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Atropo‐enantioselective biaryl coupling through C−H bond functionalization is an emerging technology allowing direct construction of axially chiral molecules. This approach is largely limited to electrophilic coupling partners. We report a highly atropo‐enantioselective C−H arylation of tetralone derivatives paired with aryl boronic esters as nucleophilic components. The transformation is catalyzed by chiral cyclopentadienyl (Cpx) iridium(III) complexes and enabled by oxidatively enhanced reductive elimination from high‐valent cyclometalated Ir‐species., A highly atropo‐enantioselective C−H arylation of tetralone derivatives paired with aryl boronic esters as nucleophilic components is presented. The transformation is catalyzed by chiral cyclopentadienyl (Cpx) iridium(III) complexes and enabled by oxidatively enhanced reductive elimination from high‐valent cyclometalated Ir‐species.

To show the synthetic utility of the catalytic C-C activation of less strained substrates, described here are the collective and concise syntheses of the natural products (-)-microthecaline A, (-)-leubehanol, (+)-pseudopteroxazole, (+)-seco-pseudopteroxazole, pseudopterosin A-F and G-J aglycones, and (+)-heritonin. The key step in these syntheses involve a Rh-catalyzed C-C/C-H activation cascade of 3-arylcyclopentanones, which provides a rapid and enantioselective route to access the polysubstituted tetrahydronaphthalene cores presented in these natural products. Other important features include 1) the direct C-H amination of the tetralone substrate in the synthesis of (-)-microthecaline A, 2) the use of phosphoric acid to enhance efficiency and regioselectivity for problematic cyclopentanone substrates in the C-C activation reactions, and 3) the direct conversion of serrulatane into amphilectane diterpenes by an allylic cyclodehydrogenation coupling.

Here, ketones bearing two bulky substituents, named bulky-bulky ketones, were successfully reduced to their corresponding optically-enriched alcohols using various mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). Substituted 2-tetralones in particular were reduced to 2-tetralols with high conversion and high enantioselectivity. The pharmacological importance of substituted 2-tetralols as key drug-building blocks makes our biocatalytic reduction method a highly essential tool. We showed that changing the position of the substituent on the aromatic ring of 2-tetralones impacted their binding affinity and the reaction maximum catalytic rate. Docking studies with several TeSADH mutants explained how the position of the substituent on the tetralone influences the binding orientation of substituted 2-tetralones and their reaction stereoselectivity.

High-performance liquid chromatography (HPLC) is a powerful method in the area of chiral separation. In this study, a method of HPLC using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector was developed for enantioseparation of nine indanone and tetralone derivatives. The separation was performed on a conventional C18 column. The optimal mobile phase was a mixture of methanol and 0.05 mol/L phosphate buffer at pH 1.8 (55:45, v/v) containing 22.9 mmol/L CM-β-CD. Under such conditions, the resolutions of all analytes were over 1.8 except for Compound F. The results of the study indicate the presence of a complex with 1:1 stoichiometry of the inclusion complex. In addition, it can be inferred from thermodynamic analysis that the behavior of formation of the inclusion complex and enantioseparation occurred simultaneously, while they were driven by different forces. The effect of analyte structure is also discussed.

Five new spirobisnaphthalenes (1–5), one new tetralone derivative (6), and six new lactones (7–12) together with the known compound urnucratin C (13) have been isolated from the solid culture of the cup fungus Plectania sp. The structures of the new compounds were unambiguously elucidated on the basis of one- and two-dimensional NMR spectroscopy, high-resolution mass spectrometry, and circular dichroism (CD) spectroscopy. Compounds 1–6 were found to be active against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Bacillus subtilis, and Pseudomonas aeruginosa. In addition, the cytotoxicities of 1–13 were evaluated against the HepG2 and K562 cell lines by using the CCK8 assay. Compounds 1–3 and 13 showed moderate cytotoxicity against HepG2 and K562 with IC50 values in the range 10.7–38.5 µm. This is the first report of secondary metabolites from this cup fungus.

A convergent synthesis of (–)-dehydro-3-O-methyl-C/D-cis-estradiol started from stereochemically defined substituted optically active 3-(2-arylethyl)-γ-butyrolactones. Regioselective bromination of the anisyl moiety, reductive ring opening of the iodolactone, and protecting-group changes led to a Weinreb amide. This then underwent an intramolecular Grignard reaction closing the B-ring to give a tetralone with defined configuration. Introduction of C-11 through an allyl Grignard addition and subsequent ring-closing metathesis gave a tetrahydro phenanthrene derivative. Oxidation of the side-chain alcohol resulted in the key aldehyde group, and a final samarium-diiodide-mediated reductive D-ring annulation resulted in the generation of the target dehydro-C/D-cis-estradiol derivatives with high stereoselectivity. Structure elucidation was carried out using NOEDS (nuclear Overhauser enhanced differential spectroscopy) analysis on the one hand, and conversion into known 3-O-methyl-13β-estradiols by double-bond hydrogenation on the other. Further efforts to use this estradiol synthetic strategy to generate more complex steroidal natural products and pharmaceutically interesting compounds are in progress.

