Sequential Visible-Light Photoactivation and Palladium Catalysis Enabling Enantioselective [4+2] Cycloadditions

Abstract

Catalytic asymmetric cycloadditions of reactive ketene intermediates provide new opportunities for the production of chiral heterocyclic molecules. Though known for over 100 years, ketenes still remain underexplored in the field of transition-metal (TM)-catalyzed asymmetric cycloadditions because (1) ketenes, as highly electron-deficient species, are possibly unstable to low-valence TMs (i.e., decarbonylation or aggregation) and (2) the conventional thermal synthesis of ketenes from acyl chlorides and amines may be incompatible with TM catalysis (i.e., reactive acyl chloride and amine hydrochloride byproducts). Herein, we detail the unprecedented asymmetric [4+2] cycloaddition of vinyl benzoxazinanones with a variety of ketene intermediates via sequential visible-light photoactivation and palladium catalysis. It is well demonstrated that the traceless and transient generation of ketenes from α-diazoketones through visible-light-induced Wolff rearrangement is important for the success of present cycloaddition. Furthermore, chiral palladium catalysts with a new, chiral hybrid P, S ligand enable asymmetric cycloaddition with high reaction selectivity and enantiocontrol.

Synergetic iridium and amine catalysis enables asymmetric [4+2] cycloadditions of vinyl aminoalcohols with carbonyls

“…Among existing methods for synthesizing chiral hydroquinolines, catalytic asymmetric [4+2] cycloadditions stand out as one of the most streamlined approaches 45–49 . As part of our ongoing studies on the synthesis of heterocycles via TM-catalyzed cycloadditions 15,50–55 , in this work, we plan to develop reaction methodologies that utilize readily available reagents and feature good selectivity and high synthetic efficiency. A detailed description of a possible mechanism is outlined in Fig.…”

“…of H 2 O as additives, gave hemiaminal 4aa as a white solid in 92% yield; 4aa can be further oxidized to desired hydroquinone 3aa by PCC in 67% yield with 99% ee and >19:1 dr. The absolute configuration of product 3aa was determined by comparing the chiral HPLC spectra with a previous literature 55 . To circumvent the isolation of intermediate 4aa , we adopted an improved procedure that simply combined these two processes in one pot.…”

Inverse‐Electron‐Demand Palladium‐Catalyzed Asymmetric [4+2] Cycloadditions Enabled by Chiral P,S‐Ligand and Hydrogen Bonding

“…In our efforts towards transition metal catalyzed dipolar cycloadditions, we have developed chiral hybrid P,S‐ligands for the asymmetric [4+2] cycloaddition of vinyl carbamates with electrophilic dipolarophiles (EDs), namely, normal‐electron‐demand cycloadditions (Scheme b) . In this work, we further exploited the potential of these ligands in the Pd‐catalyzed asymmetric [4+2] cycloaddition of vinyl carbamates and a nucleophilic dipolarophile (NuD), namely, inverse‐electron‐demand cycloadditions (Scheme c) .…”

“…Given the importance of chiral ligands for the reaction efficiency and enantioselectivity, this study began with the evaluation of our chiral hybrid P,S‐ligands for cycloaddition between the the vinyl carbamate 1 a and deconjugated butenolide 2 a (Table ) . Initially, the combination of Pd 2 (dba) 3 ⋅CHCl 3 and either the chiral P,S‐ligand L1 or L2 , the two catalyst systems that showed good catalytic efficiency and high stereoinduction in our previous Pd‐catalyzed NEDC reactions, was chosen to check the proposed cycloaddition. To our delight, the desired products 3 aa were indeed afforded in good yields and with moderate enantioselectivities (entries 1 and 2).…”

Palladium‐Catalyzed Decarboxylative Asymmetric Allylic Alkylation: Development, Mechanistic Understanding and Recent Advances

“…The authors suggest that the intramolecular allylation, which follows a reversible Michael addition, controls the selectivity. Xiao recently reported the decarboxylative [4+2] cycloaddition of ketene intermediates 272 with benzoxazinanones 217 (Scheme B) . Interception of the ketenes 272 generated in situ by a photolytic Wolff rearrangement led to the formation of chiral quinolinones 273 in excellent yields and stereoselectivities (up to 96% ee and >95:5 dr ).…”