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A stereoselective hydroxyallylation reaction of cyclopropenes with cyclopropanols is achieved under zinc‐mediated conditions, affording densely functionalized cyclopropanes with excellent diastereocontrol over three contiguous stereocenters within and outside the cyclopropane ring. A racemic variant of the reaction is synergistically promoted by catalytic N‐heterocyclic carbene (NHC) and organic base, whereas chiral amino alcohol‐derived bifunctional NHC enables a catalytic enantioselective variant. The reaction likely involves the generation of enolized zinc homoenolate via ring‐opening of zinc cyclopropoxide and enolization of the resulting homoenolate, followed by its addition to the cyclopropene as a prochiral allylzinc nucleophile. Our mechanistic investigations highlighted the transient nature of enolized homoenolate, which, once generated from thermodynamically predominant cyclopropoxide, immediately proceeds to allylzincation with cyclopropene. The NHC not only promotes the rate‐determining generation of enolized homoenolate but also engages in the allylzincation process. The resulting cyclopropylzinc species undergoes partial in situ protonation while partially remaining intact, thereby leaving an opportunity for trapping with an external electrophile. [ABSTRACT FROM AUTHOR]

Herein, we report Rh(III) catalyzed aldehydic or aryl C–H alkylation via C–C bond activation of cyclopropanols, facilitating the synthesis of β-functionalized ketones. The protocol employs cyclopropanol as the alkylating agent with 2-aminobenzaldehyde or aniline derivatives to access a variety of unsymmetrical 1,4-diketones or β-aryl ketones, respectively. The practicality of these transformations is showcased through the modification of natural products, gram-scale synthesis, broad substrate scope and postfunctionalizations. [ABSTRACT FROM AUTHOR]

Despite the importance of heteroatom‐substituted cyclopropane derivatives in drug design and organic synthesis, cyclopropanethiols remain critically underexplored. Inspired by the wide use of the Newman‐Kwart rearrangement to access valuable thiophenols from phenol feedstocks, we report the development of a photocatalytic approach for efficient ambient temperature aliphatic O‐ to S‐rearrangement on tertiary cyclopropanol derivatives. After demonstrating that a range of cyclopropanethiols—that are difficult to access by other methods—can be obtained with this strategy, we show that these rearranged products can be easily hydrolyzed and further derivatized. We conclude this study with mechanistic findings that enabled an initial extension of this approach toward other classes of aliphatic alcohols. [ABSTRACT FROM AUTHOR]

A photoredox/copper co‐catalyzed ring‐opening cross‐coupling of aryl azides with cyclopropanols has been developed with fac‐Ir(ppy)3 as the photocatalyst. The reaction involves intermediacy of the anilino radical generated through reduction of the azido group by fac‐Ir(ppy)3* and [CuII]‐enabled oxidative ring‐opening of the cyclopropanol. An array of β‐aminoketone compounds were synthesized under redox‐neutral conditions by using this method. [ABSTRACT FROM AUTHOR]

Selected volatile organic compounds (VOCs), such as benzene (C6H6), cyclohexane (C6H12), isoprene (C5H8), cyclopropanone (C3H4O), propanol (C3H8O), and butyraldehyde butanal (C4H8O), in exhaled human breath can act as indicators or biomarkers of lung cancer diseases. Detection of such VOCs with low density would pave the way for an early diagnosis of the disease and thus early treatment and cure. In the present investigation, the density-functional theory (DFT) is applied to study the detection of the mentioned VOCs on Ti3C2TX MXenes, saturated with the functional groups Tx = O, F, S, and OH. For selectivity, comparative sensing of other interfering air molecules from exhaled breath, such as O2, N2, CO2, and H2O is further undertaken. Three functionalization (Tx = O, F, and S) are found promising for the selective detection of the studied VOCs, in particular Ti3C2O2 MXenes has shown distinct sensor response toward the C5H8, C6H6, C6H12, and C3H4O. The relatively strong physisorption ( E ads ≅ - 0.45 t o - 0.65 eV ), triggered between VOC and MXene due to an enhancement of van der Waals interaction, is found responsible to affect the near Fermi level states, which in turn controls the conductivity and consequently the sensor response. Meanwhile, such intermediate-strength interactions remain moderate to yield small desorption recovery time (of order τ ≅ μ s - ms) using visible light at room temperature. Thus, Ti3C2O2 MXenes are found promising candidate material for reusable biosensor for the early diagnosis of lung cancer diseases through the VOC detection in exhaled breath. [ABSTRACT FROM AUTHOR]