Metal-triflate-catalyzed intramolecular Friedel–Crafts acylation of 3-arylpropanoic and 4-arylbutanoic acids in triflate-anion ionic liquids under monomodal microwave irradiation is reported. The environmentally benign synthetic procedure allows the formation of cyclic ketones in good yields within a short reaction time. The catalytic metal triflate in triflate-anion ionic liquids can be easily recovered and reused several times without significant loss of the catalytic performance.

Biocatalytic reduction of prochiral ketones using freshly ripened clementine mandarin (Citrus reticulata) in aqueous medium is reported. High enantioselectivities were observed, especially for the bioreduction of indanone 3, tetralone 4, and thiochromanone 5 with respectively 95%, 99%, and 86% enantiomeric excess (ee). Enantioselective bio- and metal-catalyzed reactions were compared. Chiral ruthenium catalysts afforded good asymmetric inductions (>75% ee) in most cases, enantiomeric excesses depending on the nature of substrate and ligand. N-aminoindanol prolinamide L3 was revealed as the best ligand for most ketones. Interestingly, for several substrates both enantiomers could be obtained using either Citrus reticulata or ruthenium complex. Chirality 27:205–210, 2015. © 2014 Wiley Periodicals, Inc.

WOS: 000401253900001, PubMed ID: 27780313, Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti-HIV agents. In this study, the synthesis of novel tetralone-based benzothiazepine derivatives (1-16) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II ( hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography from fresh human red blood cells. All compounds demonstrated the low nanomolar inhibitory effects on both isoenzymes using esterase activity. Benzothiazepine derivative 2 demonstrated the best hCA I inhibitory effect with Ki value of 18.19 nM. Also, benzothiazepine derivative 7 showed the best hCA II inhibitory effect with Ki value of 11.31 nM. On the other hand, acetazolamide clinically used as CA inhibitor, showed Ki value of 19.92 nM against hCA I and 33.60 nM against hCA II, respectively., Gaziosmanpasa University, Scientific Research Projects Commission [BAP2014/33]; King Saud University, Contract Grant Sponsor: Gaziosmanpasa University, Scientific Research Projects Commission.; Contract Grant Number: BAP2014/33.; Contract Grant Sponsor: King Saud University.

973 Programs [2010CB833802, 2012CB721005]; National Science Fund for Distinguished Young Scholars [30325044]

Four new tetralone derivatives, clindanones A and B (1 and 2) and cladosporols F and G (3 and 4), together with three known biogenetically related polyketides (5–7), were isolated from the deep-sea derived fungus Cladosporium cladosporioides HDN14-342. The structures of 1–4, including absolute configurations, were deduced based on MS, NMR and TD-DFT calculations of specific ECD spectra. The absolute configurations of the known cladosporols C (5) and E (6) were also revised. Compounds 1 and 2 possessed new dimeric forms of the skeleton composed by coupling of indanone and 1-tetralone units, and 4 showed the best cytotoxic activity against HeLa cells with an IC50 value of 3.9 μM.

The development of a stereoselective one-pot oxidative [3,3] sigmatropic rearrangement/Friedel-Crafts arylation that provides enantioenriched benzhydryl compounds is reported. The utility of this new transformation is demonstrated by the concise synthesis of several tetralone- and naphthyl-type lignan natural products, many of which display anti-malarial activity.

Highly enantioselective catalytic oxidation of 1-tetralone-derived β-keto esters was achieved by using a guanidine–urea bifunctional organocatalyst in the presence of cumene hydroperoxide (CHP), a safe, commercially available oxidant. The α-hydroxylation products were obtained in 99 % yield with up to 95 % enantiomeric excess (ee). The present oxidation was successfully applied to synthesize a key intermediate of the anti-cancer agent daunorubicin (2).

The asymmetric protonation of silyl enolates derived from tetralone, benzosuberone, and cyclohexanone has been successfully achieved by using simple and original betaine catalysts derived from Cinchona alkaloids (quinine and quinidine series) to afford the desired α-substituted ketones in high yields and moderate enantioselectivities. The ease of implementation of this approach along with the easy accessibility of the betaine catalyst (four steps from cheap and commercially available quinine or quinidine) make this approach very appealing for the preparation of enantioenriched α-monosubstituted carbonyl compounds.

