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A Pd/phase-transfer catalyst cooperatively catalyzed domino Heck/allylation reaction is first reported, which represents interesting substrate-dependent regioselectivity. Under the same conditions, Ts-protected

A simple and sustainable KI-mediated electrochemical enantioselective dihydroxylation reaction for the synthesis of chiral acyclic nucleosides was developed for the first time with only a 0.1 mol% Os catalyst.

Dehydrogenative coupling of arenes with fluoroaryl nucleophiles enables the efficient synthesis of fluoroaromatic compounds from readily available starting materials.

An environmentally benign electrooxidative approach to the intramolecular aminooxygenation of alkynes through an electrophilic cyclization reaction has been developed, providing an efficient approach toward diverse formyl- and acyl-substituted indolizines.

An efficient and eco-friendly electrochemical synthesis of various cyclic N-sulfonylamidines from cyclic sulfamidate imines and amines via oxidative C–H/N–H cross-coupling under mild reaction conditions has been developed.

The first catalytic asymmetric route to synthesize chiral thiohydantoins using a chiral phosphoric acid-catalyzed domino cyclization reaction of N,N′-dialkyl thioureas with β,γ-unsaturated α-ketoesters.

A palladium-catalyzed enantioselective Heck cyclization/dearomatization cascade via capturing the cyclized Heck π-allylpalladium intermediate by β-naphthols is reported, which provides a new strategy for the construction of chiral indole-terpenoid frameworks. This method affords indole-functionalized β-naphthalenone compounds bearing an all-carbon-substituted quaternary chiral center in excellent yields (up to 92%) and enantioselectivities (up to 94% ee). In addition, the utility of this method is showcased by the gram-scale syntheses and diverse transformations of the dearomatized products.

A Ni(II)/bisoxazoline-catalyzed asymmetric dearomative [3+2] cycloaddition of substituted purines with donor-acceptor oxiranes was developed. This reaction, which proceeds via highly chemoselective C-C bond cleavage of the oxiranes, accesses chiral purino[3,2-ic/i]oxazole compounds (≤99% ee after enrichment via crystallization). The electronic effects of the purine ring determine the reactivity of the substrate. The general applicability of this method was illustrated by gram-scale synthesis, the diverse transformations of the product, and the promising biological activities of selected derivatives.

A palladium-catalyzed domino Heck/decarboxylative alkynylation reaction of trisubstituted alkenes or enamines is reported. For two different types of substrates, the current domino reaction employing different solvents and bases led to 3,3-disubstituted oxindoles and hydropyrimidinyl spirooxindoles containing vicinal quaternary and tertiary stereocenters in moderate to good yields, respectively. The general applicability of this method was shown by gram-scale syntheses and diverse transformations of the reaction products. The enantioselective version for this domino process was also studied.

Described herein is an efficient strategy for assembling a new library of functionalized polycyclic purinium salts with a wide range of anions through Rh

Bifunctional chiral tridentate bis(pyrroloimidazolone)pyridine (PyBPI) ligands have been designed, synthesized, and applied in an asymmetric Michael addition. With a 0.05 mol % PyBPI-Co(II) complex, β,γ-unsaturated α-keto esters reacted with 4-hydroxycoumarin to give the adducts in 93-99% yields and 90-97% ee. Experiments and DFT calculations supported the dual activation manner, in which the tridentate ligand coordinated with Co(II) to activate the keto ester, and the hydroxyl and carbonyl groups in PyBPI interacted with 4-hydroxycoumarin via two different H bonds.

In this study, an environmentally benign electrochemical protocol for intramolecular oxidative amination is developed, which offers an efficient and sustainable route to access diverse fused tricyclic systems of pyrido[1,2-e]purine-2,4-dione derivatives with pharmacological interest, exhibiting broad scope and generality (>50 examples, yields up to 99%). This electrochemical strategy features good functional group tolerance and permits access to compounds that were previously not achievable under thermal conditions. The photoluminescence properties of the representative N9-fused tricyclic xanthines have also been investigated.

The first ring-opening of D–A oxiranes with N-heteroaromatics in a chemoselective C–C bond cleavage manner was achieved. In the presence of 5 mol% of Y(OTf)3 as the catalyst, diverse N-heteroaromatics, including benzotriazoles, purines, substituted benzimidazole, imidazole and pyrazole, reacted well with various D–A oxiranes, providing acyclic nucleoside analogues containing a N-glycosidic bond in up to 97% yield and up to >95 : 5 regioselectivity. Through simple transformation, the Ganciclovir analogue could also be obtained.

