Cascade polycyclizations in natural product synthesis

Abstract

Cascade (domino) reactions have an unparalleled ability to generate molecular complexity from relatively simple starting materials; these transformations are particularly appealing when multiple rings are forged during this process. In this tutorial review, we cover recent highlights in cascade polycyclizations as applied to natural product synthesis, including pericyclic, heteroatom-mediated, cationic, metal-catalyzed, organocatalytic, and radical sequences.

Gold(I)‐Catalysis for the Synthesis of Terpenoids: From Intramolecular Cascades to Intermolecular Cycloadditions

“…Armed with this mechanistic background, we decided to examine the scope and limitations of gold(I)‐catalyzed cycloisomerizations and related processes for the construction of different carbocyclic skeletons, by using differently functionalized 1,n‐enynes as substrates in the development of complex cascade cyclizations, a type of transformations that has found widespread application in natural product synthesis ,. A final goal was to move forward from intramolecular to more challenging intermolecular reactions between alkynes and alkenes, particularly in the context of asymmetric catalysis.…”

Ruthenium‐Catalyzed Cascade Annulation of Indole with Propargyl Alcohols

“…[1] This atom-economic approach to the one-pot synthesis of complex molecular scaffolds from readily available starting materials improves practical efficiency in synthesis and provides rapid access to intricate molecular structures. [1] This atom-economic approach to the one-pot synthesis of complex molecular scaffolds from readily available starting materials improves practical efficiency in synthesis and provides rapid access to intricate molecular structures.…”

“…The rapid production of molecular complexity by transitionmetal-catalyzed cascade reactions facilitates the preparation of natural-product-inspired frameworks and drug-like molecules,which are important lead structures in the development of bioactive compounds. [1] This atom-economic approach to the one-pot synthesis of complex molecular scaffolds from readily available starting materials improves practical efficiency in synthesis and provides rapid access to intricate molecular structures. [2] Annulated indole derivatives such as cyclopenta [b]indoles,c arbazoles,o rc yclohepta [b]indoles occupy ap rominent position among bioactive natural products and pharmaceutically important compounds.…”

Intramolecular Pd‐Catalyzed Formal anti‐Carboalkoxylation of Alkynes: Access to Tetrasubstituted Enol Ethers

“…Dicarbofunctionalizations of internal alkynes by the addition of two carbon moietiest oac arbon-carbon triple bond have paved the way to numerous products with embeddedt etrasubstituted alkene units.F or this purpose, several transitionmetal-catalyzed approaches have been developed;i np articular,P dc atalysis has proved av ery powerful method.I nitially, carbopalladation reactions of alkynes were integrated in cascades (domino processes) [1] leading to steroid derivatives and highly substituted arenes. [2,3] Recently,n ovel domino processes with one or several carbopalladationsa sk ey reactions have been designed affording highly complex natural products or natural product analogs, [4] and also other more specific targets such as spirocycles, [5] (oligo)cyclic compounds, [6] dibenzopentafulvalenes, [7] helical oligoenes, [8] fenestranes, [9] persubstituted cyclooctatetraenes, [10] and molecular switches. [11] Because the emerging organopalladium species, which is formed at the beginningo fs uch ac ascade,c ommonly attackst he carboncarbon triple bond in a syn-fashion, both residues are located at the same side of the newly generated double bond.…”