A chiral Lewis base or a phase-transfer catalyst (PTC) can mediate the highly enantioselective trifluoromethylthiolation of β-ketoesters with the previously developed SCF3 reagent. Reactions of indanone-derived β-ketoesters occurred with high yield and excellent enantioselectivity with quinine as catalyst. Reactions of tetralone- or 1-benzosuberone-derived β-ketoesters occurred with moderate to good enantioselectivity with a quinine-derived PTC.

Starting from cyclohexanone derivatives and alcohols, both non-aromatic precursors, aryl ethers could be synthesized in good yields and with good selectivities in the presence of a catalytic amount of Pd/C, in one step, without added solvent, in a reaction vessel open to air. For less reactive substrates, the addition of 1-octene in a closed system under non-aerobic conditions improved the conversion. In addition, the catalyst could be recycled several times with no decrease in the yield of the aryl ether. The process was also used with tetralone derivatives and polyols. Several reactions were performed to propose a mechanism for this transformation. The formation of an enol ether followed by a dehydrogenation reaction seem to be the key steps of this reaction.

Two novel tetralone dimers, with an O-bridge, named juglanones A and B (1 and 2, resp.), were isolated from the AcOEt extract of walnut pericarps. These compounds are the first examples of O-bridged dimeric tetralones. Their structures were determined by spectroscopic methods, including HR-TOF-MS, and 1D- and 2D-NMR. Biological evaluation of these two isolates against a number of human cancer cell lines is also described.

Four known hydroxyanthraquinones (1-4) together with four new derivatives having a tetralone moiety, namely coniothyrinones A-D (5-8), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations of coniothyrinones A (5), B (6), and D (8) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C (7) as well. Coniothyrinones A (5), B (6), and D (8) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives. This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp. These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium.

The efficient, highly enantioselective preparation of a variety of tetralone derivatives with two contiguous stereocenters and diverse functional groups is described.

Enamines derived from β-tetralone and morpholine and dimethylamine (Ia,b), react with carbenes IIa,b to give 1:1 adducts IIIa,b and ring-insertion products IVa,b, respectively. The reaction of pyrrolidine enamine Ic with the carbenes leads to the formation of new types of products which have been identified as VI and VII. Possible mechanisms for the formation of the reaction products are presented.

Synthesis of enamines 2a-f, derived from α-tetralones 1a, 1b, is described. Steric effects in the formation of these enamines and in the spectral properties of the corresponding 2-substituted derivatives are discussed.

Ausgehend von Flavon und Flavanon, zwei Naturstoffen mit schwacher Aromatase-inhibitorischer Wirkung, wurden die Verbindungen 1-7 synthetisiert und auf ihre Hemmaktivitat gegenuber Aromatase und Desmolase unlersucht. Mit Ausnahme von Verbindung 2 zeigen alle Derivate eine starkere Aromatase-Hemmung als die Ausgangsverbindungen und erweisen sich auch als potentere Aromatase-Inhibitoren als Aminoglutethimid (AG), der einzige im Handel befindliche Wirkstoff. Im Gegensatz zu AG zeigen die Verbindungen 1 und 3-7 keine Hemmung der Desmolase, die bei AG zu unerwunschten Nebenwirkungen fuhrt. Pyridyl-substituted Tetralone Derivatives: A New Class of Nonsteroidal Aromatase Inhibitors Structural modification of flavone and flavanone, two weak inhibitors of aromatase, led to the new compounds 1-7, the syntheses of which are described as well as the evaluation of their aromatase and desmolase inhibitory potency. With the exception of 2 all compounds show a stronger inhibition of aromatase than the parent compounds and are more effective inhibitors than aminoglutethimide (AG), the only commercially available compound. In contrast to AG compounds 1 and 3-7 exhibit no desmolase inhibitory activity. In case of AG this effect leads to undesirable side effects.

Three new alpha-tetralone galloylghlcosides, 1-3, were isolated from the fresh pericarps of Juglans sigillata (Juglandaceae), together with six known compounds. The structures of the new compounds were determined as 1,2,3,4-tetrahydro-7-hydroxy-4-oxonaphthalen-1-yl 6-O-[(3,4,5-trihydroxyphenyl)carbonyl]-beta-D-glucopyranoside (1), (IS)-1,2,3,4-tetrahydro-8-hydroxy-4-oxonaphthalen-1-yl 6-O-[(3,4,5-trihydroxyphenyl)carbonyl]-beta-D-glycopyranoside (2), and 1,2,3,4-tetrahydro-7,8-dihydroxy-4-oxonaphthalen-1-yl 6-O-[(3,4,5-trihydroxphenyl)carbonyl]-beta-D-glucopyranoside (3), respectively, on the basis of detailed spectroscopic analyses, and acidic and enzymatic hydrolysis. The antimicrobial activities of the isolated compounds 2, 4, and 7-9 were evaluated.

