Annulative Allylic Alkylation Reactions between Dual Electrophiles and Dual Nucleophiles: Applications in Complex Molecule Synthesis

Abstract

Metal-catalyzed allylic alkylation reactions between dual nucleophiles and dual electrophiles represent ap owerful set of methodsf or the synthesis of small-, medium-, and even large-sized rings. Using this strategy,ahandful of simple allylic diol derivatives can be transformed into a broad array of complexc arbo-and heterocycles of varying ring sizes in just as ingle step. Because of their ability to rapidly generate complexity, annulative allylic alkylationr eactions between dual nucleophiles and dual electrophiles have been extensively employed in the total synthesis of both naturalp roducts and pharmaceuticalcompounds.Scheme1.GeneralScheme for metal-catalyzed allylic alkylation.Scheme2.GeneralScheme for annulative allylic alkylation reactionsu sing a dual electrophile.Scheme3.Differenttypesofa nnulativeallylic alkylation reactions.Scheme4.GeneralScheme for allylic alkylation reactionsi nvolving 1,1-substitutions.

Pd-Catalyzed Formal [3 + 3] Heteroannulation of Allylic gem-Diacetates: Synthesis of Chromene-Based Natural Products and Exploration of Photochromic Properties

“…The allylic gem -diacetates D are rarely employed substrates under palladium catalysis . Trost and Lee demonstrated the synthetic utility of D in the formation of chiral allyl acetates and subsequently the 1,3-dicationic behavior of D through stepwise elaborations .…”

Pd‐Catalyzed Chemoselective Bis‐Allylic Substitution of Allylic Dicarbonates with Arylated Nitromethanes: A Route to 1,2‐Oxazine N‐Oxides

“…Transition metal‐catalyzed bis ‐allylic substitution of dual allylic donors with dual nucleophiles is a useful approach to construct structurally distinct cyclic compounds [7] . Allylic donors derived from 2‐methylenepropane‐1,3‐diol are one of the most prevalent dual substrates for this type of transformation to construct various functionalized carbo‐ and heterocycles (Scheme 1a) [8] .…”

Total Synthesis in the Trost Laboratories: Selected Milestones From the Past Twenty Years

“…This route remains the shortest to date and highlights the incredible efficiency of the key annulative allylic alkylation cascade. In addition to being a powerful tool for rapidly constructing polycyclic systems, [56] this transformation enabled Trost and Dong to prepare both enantiomers of agelastatin A by changing nucleophiles rather than by reversing the chirality of L2 – a creative and unorthodox approach.…”