Frederick G. West
The activities of my research group are centered on various aspects of chemical synthesis. Synthesis provides access to otherwise unavailable compounds for asking important research questions concerning topics ranging from biology to catalysis to basic chemical reactivity. Our interests can be divided into three main areas: (1) novel strategies for the efficient construction of complex natural products; (2) new methodology based on unusual reactive intermediates; and (3) de novo design of bioactive small molecules with unique binding or transport properties. Students in my group become proficient in diverse synthetic methodology and spectroscopic techniques in the course of pursuing their research, and are exposed to wider scientific horizons as a consequence of their interactions with others in the group as well as our collaborators. Some of our current projects are listed below.
New Approaches to the Taxane Skeleton: We have developed an efficient entry to functionalised taxane AB or ABC ring systems (Fig. 1) utilizing stereoselective Nazarov cyclization of dienones such as 1, followed by a later oxidative fragmentation to unveil the 8-membered B-ring. We are currently focusing on converting these intermediates into structural analogues of the potential MDR reversal agent taxinine, and also exploring second-generation approaches to further streamline the route
A related project involves the development of new methodology based upon domino processes initiated by the Nazarov reaction.
Ammonium Ylide Rearrangements for the Synthesis of Alkaloids: Previous work in our labs has shown that polycyclic amine structures found in many classes of alkaloids can be easily accessed via metallocarbene-derived ammonium ylides. A current focus in our group is the ergot alkaloid class, as exemplified by lysergic acid (Fig. 2). Dizaoketones, when treated with transition metal catalysts, generate transient metallocarbenes. If there is a nearby basic amine, ring-closure to an intermediate ammonium ylide ensues, followed by rearrangement to give a substituted heterocycle. Analogous chemistry with oxonium ylides is being applied to the synthesis of the tumor promoter phorbol.
Photochemical [4 + 4]-Cycloadditions for Synthesis of Cyclooctanoid Natural Products: Pyran-2-ones with pendant 1,3-dienes can undergo efficient intramolecular [4 + 4]-cycloaddition when they are irradiated with long-wavelength UV light. This reaction is being used as the key transformation in approaches to the chemical synthesis of the terpenoid natural product traversianal (Fig 3). Similar chemistry is being applied to the synthesis of 7,8-epoxy-4-basmen-6-one.
Benson, C. L.; West, F. G. "Highly Stereoselective 6π Electrocyclization of Bridged Bicyclic 1,3,5-Treines," Org. Lett. 2007, 9, 2545-2548.
Song, D.; Rostami, A.; West, F. G. "Domino Electrocyclization/Azide-Capture/Schmidt Rearrangement Employing Simple Dienones and Azides," J. Am. Chem. Soc. 2007, 129, 12019-12022.
Grant, T. N.; West, F. G. "Interrupted Nazarov Reactions Using Dichlorocyclopropanes: A Novel Mode of Arene Trapping," Org. Lett. 2007, 9, 789-3792.
Rieder, C. J.; Fradette, R. J.; West, F. G. "Construction of Aryl-Substituted Triquinanes Through the Interrupted Nazarov Reaction," Chem. Commun. 2008, 1572-1574.
Li, L.; Chase, C. E.; West, F. G. "Facile Assembly of Cyclooctatrienes via Tandem Photo-[4+4]-Cycloaddition/Decarboxylation of Pyran-2-ones," Chem. Commun. 2008, 4025-4027.
Li, L.; McDonald, R.; West, F. G. "Concise Route to Triquinanes from Pyran-2-ones," Org. Lett. 2008, 10, 3733-3736.
Grant, T. N.; Benson, C. L.; West, F. G. "Ring Expansion of Lactones and Lactams via One-Carbon Intercalation of Propiolate Ester," Org. Lett. 2008, 10, 3985-3988.