Two new tetralones, pyrolones A (1) and B (2), and a new flavonol glycoside, 2''-O-(4-hydroxybenzoyl)hyperin (3), were isolated from Pyrola calliantha (whole plant), together with six structurally related compounds, including 2''-O-galloylhyperin (4), hyperin (5), formononetin (6), quercetin 3-O-alpha-L-arabinopyranoside (7), quercetin 3-O-alpha-L-arabinofuranoside (8), and kaempferol 3-O-beta-D-galactopyranoside (9). The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic (UV, ORD, CD, NMR) and mass-spectrometric (HR-ESI-MS) analyses.

Benzoic acid esters (I) and (V), heteroaromatic esters (VIII) and (X), acetophenones (XII), benzaldehydes (XVII) as well as tetralone (XV) form corresponding annelated Si-dialkylated 1,2-oxasilol derivatives via respective dialkylsilylated alcohols, e.

A novel protocol for the synthesis of title compounds (III) and (V) from the three-component reaction of tetralone (I) or indanone (IV), 2-hydroxyphenyl functionalized α,β-unsaturated ketones (II) and iodine is reported.

Results are reported on the regioselective C-deuteriation of 2-methyl-tetralone using a series of D-sources and tertiary amines as potential mediators. The results presented further aid the understanding of kinetic deuteriation of both ‘base-containing’ and ‘base-free’ enolates. Copyright © 2006 John Wiley & Sons, Ltd.

Results are reported on the regioselective C-deuteriation of 2-methyl tetralone using piperidine-d11 as a deuterium source. The results presented further aid the understanding of kinetic deuteriation of amine–enolate complexes. Copyright © 2004 John Wiley & Sons, Ltd.

3,3-Diphenyl-3H-naphtho[2,1-b]pyrans linked to one, two, or three thiophene nuclei in different positions of the naphthalene moiety (5, 6, 8, and 9) by a covalent bond have been prepared in good yields. A Suzuki cross-coupling reaction was used with two possible strategies: chromenization before the coupling with oligothiophenes or chromenization after the coupling, the main intermediates being the diphenyl propargylic alcohol, the functionalized naphthol derivatives, and the thiophenic boronates. The overall yields for obtaining such photochromic compounds are generally quite satisfying. For the 7-position, the coupling reaction has been realized using a Grignard reaction between a tetralone derivative and a thiophenic bromo magnesium intermediate. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

The crystal structure of the title compound 1',2',3',4'-tetrahydro-1,3-diphenyl-4-chlorospiro[2-pyrazoline-5,2-napthalen] 1'one has been determined. The structure consists of a pyrazoline ring, three aromatic rings and a tetralone moiety. All the aromatic rings are planar while the cyclohexonone ring of the tetralone moiety is in the distorted sofa conformation. The molecular packing is stabilized by C-H...O and C-H…π type inter molecular interactions.

Results are reported on the regioselective C-deuteriation of 2-methyl tetralone using a series of diisopropylamine derived D-sources. The results presented further aid the understanding of kinetic deuteriation of both ‘base-containing’ and ‘base-free’ enolates. Copyright © 2002 John Wiley & Sons, Ltd.

Eight new metabolites, including new sesquiterpenoids (I), a new backbone sesquiterpene rearranged from guaiane, two disecoguaianes (II), two new dihydroisocoumarins (IV), and one new tetralone (III) are isolated together with ten known compounds.

A stereoselective one-pot oxidative [3,3] sigmatropic rearrangement/Friedel—Crafts arylation is developed to provide a convenient synthesis of benzhydryl compounds.

Highly enantioselective catalytic oxidation of 1-tetralone-derived β-keto esters was achieved by using a guanidine–urea bifunctional organocatalyst in the presence of cumene hydroperoxide (CHP), a safe, commercially available oxidant. The α-hydroxylation products were obtained in 99 % yield with up to 95 % enantiomeric excess (ee). The present oxidation was successfully applied to synthesize a key intermediate of the anti-cancer agent daunorubicin (2).