Highly enantioselective allylation of a vinylethylene carbonate by asymmetric palladium catalysis has been developed for a variety of N-heteroaromatic substrates. The employed procedure allows for the efficient synthesis of various acyclic nucleoside analogs in good yields (up to 96%) and with high enantioselectivities (up to 99%) at the Pd catalyst amount of 0.5 mol%. In addition, these acyclic nucleosides are demonstrated to undergo rapid transformation to a variety of interesting structurally diverse chiral acyclic nucleosides and isonucleosides.

A generally useful Ni(II)/trisoxazoline-catalyzed asymmetric sulfa-Michael/Aldol cascade reaction is introduced to access chiral 3-amine-tetrahydrothiophene derivatives containing a quaternary stereocenter (32 examples, up to 93% yield, > 20:1 dr and 92% ee). Moreover, the novel strategy offers an efficient and convenient approach to construct chiral thionucleoside analogues.

A novel concept that conversion of chiral 2-substituted DMAP into its DMAP-N-oxide could significantly enhance the catalytic activity and still be used as an acyl transfer catalyst is presented. A new type of chiral 2-substituted DMAP-N-oxides, derived from l-prolinamides, has been rationally designed, facilely synthesized, and applied in the dynamic kinetic resolution of azlactones. Using simple MeOH as the nucleophile, various l-amino acid derivatives were produced in high yields (up to 98% yield) and enantioselectivities (up to 96% ee). Furthermore, α-deuterium labeled l-phenylalanine derivative was also obtained. Experiments and DFT calculations revealed that in 2-substituted DMAP-N-oxide, the oxygen atom acted as the nucleophilic site and the N-H bond functioned as the H-bond donor. High enantioselectivity of the reaction was governed by steric factors, and the addition of benzoic acid reduced the activation energy by participating in the construction of a H-bond bridge. The theoretical chemical study indicated that only when attack directions of the chiral catalyst were fully considered could the correct calculation results be obtained. This work paves the way for the utilization of the C2 position of the pyridine ring and the development of chiral 2-substituted DMAP-N-oxides as efficient acyl transfer catalysts.

Highly enantioselective [5 + 4] annulation of ortho-quinone methides with vinylethylene carbonates has been developed by asymmetric palladium catalysis. The reaction allows for efficient synthesis of various nine-membered benzodioxonines in good yields (up to 88%) with high enantioselectivity (up to 98%). Mechanistic studies indicate that the [5 + 4] annulation occurs through an unusual action of chiral phosphine and achiral palladium catalysts.

A highly enantioselective cyclopropanation to synthesize pyrimidine-substituted diester D–A cyclopropanes is reported. Various N1-vinylpyrimidines react well with phenyliodonium ylides, delivering chiral cyclopropanes in up to 97% yield with up to 99% ee. Through simple [3+2] annulation with benzaldehyde or ethyl glyoxylate, different chiral pyrimidine nucleoside analogues with a sugar ring could be obtained.

A straight synthetic approach to fused polycyclic tropane scaffold formation through an asymmetric dearomatization cycloaddition process of 2-nitrobenzofurans with cyclic azomethine ylides was successfully developed. In the presence of a chiral copper complex, derived from Cu(OAc)

A DMAP-N-oxide, featuring an α-amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O-acylated azlactones afforded C-acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP-N-oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP-N-oxides for asymmetric acyl transfer reactions.

The first ring-opening of D-A oxiranes with N-heteroaromatics in a chemoselective C-C bond cleavage manner was achieved. In the presence of 5 mol% of Y(OTf)3 as the catalyst, diverse N-heteroaromatics, including benzotriazoles, purines, substituted benzimidazole, imidazole and pyrazole, reacted well with various D-A oxiranes, providing acyclic nucleoside analogues containing a N-glycosidic bond in up to 97% yield and up to95 : 5 regioselectivity. Through simple transformation, the Ganciclovir analogue could also be obtained.

Electrochemically driven, Cp*Ir(III)-catalyzed regioselective annulative couplings of benzoic acids with alkynes have been established herein. The combination of iridium catalyst and electricity not only circumvents the need for stoichiometric amount of chemical oxidant, but also ensures broad reaction compatibility with a wide array of sterically and electronically diverse substrates. This electrochemical approach represents a sustainable strategy as an ideal alternative and supplement to the oxidative annulations methodology to be engaged in the synthesis of isocoumarin derivatives.

A novel concept that conversion of chiral 2-substituted DMAP into its DMAP

A highly enantioselective cyclopropanation to synthesize pyrimidine-substituted diester D-A cyclopropanes is reported. Various N1-vinylpyrimidines react well with phenyliodonium ylides, delivering chiral cyclopropanes in up to 97% yield with up to 99% ee. Through simple [3+2] annulation with benzaldehyde or ethyl glyoxylate, different chiral pyrimidine nucleoside analogues with a sugar ring could be obtained.

