Merging Ring-Opening 1,2-Metallate Shift with Asymmetric C(sp3)-H Borylation of Aziridines.

Chiral secondary alkyl amines with a vicinal quaternary stereocenter are undoubtedly important and ubiquitous subunits in natural products and pharmaceuticals. However, their asymmetric synthesis remains a formidable challenge. Herein, we merge the ring-opening 1,2-metallate shift with iridium-catalyzed enantioselective C(sp3)-H borylation of aziridines to deliver these frameworks with high enantioselectivities. We also demonstrated the synthetic application by downstream transformations, including the total synthesis of two Amaryllidaceae alkaloids, (-)-crinane and (+)-mesmebrane.

Unveiling the Selectivity of Ru(II)-Catalyzed C-H Activation for Defluorinative Cyclization of 2-Arylbenzimidazole and Trifluoromethyl Diazo: A DFT Study.

The synthesis of monofluorinated heterocyclic compounds by C-H activation combined with defluorination is useful. Studies on the reaction mechanism and selectivity have shown that these processes play a positive role in promoting the development of monofluorinated reactions. Density functional theory (DFT) calculations were performed to investigate the mechanism and selectivity of Ru(II)-catalyzed 2-arylbenzimidazole with trifluoromethyl diazo. DFT calculations showed that C-H activation occurs through a concerted metalation/deprotonation (CMD) mechanism. After that, deprotonation and defluorinative cyclization are assisted by acetate and trifluoroethanol (TFE). Further mechanistic insights through noncovalent interaction (NCI) analysis were also obtained to elucidate the origin of the selectivity in the defluorination process.

Chiral Phosphine Ligands of COAP and SKP Switched Regiodivergent Asymmetric Allylic Alkylation of MBH Adducts.

The palladium-catalyzed highly regioselective asymmetric allylic alkylation of 3'-indolyl-3-oxindole derivatives with Morita-Baylis-Hillman (MBH) carbonates was developed to facilely construct chiral 3,3'-bisindole derivatives under mild reaction conditions. The regioselectivity (α/γ) of MBH carbonates was efficiently switched in the presence of chiral oxalamide phosphine or spiroketal-based diphosphine/Pd(0) complexes as a chiral catalyst. A series of multifunctional 3,3'-bisindole derivatives with all-carbon quaternary stereogenic centers were obtained in high yields with good to excellent enantio-, diastereo-, and regioselectivity. The present process is endowed with some salient features such as broad substrate scope, N-protecting group-free, excellent stereoselectivity, as well as adjustable regioselectivity.

COAP-Pd Catalyzed Asymmetric Allylic Alkylation of Azlactones with MBH Carbonates: Access to Unnatural α-Quaternary Stereogenic Glutamic Acid Derivatives.

A palladium-catalyzed regioselective and asymmetric allylic alkylation of azlactones with MBH carbonates has been developed with chiral oxalamide-phosphine ligands. The corresponding reaction afforded a range of optically active γ-arylidenyl glutamic acid derivatives bearing an α-chiral quaternary stereocenter in good yields with excellent linear regio- and high enantioselectivity. This protocol furnishes an alternative approach for the construction of enantio-enriched unnatural α-amino acid derivatives.

Box-copper catalyzed cascade asymmetric amidation for chiral exo-methylene aminoindoline derivatives.

Enantioselective copper-catalyzed cascade inter- and intramolecular amidation was achieved between ethynyl benzoxazinanones and α-halohydroxamates in the presence of an indapybox ligand. The one-pot cascade transformation was triggered by the attack of hydroxamates to dipolar copper-allenylidene intermediates, followed by a nucleophilic annulation reaction. Thus, a series of exo-methylene 3-aminoindoline derivatives were obtained in good yields with high enantioselectivities under mild reaction conditions.

Pd-Catalyzed Asymmetric Dearomative Cycloaddition for Construction of Optically Active Pyrroloindoline and Cyclopentaindoline Derivatives: Access to 3a-Aminopyrroloindolines.

Asymmetric dearomative [3 + 2] cycloaddition reactions of 3-nitroindoles with vinyl aziridine and vinyl cyclopropanes have been respectively successfully developed in the presence of a chiral box/Pd(0) complex. A series of enantiomerically enriched 3a-nitro-hexahydropyrrolo[2,3-b]indole and 8b-nitrohexahydrocyclopenta[b]indole derivatives containing three contiguous chiral centers are smoothly obtained in high yields with satisfactory regio-, chemo-, and enantioselectivity. Remarkably, the synthetic utility of this process was demonstrated through direct reductive amination and functionalization of the carbon-carbon double bond of the desired products.

Organocatalytic regioselective asymmetric Michael addition of azlactones to o-hydroxy chalcone derivatives.

The regioselective and enantioselective Michael addition between azlactones and o-hydroxy chalcone derivatives is reported. Enantiomerically enriched N,O-aminals with two continuous stereogenic centers are exclusively obtained in moderate to good yields with excellent diastereoselectivities and good to excellent enantioselectivities. The experimental results show that an o-hydroxy group on the cinnamenyl motif of chalcone derivatives plays a crucial role at the reaction sites for the regioselective Michael addition. In addition, circular dichroism (CD) spectroscopy and density functional theory (DFT) are used to investigate the absolute configuration of N,O-aminals and the corresponding transition-state structures.

