Asymmetric Cascade Annulation Based on Enantioselective Oxa-Diels–Alder Cycloaddition of in Situ Generated Isochromenyliums by Cooperative Binary Catalysis of Pd(OAc)₂ and (S)-Trip

Abstract

An asymmetric cascade annulation between 2-hydroxystyrenes and 2-alkynylbenaldehyes or 1-(2-alkynylphenyl)ketones has been established with good to excellent enantioselectivities (up to >99.5% ee), on the basis of an enantioselective oxa-Diels-Alder cycloaddition of in situ generated metallo-isochromenylium intermediates, by cooperative binary catalysis of Pd(OAc)2 and (S)-Trip. The developed methodology is workable for a broad spectrum of substrates and shows great efficiency in establishing dense multiple chiral centers including quaternary carbons of variable bridged ring systems. The mechanism study suggests that (S)-Trip plays multiple roles in assembling the reactants and controlling the stereoselectivity.

Enantioselective cooperative catalysis

“…Subsequently, the addition of In 2012, Ibrahem, Córdova and coworkers reported chemo-and enantioselective direct α-allylic alkylation of aldehydes with allylic acetates using Pd(0)/secondary amines catalysts (Scheme 23). 26 In principle, the mechanism of the reaction is similar to that reported by List 29 Controlled study revealed that suitable counteranion on Pd had a special effect: when Pd(OAc) 2 was replaced with PdCl 2 , the product was not obtained. When the styrene whose hydroxyl group was protected with -Me group was used as substrate, no product formation was observed indicating ortho-phenolic hydroxyl group is essential for the reaction to …”

Chiral Silver Phosphate Catalyzed Transformation of ortho‐Alkynylaryl Ketones into 1H‐Isochromene Derivatives through an Intramolecular‐Cyclization/Enantioselective‐Reduction Sequence

“…[6,7] Indeed, successful examples are quite limited and have been based on the use of metal catalysts with electronically neutral chiral ligand(s). [8,9] To develop such a catalytic enantioselective transformation, we took advantage of the chemical properties of the isobenzopyrylium ion; notably, the formation of ion-pair salts between the isobenzopyrylium ion and less nucleophilic counteranions. [8,9] To develop such a catalytic enantioselective transformation, we took advantage of the chemical properties of the isobenzopyrylium ion; notably, the formation of ion-pair salts between the isobenzopyrylium ion and less nucleophilic counteranions.…”

Chiral Copper(II) Phosphate Catalyzed Enantioselective Synthesis of Isochromene Derivatives by Sequential Intramolecular Cyclization and Asymmetric Transfer Hydrogenation of o‐Alkynylacetophenones

“…Intramolecular cyclization initiated by activation of the alkyne moiety using transition-metal catalysis has been extensively investigated, [4] and cyclized metal-containing intermediates could also be employed for further reactions in a tandem manner. [8] Although a CPA (1)-catalyzed transfer hydrogenation of imines using a hydrogen donor has been recently developed by many research groups, [9] the application of this method for ketones, in place of imines, is limited to a few examples. [5] Transition-metal-containing carbonyl ylides are highly reactive intermediates, which are generated by 6-endo-dig cyclization reactions of alkynyl carbonyl compounds.…”

“…[8] Although a CPA (1)-catalyzed transfer hydrogenation of imines using a hydrogen donor has been recently developed by many research groups, [9] the application of this method for ketones, in place of imines, is limited to a few examples. [8] Although a CPA (1)-catalyzed transfer hydrogenation of imines using a hydrogen donor has been recently developed by many research groups, [9] the application of this method for ketones, in place of imines, is limited to a few examples.…”