Bifunctional chiral DMAP-N-oxides have been reported for the highly enantioselective rearrangement of indolyl carbonates. Using 2.5 mol% of chiral DMAP-N-oxide, diverse oxindoles containing an all-carbon quaternary stereocenter were obtained in excellent yields (up to 98% yield) with high enantioselectivities (up to 96% ee). Compared to the widespread use of chiral DMAP and isothiourea catalysts, in which the nitrogen atom serves as a nucleophilic site, we found that chiral DMAP-N-oxides, which utilize the oxygen atom as a nucleophilic site, were also efficient organocatalysts in this rearrangement.

Intermolecular asymmetric dearomative 1,3-dipolar cycloaddition of 2-nitrobenzofurans with azomethine ylides was enabled by using a chiral Cu(i)/(S,Sp)-iPr-Phosferrox catalyst. As a result, a series of highly stereoselective chiral [2,3]-fused hydrobenzofurans possessing four contiguous stereogenic centers were obtained with good to high yields, diastereoselectivities and enantioselectivities. The reaction has broad substrate scope tolerating various functional groups.

Chemoselective asymmetric [3 + 2] cycloaddition reactions of purines with aminocyclopropanes for the dearomatization of purines have been successfully developed. In the presence of a copper complex, derived from Cu(OTf)2 and bisoxazoline, a series of hydropyrrolo-purine compounds were obtained in high yields (up to 98%) with excellent enantioselectivities (up to 99% ee). The chemoselectivity in current cycloaddition reactions has been explained by density functional theory calculations.

Summary Heterocycles are a very important class of compounds that exist extensively as structural cores in natural products and biologically active molecules. Catalytic asymmetric dearomatization (CADA) is an efficient strategy for the construction of chiral fused- or spiro-heterocycles from simple planar aromatic compounds. Herein, we report the development of enantioselective dearomative [3 + 2] cycloaddition reactions of benzazoles with aminocyclopropanes via kinetic resolution. In the presence of a copper complex, derived from Cu(OTf)2 and bisoxazoline, a series of hydropyrrolo-benzazole derivatives containing quaternary stereogenic centers were obtained in high yields (up to 99%) with excellent enantioselectivity (up to 99% enantiomeric excess [ee]). With the same catalytic system, 2-amino cyclopropane-1,1-dicarboxylates with a high enantiomeric purity (up to 98% ee) were also obtained by an efficient kinetic resolution (s values of up to 95). In addition, the utility of this method was showcased by the facile transformation of products into several important heterocyclic frameworks, including pyrrolo-benzothiazine and 1,5-benzothiazepine.

The binding selectivity of an adenine-monofunctionalized pillar[5]arene (H) with a series of pyrimidine derivatives were investigated through 1H NMR experiments and density functional theory (DFT) study. High binding-selectivity was demonstrated. Typically, H displayed very strong binding strength with 6-(2,4-dioxo-3, 4-dihydropyrimidin-1 (2H)-yl)hexanenitrile (G1) [Ka >105 M−1], up to about 3000-fold as compared with 1-hexylpyrimidine-2,4(1H, 3H)-dione (G5) [Ka = 31 M−1]. The strong binding ability of H with G1 was due to the cooperative multiple hydrogen bond, dipole-dipole, C-H···π and π···π interactions. The high binding-selectivity was also verified by calculation results. The calculated interaction energy (ΔEi) of G1⊂H was −12.92 Kcal·mol−1 while that of G5⊂H was −2.85 Kcal·mol−1.

A direct route to chiral six-membered carbocyclic purine nucleoside analogues with three chiral stereocenters, including a chiral tetrasubstituted carbon center, via a highly enantioselective [3 + 3] annulation has been established. With the application of Takemoto's catalyst, various chiral six-membered carbocyclic purine nucleoside analogues were obtained in high yields (up to 89%) with moderate to good diastereoselectivities (up to 90:10 dr) and excellent enantioselectivities (92-98% ee). Furthermore, diverse chiral six-membered carbocyclic purine nucleoside analogues were generated by simple transformations.

Diversity-oriented synthesis of pyrazoline derivatives that contain a quaternary carbon center has been achieved via the 1,3-dipolar cycloaddition between N-purine-substituted allenes and α-alkyl/aryl diazoesters. Using Pd2(dba)3 as a catalyst, only 1-pyrazoline derivatives are produced in a regioselective manner. When DPPB is used as a catalyst, diverse 1-pyrazolines and 2-pyrazolines are obtained in moderate to good total yields.

Optical ratio two-photon probe utilizing fluorescent responses for the imaging and detecting of hypochlorite (ClO − ) require smart molecular systems able to operate selectively in the weak alkaline watery environment. Herein, we report a three-input “AND-type” fluorescent logic gate (NPA-CN) that demonstrates effective quantification of ClO − in the weak alkaline watery environment. NPA-CN with high signal-to-noise ratio provides a linear response to the three-input (ClO − , OH − and H 2 O) in rough endoplasmic reticulum (RER) of living cells on ratio-mode. More inportantly, NPA-CN can be used to whilst simultaneously image and quantify the changes of three-input.

