Base-Promoted Formal (3 + 2) Cycloaddition of α-Halohydroxamates with Electron-Deficient Alkenyl-iminoindolines To Synthesize Spiro-indolinepyrrolidinones.

Construction of pyrrolidinyl-spiroindoles with easily available starting materials has attracted considerable attention from the synthesis community and is in great demand. Here, we describe a base-promoted formal (3 + 2) cycloaddition of α-halohydroxamates with alkenyl-iminoindolines. The present methodology features mild reaction conditions and a broad substrate scope with up to 99% yield and excellent diastereoselectivity. The versatility of this approach is demonstrated through valuable synthetic transformations. Preliminary mechanistic studies shed light on the mechanism of this cycloaddition process.

Direct Acylation of Unactivated Alkyl Halides with Aldehydes through N-Heterocyclic Carbene Organocatalysis.

Catalytic acylation of organohalides with aldehydes is an ideal strategy for the direct synthesis of ketones. However, the utilization of unactivated alkyl halides in such a transformation remains a formidable challenge. In this study, we developed a cross-coupling reaction of aldehydes with unactivated alkyl halides through N-heterocyclic carbene catalysis. With this protocol, various ketones could be rapidly synthesized from readily available starting materials under mild conditions. This organocatalytic system was successfully applied in the late-stage functionalization of pharmaceutical derivatives. Mechanistic investigations suggest a closed-shell nucleophilic substitution mechanism for this reaction.

Oxidative Radical NHC Catalysis: Divergent Difunctionalization of Olefins through Intermolecular Hydrogen Atom Transfer.

Oxidative N-heterocyclic carbene (NHC) organocatalysis, typically leading to the formation of acyl azolium reactive intermediates, constitutes one of the most important activation strategies for the NHC-catalyzed chemical transformations. Here, we report an unprecedented oxidative radical NHC catalysis by using peroxyester as the external single-electron oxidant to realize divergent difunctionalization of olefins. The key to success of this chemistry is the catalytic generation of oxygen radicals that could trigger an intermolecular hydrogen atom transfer to activate the inert C-H bonds, thereby enabling the productive radical relay process. With this protocol, commonly used general chemicals could serve as radical precursors to allow efficient synthesis of value-added products in a straightforward and cost-effective manner. Preliminary mechanistic investigations, including control experiments and DFT calculations, shed light on the NHC organocatalytic radical reaction mechanism.

Sulphur ylide-mediated cyclopropanation and subsequent spirocyclopropane rearrangement reactions.

The efficient construction of cyclopropyl spiroindoline skeletons and the exploration of related follow-up synthetic transformations have elicited considerable interest amongst members of the chemistry community. Here, we describe a formal (2 + 1) annulation and three-component (1 + 1 + 1) cascade cyclisation via sulphur ylide cyclopropanation under mild conditions. The spiro-cyclopropyl iminoindoline moiety can be readily transformed into another medicinally interesting pyrrolo[3,4-c]quinoline framework through a novel rearrangement process.

Radical Acylalkylation of 1,3-Enynes To Access Allenic Ketones via N-Heterocyclic Carbene Organocatalysis.

An N-heterocyclic carbene organocatalytic 1,4-difunctionalization of 1,3-enynes was developed. This organocatalytic strategy was suitable for a broad spectrum of substrates to efficiently synthesize allenic ketones bearing diverse substituents. Preliminary mechanistic studies suggest a radical reaction pathway for this organocatalytic acylalkylation process.

Suzuki-type cross-coupling of alkyl trifluoroborates with acid fluoride enabled by NHC/photoredox dual catalysis.

The Suzuki-Miyaura cross-coupling of C(sp3)-hybridised boronic compounds still remains a challenging task, thereby hindering the broad application of alkyl boron substrates in carbon-carbon bond-forming reactions. Herein, we developed an NHC/photoredox dual catalytic cross-coupling of alkyl trifluoroborates with acid fluorides, providing an alternative solution to the classical acylative Suzuki coupling chemistry. With this protocol, various ketones could be rapidly synthesised from readily available materials under mild conditions. Preliminary mechanistic studies shed light on the unique radical reaction mechanism.

Remote C(sp3 )-H Acylation of Amides and Cascade Cyclization via N-Heterocyclic Carbene Organocatalysis.

The direct functionalization of inert C(sp3 )-H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote C(sp3 )-H acylation of amides and cascade cyclization through a radical-mediated 1,5-hydrogen atom transfer mechanism using N-heterocyclic carbene as the catalyst. Notably, a diversity of nitrogen-containing substrates, including simple linear aliphatic carbamates and ortho-alkyl benzamides, can be successfully applied to this organocatalytic system. With the established protocol, over 120 examples of functionalized δ-amino ketones and isoquinolinones with diverse substituents were easily synthesized in up to 99 % yield under mild conditions. The robustness and generality of the organocatalytic strategy were further highlighted by the successful acylation of unactivated C(sp3 )-H bonds and late-stage modification of pharmaceutical molecules. Then, the asymmetric control of the radical reaction was attempted and proven feasible by using a newly designed chiral thiazolium catalyst, and moderate enantioselectivity was obtained at the current stage. Preliminary mechanistic investigations including several control reactions, KIE experiments, and computational studies shed light on the organocatalytic radical reaction mechanism.