Presented herein is a synthesis of indane fused bicyclic pyrazolidinones based on the reactions of aryl azomethine imines with cyclopropanols. Mechanistically, the formation of product involves Rh(III)‐catalyzed direct aryl C(sp2)−H alkylation of aryl azomethine imine with cyclopropanol through in situ ring‐opening, followed by cascade intramolecular C‐ and N‐nucleophilic addition. In this tandem process, cyclopropanol acts as not only an alkylating agent but also masked nucleophile and electrophile to participate in the construction of both the indane and the bicyclic pyrazolidinone scaffolds. To our knowledge, such a cascade reaction pattern has not been disclosed. In general, this synthetic protocol has advantages such as easily obtainable substrates, valuable products, concise synthetic procedure, unique reaction pathway, and good compatibility with diverse functional groups. [ABSTRACT FROM AUTHOR]

β‐Silyl ketones reacted with aldehydes by treatment with KMMDS in the presence of 18‐crown‐6 to give β,γ‐unsaturated ketones accompanied with a skeletal rearrangement. The reactions proceeded by aldol reaction of β‐silyl ketones with aldehydes followed by [1,4]‐Brook rearrangement and intramolecular 1,2‐addition to form cyclopropanol derivatives, in which carbon‐carbon bond cleavage took place to afford β,γ‐unsaturated ketones. The β,γ‐unsaturated ketones were prepared in a one‐pot manner by conjugate addition of silyl anions to α,β‐unsaturated ketones followed by reactions with aldehydes. The Brook rearrangement proceeded with complete inversion of configuration at the carbon center. [ABSTRACT FROM AUTHOR]

The enantioselective reductive coupling of oxabenzonorbornadiene with vinyl bromide is developed with earth‐abundant nickel catalyst with copper as Lewis acid co‐catalyst. The asymmetric reductive coupling is applicable with a wide range of azabenzonorbornadienes and vinyl bromides under nickel/copper co‐catalytic system, affording the cis ring‐opening vinylation products in good yields with high optical purities. The present study has enabled straightforward stereoselective preparation of chiral 2‐vinyl‐tetrahydronaphthalens from vinyl halides. [ABSTRACT FROM AUTHOR]

A radical decarboxylative C(sp3)-C(sp3) cross-coupling of NHPI esters and cyclopropanols was developed by combining photocatalysis and copper catalysis, which presents the efficient access to β-benzyl ketones in excellent yields. Terpyridin-4′-one used as the ligand is vital for the reaction, which could facilitate the capture of benzylic radicals by alkyl-copper species generated from copper-catalyzed ring-opening of cyclopropanols. The reaction exhibited broad substrate scope and wide functional group compatibility, providing an alternative approach for C(sp3)-C(sp3) bond formation. [ABSTRACT FROM AUTHOR]

We report here a homo‐Mannich reaction of cyclopropanol with an iminium ion, generated by an asymmetric allylic dearomatization of indole, to construct a tricyclic hydrocarbazole core, which is shared by a variety of monoterpenoid indole alkaloids across families. Through this approach, an all‐carbon quaternary stereogenic center as well as an allyl and a ketone group were installed. Using this functionalized hydrocarbazole as the structural platform, D ring and E rings of different sizes (i.e. five‐, six‐, and seven‐membered) were successively or simultaneously assembled, leading to a collective asymmetric synthesis of seven alkaloids belonging to the ibophyllidine, Aspidosperma, Kopsia, and Melodinus alkaloid families. [ABSTRACT FROM AUTHOR]

Sarpagine alkaloids offer signicant opportunities in drug discovery, yet the efficient total syntheses and diverse structural modifications of these natural products remain highly challenging due to the architectural complexity. Here we show a homo-Mannich reaction of cyclopropanol with imines generated via a Bischler-Napieralski reaction enables a protecting-group-free, redox economic, four-step access to the tetracyclic sarpagine core from L-tryptophan esters. Based on this advancement, diversified syntheses of sarpagine alkaloids and analogues are achieved in a short synthetic route. The systematic anticancer evaluation indicates that natural products vellosimine and Na-methyl vellosimine possess modest anticancer activity. Intensive structural optimization of these lead molecules and exploration of the structure−activity relationship lead to the identification of analogue 15ai with an allene unit showing a tenfold improvement in anticancer activities. Further mechanism studies indicate compound 15ai exertes antiproliferation effects by inducing ferroptosis, which is an appealing non-apoptotic cell death form that may provide new solutions in future cancer therapies. The Mannich reaction is a well-established method for the synthesis of β-amino carbonyl compounds while the analogous reactions of homo-enol or its equivalents with imines or iminium ions are much less explored. Here, the authors describe a homo-Mannich reaction of cyclopropanol with imines generated via a Bischler-Napieralski reaction. [ABSTRACT FROM AUTHOR]

