Daniel R. Griffith

Research: Bridged azapolycycles are compounds that consist of multiple rings with a “bridging” linkage between the rings and include at least one nitrogen atom. Structural features of this type are found in many biologically active alkaloids and pharmaceuticals. Research in the Griffith lab focuses on the synthesis of bridged azapolycycles that contain a seven-membered ring, which are particularly challenging to create. As such, these types of compounds are under-represented in compound collections used in drug discovery efforts.

An active area of investigation has been the development of methods for accessing diverse, complex alkaloid-like scaffolds from a simple, seven-membered ring building block–tropone.  We have found that amines with a variety of functionalized side chains can be added to the iron complex (η⁴-tropone)Fe(CO)₃. These different functionalized side chains enables a variety of downstream reactions enabling access to diverse bridged azapolycycles. Specific examples can be found in the publications listed below.

Selected Recent Publications:

• A. H. Shoemaker, D. R. Griffith, “Synthetic Approaches to Non-Tropane, Bridged, Azapolycyclic Ring Systems Containing Seven-Membered Carbocycles,” Synthesis, 2021, 53, 65-78
• K. Phelan, P. S. Weiss, Y. He, Z. Guan, D. M. Thamattoor, D. R. Griffith, “Synthetic Entry to the 2-Azatricyclo[4.3.2.0^4,9]undecane Ring System via Tropone,” J. Org. Chem. 2020, 85, 2202-2212
• Huang, Z. K. Phelan, R. L. Tritt, S. D. Valent, Z. Guan, Y. He, P. S. Weiss, D. R. Griffith, “Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron,” J. Visualized Exp. 2019, (150), e60050, doi: 10.3791/60050
• Huang, Z. K. Phelan, R. L. Tritt, S. D. Valent, D. R. Griffith, “Formal aza-Michael additions to tropone: Addition of diverse aryl- and alkylamines to tricarbonyl(tropone)iron and [(C₇H₇O)Fe(CO)₃]BF₄,” Tetrahedron Lett. 2018, 59, 3432-3434

undergraduate student coauthors underlined