Comprehensive Transcriptome and Metabolic Profiling of Petal Color Development in Lycoris sprengeri.

Lycoris sprengeri (L. sprengeri) is an important ornamental bulbous plant, and its numerous varieties in different color forms are widely planted. Multiple color types of petals in L. sprengeri provide us with possibilities to delineate the complicated metabolic networks underlying the biochemical traits behind color formation in this plant species, especially petal color. In this study, we sequenced and annotated a reference transcriptome of pink and white petals of L. sprengeri and analyzed the metabolic role of anthocyanin biosynthesis in regulating color pigment metabolism. Briefly, white and pink petal samples were sequenced with an Illumina platform, to obtain the reads that could be assembled into 100,778 unique sequences. Sequences expressed differentially between white vs. pink petals were further annotated with the terms of Gene Ontology (GO), Clusters of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG), and eggNOG. Gene expression analyses revealed the repression of anthocyanin and steroid biosynthesis enzymes and R2R3 MYB transcription factor (TF) genes in white petals compared to pink petals. Furthermore, the targeted metabolic profiling of anthocyanins revealed that color-related delphinidin (Del) and cyanidin (Cy) pigments are lower in white petals, which correlate well with the reduced gene expression levels of anthocyanin biosynthesis genes. Taken together, it is hypothesized that anthocyanin biosynthesis, steroid biosynthesis, and R2R3 MYB TFs may play vital regulatory roles in petal color development in L. sprengeri. This work provides a valuable genomic resource for flower breeding and metabolic engineering in horticulture and markers for studying the flower trait evolution of L. sprengeri.

Diastereoselective [3 + 1] Cyclization Reaction of Oxindolyl Azaoxyallyl Cations with Sulfur Ylides: Assembly of 3,3'-Spiro[ß-lactam]-oxindoles.

Oxindoles and ß-lactams are attractive structural motifs because of their unique biological importance. However, the fusion of the two moieties featuring 3,3'-spirocyclic scaffolds is a challenging task in organic synthesis. Herein we designed a novel type of oxindole-based azaoxyallyl cation synthons, which could readily participate in the [3 + 1] cyclization with sulfur ylides. With this protocol, a collection of 3,3-spiro[ß-lactam]-oxindoles were facilely produced in up to 94% yield with perfect diastereoselectivity.

Construction of a Benzo[b]azepine Skeleton through Decarboxylative Ylide [6+1] Annulations with Modified Vinyl Benzoxazinanones.

A Lewis acid-promoted [6+1] annulation between sulfur ylides and modified vinyl benzoxazinanones was described. In this reaction, the newly designed vinyl benzoxazinanones could serve as a novel six-atom synthon, and the key to success is the installation of an electron-withdrawing group on the alkene moiety of the benzoxazinanones. A broad range of substrates are compatible with this mild reaction system, thereby providing a facile and practical approach for constructing a benzo[b]azepine skeleton.

Single-Electron Transfer Reactions Enabled by N-Heterocyclic Carbene Organocatalysis.

Over the past decades, N-heterocyclic carbene (NHC) organocatalysis has undergone a flourish of development on the basis of closed-shell reaction paths. By contrast, the emerging area of single-electron transfer (SET) reactions enabled by NHC catalysis still remain underdeveloped, but offer plenty of opportunities to develop new catalytic modes and useful synthetic methods. A number of interesting transformations were triggered by the SET process from the electron-rich Breslow intermediates to various single-electron acceptors. In additions, recent studies revealed that the Breslow radical cations could also be generated by single-electron reduction of the electron-deficient acyl azolium intermediates. These discoveries open a new avenue for NHC organocatalysis to harness radical reactions. The present review will focus on the exciting advancements in the dynamic area of radical NHC organocatalysis.

Palladium-catalysed cyclisation of vinylethylene carbonates and anhydrides: a new approach to diverse medium-sized bislactones.

Efficient construction of medium-sized lactones has attracted considerable interest over several decades, but remains a formidable challenge in synthetic chemistry. Here, we describe an unprecedented palladium-catalysed regioselective [5 + n] cyclisation (n = 5, 6, and 7) between vinylethylene carbonates and various anhydrides. Catalytic transformation occurs under mild, room-temperature conditions and offers an exceptional substrate scope. A broad spectrum of medium-sized bislactones with skeletal diversity can be obtained easily.

Bifunctional Brønsted Base Catalyzed [3 + 3] Annulations of Indolin-2-imines and α,ß-Unsaturated Imides: An Enantioselective Approach to α-Carbolinones.

Asymmetric construction of α-carbolinones with easily available starting materials has recently attracted considerable attention from the synthesis community, and the development of effective catalysis for this target is in great demand. Here, a bifunctional Brønsted base catalyzed asymmetric [3 + 3] cyclization of indolin-2-imines and α,ß-unsaturated N-acylated succinimides was developed by using the strategy of noncovalent bonding catalysis. With this organocatalytic protocol, a variety of tetrahydro-α-carbolinones bearing different substituents were synthesized with up to 99% yield and up to 96:4 er.

