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Chlorinated malonic acid half thioesters were established as chloroacetate surrogates and used in stereoselective organocatalyzed decarboxylative aldol-type additions. Enantioenriched alpha-chloro-beta-hydroxy thioesters were obtained under mild reaction conditions in high yields and allowed for diverse derivatization as highlighted by the synthesis of (+)-prebalamide and (+)-norbalasubramide analogs. ISSN:1523-7060 ISSN:1523-7052

The [3+2] cycloaddition reaction of N-aryl-C-carbamoylnitrone (nitrone 1) with N-arylitaconimide (ethylene 2) was computationally studied using the B3LYP/6-31G(d) level of theory. An analysis of the different energetic profiles and the transition states’ optimized structures clearly indicated that this 32CA occurred through a non-polar, asynchronous, one-step mechanism, favoring the formation of the ortho–endo cycloadduct, as observed experimentally. The analysis of the reactivity indices derived from the conceptual DFT explains well the low polarity of this 32CA reaction. Parr functions and a dual reactivity descriptors analysis correctly explained the regioselectivity ortho of this 32CA reaction. Solvent effects did not modify the obtained selectivity but it increased the activation energies and decreased the exothermic character of this 32CA reaction. A thermodynamic parameters analysis indicated that this 32CA wascharacterized by an ortho regioselectivity and endostereoselectivity and exothermic and exergonic characters.

Enantiopure vicinal diols are important building blocks used in the synthesis of fine chemicals and pharmaceutical compounds. Diol dehydrogenase (DDH) mediated stereoselective oxidation of racemic vicinal is an efficient way to prepare enantiopure vicinal diols. In this study, four new bacterial DDHs (AnDDH from Anoxybacillus sp. P3H1B, HcDDH from Hazenella coriacea, GzDDH from Geobacillus zalihae and LwDDH from Leptotrichia wadei) were mined from the GenBank database and expressed in E. coli T7. The four DDHs were purified and biochemically characterized for oxidation activity toward (R)-1-phenyl-1,2-ethanediol, with the optimal reaction condition of pH9.0 (AnDDH), 10.0 (HcDDH) and 11.0 (GzDDH and LwDDH) and the temperatures at 40°C (AnDDH), 50°C (HcDDH) and 60°C (GzDDH and LwDDH), respectively. The four enzymes were stable at the pH from 7.0 to 9.0 and below 40°C. Kinetic parameters of four DDHs showed that the HcDDH from Hazenella coriacea had high activity toward a broad range of vicinal diols. A series of racemic vicinal diols were successfully resolved by recombinant E. coli (HcDDH-NOX) resting cells co-expression of an NADH oxidase (NOX), affording (S)-diols and (1S, 2S)-trans-diols in ≥99% ee. The synthetic potential of HcDDH was proved by E. coli (HcDDH-NOX) via kinetic resolution of racemic trans-1,2-indandiol on a 100 ml scale reaction, (S, S)- trans-1,2-indandiol was prepared in 46.7% yield and >99% ee. In addition, asymmetric reduction of four α-hydroxy ketones (10-300 mmol•L-1) by E. coli (HcDDH-GDH) resting cells resulted in >99% ee and 69-98% yields of (R)-vicinal diols. The current research expands the toolbox of DDHs to synthesize chiral vicinal diols and demonstrated that the mined HcDDH is a potential enzyme in the synthesis of a broad range of chiral vicinal diols.

International audience; We describe an efficient catalytic strategy for enantio- and diastereoselective synthesis of homochiral β-CF3, β-SCF3, and β-OCF3 benzylic alcohols. The approach is based on dynamic kinetic resolution (DKR) with Noyori–Ikariya asymmetric transfer hydrogenation leading to simultaneous construction of two contiguous stereogenic centers with up to 99.9% ee, up to 99.9:0.1 dr, and up to 99% isolated yield. The origin of the stereoselectivity and racemization mechanism of DKR is rationalized by density functional theory calculations. Applicability of the previously inaccessible chiral fluorinated alcohols obtained by this method in two directions is further demonstrated: As building blocks for pharmaceuticals, illustrated by the synthesis of heat shock protein 90 inhibitor with in vitro anticancer activity, and in particular, needle-shaped crystals of representative stereopure products that exhibit either elastic or plastic flexibility, which opens the door to functional materials based on mechanically responsive chiral molecular crystals.

