Synthetic Approaches to Non-Tropane, Bridged, Azapolycyclic Ring Systems Containing Seven-Membered Carbocycles

Abstract

This Short Review highlights various synthetic approaches to bridged azabicyclic ring systems containing seven-membered carbocyclic rings. Such ring systems are common to a number of biologically active natural products. The seven-membered ring in such systems is generally formed in one of four ways: 1) cyclization of an acyclic precursor; 2) ring expansion or rearrangement of a different ring size; 3) cycloaddition; and 4) use of a synthetic building block with the seven-membered ring already present. Representative examples of each approach from both total synthesis and methodological studies are discussed, with an emphasis on work publishedin the last twenty years.1 Introduction2 Cyclization Reactions3 Ring Expansions and Rearrangements4 Cycloadditions5 Strategies Involving Seven-Membered Ring Building Blocks6 Conclusion

Crystal structure of tricarbonyl[η4-6-exo-(triphenylphosphino)cyclohepta-2,4-dien-1-one]iron(0) tetrafluoroborate

“…The research focus of one author lies in the synthesis of unique and diverse azapolycyclic skeletons from common synthetic building blocks such as compound I due to the biological importance of such scaffolds. Although seven-membered carbocyclic rings are found in a number of biologically active natural products (Shoemaker & Griffith, 2021), their synthesis tends to present a greater challenge compared to similar five-or six-membered rings because of the increased enthalpic and entropic barriers associated with their formation (Phelan et al, 2020;Huang et al, 2018). The addition of a number of different nucleophiles to compound II has previously been reported, including amines (Phelan et al, 2020), azide, and cyanide (Eisenstadt, 1975).…”

Synthesis of 7-azabicyclo[4.3.1]decane ring systems from tricarbonyl(tropone)iron via intramolecular Heck reactions

“…As such, novel approaches to the synthesis of these motifs have attracted considerable interest. The synthesis of azapolycycles containing a seven-membered carbocyclic ring is particularly challenging in contrast to comparable skeletons containing only five- or six-membered rings [ 3 ]. Thus, comparatively few general methods exist for accessing these scaffolds, even though they are found within a number of biologically active alkaloids.…”

Synthesis of 7-azabicyclo[4.3.1]decane ring system from tricarbonyl(tropone)iron via intramolecular Heck reactions

“…As such, novel approaches to the synthesis of these motifs have attracted considerable interest. The synthesis of azapolycycles containing a seven-membered carbocyclic ring is particularly challenging in contrast to comparable skeletons containing only five-or sixmembered rings [3]. Thus, comparatively few general methods exist for accessing these scaffolds, even though they are found within a number of biologically active alkaloids.…”