Phosphine-catalyzed enantioselective and diastereodivergent [3+2] cyclization for the construction of oxetane dispirooxindole skeletons.

We have developed a phosphine catalyzed asymmetric [3+2] cyclization of 3-oxetanone derived MBH carbonates with activated methyleneoxindole, to construct oxetane dispirooxindole skeletons. Diastereodivergent synthesis was realized via the control of the phosphine catalyst. The (-)-DIOP provides the syn diastereoisomers, while the spiro phosphine (R)-SITCP achieves the anti-epimers.

Rapid Construction of Cycloheptatriene through Organocatalyzed [4 + 3] Annulation of Coumalates.

A protocol for the construction of cycloheptatrienes has been developed. 4-(Dimethylamino)pyridine (DMAP) was found to be an efficient catalyst to promote the [4 + 3] annulation between coumalates and γ-alkyl-substituted allenoate or γ-aryl-3-butynoates to deliver a variety of cycloheptatrienes in moderate to good yield with excellent chemoselectivity. The asymmetric version of this annulation was also realized by using bifunctional phosphine catalyst to provide the chiral products with 32-97% ee and 29-64% yield.

gem-Difluoroalkylation of Cyclic Ethers Enabled by Cobalt-Catalyzed C(sp3)-H Oxidation under Mild Conditions.

Fluorinated rings have emerged as privileged structural modules in the fields of drug discovery and materials research. The incorporation of fluorine atoms into aromatic rings or heterocycles can lead to significant improvements in the physicochemical and biological properties of small molecules, making them valuable components in the design of new drugs and functional materials. Herein, we presented a cobalt-catalyzed C-H oxidation/gem-difluorination cascade reaction of readily available cyclic ethers with difluoroenoxysilanes, affording a series of gem-difluorinated analogues with moderate to high yields. The obtained products as versatile fluoroalkyl building blocks were showcased through divergent-oriented transformations.

Phosphine-Catalyzed Stereospecific and Enantioselective Desymmetrizative [3+2] Cycloaddition of MBH Carbonates and N-(2-tert-Butylphenyl)maleimides.

Herein, we report an l-valine-derived amide phosphine-catalyzed [3+2] cyclization of MBH carbonates and N-(2-tert-butylphenyl)maleimides via asymmetric desymmetrization. Bicyclic N-aryl succinimide derivatives bearing three continuous chiral centers with a remote C-N atropisomeric chirality were constructed stereospecifically and enantioselectively. A wide variety of MBH carbonates could be employed in this process to deliver highly optically pure succinimide derivatives in moderate to excellent yields.

Electric charging effects on insulating surfaces in cryogenic liquids.

This paper presents a new technique to study the adsorption and desorption of ions and electrons on insulating surfaces in the presence of strong electric fields in cryoliquids. The experimental design consists of a compact cryostat coupled with a sensitive electro-optical Kerr device to monitor the stability of the electric fields. The behavior of nitrogen and helium ions on a poly(methyl methacrylate) (PMMA) surface was compared to a PMMA surface coated with a mixture of deuterated polystyrene and deuterated polybutadiene. Ion accumulation and removal on these surfaces were unambiguously observed. Within the precision of the data, both surfaces behave similarly for the physisorbed ions. The setup was also used to measure the (quasi-)static dielectric constant of PMMA at T ≈ 70 K. The impact of the ion adsorption on the search for a neutron permanent electric dipole moment in a cryogenic environment, such as the nEDM@SNS experiment, is discussed.

Accessing ladder-shape azetidine-fused indoline pentacycles through intermolecular regiodivergent aza-Paternò-Büchi reactions.

Small molecules with conformationally rigid, three-dimensional geometry are highly desirable in drug development, toward which a direct, simple-to-complexity synthetic logic is still of considerable challenges. Here, we report intermolecular aza-[2 + 2] photocycloaddition (the aza-Paternò-Büchi reaction) of indole that facilely assembles planar building blocks into ladder-shape azetidine-fused indoline pentacycles with contiguous quaternary carbons, divergent head-to-head/head-to-tail regioselectivity, and absolute exo stereoselectivity. These products exhibit marked three-dimensionality, many of which possess 3D score values distributed in the highest 0.5% region with reference to structures from DrugBank database. Mechanistic studies elucidated the origin of the observed regio- and stereoselectivities, which arise from distortion-controlled C-N coupling scenarios. This study expands the synthetic repertoire of energy transfer catalysis for accessing structurally intriguing architectures with high molecular complexity and underexplored topological chemical space.