Copper-catalyzed divergent annulations between α-diketones and alkynyl α-diketones have been achieved, delivering a series of highly functionalized and biologically important cis-hexahydro-2H-cyclopenta[b]furan (HCPF) and 2-hydroxydihydrofuran-3(2H)-one (HDFO) products with high levels of stereoselectivity under identical conditions. The protocol features the use of earth-abundant copper catalyst, mild conditions, shortening synthetic routes in constructing different molecular frameworks, and reducing the corresponding possible waste production. The substituents of the nucleophilic α-diketones play crucial roles in switching the reaction pathways.

A copper-catalyzed three-component reaction of alkenes, cycloketone oximes and DABCO•(SO2)2 is developed, which provides a convenient route for the synthesis of diverse (E)-cyanoalkylsulfonyl alkenes in moderate to good yields with excellent regio- and stereoselectivity. A broad substrate scope with excellent functional group tolerance is observed. A plausible radical pathway is proposed, which involves copper-catalyzed ring-opening C-C bond cleavage of O-acyl oxime and insertion of sulfur dioxide. During the reaction process, cyanoalkyl radical and cyanoalkylsulfonyl radical are the key intermediates.

An efficient diastereoselective route for the preparation of chiral oxathiazine 2-oxide scaffolds as sulfinyl transfer agents, using tert-butanesulfinamide (tBSA) both as the source of chirality and as the precursor to the required nitrogen electron withdrawing group on the scaffold, was developed. This methodology allows the introduction of different substituents on the chiral scaffold, using commercially available reagents and standard synthetic transformations. The synthesized scaffolds were tested in the preparation of enantioenriched sulfinamides, providing results comparable to the sulfinyl transfer agents so far proposed in the literature, and opening the possibility to further elaborate these scaffolds, with the aim to support them on solid phases so to facilitate their recovery and reuse. (Figure presented.).

The examination of cross metathesis reactions leading to the desired product has been conducted to uncover computationally the origin of the chemo-, regio- and stereoselectivity. The comparison between the relative stabilities of all involved intermediates and products, together with the transition states, links to the probability for the respective pathway. Particularly, the respective transition states for each reaction tune the regio- and stereoselectivity because they define the energy barriers needed to be overcome to form the new olefin as final product. The broad range of studied reactions with the 2nd generation Grubbs catalysts allows concluding in detail the points to pay attention and thus helps to understand the chemo-, regio- and stereoselectivity in new olefin metathesis reactions. Here, a web-server joins all these mechanistic insights which is intended to support future predictive olefin metathesis catalysis.

Stereoselective polymerization can yield polymers with specific tacticity and properties, and it is an essential topic throughout polymer synthesis history. Herein, we report for the first time on ...

Saccharomyces cerevisiae, commonly known as baker’s yeast, has gained significant importance as a mild, low-cost, environmentally benign biocatalyst. Initially it was mostly employed as an efficient catalyst for the enantioselective reduction of carbonyl compounds. Over the last decade, baker’s yeast has found versatile catalytic applications in various organic transformations. Many multicomponent reactions were also catalyzed by baker’s yeast. Various heterocyclic scaffolds with immense biological activities were synthesized by employing baker’s yeast as catalyst at room temperature. In this communication, we have summarized baker’s yeast catalyzed various organic transformations focusing primarily on heterocyclic synthesis.

Herein, we report an organocatalytic asymmetric [8+2] higher-order cycloaddition of tropones with azlactones employing bifunctional guanidines as hydrogen-bond-mediated catalysts via a 1,8-addition...

SmI2-mediated desymmetrization of a meso-cyclic 1,3-dione pinacol coupling is described. The reaction proceeds with high stereoselectivity to provide fused carbocyclic compounds with three contiguous stereogenic centers featuring an all-carbon quaternary center and a cis-1,2-diol moiety.

