Iridium‐Catalyzed, Enantioselective, Allylic Alkylations With Carbon Nucleophiles

Abstract

Iridium‐catalyzed, enantioselective allylic alkylation is a powerful method for the construction of a stereogenic center adjacent to a vinyl group. The starting materials are readily available, generally either branched allylic alcohols or esters of linear allylic alcohols. The reaction is compatible with a wide variety of functional groups and generally proceeds with very high enantio‐ and site selectivity. Mechanistic aspects, as well as reaction methods, are presented in detail. The scope of the method is defined primarily by the nucleophilic component. Compounds that are CH‐acidic, such as malonic acid derivatives, β‐keto esters, iminoglycinates, azlactones, aliphatic nitro compounds, and sulfones are employed, often without stoichiometric amounts of base. Diastereomers are formed in the case of prochiral nucleophiles; the control of diastereoselectivity by dual catalysis, using both an iridium and an organocatalyst, is very efficient. Other nucleophilic components include silyl enol ethers, enamines, alkenes, and arenes, in particular, heterocycles. The application of the latter in cyclization reactions, such as polyene cyclizations and dearomatizations, furnishes highly complex structures with excellent stereocontrol. Finally, applications in natural product synthesis and medicinal chemistry are presented, as well as experimental procedures.

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

“…In 2022, an alternative ligand was used in the alkynylation of allyl alcohols toward chiral enynes, as disclosed by Wong and Cui . Comprehensive reviews on enantioselective allylic substitution via iridium catalysis have been published, with You detailing advancements prior to 2018 , and Takeuchi detailing advancements between 2018 and 2022 …”

Recent advances in iridium-catalyzed enantioselective allylic substitution using phosphoramidite-alkene ligands

“…Stabilized enolates such as malonates, β-ketoesters, β-sulfonylacetates and disulfones have been studied as representative carbon nucleophiles for Ir-catalyzed enantioselective allylic alkylation. 26,27 However, unstabilized enolates are still a challenging target. Cao reported enantioselective allylation with vinyl azides as an acetoamide enolate or an acetonitrile carbanion surrogate (Scheme 9).…”

“…[21][22][23][24][25] Two comprehensive reviews on Ir-catalyzed allylic substitution were published in the winter of 2018 26 and summer of 2019. 27 With these two comprehensive reviews, we can follow the advances in Ir-catalyzed enantioselective allylic substitution up until around 2018. This chemistry has grown rapidly since then.…”

Enantioselective Synthesis of Skipped Dienes via Iridium-Catalyzed Allylic Alkylation of Phosphonates

“…Cinnamyl carbonates bearing an electron-deficient arene ring ( 2h – j ) also fared well under our reaction conditions (entries 8–10). Against the usual trend of the catalyst system employed herein, o -methoxycinnamyl carbonate 2k reacted smoothly to afford the desired product in decent yield and with good enantioselectivity (entry 11). However, the deleterious effect of the ortho -substitution was obvious from the comparative outcome of the reactions with the two isomeric dichloro-substituted cinnamyl carbonates 2l and 2m (entries 12 and 13).…”