Organocatalytic diversity-oriented asymmetric synthesis of tricyclic chroman derivatives.

The tandem oxo-Michael-IED/HDA and oxo-Michael-IED/HDA-Michael-Aldol condensation transformations between (E)-2-hydroxyaryl-2-oxobut-3-enoate derivatives with enals have been developed in the presence of (S)-diphenylprolinol trimethylsilyl ether as an organocatalyst. Two types of tricyclic chroman derivatives were, respectively, obtained, by adjusting the reactant ratio and reaction temperature, in good yields (up to 96%) with excellent enantioselectivities (up to >99%) and good diastereoselectivities (up to >30/1). It should be noted that the divergent chiral chroman derivatives were obtained by successive reaction of (E)-2-hydroxyaryl-2-oxobut-3-enoate derivatives with two different enal substrates in highly catalytic results.

Highly enantioselective phosphination and hydrophosphonylation of azomethine imines: using chiral squaramide as a hydrogen bonding organocatalyst.

Enantioselective phosphination and hydrophosphonylation reactions between azomethine imines and diarylphosphine oxides or dialkyl phosphites were respectively developed by the use of a chiral squaramide as the hydrogen bonding organocatalyst, which afforded two types of phosphorus containing product in high yields with good to excellent enantioselectivities.

Organocatalytic enantioselective construction of multi-functionalized spiro oxindole dienes.

A diastereo- and enantio-selective domino Michael-cyclization-tautomerization reaction of isatylidene malononitriles with α,α-dicyanoalkenes catalyzed by a cinchona alkaloid-derived bifunctional thiourea catalyst has been developed. A series of multi-functionalized spiro oxindole diene derivatives have been obtained in good to excellent yields (up to 97%) with good to excellent enantioselectivities (up to 96%) as well as good diastereoselectivities (up to 7.9 : 1). In addition, an anomalous temperature effect on the enantioselectivity has also been studied for this transformation.

Robust, Sprayable, and Multifunctional Hydrogel Coating through a Polycation Reinforced (PCR) Surface Bridging Strategy.

The sprayable hydrogel coatings that can establish robust adhesion onto diverse materials and devices hold enormous potential; however, a significant challenge persists due to monomer hydration, which impedes even coverage during spraying and induces inadequate adhesion post-gelation. Herein, a polycation-reinforced (PCR) surface bridging strategy is presented to achieve tough and sprayable hydrogel coatings onto diverse materials. The polycations offer superior wettability and instant electrostatic interactions with plasma-treated substrates, facilitating an effective spraying application. This PCR-based hydrogel coatings demonstrate tough adhesion performance to inert PTFE and silicone, including remarkable shear strength (161 ± 49 kPa for PTFE), interfacial toughness (198 ± 27 J m-2 for PTFE), and notable tolerance to cyclic tension (10 000 cycles, 200% strain, silicone). Meanwhile, this method can be applied to various hydrogel formulations, offering diverse functionalities, including underwater adhesion, lubrication, and drug delivery. Furthermore, the PCR concept enables the conformal construction of durable hydrogel coatings onto sophisticated medical devices like cardiovascular stents. Given its simplicity and adaptability, this approach paves an avenue for incorporating hydrogels onto solid surfaces and potentially promotes untapped applications.

COAP-Pd Catalyzed Asymmetric Formal [3+2] Cycloaddition for Optically Active Multistereogenic Spiro Cyclopentane-Indandiones Bearing Cyclic N-Sulfonyl Ketimine Skeletons.

We reported a chiral oxamide-phosphine ligand (COAP-Ph)-Pd-catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane compounds derived from 1,3-indanedione and 2-vinylcyclopropane-1,1-dicarboxylates with cyclic sulfonyl 1-azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane-indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo- and enantioselectivity. The COAP-Pd complex serves not only to promote generation of chiral π-allyl-palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction.

UV-Triggered Hydrogel Coating of the Double Network Polyelectrolytes for Enhanced Endothelialization.

The left atrial appendage (LAA) occluder is an important medical device for closing the LAA and preventing stroke. The device-related thrombus (DRT) prevents the implantation of the occluder in exerting the desired therapeutic effect, which is primarily caused by the delayed endothelialization of the occluder. Functional coatings are an effective strategy for accelerating the endothelialization of occluders. However, the occluder surface area is particularly large and structurally complex, and the device is subjected to a large shear friction in the sheath during implantation, which poses a significant challenge to the coating. Herein, a hydrogel coating by the in situ UV-triggered polymerization of double-network polyelectrolytes is reported. The findings reveal that the double network and electrostatic interactions between the networks resulted in excellent mechanical properties of the hydrogel coating. The sulfonate and Arg-Gly-Asp (RGD) groups in the coating promoted hemocompatibility and endothelial growth of the occluder, respectively. The coating significantly accelerated the endothelialization of the LAA occluder in a canine model is further demonstrated. This study has potential clinical benefits in reducing both the incidence of DRT and the postoperative anticoagulant course for LAA closure.