An NHC-catalyzed regiospecific allylation of α-substituted allenoates with MBH carbonates derived from aryl aldehyde furnished highly functionalized 1,5-enynes bearing a quaternary carbon successfully. Combining with DFT calculations, the reaction mechanism of this conversion was proposed. This method has the advantages of high regioselectivity, good yields and mild reaction conditions. This transformation not only provided a new access to 1,5-enyne, but also enriched the chemistry of allenoates and NHC catalysis.

The first example of palladium-catalysed [3 + 2] annulation of VECs and ketones has been developed, allowing the efficient synthesis of indoloquinazolinones in generally excellent yields with good stereoselectivity.

N- Acyliminium ions are highly reactive intermediates that are important for creating CC-bonds adjacent to nitrogen atoms. Here we report the characterization of cyclic N -acyliminium ions in the gas phase, generated by collision induced dissociation tandem mass spectrometry followed by infrared ion spectroscopy using the FELIX infrared free electron laser. Comparison of the DFT calculated spectra with the experimentally observed IR spectra provided valuable insights in the conformations of the N -acyliminium ions.

A series of heterobimetallic PdII/MII complexes (MII = Mn, Co) were synthesised and tested as precatalysts for sequential Sonogashira coupling–alkyne semi-hydrogenation reactions to form Z-aryl alkenes. The carbometalated heterobimetallic PdII/CoII complex CoPdL3’ demonstrated an apparent cooperative effect compared to the corresponding monometallic counterparts. This compound was identified as a potent single-molecule catalyst for the one-pot Cu-free Sonogashira coupling of aryl bromides with terminal alkynes followed by chemo- and stereoselective semi-hydrogenation of the alkyne intermediate using NH3·BH3 as a hydrogen source. Furthermore, different aromatic substrates have been tested to show the generality of the reaction for the synthesis of Z-alkenes, including biologically active combretastatin A-4. In addition, the homogeneous nature of the catalytically active species was demonstrated.

Due to the unique activation modes, the small organic molecule catalysts (organocatalysts) have proved their potential to facilitate the remote functionalizations of the unsaturated acceptors bearing extended conjugation. The organocatalytic 1,6-addition reaction involving the attack of nucleophiles to the δ-carbon of the α,β,γ,δ-unsaturated acceptors has emerged as an excellent strategy to create a stereocenter at the δ-site with high regio- and stereo-control. Organocatalysis has also opened the window for developing the complex domino reactions involving the 1,6-addition step. A tremendous advancement has been accomplished in the organocatalytic asymmetric 1,6-addition and related domino reactions for the stereocontrolled synthesis of complex molecular structures bearing multiple stereocenters. This review article summarizes the significant advancement in stereoselective domino reactions involving 1,6-addition as a critical step.

A total synthesis of the trisaccharide repeat unit of Salmonella serogroup E1 O-antigen is reported. This synthesis features a key β-mannosylation reaction via cesium carbonate-mediated anomeric O-alkylation of a partially protected D-mannose with an L-fucose-derived electrophile for the first time.

International audience; Out-of-plane deformations of metalloporphyrin skeletons have been well documented as playing important roles in relevant biological processes. In contrast, out-of-plane binding to the N-core of large metal cations as period 6 post-transition elements has remained poorly investigated. We describe herein monometallic complexes of Pb(II) and Bi(III) with 5,10 single strapped porphyrin ligands bearing a carboxylic acid group with two possible “in/out” orientations, in which the metal ions are bound to the N-core of the macrocycle either from the strap side or from the naked side. In the case of Pb(II), both the kinetics of insertion and resulting OOP stereoselectivity are influenced by the “in/out” stereoisomerism of the overhanging COOH. Remarkably, Bi(III) insertion proceeded quasi-instantaneously at RT owing to the transmetalation of its Pb(II) counterpart. The addition of a cyano group in position of the carboxylic acid group generates a ligand exhibiting an increased stereoselectivity in the metalation processes with Pb(II) and Bi(III): these cations are coordinated exclusively from the naked and strap side of the macrocycle, respectively. This difference in behavior is likely explained by steric hindrance for the divalent cation, which is counterbalanced by the establishment of the second sphere of coordination with the strap for the trivalent cation. Such a behavior is thought of interest for the further design of adaptable supramolecular coordination assemblies.

