantitative structure selectivity (QSSR) relationships for accurate and precise enantiomeric excess predictions of chiral catalysts. In one example, we correlated the structures of various beta-amino alcohol catalysts to their enantioselectivities in the asymmetric addition of diethylzinc to benzaldehyde. With our method the selectivities of new catalysts were also calculated. Subsequent chemical synthesis and analysis of the new catalysts indicated that the model was very useful and easily distinguished catalysts of low, moderate, and high selectivity. 

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

215.898.8317 voice | 215.573.2112 fax | web@chem.upenn.edu

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