Organocatalytic asymmetric Michael addition of aliphatic aldehydes to indolylnitroalkenes: access to contiguous stereogenic tryptamine precursors.

Because of the importance of the indole framework and the versatile transformation of nitro and formyl groups, the efficient synthesis of optically pure 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanals, one type of tryptamine precursors are of great interest for pharmaceutical and biological research. Herein, the Michael addition of aliphatic aldehydes to indolylnitroalkenes has been developed using (S)-diphenylprolinol trimethylsilyl ether as an organocatalyst, which provides the desired optically pure syn 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanal derivatives in up to 98% yield with up to >99:1 dr and >99% ee. To show the synthetic usefulness of this methodology, optically active 2-alkyl-4-nitro-3-(1-tosyl-1H-indol-3-yl)butan-1-ol and tryptamine derivatives are readily obtained by stepwise systematic transformations.

A Class of Enantiomerically Pure Bis-oxamide Palladium Complexes: Modular Synthesis via Domino C(sp2)-H Bond Arylation and Photophysical Property.

A one-pot, five-step domino reaction was developed for the arylation of bis-oxamides derived from optically pure 1,2-diphenylethylenediamine, leading to the formation of a series of chiral bis-oxalamide palladium(II) complexes bearing tetraaryl-conjugated substituents in good yields. In addition, these palladium(II) complexes exhibited perceptible blue fluorescence under ultraviolet light irradiation.

COAP/Pd-Catalyzed Linear Asymmetric Allylic Alkylation for Optically Active 3,3-Disubstituted Oxindole Derivatives with a Four-Carbon Amino Side Chain.

An asymmetric linear selective allylic alkylation of vinylaziridines with 3-aryl oxindoles has been developed by using a chiral oxamide-phosphine (COAP-Bn-OMe-p)/palladium complex in methanol, which furnished a wide variety of 3,3-disubstituted oxindole derivatives in good yields with excellent regio- and enantioselectivities.

Enantioselective construction of multifunctionalized spirocyclohexaneoxindoles through organocatalytic Michael-Aldol cyclization of isatin derived alkenes with linear dialdehydes.

Optically active spirocyclohexaneoxindole motifs are very important building blocks for preparations of biologically active complexes, natural products, and pharmaceutical compounds. Herein, we report the syntheses of enantiopure spirocyclohexaneoxindoles through domino Michael-Aldol reactions between isatin derived alkenes and pentane-1,5-dial in the presence of diphenylprolinol silyl ether as an aminocatalyst. As a result, a series of multistereogenic and functionalized spirocyclohexaneoxindoles have been obtained in good yields with moderate diastereoselectivities and excellent enantioselectivities. In addition, electronic circular dichroism (ECD) spectroscopy and time-dependent density functional theory (TD-DFT) were used to investigate the rational structures of spirocyclohexaneoxindoles.

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,ß-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives.

The catalytic synthesis of nitrogen-containing heterocycles is of great importance to medicinal and synthetic chemists, and also a challenge for modern chemical methodology. In this paper, we report the synthesis of pyrazolidine derivatives through a domino aza-Michael/hemiacetal sequence with chiral or achiral secondary amines as organocatalysts. Thus, a series of achiral pyrazolidine derivatives were obtained with good yields (up to 90%) and high diastereoselectivities (>20:1) with pyrrolidine as an organocatalyst, and enantioenriched pyrazolidines are also achieved with good results (up to 86% yield, >10/1 regioselectivity, >20:1 dr, 99% ee) in the presence of (S)-diphenylprolinol trimethylsilyl ether catalyst.

Dinuclear zinc catalyzed asymmetric Friedel-Crafts amidoalkylation of indoles with aryl aldimines.

The asymmetric Friedel-Crafts amidoalkylation of indoles with aryl aldimines could be efficiently catalyzed by Trost's bis-ProPhenol dinuclear zinc complexes to attain 3-indolyl methanamine derivatives in good to excellent yields (85-98%) with moderate to high enantiomeric ratios (from 70 : 30 up to 95 : 5 er). Remarkably, this approach provides efficient access to enantiomerically enriched 3-indolyl methanamines, which avoids the formation of the undesirable bis- and tris(indolyl)methanes (BIMs and TIMs) byproduct.

Chiral Bidentate Phosphoramidite-Pd Catalyzed Asymmetric Decarboxylative Dipolar Cycloaddition for Multistereogenic Tetrahydrofurans with Cyclic N-Sulfonyl Ketimine Moieties.

An asymmetric [3 + 2] cycloaddition of vinyl ethylenecarbonates (VECs) and (E)-3-arylvinyl substituted benzo[d] isothiazole 1,1-dioxides has been developed using the Pd complex of a bidentate phosphoramidite (Me-BIPAM) as the catalyst, providing a wide variety of chiral multistereogenic vinyltetrahydrofurans in good yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, 99% ee).