We report herein the development of α-borylmethyl-(Z)-crotylboronate reagent and the application in highly stereo- and enantioselective syntheses of (E)-δ-hydroxymethyl-syn-homoallylic alcohols. Starting from 1,4-pentadiene, α-borylmethyl-(Z)-crotylboronate was synthesized in two steps with high Z-selectivity and enantioselectivity. Subsequent aldehyde allylboration with the developed boron reagent gave highly enantioenriched (E)-δ-hydroxymethyl-syn-homoallylic alcohols upon oxidative workup.

Reported herein is the total synthesis of the trisaccharide repeating unit of Streptococcus pneumoniae zwitterionic polysaccharide Sp1 containing a rare sugar, 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose (AAT), and three consecutive 1,2-cis-glycosidic linkages. The total synthesis was completed via highly stereoselective glycosylations and late-stage oxidation as key steps involving a longest linear sequence of 21 steps with 4.4% overall yield.

A highly enantioselective O-propargylation catalyzed by combining a phosphine-nickel complex and an axially chiral sodium dicarboxylate has been developed. The transformation features mild reaction conditions, a broad substrate scope, and excellent functional group tolerance, offering an efficient approach to an array of enantioenriched O-propargyl hydroxylamines. Mechanistic studies support the presumed role of the chiral carboxylate as a counterion for nickel catalysis enabling the discovery of highly stereoselective transformations. The power of this reaction is illustrated by its application in the asymmetric total synthesis of potent firefly luciferase inhibitors and (S)-dihydroyashabushiketol.

A promoted synthetic protocol for the β-lactams synthesis in the presence of [BmIm]OH as a basic reagent under microwave irradiation [M.W.I.] is described. The reaction was highly diastereoselective. In all cases, this protocol provided trans-β-lactams as major isomers, and β-lactams were obtained with good yields. Further, the effect of the order of addition of the reagents was particularly investigated; we found that this order is very important. The best results are obtained when the imine is added gradually. This work shows that [BmIm]OH is an advantageous recyclable basic reagent. A qualitative molecular orbital diagram is illustrated to interpret the observed diastereoselectivity.

Summary C-Alkyl glycosides occur widely in nature and are indispensable in drug development programs, owing to their diverse range of medicinal properties. Previous synthetic efforts often utilize stoichiometric reagents, and catalytic methods that afford such glycosides exhibit limited scope. Here, we describe a stereoselective Ti-catalyzed regime that efficiently merges a vast array of readily available glycosyl chlorides with activated olefins, through stereocontrolled glycosyl radical addition to deliver an assortment of C-alkyl glycosides. By employing alkynes as radical acceptors, the present strategy is amenable to the synthesis of C-alkenyl glycosides bearing a Z olefin appendage. The unexpected greater reactivity of glycosyl chlorides (compared with simple tertiary chloroalkanes) in the presence of an organotitanium complex is elucidated through mechanistic and computational studies. Utility of the protocol is underscored by the concise preparation of therapeutically important carbohydrates and glycopeptide conjugates, which are difficult to access using alternative approaches.

The confused-prism[5]arene macrocycle (c-PrS[5](Me)) shows conformational adaptive behavior in the presence of ammonium guests. Upon guest inclusion, the 1,4-bridged naphthalene flap reverses its planar chirality from pS to pR (with reference to the pS(pR)(4) enantiomer). Stereoselective directional threading is also observed in the presence of directional axles, in which up/down stereoisomers of homochiral (pR)(5)-c-PrS[5](Me) pseudorotaxanes are formed.

