Iridium-catalyzed regioselective decarboxylative allylation of β-ketoacids: efficient construction of γ,δ-unsaturated ketones

Abstract

A highly regioselective protocol for the direct synthesis of γ,δ-unsaturated ketones from β-ketoacids and allylic alcohols was proposed and accomplished relying on the combination of [Ir(cod)Cl]2 and 10-camphorsulfonic acid via decarboxylative allylation.

Metal-Catalyzed Ionic Decarboxylative Cross-Coupling Reactions of C(sp3) Acids: Reaction Development, Mechanisms, and Application

“…Cai and co-workers established that mixtures of [Ir(COD)Cl] 2 and camphorsulfonic acid (CSA) catalyze the decarboxylative alkylation of α-aryl branched allylic alcohols (Figure 21). 42 This approach is a particularly efficient method to prepare allyl ketone products as neither activation of the carboxylate or the alcohol is required for reactivity. Both aryl and alkyl β-keto acids, including those with reactive groups such as aryl iodides, can be used as substrates.…”

Arylboronic Acid Catalyzed Dehydrative Mono-/Dialkylation Reactions of β-Ketoacids and Alcohols

“…The alkylation reaction is one of the most efficient tools to build up molecular complexity and synthesize pharmaceutical agents . Remarkable progress has been made over the past several decades with the employment of diverse alkylating reagents. − Among them, the direct dehydration of alcohol is intrinsically environmentally friendly with H 2 O being the sole byproduct, which makes it a priority choice for alkylation reactions and has been extensively studied in many groups . However, the dehydration process usually proceeds under harsh conditions as hydroxyl is a “bad leaving group” .…”

The Enantioselective Intermolecular Saegusa Allylation

“…22,23 In 2015, the Cai group reported an Ir-catalyzed decarboxylative allylation reaction using benzyl alcohol substrates to generate branched products (>30:1, b:l). 24 These reports detailed racemic reactions, however, Lundgren published an elegant catalytic enantioselective benzylation to produce tertiary carbon stereocenters, whereby decarboxylation seems to follow the allylation instead of preceding it. 25 Despite these advances, the Saegusa reaction does not appear to have been explored in the quest for catalytic enantioselective transformations.…”

“…For example, the Breit group demonstrated that mono- and 1,1-disubstituted terminal allenes could be used to access α-allylated ketones with branched tertiary and all-carbon quaternary centers, albeit in racemic form, under rhodium catalysis . By varying the ligand, it was discovered that alkynes could also be used as electrophiles. , In 2015, the Cai group reported an Ir-catalyzed decarboxylative allylation reaction using benzyl alcohol substrates to generate branched products (>30:1, b:l) . These reports detailed racemic reactions, however, Lundgren published an elegant catalytic enantioselective benzylation to produce tertiary carbon stereocenters, whereby decarboxylation seems to follow the allylation instead of preceding it .…”