Rhodium-catalyzed addition reactions of benzylic C–H bonds to cyclic N-sulfonyl ketimines viaπ-coordination

Mannich-type reactions are a widely used method for the synthesis of amines due to the readily availability of nucleophiles and electrophiles.However,the inclusion of alkylarenes instead of active carbon pronucleophiles such as aldehydes and ketones in these addition reactions has been a challenge due to the inherent difficulty of benzylic deprotonation.In this study,we present a novel approach for the construction of N-sulfonyl amines via rhodium-catalyzed addition of unbiased benzylic C–H bonds to cyclic N-sulfonyl ketamines throughπ-coordination.This strategy enables the synthesis of a diverse range of N-sulfonyl amines,and subsequent diversification of the addition products showcases the synthetic potential of this protocol.

Copper(Ⅰ)-catalyzed interrupted click/radical relay:A four-component modular synthesis of triazole sulfones

A new,four component copper(Ⅰ)-catalyzed interrupted click/radical relay cascade has been developed.This unprecedented interrupted click reaction provides a rapid modular synthesis of triazole sulfones,important privileged heterocyclic pharmacophores which cannot be accessed by a traditional click reaction.Radical interception of cuprate-triazole,the key reaction intermediate formed in situ,is an important feature of this process.

Hierarchical Self-assembly of G-Quadruplexes Based Hydrogel Consisting of Guanine and Peptide Epitope

Guanosine-based hydrogels have attracted considerable attention because of their simplicity and easy preparation.However,the sugar moiety limits its further applications because of the necessity of sugar in the hydrogel formation.This work reports a G-quadruplexes-based hydrogel consisting of guanine and peptide epitope to form a supramolecular hydrogel in the presence of metal cations.Using the metal ion-responsive peptide epitope from the ion channel to replace sugar motif at N9 position of guanosine results in a novel nucleopeptide.The results show that the gelation time,the diameter of nanofibers,the anisotropic property,and the mechanical property of the hydrogel can be simply controlled using metal cations.The magnesium and calcium ions direct the alignment of nanofibers to form anisotropic nano-bundles.The mechanistic studies indicate the formation of G-quadruplexes in the hydrogel.Compared to the storage modulus of nucleopeptide without the metal cation,adding zinc ions results in an over three-order increase in mechanical properties.Cytotoxicity experiment indicates the good biocompatibility of our hydrogel.Moreover,we demonstrate that the guanine-capped peptide could release STING agonist in a controlled manner.This work illustrates a simple way to modulate the property of the nucleopeptide hydrogel to develop soft materials.

Au-catalyzed neighboring hydroxymethyl group directed cycloaddition of alkyne with diazadienes:Synthesis of polysubstituted pyrroles

Polysubstituted pyrroles are very important scaffolds in many bioactive natural products and synthetic pharmaceuticals.Here,a new gold-catalyzed cycloaddition of alkynes with azadienes to access tetrasubstituted pyrroles is demonstrated.The neighboring hydroxylmethyl group serves a very important directing group through an addition/cycloaddition/elimination cascade.Diverse polysubstituted pyrroles were synthesized in good yields under mild conditions in one step,and tricyclic pyrrole containing heterocycles were easily obtained through derivatization.

Cobalt-catalyzed divergent functionalization of N-sulfonyl amines via β-carbon elimination

This article demonstrates a catalytic method for C(aryl)-C(alkyl) bond functionalization of N-sulfonyl amines. A cobalt(III)catalyst was used to cleave the C-C bond via β-carbon elimination, providing a metallacycle intermediate. Subsequent allylation,amidation, or alkenylation of the intermediate led to divergent conversions in the presence of diverse coupling partners. when the coupling partner was a diene, an insertion-type functionalization was realized with an exclusive 1,3-regioselectivity, in which both of the fragments derived from N-sulfonyl amines were utilized.