A novel palladium-catalyzed Oppolzer-type cyclization reaction aided by the aminomethyl cyclopalladated complex has been developed, which provides rapid access to functionalized benzofulvenes with excellent stereoselectivity. The corresponding products can undergo Diels-Alder reaction with maleimides, providing a series of complex polycyclic compounds with excellent regio- and stereoselectivities.

Ansalactam A is an ansa macrolide natural product that contains a densely functionalized spiro-γ-lactam core containing three contiguous stereocenters. This unusual motif distinguishes it from other members of this family and represents a significant synthetic challenge. Herein, we report the development of a stereoselective formal [3+2] cycloaddition reaction for the construction of this key spiro-γ-lactam motif for the first time, thereby enabling access to the northern domain of ansalactam A.

A direct, efficient, and versatile glycosylation methodology promises the systematic synthesis of oligosaccharides and glycoconjugates in a streamlined fashion like the synthesis of medium to long-chain nucleotides and peptides. The development of a generally applicable approach for the construction of 1,2-cis-glycosidic bond with controlled stereoselectivity remains a major challenge, especially for the synthesis of β-mannosides. Here, we report a direct mannosylation strategy mediated by ZnI2, a mild Lewis acid, for the highly stereoselective construction of 1,2-cis-β linkages employing easily accessible 4,6-O-tethered mannosyl trichloroacetimidate donors. The versatility and effectiveness of this strategy were demonstrated with successful β-mannosylation of a wide variety of alcohol acceptors, including complex natural products, amino acids, and glycosides. Through iteratively performing ZnI2-mediated mannosylation with the chitobiosyl azide acceptor followed by site-selective deprotection of the mannosylation product, the novel methodology enables the modular synthesis of the key intermediate trisaccharide with Man-β-(1 → 4)-GlcNAc-β-(1 → 4)-GlcNAc linkage for N-glycan synthesis. Theoretical investigations with density functional theory calculations delved into the mechanistic details of this β-selective mannosylation and elucidated two zinc cations' essential roles as the activating agent of the donor and the principal mediator of the cis-directing intermolecular interaction. We thank the Fundamental Research Funds for the Central Universities (no. 31610011 to F.D.), the Province Natural Science Fund of Guangdong (no. 42030015 to F.D.), and the Sun Yat-sen University Startup Fund (no.18841224 to F.D.) for financial support and the grant-in-aid for Specially Promoted Research (no. 16H06290 to Y.I. and A.I.) and for Scientific Research (no.18K05345 and 19H00929 to A.I.) from the Japan Society for the Promotion of Science.

Chiral amphiphiles are useful for controlling the structures and properties of supramolecular assemblies, but their stereocontrolled synthesis is generally difficult, because their long alkyl chains tend to bring unfavorable effects on the solubility, reactivity, and crystallinity of molecules. Typical examples are amphiphilic 1,2-amino alcohols (S)-1 and (1S,2S)-2 developed by our group, which were known to serve as chiral reaction media for controlling the stereochemistry of asymmetric photoreactions. We previously developed synthetic schemes for these 1,2-amino alcohols, but their synthetic efficiencies were unsatisfactory (13 steps with 2% overall yield for (S)-1; eight steps with 8% yield for (1S,2S)-2). As the main reason of such low efficiencies, the stereocontrolling methods we previously employed (diastereomer-salt crystallization for (S)-1; stereoselective reactions for (1S,2S)-2) were not ideal. Here, we report highly improved synthetic schemes for (S)-1 and (1S,2S)-2 based on the enantioselective high performance liquid chromatography (HPLC) separation of intermediates in preparative scales. Compared with the previous schemes, the new schemes are advantageous in fewer number of steps, higher overall yield, and lower risk of racemization (seven steps with 15% overall yield for (S)-1; seven steps with 26% overall yield for (1S,2S)-2).

Chiral homoallylic vicinal diols are found in many bioactive compounds and are among the most versatile functional groups in organic chemistry. Here, we describe an asymmetric carbonyl allylation of aldehydes with allyl ethers proceeding via allylic C-H borylation enabled by palladium and chiral phosphoric acid sequential catalysis, providing facile access to homoallylic vicinal anti-diols in high yields and with excellent stereoselectivity. This protocol enables the total synthesis of aigialomycin D to be finished within 7 steps.