Palladium-catalysed decarboxylative annulations of vinylethylene carbonates leading to diverse functionalised heterocycles.

Heterocycles are the fundamental structural motifs found in natural products and biologically active compounds. The construction of these structures is therefore an important task in organic chemistry. Vinylethylene carbonates (VECs) are versatile building blocks that can undergo transition metal catalysed decarboxylation to enable various kinds of interesting transformations. This review provides an overview of the significant achievements of VECs in palladium-catalysed annulations over the past five years. The flexible reactivity of VECs is demonstrated by various [3 + 2], [5 + n] and other types of annulations, which could offer powerful protocols for accessing diverse functionalised heterocycles.

Radical Acylfluoroalkylation of Olefins through N-Heterocyclic Carbene Organocatalysis.

Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N-heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late-stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process.

Highly Chemo- and Diastereoselective Construction of Quaternary Stereocenters through Palladium-Catalyzed [3 + 2] Cyclization of 5-Alkenyl Thiazolones.

We report a highly chemo- and diastereoselective [3 + 2] cyclization of vinylethylene carbonates and 5-alkenyl thiazolones through palladium catalysis. The previously inert aza-thioester moiety on the thiazolone substrates is reacted selectively with the zwitterionic π-allylpalladium species. A variety of amide monothioacetals (AMTA) with two quaternary stereocenters are facilely synthesized. An additional spirocyclic quaternary stereocenter could be further installed by Rh-catalyzed metal-carbene insertion into the C-S bond on the AMTA moiety in a highly stereoselective manner.

[Characteristics of mandible and mandibular dentition according to vertical facial skeletal features of adolescents].

OBJECTIVE: We aim to examine teenagers with varying vertical facial skeletal types with near-normal occlusion. We further aim to identify and study mandibular morphology and dentition characteristics to establish normal ranges and variations for future clinical reference. METHODS: According to the results of the case studies, 42 adolescents with near-normal occlusion were divided into three groups, namely, low- (7 cases), average- (23 cases) and high-angle (12 cases) groups. We used Invivo 5 software for Digital Imaging and Communications in Medicine (DICOM) data to calculate the cant of occlusal plane, axis corner of L6, ∠L1/MP, ∠L6/MP, Balkwill angle and Bonwill triangle of each group. RESULTS: Markedly, the finding shows that the cant of occlusal plane and axis corner of L6 in the low-angle group were smaller than those of the other two groups. In the average-angle group, ∠L1/MP was larger than that of the high-angle group. Lastly, in the high-angle group, ∠L6/MP was smaller than those of the two other groups. On the one hand, these differences were considered statistically significant (P<0.05). On the other hand, other measurements show that these differences were considered statistically non-significant (P>0.05). CONCLUSIONS: In the low-angle group, the parallelisation of the occlusal plane tends to be more obvious compared with the two other groups. In the coronal section of the low-angle group, the axis of the mandibular first molar is up-right, whereas it is distally tilted in the sagittal section of the high-angle group. Furthermore, a number of differences are noted in the adult groups. Factors, such as aging and development in the craniofacial region, lead to changes in functional occlusion.

Construction of Azepino[2,3- b]indole Core via Sulfur Ylide Mediated Annulations.

A novel [4 + 3] annulation of indoline-based aza-dienes and crotonate-derived sulfur ylides is described. This method could be further expanded by using more efficient synthetic strategies, including three-component [3 + 1 + 3] cascade and the direct sulfide-catalyzed [4 + 3] cyclization. These protocols enable the rapid construction of azepino[2,3- b]indole cores, and a broad spectrum of the desired products with diverse substituents was facilely accessed in generally high yield.

Highly Stereoselective Assembly of α-Carbolinone Skeletons via N-Heterocyclic Carbene-Catalyzed [4 + 2] Annulations.

A series of iminoindoline-derived alkenes was found to be a new class of excellent aza-diene electrophiles in NHC-catalyzed asymmetric [4 + 2] cyclizations. This transformation is mainly characterized by excellent compatibility, which allows aza-diene substrates to incorporate various substituents and functionalities, including (hetero)aryl, (linear or branched)alkyl, alkenyl, alkynyl, and ester groups. Forty examples of the desired tetrahydro-α-carbolinones were facilely synthesized using this method, with up to 99% yield and >99% ee.

Direct Sulfide-Catalyzed Diastereoselective [4+1] Annulations of ortho-Quinone Methides and Bromides.

Direct sulfide organocatalysis is an emerging topic in research on synthetic chemistry. Here, an unprecedented sulfide-catalyzed diastereoselective [4+1] annulation of (in situ generated) ortho-quinone methides and bromides is reported. Notably, the robustness of such sulfide organocatalysis was demonstrated by performing the catalytic reaction under oxidative conditions without significantly affecting the reaction outcome. Various dihydrobenzofurans with diverse substituents were obtained with high isolated yields of up to 98% and remarkable diastereoselectivity (>19:1 dr in general).