Photoexcited Palladium-Catalyzed Deracemization of Allenes.

The different enantiomers of specific chiral molecules frequently exhibit disparate biological, physiological, or pharmacological properties. Therefore, the efficient synthesis of single enantiomers is of particular importance not only to the pharmaceutical sector but also to other industrial sectors, such as agrochemical and fine chemical industries. Deracemization, a process during which a racemic mixture is converted into a nonracemic product with 100% atom economy and theoretical yield, is the most straightforward method to access enantioenriched molecules but a challenging task due to a decrease in entropy and microscopic reversibility. Axially chiral allenes bear a distinctive structure of two orthogonal cumulative π-systems and are acknowledged as synthetically versatile synthons in organic synthesis. The selective creation of axially chiral allenes with high optical purity under mild reaction conditions has always been a very popular and hot topic in organic synthesis but remains challenging. Herein, a photoexcited palladium-catalyzed deracemization of nonprefunctionalized disubstituted allenes is disclosed. This method provides an efficient and economical strategy to accommodate a broad scope of allenes with good enantioselectivities and yields (53 examples, up to 96% yield and 95% ee). The use of a suitable chiral palladium complex with visible light irradiation is an essential factor in achieving this transformation. A metal-to-ligand charge transfer mechanism was proposed based on control experiments and density functional theory calculations. Quantum mechanical studies implicate dual modes of asymmetric induction behind our new protocol: (1) sterically controlled stereoselective binding of one allene enantiomer under the ground-state and (2) facile, noncovalent interaction-driven excited-state isomerization toward the opposite enantiomer. The success of this newly established photochemical deracemization strategy should provide inspiration for expansion to other multisubstituted allenes and will open up a new mode for enantioselective excited-state palladium catalysis.

Enantioselective Hydroaminoalkylation of Azaaryl Ketones through Asymmetric Photoredox Catalysis.

An enantioselective hydroaminoalkylation of azaaryl ketones under a transition-metal-free asymmetric photoredox catalysis platform is reported. A series of valuable azaarene-functionalized 1,2-amino alcohols featuring attractive quaternary carbon stereocenters have been synthesized in high yields with good to excellent enantioselectivities. The viability of readily accessible N-aryl glycines as reaction partners facilitates the conjugate modification of these products into important derivatives, thereby enhancing the synthetic utility of the current approach.

Enantioselective Radical SN2-Type Alkylation of Morita-Baylis-Hillman Adducts Using Dual Photoredox/Palladium Catalysis.

An enantioselective radical alkylation of 4-alkyl-1,4-dihydropyridines with Morita-Baylis-Hillman (MBH) adducts has been reported. The SN2-type products are predominant. This reaction is enabled by dual photoredox/palladium catalysis. The alkylation products are provided in good yields with good regio- and enantioselectivity. The use of Ding's spiroketal-based bis(phosphine) (SKP) ligand is crucial to achieving satisfactory regio- and enantioselectivity. The resultant α,ß-unsaturated ester can be easily reduced to a synthetically useful chiral allyl alcohol.

Organocatalytic Enantioselective Protonation for Photoreduction of Activated Ketones and Ketimines Induced by Visible Light.

The first catalytic asymmetric photoreduction of 1,2-diketones and α-keto ketimines under visible light irradiation is reported. A transition-metal-free synergistic catalysis platform harnessing dicyanopyrazine-derived chromophore (DPZ) as the photoredox catalyst and a non-covalent chiral organocatalyst is effective for these transformations. With the flexible use of a chiral Brønsted acid or base in H+ transfer interchange to control the elusive enantioselective protonation, a variety of chiral α-hydroxy ketones and α-amino ketones were obtained with high yields and enantioselectivities.

Catalytic Enantioselective γ-Selective Additions of 2-Allylazaarenes to Activated Ketones.

Reported herein is the first example of 2-allylazaarenes in asymmetric catalysis. Highly γ-selective allylation was demonstrated for activated ketones, including isatins and trifluoromethyl ketones. In the presence of either an amino-acid-based tertiary amine or quaternary ammonium salt catalyst, two series of tertiary hydroxy-containing moieties were installed at the remote δ-position of azaarenes in good chemical yields, excellent enantioselectivities, and E/Z ratios. The success of current γ-selective reactions should provide inspiration for expansion to other allylazaarene derivatives and would open up new paradigms for the synthesis of chiral γ- and/or δ-functionalized azaarenes.

A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol Reaction of Homoallylic Alcohols.

Reported is a rationally-designed one-pot sequential strategy that allows homoallylic alcohols to be employed in a catalytic, asymmetric, direct vinylogous aldol reaction with a series of activated acyclic ketones, including trifluoromethyl ketones, γ-ketoesters, and α-keto phosphonates, in high yields (up to 95%) with excellent regio- and enantio-selectivity (up to 99% ee). This modular combination, including Jones oxidation and asymmetric organocatalysis, has satisfactory compatibility and reliability even at a 20 mmol scale, albeit without intermediary purification.

Organocatalytic Enantioselective Vinylogous Aldol Reaction of Allyl Aryl Ketones to Activated Acyclic Ketones.

The first catalytic asymmetric vinylogous aldol reaction of activated allyls to activated acyclic ketones is disclosed. A variety of activated acyclic ketones, such as trifluoromethyl ketones, α-ketoesters, and α-keto phosphonates, were found to be involved forming diverse γ-selective aldol adducts with high enantioselectivities (up to >99% ee). The method provides an effective, general strategy to access valuable chiral electron-withdrawing group-substituted tertiary hydroxyl-based carboxylic acids.

L-Amino Acid Based Urea-Tertiary Amine-Catalyzed Chemoselective and Asymmetric Stereoablative Carboxylation of 3-Bromooxindoles with Malonic Acid Half Thioesters.

An L-amino acid based urea-tertiary amine-catalyzed enantioselective stereoablative carboxylation of 3-bromooxindoles with malonic acid half thioesters (MAHTs) and diverse commercially available carboxylic acids has been developed. A series of valuable 3-substituted 3-hydroxy-2-oxindoles were obtained in high enantioselectivities (up to 93% ee). This chemoselective reaction represents the first example of MAHTs as carboxylating agents.