An efficient and concise synthesis of cytotoxic 5,6-dihydro-α-pyrone (+)-brevipolide H has been accomplished in 12 long linear steps in 8.65% overall yield from readily available chiral synthons, d-galactal and ethyl l-lactate. The features of this synthesis are highly diastereoselective Simmons–Smith cyclopropanation and carbohydrate-based chiron approach to rapid access to key 5,6-dihydro-α-pyrone skeleton.

Synthetic studies on an ABC-ring model of tubiferal A, a triterpenoid isolated from the fruit bodies of the Tubifera dimorphotheca myxomycete, are described. The stereogenic centers at the angular positions were constructed through the stereoselective addition of a C-ring allylborane followed by an Eschenmoser–Claisen rearrangement reaction prior to the formation of the AB-ring system by a double intramolecular alkylation reaction of a dichloro nitrile intermediate.

We disclose that the carbonates of 4-hydroxy-2-cyclopentenones can form π-allylpalladium-based 1,2-carbodipoles, which isomerize to interesting η2 -Pd0 -cyclopentadienone complexes. Compared with the labile parent cyclopentadienone, the HOMO energy of the related η2 -complex was significantly raised via the back-bonding of Pd0 as a π-Lewis base, rendering the uncoordinated C=C bond an electron-richer dienophile in inverse-electron-demand aza-Diels-Alder-type reactions with diverse 1-azadienes. The vinylogous (aza)Morita-Baylis-Hillman or cross Rauhut-Currier addition to (imine)carbonyls or activated alkenes, respectively, was also realized to afford chiral [4+2] or [2+2] cycloadducts, respectively, after trapping the re-generated π-allylpalladium species. New C1 -symmetric ligands from simple chiral sources were developed, exhibiting high stereoselectivity even with racemic substrates via an unusual dynamic kinetic resolution process. Besides, tropone could be similarly activated by a Pd0 complex.

In recent years, the synthesis of axially chiral compounds has received considerable attention due to their extensive application as biologically active compounds in medicinal chemistry and as chiral ligands in asymmetric catalysis. Chiral phosphoric acids are recognized as efficient organocatalysts for a variety of enantioselective transformations. In this review, we summarize the recent development of chiral phosphoric acid-catalyzed synthesis of a wide range of axially chiral biaryls, heterobiaryls, vinylarenes, N-arylamines, spiranes, and allenes with high efficiency and excellent stereoselectivity.

Iron-catalyzed direct SN2' dehydroxyboration of allylic alcohols has been developed to access (E)-stereoselective allylboronates. Allylic alcohols with diverse structures and functional groups, especially derived from natural products, underwent smooth transformation. The six-membered ring transition state formed by allylic alcohols and iron-boron intermediate was indicated to be the key component involved in transfer of the boron group, activation of the C-OH bond, and control of the stereoselectivity.

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that promotes a cyclization/allylic alkylation cascade of stable α-diazo-δ-keto-esters has been developed. Highly substituted 3(2H)-furanones with a C2-quaternary center can be obtained efficiently under mild conditions via one-pot synthesis. Remarkably, this binary catalytic system shows high chemo-, regio-, and stereoselectivity and excellent tolerance to various functionalities.

Penthiopyrad is a novel succinate dehydrogenase inhibitor that has one chiral center and exists a metabolite, 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxamide in its residue definition. An efficient analytical method for the simultaneous determination of penthiopyrad enantiomers and its metabolite in eight matrices were developed using modified quick, easy, cheap, effective, rugged, safe method, coupled with chiral stationary phase and ultra-high performance liquid chromatography-tandem mass spectrometry. The absolute configuration of penthiopyrad enantiomers was confirmed by polarimetry and electronic circular dichroism. Eight polysaccharide-based chiral stationary phases were evaluated in terms of the enantioseparation of penthiopyrad and separation-related factors (the mobile phase, flow rate and the column temperature) were optimized. To obtain an optimal purification, different sorbent combinations were assessed. The linearities of this method were acceptable in the range of 0.005 to 1 mg/L with R2 > 0.998, while the limits of detection and quantification were 0.0015 mg/kg and 0.01 mg/kg for two enantiomers and its metabolite. The average recoveries of R-(-)-penthiopyrad, S-(+)-penthiopyrad and the metabolite ranged from 75.4 to 109.1, 69.5 to 112.8, and 70.0 to 108.5%, respectively. The intra-day and inter-day relative standard deviations were less than 18.8%. The analytical method was accurate and convenient, which can support their further research on stereoselective degradation, residual monitoring and risk assessment.