A zinc‐mediated annulation reaction between cyclopropanols and alkylidenemalononitriles is reported. The reaction is promoted in the presence of Et2Zn and 1,4‐diazabicyclo[2.2.2]octane (DABCO) in DMSO at 80 °C, affording cyclopropane‐fused 6‐amino‐3,4‐dihydro‐2H‐pyran‐5‐carbonitrile derivatives in moderate to good yields with high diastereoselectivity. The reaction is proposed to involve an enolized homoenolate as the key reactive intermediate, which is generated through ring opening of zinc cyclopropoxide and enolization of the resulting zinc homoenolate. The enolate moiety of this reactive species undergoes Michael addition to the alkylidenemalononitrile, which is followed by ring closure of the resulting α‐functionalized homoenolate and intramolecular cyclization between the cyclopropoxide and one of the cyano groups. [ABSTRACT FROM AUTHOR]

A general and efficient rhodium-catalyzed ortho -alkylation of N -arylpyrazoles has been accomplished with cyclopropanols as coupling partners. The reaction involves cleavage of both a C–H bond of the arene and a C–C bond of the cyclopropanol, and it offers access to a diversity of substituted 1-(ortho -alkylaryl)-1 H -pyrazoles in good to excellent yields. In addition, nonsymmetrical dialkylation and a preliminary mechanistic investigation are also discussed. [ABSTRACT FROM AUTHOR]

Due to high ring strain energies, cyclopropanols and cyclobutanols have a strong tendency of breaking the endocyclic C–C bonds to participate in versatile organic transformations. With an inherent three-dimensional structure, cyclopropanols and cyclobutanols have the advantage of synthesizing linear or cyclic molecules with stereogenic centers via ring-opening asymmetric synthesis. There are three strategies for the ring-opening of cyclopropanols and cyclobutanols usually involved in asymmetric synthesis: 1) β-carbon elimination of metal alkoxide; 2) radical ring-opening; 3) ring-opening via semipinacol rearrangement. The present review has highlighted the progress developed in the last five years.

Transition metal‐catalyzed site‐ and stereoselective C−H activation of strained (hetero)cycloalkanes remains a formidable challenge. We herein report a carbamate‐directed iridium‐catalyzed asymmetric β−C(sp3)−H borylation of cyclopropanol derivatives. A variety of densely functionalized cyclopropanols were obtained in good enantioselectivities via desymmetrization and kinetic resolution. In addition, site‐selective C(sp3)−H borylation of methine groups furnished α‐borylated (hetero)cycloalkanols in moderate to good yields. The synthetic utility of the method was further shown in a gram‐scale synthesis and diverse downstream transformations of borylated products. [ABSTRACT FROM AUTHOR]

S-Allylation of 4-pentyl- and 4-[(1-acetoxycyclopropyl)methyl]-3,4-dihydropyrimidine-2(1H)-thiones with 2-functionalized allyl bromides available from cyclopropanol intermediates has been reported for the first time. New unique heterocyclic compounds structurally related to 3rd generation calcium channel blockers have been synthesized in high yields. [ABSTRACT FROM AUTHOR]

An one‐pot three‐component synthesis of benzofuran‐3(2H)‐ones with tetrasubstituted carbon stereocenters from salicylaldehydes, cyclopropanols, and alkyl alcohols via Rh(III)‐catalyzed C−H/C−C bond activation and cascade annulation has been successfully developed. [ABSTRACT FROM AUTHOR]

Enantioselective copper‐catalyzed ring‐opening allylic alkylation of a cyclopropanol with an allyl phosphate was developed using a phenol‐NHC chiral ligand. DFT calculations indicated that a copper homoenolate is formed via Li−Cu bimetallic activation of a cyclopropoxide and that syn‐SN2' attack of the Cu center of the homoenolate to the allyl phosphate followed by facile C−C bond formation affords the β‐allylated ketone. Noncovalent interaction analysis showed that the enantiocontrol is achieved by the synergy of electrostatic interactions among Cu, Li, and O atoms, C−H⋅⋅⋅O interactions, and C−H/π London dispersions. [ABSTRACT FROM AUTHOR]