Enantioselective Construction of C4-Quaternary Quinolinones via Copper(II)-Catalyzed Asymmetric [1,3] O-to-C Rearrangement.

An efficient asymmetric [1,3] O-to-C rearrangement of quinolin-2(1H)-ones enabled by a chiral bisoxazoline/copper complex has been developed. This strategy tolerated a wide range of substrates to provide a series of 1,4-dihydroquinoline-2,3-diones containing a quaternary stereocenter. A further cyclization of the [1,3] O-to-C rearrangement products was also realized, which led to various optically active 3,4-dihydroquinolin-2-ones with broad substrate scope.

Construction of Enantioenriched Quaternary C-Cl Oxindoles through Palladium-Catalyzed Asymmetric Allylic Substitution with Chloroenolates.

A palladium-catalyzed asymmetric chloroenolate allylation with vinyl benzoxazinanones under mild reaction conditions has been developed, affording a series of optically active 3,3-disubstituted oxindoles exhibiting a chloro-group and a linear aryl amino side chain in good yields with up to 96% ee. Versatile functional group tolerance on the benzene ring has been demonstrated, and the utility of this method was probed by a scale-up synthesis and highlighted by product derivatizations.

Phosphine-catalyzed Rauhut-Currier reaction of γ-alkyl allenoate and subsequent trapping using the Diels-Alder reaction.

We have disclosed a Rauhut-Currier reaction of γ-alkyl-substituted allenoate, catalyzed by L-valine-derived amide phosphine, to form trisubstitued allenoate, which was trapped by maleimide or DMAD via the Diels-Alder reaction. Exo-bicyclic succinimide derivatives including three continuous stereocenters with an exo-carbon-carbon double bound were constructed in up to quantitative yields with high stereospecificity.

Synthesis of Fluorinated Pyrrolo[2,1-a]isoquinolines through Decarboxylative/Dehydrofluorinative [3 + 2] Cycloaddition Aromatization of Isoquinolinium N-Ylides with Difluoroenoxysilanes.

A decarboxylative/dehydrofluorinative formal [3 + 2] cycloaddition aromatization of isoquinolinium N-ylides with difluoroenoxysilanes has been developed. This methodology provides a facile and straightforward synthetic pathway to afford highly functionalized fluorinated pyrrolo[2,1-a]isoquinolines in good to excellent yields under mild conditions. Moreover, gram-scale and synthetic derivatization experiments for the late-stage functionalization of drug molecules have also been demonstrated.

Asymmetric Synthesis of Multicyclic Spirooxindole Derivatives Bearing Stereogenic Quaternary Carbon Atoms.

An organocatalyzed stereoselective domino reaction as a facile approach to multicyclic spirooxindole derivatives bearing two stereogenic quaternary carbon atoms is reported. The alkyl-substituted chiral thiourea catalyst was efficient for the reaction to tolerate a wide range of substrates, furnishing a new class of spirooxindole derivatives bearing an O,O-acetal-fused tricyclic skeleton or tetrahydroxanthone moiety in moderate to good yields with good to excellent selectivities. The products generated from this method have promising anticancer activities.

Visible-Light-Induced Radical gem-Iodoallylation of 2,2,2-Trifluorodiazoethane.

A visible-light-induced radical gem-iodoallylation of CF3CHN2 was developed under mild conditions, delivering a variety of α-CF3-substituted homoallylic iodide compounds in moderate to excellent yields. The transformation features broad substrate scope, good functional group compatibility, and operational simplicity. The described protocol provides a convenient and attractive tool to apply CF3CHN2 as CF3-introduction reagent in radical synthetic chemistry.

Rapid Construction of Tricyclic Furanobenzodihydropyrans by Asymmetric Tandem Reaction.