A direct aza-Diels-Alder reaction between 2-aryl-3H-indolin-3-ones and cyclic-enones has been developed to access chiral indolin-3-one fused polycyclic bridged compounds. This method proceeds via proline-catalyzed Barbas-dienamine intermediate formation from various cyclic-enones such as 2-cyclopenten-1-one, 2-cyclohexene-1-one, and 2-cycloheptene-1-one, followed by a reaction with 2-aryl-3H-indol-3-ones. Several indolin-3-ones fusing [2.2.2], [2.2.1], and [3.2.1] skeletons decorated with a tertiary carbon chiral center have been prepared. Computational studies (DFT) supported the observed stereoselectivity in the method. The synthesized compounds have shown exciting photophysical activities and selective sensing of Pd2+ and Fe3+ ions through the fluorescence quenching "switch-off" mode.

Here we report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry. Mediated by a nitrogen extrusion process, the stereospecific synthesis of cyclobutanes involves a radical pathway. Unprecedented unsymmetrical spirocyclobutanes were prepared successfully, and a concise, formal synthesis of the cytotoxic natural product piperarborenine B is reported.

A 14-membered hexamethyl-tetraazamacrocycle, viz. Me6[14]diene.2HClO4 (L.2HClO4), afforded a mixture of isomeric ligands, Me6[14]anes, upon reduction with NaBH4 and extraction by CHCl3 at pH > 12. These ligands were separated by fractional crystallization from xylene and were designated as ‘tet-a’ and ‘tet-b.’ The interaction of ‘tet-b’ with excess acrylonitrile was fairly stereoselective and formed an N-pendent derivative, ‘tet-bx’, in which two cyano-ethyl groups were attached to trans N-atoms that are sterically less crowded. Aeration of ‘tet-bx’ and cobalt(II) acetate salt in methanol, followed by its treatment with HCl, yielded a bluish-green product, viz. trans-[Co(‘tet-bx’)Cl2]Cl. trans-[Co(‘tet-bx’)Cl2]Cl underwent axial substitution reactions with KSCN and KNO3 and subsequent axial substitution and anion exchange reactions with NaNO2, KBr, and KI to produce six-coordinated octahedral complexes, viz. bluish-green trans-[Co(‘tet-bx’)(NCS)2]Cl, light-blue trans-[Co(‘tet-bx’)(NO3)2]Cl, yellow trans-[Co(‘tet-bx’)(NO2)2]NO2, green trans-[Co(‘tet-bx’)Br2]Br, and red trans-[Co(‘tet-bx’)I2]I. These complexes were characterized using different modern analytical and spectroscopic techniques. The antibacterial activities of the N-pendent ligand and its cobalt(III) complexes on four types of selected bacteria were investigated.

A new imine-induced 1,2-boronate migration has been developed for achieving chemo- and stereoselective dearomative coupling of C3-substituted indoles and bi-electrophilic β-imino boronic esters, providing rapid access to complex chiral indoline boronic esters with four stereocenters including an all-carbon quaternary stereocenter and a tertiary α-aminoboronic ester. In contrast, coupling of indoles without C3 substitution and β-imino boronic esters provided tetrahydro-1H-pyrido[4,3-b]indoles via imine-induced 1,2-boronate migration followed by deborylative rearomatization.