Recent advances in the synthesis and applications of furocoumarin derivatives

Furocoumarins are an important class of heterocyclic compounds with a fused tricyclic structure of coumarin and furan rings.They are commonly found in bioactive natural products and have a diverse range of biological and pharmaceutical properties,including cytotoxicity,photosensitivity,insecticidal,antibacterial,and antifungal activity,among others.The elegant linear/angular tricyclic skeleton and superior pharmacological properties,make them ideal for building and developing advanced biological scaffolds for biomedical applications.As a result,the family of furocoumarins has been the focus of intensive research,and lots of encouraging progress have been achieved in recent years.This review summarizes the most recent methods reported for the synthesis of the furocoumarin derivative family,along with their applications in medicinal chemistry covering from 2018 to 2022.

Chiral Betaine-Mediated Asymmetric Peroxidation-Kinetic Resolution Cascade for the Synthesis of Optically Pure Peroxides

An array of natural products bearing chiral peroxide motifs display antitumor,anticancer,and antiparasitic activities.However,there are very few catalytic asymmetric syntheses of chiral peroxides.Moreover,effective catalysts for asymmetric catalytic peroxidations are limited to chiral amines.To further expand synthetic access to chiral peroxides,the development of new catalysts realizing catalytic asymmetric peroxidation is highly desirable yet challenging.We report here a catalytic asymmetric peroxidation of anα,β-unsaturated triflone-kinetic resolution cascade reaction,which furnishes chiral peroxides in greater than 99.9%ee.The realization of this cascade reaction resulted from the development of two betaines as novel catalysts for chiral peroxide synthesis;one betaine promoted enantioselective peroxidation ofα,β-unsaturated triflones via conjugate addition affording peroxides in 80-92%ee,while the other betaine catalyzed kinetic resolution of the newly generated chiral peroxides to further increase the ee to greater than 99.9%.

Cr-catalyzed allylic C(sp~3)–H addition to aldehydes enabled by photoinduced ligand-to-metal charge transfer

Photoinduced ligand-to-metal charge transfer(LMCT) has emerged as an effective strategy for synthesizing organic molecules in a sustainable manner. However, the majority of existing reports on selective C(sp~3)–H bond functionalization via photoinduced LMCT focus on the use of late transition metals or rare-earth metals for radical additions or cross-couplings. In contrast, the utilization of photoinduced LMCT with 3d early transition metals poses a significant challenge. Herein, we describe an unprecedented approach to allylic C(sp~3)–H addition to aldehydes, employing chromium(Cr) complexes as catalysts through visible-light-induced LMCT. By investigating the reaction pathway through various mechanistic studies, including radical trapping, kinetic isotope effect(KIE) analysis, and transient absorption spectroscopy, valuable insights have been gained. The proposed mechanism suggests the intermediacy of bromine radicals through homolysis of the Cr–Br bond. Notably, this protocol expands our understanding of the photochemical properties of earth-abundant Cr complexes.

Machine Learning Prediction of Structure-Performance Relationship in Organic Synthesis

Data-driven approach has emerged as a powerful strategy in the construction of structure-performance relationships in organic synthesis.To close the gap between mechanistic understanding and synthetic prediction,we have made efforts to implement mechanistic knowledge in machine learning modelling of organic transformation,as a way to achieve accurate predictions of reactivity,regio-and stereoselectivity.We have constructed a comprehensive and balanced computational database for target radical transformations(arene C—H functionalization and HAT reaction),which laid the foundation for the reactivity and selectivity prediction.Furthermore,we found that the combination of computational statistics and physical organic descriptors offers a practical solution to build machine learning structure-performance models for reactivity and regioselectivity.To allow machine learning modelling of stereoselectivity,a structured database of asymmetric hydrogenation of olefins was built,and we designed a chemical heuristics-based hierarchical learning approach to effectively use the big data in the early stage of catalysis screening.Our studies reflect a tiny portion of the exciting developments of machine learning in organic chemistry.The synergy between mechanistic knowledge and machine learning will continue to generate a strong momentum to push the limit of reaction performance prediction in organic chemistry.