A process based on the organocatalyzed Mannich/cycloketalization/transesterification tandem reaction of 1-(2-hydroxyaryl)-1,3-diketones and ß,γ-alkynyl α-imino esters has been developed, delivering a variety of tricyclic furanobenzodihydropyrans with excellent results (up to 99% yield, 99% ee, and >19:1 dr).

Rhodium-Catalyzed Chemodivergent Pyridylation of Alkynes with Pyridylboronic Acids.

The pyridylation of alkynes with pyridylboronic acids is realized under rhodium catalysis. Chemodivergent pyridylation products, including alkenylpyridines produced via the hydropyridylation pathway and cyclopenta[c]pyridines produced via the pyridylation/cyclization pathway, were selectively produced by fine-tuning the reaction conditions. A mechanistic study revealed that 1,4-rhodium migration to the pyridine ring was involved as the key step in the chemodivergent synthesis.

Access to Chiral Chromenones through Organocatalyzed Mannich/Annulation Sequence.

Herein we report an efficient and practical method to access chiral chromenones bearing one α-amino stereogenic center in the ß position of the carbonyl group. The quinine-derived squaramide could efficiently promote Mannich/cycloketalization/dehydration tandem reactions between 1-(2-hydroxyaryl)-1,3-diketones and functionalized imines generated in situ, providing a wide range of chiral chromenones with propargylamine or α-amino ester moieties with good results (54 examples, up to 98% ee).

Enantioselective Phosphine-Catalyzed Trimerization of γ-Aryl-3-butynoates via Isomerization/[3 + 2] Cyclization/Michael Addition Cascade.

We disclose an l-isoleucine-derived amide phosphine-catalyzed trimerization of γ-aryl-3-butynoates, which undergo an isomerization to allenoate, [3 + 2] cyclization, and Michael addition cascade. Exocyclopentene derivatives bearing an all-carbon quaternary stereocenter were constructed stereospecifically and enantioselectively. A wide variety of γ-aryl-3-butynoates could be employed to deliver optically pure cyclopentene derivatives in moderate to good yields with ee values of ≥95% and in most cases ≥98%.

Palladium-Catalyzed Selective [2 + 2 + 2] Annulation of 2-(2-Enynyl)pyridines with Arynes.

The palladium-catalyzed chemo- and stereoselective [2 + 2 + 2] annulation reaction of 2-(2-enynyl)pyridines with arynes has been developed. A wide range of (E)- or (E/Z)-isomers of 2-(2-enynyl)pyridines and arynes was tolerated, providing a spectrum of (E)-phenanthrenylated 2-alkenylpyridines in good yield, together with the generation of a chiral axis between an alkene and a phenanthrene ring.

Correction: Assembly of fluorinated chromanones via enantioselective tandem reaction.

Correction for 'Assembly of fluorinated chromanones via enantioselective tandem reaction' by Mengxue Lu et al., Chem. Commun., 2021, 57, 4722-4725, DOI: 10.1039/D1CC01187A.

Assembly of fluorinated chromanones via enantioselective tandem reaction.

The enantioselective synthesis of fluorinated tricyclic chromanones with multiple vicinal stereogenic centers has been realized for the first time, through the tandem reaction between 2-fluorinated 1-(2-hydroxyaryl)-1,3-diketones and α,ß-unsaturated aldehydes. In the presence of chiral amine, the organo-tandem reaction including catalytic Michael addition/cycloketalization/hemiacetalization and acylation sequence provided a wide range of fluorinated tricyclic chromanones with excellent outcomes (>30 examples, up to >99% ee and >19 : 1 d.r.). A plausible catalytic cycle and transition state are also provided for this tandem reaction to rationalize the observed sense of asymmetric induction.

Phosphine catalyzed [3+2] cyclization/Michael addition of allenoate with CS2 to form 2-thineyl vinyl sulfide.

We have developed a DPPE-catalyzed three molecular two component tandem reaction of γ-substituted allenoate and CS2 to construct 2-thineyl vinyl sulfide through phosphine catalyzed [3+2] cyclization followed by Michael addition. The synthetic value of the 2-thineyl vinyl sulfide was demonstrated by a concise synthesis of an anti-glaucoma agent.