Bioproduction of optical pure (R)-citronellal from (E/Z)-citral at high substrate loading remains challenging. Low catalytic efficiency of (R)-stereoselective ene reductases towards crude citral mixture is one of the major bottlenecks. Herein, a structure-based engineering strategy was adopted to enhance the catalytic efficiency and stereoselectivity of an ene reductase (OYE2p) from Saccharomyces cerevisiae YJM1341 towards (E/Z)-citral. On basis of homologous modelling, molecular docking analysis and alanine scanning at the binding pocket of OYE2p, a mutant Y84A was obtained with simultaneous increase in catalytic efficiency and stereoselectivity. Furthermore, site-saturation mutagenesis of Y84 yielded seven mutants with improved activity and stereoselectivity in the (E/Z)-citral reduction. Among them, the variant Y84V exhibited an 18.3% and 71.3% rise in catalytic efficiency (kcat /Km ) for (Z)-citral and (E)-citral respectively. Meanwhile, the stereoselectivity of Y84V was improved from 89.2% to 98.0% in the reduction in (E/Z)-citral. The docking analysis and molecular dynamics simulation of OYE2p and its variants revealed that the substitution Y84V enabled (E)-citral and (Z)-citral to bind with a smaller distance to the key hydrogen donors at a modified (R)-selective binding mode. The variant Y84V was then co-expressed with glucose dehydrogenase from Bacillus megaterium in E. coli D4, in which competing prim-alcohol dehydrogenase genes were deleted to prevent the undesired reduction in the aldehyde moiety of citral and citronellal. Employing this biocatalyst, 106 g l-1 (E/Z)-citral was completely converted into (R)-citronellal with 95.4% ee value and a high space-time yield of 121.6 g l-1 day-1 . The work highlights the synthetic potential of Y84V, which enabled the highest productivity of (R)-citronellal from (E/Z)-citral in high enantiopurity so far.

Conjugated dienes are versatile building blocks and prevalent substructures in synthetic chemistry. Herein, we report a method for the stereoselective hydroalkenylation of alkynes, utilizing readily available enol triflates. We leveraged an in situ generated and geometrically pure vinyl-Cu(I) species to form the Z,Z- or Z,E-1,3-dienes in excellent stereoselectivity and yield. This approach allowed for the synthesis of highly substituted Z-dienes, including pentasubstituted 1,3-dienes, which are difficult to prepare by existing approaches.

Exploring multistep cascade reactions triggered by C–H activation are recognized as appealing, yet challenging. Herein, we disclose a Rh(III)-catalyzed domino C–H coupling of N-carbamoyl indoles an...

We have developed a stereoselective, glycosyl radical-based method for the synthesis of C-alkyl glycosides via a photomediated defluorinative gem-difluoroallylation reaction. We demonstrate for the first time that glycosyl radicals, generated from glycosyl bromides, can readily participate in a photomediated radical polar crossover process, affording a diverse array of gem-difluoroalkene containing C-glycosides. Notable features of this method include scalability, mild conditions, broad substrate scope, and suitability for the late-stage modification of complex molecules.

The perfluoroalkylsulfonylation (CF3SO2, C2F5SO2 and CHF2SO2) in the enaminone C H bonds has been developed simply via the promotion of molecular iodine by using stable and cheap sodium perfluoroalkyl sulfinates as coupling partners. The stereoselective synthesis of E-configurated α-perfluoroalkylsulfonyl enaminones has been realized via unprecedented C H bond elaboration and C C double bond configuration inversion by free radical process.

Various cis-s-phosphinolactams are synthesized stereoselectively for the first time from imines and diazo(aryl)methyl(diaryl)phosphine oxides under microwave irradiation. Diazo(aryl)methyl(diaryl)phosphine oxides first undergo the Wolf rearrangement to generate phosphenes. Imines nucleophilically attack the phosphenes followed by an intramolecular nucleophilic addition via less steric transition states to give final cis-s-phosphinolactams. C-Styrylimines generally give rise to s-phosphinolactams in higher yields than C-arylimines. The stereoselectivity and proposed mechanism are rationalized by DFT theoretical calculation.