For the enantioselective diversification of a single starting material, a different chiral catalyst is usually required for each transformation. Herein, we extend the concept of catalytically formed chiral auxiliary from hydrogenation to the asymmetric cyclopropanation and epoxidation of tetra‐substituted olefins, alleviating the need for different chiral catalysts in the alkene functionalization step. The chiral auxiliary is catalytically constructed from propargylic amines in a Pd‐catalyzed enantioselective carboetherification step using a commercially available trifluoroacetaldehyde hemiacetal tether. The installed auxiliary is then controlling the stereochemistry of the cyclopropanation and the epoxidation using standard highly reactive reagents to give enantioenriched spirocyclic aminomethylcyclopropanols and α‐amino‐α‐hydroxy ketones. [ABSTRACT FROM AUTHOR]

The site‐selective C−H functionalization of heteroarenes is of considerable importance for streamlining the rapid modification of bioactive molecules. Herein, we report a general strategy for visible‐light‐induced β‐carbonyl alkylation at the C4 position of pyridines with high site selectivity using various cyclopropanols and N‐amidopyridinium salts. In this process, hydrogen‐atom transfer between the generated sulfonamidyl radicals and O−H bonds of cyclopropanols generates β‐carbonyl radicals, providing efficient access to synthetically valuable β‐pyridylated (aryl)ketones, aldehydes, and esters with broad functional‐group tolerance. In addition, the mild method serves as an effective tool for the site‐selective late‐stage functionalization of complex and medicinally relevant molecules. [ABSTRACT FROM AUTHOR]

Catalytic generation of cobalt enolates through ring-opening of easily accessible cyclopropanols, subsequent β-hydride elimination and site-selective reinsertion followed by diastereo- and enantioselective additions to aldimines is presented. Such a process represents an unprecedented reaction pathway of cobalt homoenolates, affording a wide range of β-amino-ketones in up to 95% yield, 90:10 dr and 99:1 er without the need of any stoichiometric amount of additive or reagent. [ABSTRACT FROM AUTHOR]

A facile synthesis of methyl 1,5‐diaryl‐1H‐pyrrole‐2‐carboxylates was reported in this article. Acid‐catalyzed reaction of methyl 2‐aroyl‐1‐phenoxycyclopropanecarboxylates with aromatic amines underwent smoothly to give methyl 1,5‐diaryl‐1H‐pyrrole‐2‐carboxylates in high to excellent yields under mild conditions. [ABSTRACT FROM AUTHOR]

Previous transition metal-catalyzed synthesis processes of δ-diketones are plagued by the high cost of the rhodium catalyst and harsh reaction conditions. Herein a low-cost, room temperature ruthenium catalytic method is developed based on the coupling of α-keto sulfoxonium ylides with cyclopropanols. The mild protocol features a broad substrate scope (47 examples) and a high product yield (up to 99%). Mechanistic studies argue against a radical pathway and support a cyclopropanol ring opening, sulfoxonium ylide-derived carbenoid formation, migratory insertion C–C bond formation pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Thiochroman-4-one 1,1-dioxide derivatives possess efficient antibacterial, antitumor, and HIV inhibitory activity. • The triplet excited state of thiochroman-4-one 1,1-oxide shows a remarkable reactivity. • Absolute rate constants for phenolic hydrogen abstraction and electron transfer reactions are diffusion controlled. • The triplet excited state of the lowest energy for thiochroman-4-one 1,1-oxide has a nπ* character. • Reactive intermediates such as the ketyl and the anion radical derived from the triplet thiochromanone were fully characterized. The phosphorescence spectrum of thiochroman-4-one 1,1-dioxide (1) in EPA rigid glass, at 77 K, showed vibrational resolution, characteristic of an nπ* triplet excited state. From this spectrum, triplet energy (E T) of 70.5 kcal mol−1 was calculated. Laser flash photolysis (λ exc = 266 nm) of a solution of 1 in acetonitrile resulted in the formation of a transient with λ max = 290 and 370 nm and a lifetime (τ T) of 2.0 ± 0.1 μs, with a self-quenching rate constant of (7.07 ± 0.59)x107 L mol−1 s−1. This transient was characterized as the excited state triplet of 1 by quenching experiments with 1,3-cyclohexadiene, trans -stilbene, cis -stilbene, and 1-methylnaphthalene. In all cases, the observed energy transfer quenching rate constant was equal to the diffusion rate constant for acetonitrile (k et ∼ 1010 L mol−1 s−1). Quenching studies for the hydrogen abstraction reaction (2-propanol or 1,4-cyclohexadiene) or electron transfer (triethylamine or DABCO) revealed the formation of new transients derived from thiochroman-4-one 1,1-dioxide, i.e. , the ketyl radical for the former and the radical anion for the later process. The quenching rate constants measured ranged from (3.71 ± 0.18)x107 L mol−1 s−1 (2-propanol) to (5.32 ± 0.15)x109 L mol−1 s−1 (triethylamine). The triplet state of 1 was also efficiently quenched by substituted phenols containing polar groups and indole (k q = 109 L mol−1 s−1). For all these quenchers, new transients were formed, which were assigned to the corresponding radical pair ketyl/aryloxyl (for phenols) and ketyl/indolyl (for indole). It was concluded from the results of the steady-state phosphorescence emission of thiochroman-4-one 1,1-dioxide and the rate constants measured for the several quenching processes using the laser flash photolysis technique that the remarkable reactivity of triplet 1 must be attributed to the n,π* character of its carbonyl chromophore. [ABSTRACT FROM AUTHOR]