Visible light and base promoted O-H insertion/cyclization of para-quinone methides with aryl diazoacetates: An approach to 2,3-dihydrobenzofuran derivatives

A visible light and base promoted O-H insertion/cyclization of para-quinone methides with aryl diazoacetates is developed. This one-pot two step reaction offers a mild and efficient approach for the synthesis of biologically important 2,3-dihydrobenzofuran derivatives in good yields and moderate diastereoselectivities.

Asymmetric synthesis of tricyclic 6,5,5-fusedpolycycles by the desymmetric Pauson–Khandreaction

A new rhodium(I)–BINAP-catalyzed enantioselective desymmetric Pauson–Khand (PK) reaction of prochiral 1,6-enynes with CO has been developed. Diverse tricyclic 6,5,5-fused bowl type polycycles withthree continuous chiral centers were synthesized in one step with a single diastereomer and extremelyhigh enantioselectivities.

Mechanical Trapping of the Phlorin Intermediate

Trapping unstable intermediates for elucidating reaction mechanisms in chemistry presents a formidable challenge.There has long been a lack of direct evidence for key intermediates like the highly reactive phlorin leading to porphyrin.Here,we report a molecular-strain engineering(MSE)strategy that harnesses intramolecular strain to trap the native phlorin during porphyrin synthesis.By mechanically constraining its periphery,a phlorin stable towards oxidation was captured as an isolable intermediate and fully characterized.

A specialized role played by a redox cofactor

The redox cofactor𝛽-nicotinamide adenine dinucleotide(NAD)has been revealed to serve as a building block for the biosynthesis of an alkaloid natural product,altemicidin.The biosynthetic pathway investigation identified a unique pyridoxal pyrophosphate(PLP)-dependent enzyme that utilizes NAD and S-adenosylmethionine(SAM)to build the bicyclic alkaloid scaffold,opening the door for biosynthetic studies of NAD-derived natural products.

Light-fueled dissipative self-assembly at molecular and macro-scale enabled by a visible-light-responsive transient hetero-complementary quadruple hydrogen bond

The development of out-of-equilibrium self-assembly systems using light as input fuel is highly desirable and promising for the fabrication of smart supramolecular materials. Herein, we report the construction of new artificial light-fueled dissipative molecular and macroscopic self-assembly systems based on a visible-light-responsive transient quadruple H-bonding array, which consists of an azobenzene-modified ureidopyrimidinone(UPy) module(Azo-O-UPy) and a nonphotoactive diamidonaphthyridine(DAN) derived competitive binder(Napy-1). The visible light(410 nm) irradiation can induce the E to Z isomerization of the azobenzene unit of E-Azo-O-UPy to produce Z-Azo-O-UPy with an opened UPy binding site, which can complex with Napy-1 to form a quadruply H-bonded heterodimer. The heterodimer is metastable and can be quickly disassembled in dark, owing to the fast thermal relaxation of Z-Azo-O-UPy to E-Azo-O-UPy. While introducing such transient quadruple H-bonding interaction into a linear polymer system or a polymeric gel system, light-fueled out-of-equilibrium polymeric assembly both at molecular and macro-scale can be achieved.

Visible Light-Promoted Sulfoxonium Ylides Synthesis from Aryl Diazoacetates and Sulfoxides

A visible light-promoted reaction of donor/acceptor diazoalkanes with sulfoxides towards the synthesis of synthetically useful sulfoxonium ylides was reported.The reaction occurred under sole visible light irradiation without the need of any transition-metals or additives,affording the corresponding sulfoxonium ylides in moderate to good yields.The success of late-stage modification of natural isolates or drug candidates,scale-up reaction and transformation of sulfoxonium ylides to other useful molecules further rendered the approach valuable.