The asymmetric protonation of silyl enolates derived from tetralone, benzosuberone, and cyclohexanone has been successfully achieved by using simple and original betaine catalysts derived from Cinchona alkaloids (quinine and quinidine series) to afford the desired α-substituted ketones in high yields and moderate enantioselectivities. The ease of implementation of this approach along with the easy accessibility of the betaine catalyst (four steps from cheap and commercially available quinine or quinidine) make this approach very appealing for the preparation of enantioenriched α-monosubstituted carbonyl compounds.

A regio- and enantioselective method for the preparation of alkyl-, allyl-substituted benzothiopyran and tetralone derivatives is developed.

Enantiomeric resolution of four substituted 2-(4-pyridylalkyl)-1-tetralone derivatives has been achieved on a Chiralpak AD-RH (amylose tris(3,5-dimethylphenyl carbamate) column. The mobile phases used were acetonitrile-water-triethylamine (50:50:0.03, v/v/v) and acetonitrile-water-acetic acid (60:40:0.03, v/v/v). UV detection was carried out at 254 nm. The separation factors (α) of the resolved enantiomers of the tetralone derivatives were in the range of 1.16 to 2.84 while the resolution factor (R s ) was in the range of 0.20 to 2.64. Optimum resolution was achieved using acetonitrile-water-triethylamine (50:50:0.03, v/v/v) as the mobile phase at 0.5 mL/ min. The chiral recognition mechanisms between these analytes and the chiral selector are discussed.

A novel series of organometallic donor-conjugated-acceptor dyes derived from ferrocene as the donor group have been synthesized via the Knoevenagel reaction of ferrocene carboxaldehyde and various active methylene compounds to give a range of dyes ranging from orange to blue-green in color. The most bathochromic dye is that derived from dialkyl thiobarbituric acid and the least is that derived from the tetralone. The dyes showed an unusual negative solvatochromism. as the solvent polarity increased. All dyes synthesized are expected to have some non-linear optical properties, as evidenced from the pronounced solvatochromism. Copyright (C) 2001 John Wiley & Sons, Ltd.

Herein we present the development of asymmetric deacylative allylation of ketone enolates. The reaction directly couples readily available ketone pronucleophiles with allylic alcohols using facile retro-Claisen cleavage to form reactive intermediates in situ. The simplicity and robustness of the reaction conditions is demonstrated by the preparation of >6 g of an allylated tetralone from commercially available materials. Furthermore, use of nonracemic PHOX ligands allows intermolecular formation of quaternary stereocenters directly from allylic alcohols.

Synthesis of naphthyl pyrrolidine/pyrrolizidine-spirooxindoles has been achieved by a one pot three component 1,3-dipolar cycloaddition (1,3-DC) reaction. The azomethine ylides generated in situ from isatin/N-substituted isatin and secondary amino acids (sarcosine/ l -proline) reacted with naphthylidene tetralone as a dipolarophile to give naphthyl dispiro heterocycles, in good yields. However anthrylidene tetralone, failed to react under the same conditions as a dipolarophile to give the products as expected in 1,3-DC reaction possibly due to steric and electronic properties. The structures and stereochemistry of cycloadducts were confirmed by 1H and 13C NMR spectroscopy, mass spectrometry, and single crystal X-ray diffraction studies.

Chemoselective Suzuki–Miyaura reactions of 2-bromo-1-(trifluoromethanesulfonyloxy)naphthalene, 1-bromo-2-(trifluoromethanesulfonyloxy) naphthalene and 2-acetyl-4-bromo-1-(trifluoromethanesulfonyloxy)naphthalene, which are all readily available from the corresponding tetralone derivatives, afforded a variety of mono- and diarylnaphthalenes. The reactions generally proceed with excellent chemoselectivity in favour of the bromide position, no matter whether the bromide is located at position 1 or 2 of the naphthalene or whether the carbon attached to the triflate group is electronically more deficient by the presence of a neighbouring acetyl group.

A concise route for the synthesis of the title compound (VI), a useful intermediate in the preparation of analgesics, morphines and steroids, starting from commercially available tetralone (I) is developed.

We have developed an efficient Lewis acid-catalyzed Diels–Alder route to a series of cis-fused bicyclic ketones bearing quaternary halogenation at the angular position. We have also developed a Diels–Alder-based one-flask method for the regioselective preparation of TBS-protected 6-hydroxy tetralone and 5-hydroxy indanone derivatives.

The synthesis of the novel β-lactam fused spiroisoxazolidine tetralone and chromanone ring systems (III) is achieved by intermolecular 1,3-dipolar cycloaddition reaction of nitrone (I) with the unusual dipolarophiles (II).