The diastereoselective carbocupration reaction of alkoxy-functionalized cyclopropene derivatives, followed by a subsequent trapping of the resulting cyclopropylmetal species with an electrophilic source of oxygen (oxenoid) afforded various tetrasubstituted cyclopropanol derivatives in high diastereo- and enantiomeric ratios. Similarly, the enantioselective copper-catalyzed carbomagnesiation/oxidation (or amination) sequence on achiral nonfunctionalized cyclopropenes provided the desired cyclopropanol (and cyclopropylamine) derivatives in excellent diastereo- and enantiomeric excesses.

We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L‐tryptophan as the starting material. Two key bridged skeleton‐forming reactions, namely tandem sequential oxidative cyclopropanol ring‐opening cyclization and ketone α‐allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, Na‐methyl‐16‐epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N‐demethylkoumine) with more complex cage scaffolds has been accomplished. [ABSTRACT FROM AUTHOR]

Sex pheromone is one of the most promising and environment-friendly strategies to control the fall armyworm moth. In this review, the separation process, structure identification and application of the sex pheromone of Spodoptera frugiperda were summarized. Its compoments comprise monoolefinic esters and diolefinic esters. The chemical synthesis of the sex pherpmone were reviewed. Among them, the construction of the Z- double bond was mainly involved in catalytic hydrogenation of alkyne, Z-selective cross metathesis of olefin, Z-olefin, Wittig coupling, vinylic organoborane and ring opening of cyclooctadiene and the E-one included Grignard coupling, ring opening of cyclepropylethanol and E-olefinic ester. Besides, the current problems and the future researches of the sex pheromone of S. frugiperda were discussed. [ABSTRACT FROM AUTHOR]

A one-step catalytic oxidant-free synthesis of unsaturated ketones from 1,2-disubstituted cyclopropanols is reported. Previously for this transformation, only two- and three-step protocols have been developed. The reaction proceeds under irradiation with visible light in the presence of catalytic amounts of both an acridinium photocatalyst and a cobaloxime complex. 2-Aryl-substituted cyclopropanols react giving α,β-unsaturated ketones, while dehydrogenative ring opening of 2-alkyl-substituted substrates affords mixtures of α,β- and β,γ-enones. The reaction starts with one-electron oxidation of a cyclopropanol to cyclopropyloxy radical, presumably, by the photoexcited acridinium catalyst. We also found that Co(dmgBF2)2 (MeCN)2 complex under an air atmosphere and irradiation with blue LEDs or upon heating can serve as a hydroxycyclopropane oxidant. [ABSTRACT FROM AUTHOR]

This short review summarizes the most recent developments (since 2010) in the tandem cyclization/cycloaddition of allene intermediates-, generated from the copper-catalyzed cross-coupling of diazo compounds with terminal alkynes, to afford cyclic compounds. 1 Introduction 2 Cyclization 2.1 Cyclization with Nucleophiles 2.2 Cyclization with Electrophiles 2.3 6π-Electrocyclization 2.4 Other Cyclization 3 Cycloaddition 4 Conclusion [ABSTRACT FROM AUTHOR]

