Enantioselective Tertiary Electrophile (Hetero)Benzylation: Pd‐Catalyzed Substitution of Isoprene Monoxide with Arylacetates**

Abstract

The enantioselective generation of quaternary carbon centers remains challenging but is of growing importance for the preparation of functional molecules. Metal catalyzed allylic alkylations of tertiary electrophiles can provide access to these substructures but remain generally incompatible with organometallic benzyl nucleophiles. Here we demonstrate that electron-deficient arylacetates can serve as benzyl nucleophile surrogates to generate enantioenriched acyclic molecules containing a quaternary carbon center via a two-step substitution-decarboxylation process using isoprene monoxide. Products are often obtained in > 90 % ee using a commercially available catalyst. An array of electron-withdrawing functional groups on the arylacetate moiety are tolerated. The lactone generated by the initial substitution reaction can be used in further stereoselective transformations to prepare molecules with acyclic vicinal quaternary stereocenters.

Iridium‐Catalyzed Asymmetric Allylic Benzylation with Photogenerated Hydroxy‐o‐Quinodimethanes

“…In addition, the incorporation of the electron‐withdrawing group in the benzyl position of the substrate is another strategy for increasing the acidity of the benzylic proton [4j–l] . In this regard, the Lundgren group reported an asymmetric allylic benzylation reaction with aryl acetic acids as nucleophiles, followed by the decarboxylation to give the benzylated products [4k–m] . Very recently, the Yu group reported an elegant method adopting dual photoredox/palladium catalysis, in which benzyl radical generated from Hantzsch ester could serve as a formal nucleophilic reagent [4n–o] .…”

Palladium-Catalyzed Tsuji-Trost-Type Vinyl Epoxide Cross-Coupling with Umpolung Hydrazones

“…23,24 In 2021, Lundgren and his coworkers reported a Pd-catalyzed benzylation of isoprene with 2,2,2-trifluoroethyl (hetero)arylacetate ester enolates to generate lactone intermediates that were subjected to subsequent hydrolysis and decarboxylation to form the branched homoallylic alcohol. 25 These 2-alkyl-β-γ-unsaturated alcohol products also possess high synthetic value, as their derivatives appear as core motifs of various natural products and bio-active compounds, such as berkleasmins and hyperolactones (Figure 1C). 26,27 Although these methods provide highly efficient routes for the synthesis of these alcohols, pre-functionalized and commercially unavailable starting materials hinder the applicability of these methods.…”

A synthesis of fuctionalized 2-amino-3-cyano pyrroles from terminal alkynes, sulfonyl azides and phenacylmalononitriles

“…Although a myriad of classical methods of pyrrole synthesis, including the Paal–Knorr condensation, 12 a the Knorr reaction, 12 b the Hantzsch reaction, 12 c transition metal-catalyzed reactions, 13 multicomponent coupling reactions, 14 and intramolecular cyclization of N -propargylamines 15 for the synthesis of pyrroles have been developed over many years, the efficient synthesis of functionalized pyrroles is still challenging. Therefore, a straightforward, convenient, and highly regioselective route to synthesize pyrrole derivatives using basic chemical materials is attractive.…”