Recent Advances in [3+2]-Cycloaddition-Enabled Cascade Reactions: Application to Synthesize Complex Organic Frameworks

Abstract

Many natural products and biologically important complex organic scaffolds have convoluted structures around their core skeleton. Interestingly, with just changing the outskirts, the core reflects new and unique degrees of various physical and chemical properties. A very common but intriguing core is a five-membered ring horning heaps of organic molecules crafts. The power of [3+2] cycloaddition reactions to generate five-membered ring systems allocate chemists to envision synthetic procedures of wonder molecules and if it is facilitating a cascade sequence, then the end product will imbibe significant level of complexity having applications in medicinal and pharmaceutical fields. This Account highlights the broad interest in assembling recent advances in cascade reactions involving [3+2] cycloaddition as the power tool in order to conceive breakthrough organic architectures reported in the last ten years. We foresee that our comprehensive collection of astonishing [3+2] cycloaddition enabled cascades will provide valuable insights to polycyclic molecular construction and perseverant approach towards nonconventional synthetic procedures to the organic community.1 Introduction2 Synthesis of Oxindoles Skeleton3 Synthesis of Oxazoles Skeleton4 Synthesis of Oxadiazoles Skeleton5 Synthesis of Nitrogen-Containing Heterocycles6 Synthesis via Formal [3+2] Cycloaddition7 Synthesis of Miscellaneous Scaffolds8 Conclusion

[RhCp*Cl2]2-Catalyzed Indole Functionalization: Synthesis of Bioinspired Indole-Fused Polycycles

“…The selected topic is encouraging because functionalization has received less attention than the synthesis of indole, especially in terms of catalytic conversions, and a huge number of compilations have been devoted to it. This work aims to highlight recent advancements, focusing on creating unique, stable carbon–carbon and carbon–hetero bonds (based on our expertise in assembling C–C bonds) to create scaffolds inspired by polycyclic indoles. − The most effective ways to functionalize indoles are through catalyst-controlled chemo-divergent synthesis, oxidative cascade annulations, oxidative [4 + 2] annulations, reductive aromatization, and dearomatization via cross-coupling reaction over preactivated indole derivatives. These methods are well-illustrated using Rh­(III) catalysis pathways.…”

“…After the discovery of the parent core, the initial studies revolved around synthesizing the core skeletal system; nevertheless, more recent progress focuses on functionalizing the parent core to create biologically pertinent scaffolds using advanced synthetic procedures, including photoredox/transition metal catalysis . Recently, transition metals like Pd, Rh, Ru, and others have been used with a variety of directing group associations, such as carbonyls, sulfones, amides, etc. − The construction of a pyrrole ring and incorporation of a benzene ring in an existing pyrrole core fall under two major categories: synthesis and functionalization of indoles . Numerous techniques exist for functionalizing indole, but the best-known synthetic approaches with the most significant contributions are Fischer–Jourdan, Madelung, Batcho–Leimgruber, and Gassman. − However, some exceptions render the prominent growth in the indole functionalization, such as the need for prefunctionalization of the substrate, nonscalability of the protocol, and regio- and stereoselective concerns.…”

Metal-free transfer hydrogenation/cycloaddition cascade of activated quinolines and isoquinolines with tosyl azides

“…Conversely, the cascade reactions that address the key synthetic challenges while exploiting the reactive intermediates are highly attractive to increase molecular complexity. 3 Such a strategy avoids the preparation and isolation of unstable precursors, thereby reducing the number of steps. With the potential of cascade dearomatization strategies, notable transformations have been accomplished utilizing activated heteroarenes.…”