A new ring opening reaction was found while attempting to isolate the imines from ortho‐heteroatom substituted anilines and camphor‐like bicyclic ketones. The benzoazoles containing a cyclopentanemethyl group at position 2 of the heterocycle were isolated instead of the expected imines. The detailed study of the transformation, including EPR experiments, revealed the most probable radical mechanism. The proposed reaction pathways were confirmed by quantum chemical calculations. The dichotomy of 1–2 and 2–3 bonds cleavage is discussed together with the evaluation of the stereochemical outcome of the reactions. The benzoazoles obtained via the new reaction are of particular interest for the medicinal chemistry. [ABSTRACT FROM AUTHOR]

The mechanisms of CC activation of 1‐benzylcyclopropan‐1‐ol to produce 1,6‐diketone have been investigated by density functional theory calculations. The catalyst [Cp*RhCl2]2 and additive Ag2CO3 play an important role in controlling the selectivity. By using [Cp*RhCl2]2 as the catalyst and Ag2CO3 as the additive, the product is 1,6‐diketone, whereas the β‐hydride elimination product could not be obtained. The product would become monoketone in the absence of [Cp*RhCl2]2. In addition, the combination of catalyst [Cp*RhCl2]2 and additive AgOAc would also lead to monoketone. The observed selectivity could be attributed to the electronic effect. [ABSTRACT FROM AUTHOR]

An efficient method was developed for the alkylation of 2‐arylquinazolin‐4(3H)‐ones with cyclopropanols. The desired products β‐aryl ketones bearing the quinazolin‐4(3H)‐one scaffold were synthesized by Rh(III)‐catalyzed C−H activation of arenes and C−C cleavage of cyclopropanols. This method has a wide range of benzyl/phenyl substrate applicability and provides a theoretical guidance for our research to study quinazoline compounds. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFIs) are life threatening and existing antifungal drugs are not completely effective due to undesirable side effects and resistance emergence. Azoles are often the treatment of choice for IFIs and growing evidence suggests that copper can act synergistically with these drugs. In this work, we designed a compound bringing together azole and copper(II)-binding groups and studied the molecular mechanisms underlying its biological toxicity. Our results show that both the compound, 4, and its copper(II) complex, Cu.4, are active against Candida spp. We found that Cu.4 acts as a copper(II) ionophore, which results in the intracellular accumulation of reactive oxygen species (ROS), whereas compound 4 is an iron chelator and exerts its toxicity by decreasing iron bioavailability. Interestingly, while 4 is not very toxic to macrophages or HeLa cells, Cu.4 significantly affects their viability. Overall, this work provides evidence of how copper can be combined with azoles to deregulate copper homeostasis, opening new horizons for the development of bifunctional antifungals. [ABSTRACT FROM AUTHOR]

Utilizing the C4 reactive site of cyclopropyl ketones and a chiral N,N′-dioxide-scandium(III) complex as a catalyst, a concise ring-opening/cyclization/thio-Michael cascade method was developed for the synthesis of chiral benzothiazole derivatives from a simple 2-aminothiophenol material. The kinetic resolution and the origin of stereoselectivity were elucidated via a possible catalytic model. [ABSTRACT FROM AUTHOR]

The main objective of this study concerns the sonochemical synthesis of 1,3-dioxolane derivatives using graphene oxide catalyst by applying two methods. In the first method, we described the synthesis of 1,3-dioxolane by ring-opening of epoxides in the presence of ketones catalyzed by graphene oxide (GO) under ultrasonic irradiation. In the second sonochemical procedure, we described the synthesis of 1,3-dioxolane derivatives by the reaction of 1,2-diols with ketones using same GO catalyst. Mild reaction conditions, high yields, short reaction times, reusability of catalyst and easy isolation of the products make the developed methods very useful. [ABSTRACT FROM AUTHOR]