An efficient route to chiral carbocyclic nucleoside analogues containing a quaternary stereocenter and a C═C double bond has been established via a highly enantioselective [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with α-purine-substituted acrylates. With 20 mol % (S)-SITCP as the catalyst, various chiral carbocyclic nucleoside analogues with a quaternary stereocenter and a C═C double bond were obtained in high yields (up to 92%) with good diastereoselectivities (up to 10:1 dr) and excellent enantioselectivities (up to 96% ee). Furthermore, the corresponding products were subjected to diverse transformations to afford interesting and potentially useful chiral carbocyclic nucleosides.

An efficient route to construct 2,5-disubstituted tetrazole hemiaminal silyl ethers via one-pot three-component hemiaminal silylation of 5-substituted tetrazoles, aldehydes, and silyl triflates was developed. Diverse 2,5-disubstituted tetrazole hemiaminal silyl ethers were obtained with 37 : 63–>99 : 1 regioisomeric ratios. The regioselectivities of this reaction were significantly affected by steric hindrance and the conjugation effects of substitutions on the 5-position of tetrazoles.

An atom-economic addition of pyrimidines to allenes has been developed for the diverse synthesis of branched or linear N-allylpyrimidine analogues. With [Rh(COD)Cl]2/chiral MeOBIPHEP as the catalyst, the asymmetric allylation reaction proceeded well and afforded the branch selective adducts in good yields, with high regio- and enantioselectivities. Meanwhile, when [Pd(η3-allyl)Cl]2/DPPF was used as the catalyst, the linear-selective allylation of pyrimidines could be carried out in good yields. Here, the configuration of the CC bond in the side chain of the products was mainly found to be the E-form.

Palladium-catalyzed regio- and enantioselective allylic amination of aliphatic Morita-Baylis-Hillman (MBH) adducts with N-heteroaromatic nucleophiles (e.g., benzimidazole, 4,5-diphenylimidazole, benzotriazole, and purines) was achieved by using a spiroketal-based diphosphine (SKP) ligand, and afforded a range of chiral, branched N-allyl products with high selectivity.

An efficient route to construct chiral cyclopropyl purine nucleoside analogues has been established via the catalytic asymmetric Michael-initiated ring-closure reactions of α-purine acrylates with α-bromo-carboxylic esters. Using (DHQD)2AQN as the catalyst, various chiral cyclopropyl purine nucleoside analogues with a chiral quaternary stereocenter were obtained in 72-98% yields, excellent diastereoselectivities, and 93-97% ee. Through simple functional group transformations, diverse chiral cyclopropyl purine nucleosides with hydroxymethyl group or carboxyl group were obtained.

A direct route to chiral pyrimidine acyclic nucleoside analogues with a sulfur-contained side chain has been reported via enantioselective tandem conjugated addition-protonation reactions of thioacetic acid to α-pyrimidine substituted acrylates. In the presence of quinine-derived thiourea as the catalyst, diverse chiral sulfur-contained pyrimidine acyclic nucleoside analogues were given in excellent yields (95-99% yields) and moderate to excellent enantioselectivities (up to 99% ee).

A combined palladium- and photoredox-catalyzed monoselective arylation of 6-arylpurine nucleosides has been developed by employing purine as a directing group via the photoredox reaction, and many functional groups are well tolerated in this direct C-H arylation condition. Various of functionalized purines (nucleosides) which are potentially of great importance in medicinal chemistry could be obtained under visible light irradiation at room temperature within 4 h.

A highly efficient Pd-catalyzed asymmetric formal [3+2] cycloaddition using α-N-heterocyclic acrylates to react with vinyl epoxides has been achieved for the first time to access chiral functionalized tetrahydrofuran skeletons (34 examples, up to 93% yield, >20 : 1 dr and 99% ee). Meanwhile, using a palladium/(S,S)-tBu-FOXAP catalyst or a palladium/(R)-Segphos catalyst, purine or pyrimidine isonucleoside analogs are constructed in high yields and stereoselectivity, respectively. The commercial availability of the catalysts, broad substrate scope and easy transformation of the products make this methodology an attractive method in asymmetric synthesis.

An asymmetric transfer hydrogenation via dynamic kinetic resolution of a broad range of rac- α-(purin-9-yl)cyclopentones was first developed. A series of cis-β-(purin-9-yl)cyclopentanols were obtained with up to 97% yield,20/1 dr, and99% ee. This also provides an efficient synthetic route to a variety of chiral carbocyclic nucleosides.