Development and Applications of Double Diels‐Alder Reaction in Organic Synthesis

Abstract

The class of Double Diels‐Alder (DDA) reactions leading the targets concisely where numerous synthetic pursuits have been rewarded with conceptually novel and streamlined methods. After the tremendous development and discoveries in various Diels‐Alder reactions including its key role applications in many natural products syntheses, the DDA reaction is considered as a growing branch of Diels‐Alder reaction where two consecutive [4+2] cycloadditions trigger the streamlined construction of polycyclic and macrocyclic architectures. In light of the ever‐increasing importance of DDA reactions in chemical sciences, we review the comprehensive studies and recent advances in DDA reactions in organic synthesis. This review summarizes key achievements of DDA for the preparation of macrocyclic, bicyclic, heterocyclic, and polycyclic structures documented since its revelation in 1980 to 2020. Emphasis is put on the synthesis of various structural classes based on the selectivity of the DDA reaction.

Recent advances in cascade reactions and their mechanistic insights: a concise strategy to synthesize complex natural products and organic scaffolds

“…The divulged procedures throughout the diversified branch of organic synthesis are of considerable interest, making these endeavours among the most intriguing methods of synthetic chemistry, particularly in natural product synthesis, for proficiently assembling complex skeletons and holding great promise for future discoveries. 110 Furthermore, the review covers a wide variety of approaches that have been tweaked to enable proficiency in accessing a wide range of natural products and synthetically significant classes, emphasizing the cascade tool's versatility in organic synthesis. The classification will highlight the complexity in organic synthesis protocol based on the genre of type of cascade to access molecular frameworks in quick access using the key step as a cascade reaction.…”

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“…depending upon the type of cascade to yield targeted fascinating structural frameworks. 7 Thus, cascades involving [3+2] cycloaddition reactions are important as they can exploit the formed five-membered ring with further functionalization and increase the scope of unpredicted and marvelous synthesis of encumber organic scaffolds. 8,9 Whenever a 1,3-dipole reacts with a dipolarophile, there are chances of subsequent reactions in substituted molecules as the formed five-membered ring can act as a core skeleton and the generated intermediates can play around with other functionalities present in the molecule Alois Fürstner before he was offered an assistant professor position at IIT Jodhpur.…”

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

“…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.…”

“… 28 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. 29 − 31 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. 32 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.…”