New N-substituted enamino ketones were synthesized by directed transformation of 3-acetyl- and 3-benzoyl-5,6,7,8-tetrafluoro-4H-chromen-4-ones by the action of highly basic primary amines as a result of opening of the pyranone ring and deacylation. The synthesizedN-hexyl and N-octyl derivatives were evaluated for fungistatic and bacteriostatic activities. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria of the Burkholderia pseudomallei group cause severe infectious diseases such as glanders and melioidosis. Malleicyprols were identified as important bacterial virulence factors, yet the biosynthetic origin of their cyclopropanol warhead has remained enigmatic. By a combination of mutational analysis and metabolomics we found that sulfonium acids, dimethylsulfoniumpropionate (DMSP) and gonyol, known as osmolytes and as crucial components in the global organosulfur cycle, are key intermediates en route to the cyclopropanol unit. Functional genetics and in vitro analyses uncover a specialized pathway to DMSP involving a rare prokaryotic SET‐domain methyltransferase for a cryptic methylation, and show that DMSP is loaded onto the NRPS‐PKS hybrid assembly line by an adenylation domain dedicated to zwitterionic starter units. Then, the megasynthase transforms DMSP into gonyol, as demonstrated by heterologous pathway reconstitution in E. coli. [ABSTRACT FROM AUTHOR]

Advances in the field of phosphorus chemistry are documented, by revealing the synthetic utility of previously underutilized quaternary phosphiranium salts (QPrS) as three‐chain‐atom electrophilic building blocks. Notably, control of their challenging C‐centered electrophilicity is disclosed with an expedient synthesis of tertiary β‐anilino phosphines as a proof‐of‐concept. [ABSTRACT FROM AUTHOR]

A novel approach for enantioselective cyanation of cyclopropanols and their derivatives through copper‐catalyzed radical relay processes has been developed. Various cyclopropanols and cyclopropanone acetals are compatible to the catalytic conditions, providing β‐carbonyl nitriles with excellent enantioselectivity. These products can be readily converted to chiral γ‐amino acids derivatives and drugs such as (R)‐baclofen. Preliminary mechanistic studies have supported a ring‐opening process for cyclopropanoxy radicals followed by copper‐catalyzed enantioselective cyanation of benzylic radicals to form the C−CN bonds in an enantioselective manner. [ABSTRACT FROM AUTHOR]

Direct C–H β‐carbonyl alkylation of heteroarenes under metal‐, acid‐ and photo‐catalyst free conditions has been achieved. A wide scope of substrates, such as various substituted quinolines and isoquinolines, pyridines, pyridazine, benzo[d]thiazole and phenanthroline, underwent the β‐carbonyl alkylation efficiently via K2S2O8‐mediated ring‐opening of cyclopropanols. The corresponding β‐heteroarylated ketones were obtained in moderate to excellent yields and gram‐scale experiments further demonstrated the practicality of this synthetic protocol. The readily available reagents, mild and environmentally benign conditions make the method extremely attractive. The reaction mechanism is also proposed. [ABSTRACT FROM AUTHOR]

Direct C–H β‐carbonyl alkylation of heteroarenes under metal‐, acid‐ and photo‐catalyst free conditions has been achieved. A wide scope of substrates, such as various substituted quinolines and isoquinolines, pyridines, pyridazine, benzo[d]thiazole and phenanthroline, underwent the β‐carbonyl alkylation efficiently via K2S2O8‐mediated ring‐opening of cyclopropanols. The corresponding β‐heteroarylated ketones were obtained in moderate to excellent yields and gram‐scale experiments further demonstrated the practicality of this synthetic protocol. The readily available reagents, mild and environmentally benign conditions make the method extremely attractive. The reaction mechanism is also proposed. [ABSTRACT FROM AUTHOR]

Herein we demonstrated an approach for the synthesis of 1,3‐benzoxazines through 1,8‐Diazabicyclo(5,4,0)undec‐7‐ene (DBU) promoted annulation of geminal dibromoolefins. The key features of this work include good reaction yield, high regioselectivity, mild reaction condition, metal‐free approach, and broad scope. Synthetic application for some of the products is extended to achieve α‐bromomethyl Ketones (Phenacyl bromides) via ring opening sequence using stoichiometric amount of water and DMSO as solvent. We also successfully demonstrated the applicability to gram scale synthesis and one‐pot strategy. This protocol serves as an alternative approach to the conventional reaction of α‐bromination of ketones. [ABSTRACT FROM AUTHOR]

A general method for the synthesis of structurally diverse N-arylpyrazoles from readily available cyclopropanols and aryldiazonium salts is disclosed. The reaction was conducted at room temperature within minutes with a broad substrate scope and excellent regioselectivity. [ABSTRACT FROM AUTHOR]

New epoxides, derivatives of pyridine, 2,2′-bipyridine, and 1,10-phenanthroline, were synthesized from the respective α-methylazaarenes. The obtained racemic 2-oxiranyl-azaarenes along with styrene oxide and trans-stilbene oxide were submitted to the ring opening with chiral primary amines as a chiral auxiliary. The most effective reaction was run in the presence of Sc(OTf)3/diisopropylethylamine for 7 days at 80°C, affording a good yield of the amino alcohols. Except for styrene oxide which gave both α- and β-amino alcohols, the reactions led regioselectively to the corresponding diastereomeric β-amino alcohols. The resulting diastereomers were separated, and the configurations of their stereogenic centers were established. The obtained enantiomerically pure 2-pyridinyl- and 6-(2,2′-bipyridinyl)-β-amino alcohols were tentatively tested as chiral ligands in the zinc-catalyzed aldol reaction. [ABSTRACT FROM AUTHOR]

Burkholderia species such as B. mallei and B. pseudomallei are bacterial pathogens causing fatal infections in humans and animals (glanders and melioidosis), yet knowledge on their virulence factors is limited. While pathogenic effects have been linked to a highly conserved gene locus (bur/mal) in the B. mallei group, the metabolite associated to the encoded polyketide synthase, burkholderic acid (syn. malleilactone), could not explain the observed phenotypes. By metabolic profiling and molecular network analyses of the model organism B. thailandensis, the primary products of the cryptic pathway were identified as unusual cyclopropanol‐substituted polyketides. First, sulfomalleicyprols were identified as inactive precursors of burkholderic acid. Furthermore, a highly reactive upstream metabolite, malleicyprol, was discovered and obtained in two stabilized forms. Cell‐based assays and a nematode infection model showed that the rare natural product confers cytotoxicity and virulence. [ABSTRACT FROM AUTHOR]

Based on the discovery of copper‐catalyzed cyclopropanol ring‐opening addition to iminium ions, an unprecedented catalytic aerobic C−H oxidation/cyclopropanol cyclization cascade using CuCl2 as the multifunctional catalyst and air as the oxidant was developed to construct the azabicyclo[3.3.1]nonane skeleton, which is widespread in natural products and medicines. Using this method, concise asymmetric total synthesis of the indole alkaloid (−)‐suaveoline was achieved. This study not only provides an efficient, low‐cost, and environmentally benign method for constructing such bridged frameworks, but also enriches the realm of cyclopropanol chemistry and C−H functionalization. [ABSTRACT FROM AUTHOR]

A novel method for preparing aromatic compounds containing cyclopropoxy via nucleophilic aromatic substitution reaction (SN Ar) of fluoroaromatic compounds with cyclopropanol under relatively mild conditions is presented. As compared to the approaches reported previously for preparing 1-(cyclopropyloxy)-2-nitrobenzene, the one proposed in this work is simplified without sacrificing the yields: When the reaction was performed at 75 °C with Cs2 CO3 as the base and DMF as solvent, after 6 h the yield was up to 90%. Finally, various fluoroaromatic compounds were employed as substrates for a test that proves a wide application scope of the method. [ABSTRACT FROM AUTHOR]

Homoenolates are unique synthetic intermediates which display umpolung reactivity. Homoenolates and homoenolate equivalents like cyclopropanols have seen a recent surge in popularity due to their particular utility for accessing β‐functionalized carbonyl derivatives. This popularity has been enabled by the development of protocols for facile access to cyclopropanols and homoenolates from a variety of readily available starting materials. This microreview will highlight common strategies for generating cyclopropanols and metal homoenolates, as well as procedures for homoenolate functionalization, with a particular emphasis on protocols that have appeared after 2003. As an amphoteric molecule, two main reactivity modes have been established: the homoenolate reacts as a carbon nucleophile for β‐functionalization reactions and/or as a carbonyl electrophile, a strategy which has only emerged in the past few years. This microreview will highlight the use of homoenolates as convenient intermediates for accessing especially challenging motifs. The use of homoenolate chemistry in the context of natural product and pharmaceutical synthesis will also be presented. This microreview highlights recent strategies for the synthesis of homoenolates and cyclopropanols, as well as protocols for homoenolate functionalization, both as nucleophilic and electrophilic reagents. The unique reactivity and synthetic utility of metal homoenolates is further showcased in recent examples of their use in natural product and pharmaceutical synthesis. [ABSTRACT FROM AUTHOR]