Issue10;March2017

International Society of Heterocyclic

Chemistry

ISHC

1

TheISHCBulletinRecentPublicationsofISHCMembers

Issue10;March2017 Generation and Trapping of Nitrosocarbonyl Intermediates Misal Giuseppe Memeo and Paolo Quadrelli Chem. Rev. 2017, 117, 2108–2200. DOI: 10.1021/acs.chemrev.6b00684

Abstract: The idea of this review can be symbolized by the famous Botticelli painting La Nascita di Venere (The Birth of Venus, Galleria degli Uffizi, Florence) where a wind of generation comes from the starting materials and the nitrosocarbonyls are obtained and instantly trapped by the handmaid’s wrap to keep these intermediates safe and usable by chemists. The Nitrosocarbonyls (R-CONO) are highly reactive species and remarkable intermediates towards different synthetic targets. This review will cover a research area whose impact in the current organic synthesis is constantly increasing in the chemical community. This review represents the first and comprehensive picture on the generation and trapping of nitrosocarbonyls and is solidly built on more than 380 papers. Six different classes of key starting materials such as hydroxamic acids, N-hydroxy carbamates, N-hydroxy ureas, nitrile oxides and 1,2,4-oxadiazole 4-oxides were highlighted. The content of the review surveys all the methods to generate the nitrosocarbonyls through different approaches (oxidative, thermal, photochemical, catalytic, aerobic and the less common ones) in the light of efficiency, yields and mildness. The most successful trapping agents employed to catch these fleeting intermediates are reviewed, exploiting their superior dienophilic, enophilic and electrophilic power. The work is completed by paragraphs dedicated to the detection of the intermediates, theoretical studies and insights about the challenges and future directions for the field. Metal-Free Oxidative Cross-Coupling Reaction of Thiophene Iodonium Salts with Pyrroles Koji Morimoto, Akira Nakamura, Toshifumi Dohi, Yasuyuki Kita Eur. J. Org. Chem. 2016, 4294–4297. DOI: 10.1002/ejoc.201600791

Abstract: The hypervalent iodine mediated oxidative cross-coupling reaction of 3,4-ethylenedioxythiophene (EDOT) with various pyrroles has been developed. The corresponding EDOT-pyrrole derivatives, bearing organic functional groups, were obtained in moderate to high yields (up to 85%). This method features a high efficiency and regioselectivity, and functional-group tolerance. We also determined the highly planar characteristics of the EDOT-pyrrole dimers caused by the intramolecular hydrogen bonding and thus clarified the efficient conductive properties of the EDOT-pyrrole.

Issue10;March2017

International Society of Heterocyclic

Chemistry

ISHC

2

Stabilized Pyrrolyl Iodonium Salts and Metal-Free Oxidative Cross-Coupling Koji Morimoto, Yusuke Ohnishi, Daichi Koseki, Akira Nakamura, Toshifumi Dohi, Yasuyuki Kita Org. Biomol. Chem. 2016, 14, 8947–8951. DOI: 10.1039/C6OB01764A

Abstract: Pyrrole-aryl derivatives are important due to their unique biological activities in medicinal chemistry. We now report a new oxidative biaryl coupling for pyrroles and indoles toward various arenes using the hypervalent iodine reagent and appropriate stabilizer for pyrrolyl iodonium intermediates. The reactions readily provide a variety of desired coupling products in good yields. This method features high efficiency, completion in a short time, and the reaction proceeds under very mild conditions. Metal-Free Regioselective Tandem Synthesis of Diversely Substituted Benzimidazo-Fused Polyheterocycles in Aqueous Medium Pawan K. Mishra and Akhilesh K. Verma Green Chem. 2016, 18, 6367–6372. DOI: 10.1039/c6gc02330d

Abstract: An operationally simple approach for the synthesis of diversely substituted benzimidazo-fused polyheterocycles under metal-free conditions in water has been described. The aqueous medium accelerates the formation of the desired product by avoiding side-products as well as harsh reaction conditions. The reaction proceeds through inter and intramolecular C–N bond formation in one-pot via 6-endo-dig cyclization. Deuterium labelling and X-ray crystallographic studies supported the proposed mechanistic pathway for the targeted cyclized product. Palladium-Catalyzed Intramolecular Fujiwara-Hydroarylation: Synthesis of Benzo[a]phenazines Derivatives Sonu Kumar, Rakesh K. Saunthwal, Mohammad Mujahid, Trapti Aggarawal, Akhilesh K. Verma J. Org. Chem. 2016, 81, 9912–9923. DOI: 10.1021/acs.joc.6b02096

Abstract: An atom-economical Pd-catalyzed approach for the synthesis of benzophenazine derivatives using substituted 2-aryl-3-(aryl/alkylethynyl) quinoxaline in the presence of trifluoroacetic acid at 65 °C has been described. The chemistry involves in situ generation of cationic Pd(II) species, which functionalized the aromatic C−H bonds via electrophilic metalation followed by concomitant intramolecular transinsertion of C−C triple bond to aryl-Pd complex. The results were supported by various control experiments including with electron−deficient arenes and deuterium labeling studies. The deuterium labeling studies supports electrophilic palladation of aromatic C−H over activation of C−C triple bond of alkyne. The structure of synthesized compounds was further confirmed by X-ray crystallography studies. This catalytic protocol has been efficiently applied for novel synthesis of highly functionalized benzo fused phenazines.

Issue10;March2017

International Society of Heterocyclic

Chemistry

ISHC

3

Regio- and Stereoselective Domino Synthesis of Oxazolo Fused Pyridoindoles and Benzofurooxazolo Pyridines from ortho-Alkynylarylaldehydes Shilpi Pal, Deepak Choudhary, Mohit Jainth, Sonu Kumar, Rakesh K. Tiwari, Akhilesh K. Verma J. Org. Chem. 2016, 81 9356–9371. DOI: 10.1021/acs.joc.6b02062

Abstract: An environmentally benign Au(III)-catalyzed regio- and stereoselective domino synthesis of oxazolo fused pyridoindoles 7a−v and benzofurooxazolo pyridines 8a−n by the reaction of o-alkynylaldehydes 4a−t and 5a−k with (S)-phenylglycinol 6a and (R)-phenylglycinol 6b under mild reaction conditions using water as reaction medium is reported. The reaction proceeded via selective C−N bond formation on the more electrophilic alkynyl carbon through 6-endo-dig cyclization. The reaction tolerates a wide variety of functional groups. The developed chemistry has been successfully extended for the synthesis of a diverse class of g-carbolines and benzofuro[3,2-c]pyridines using corresponding ester hydrochlorides of serine, threonine, and cystine as a nitrogen source. Syntheses of Combretastatins D-1, D-2, and D-4 via Ring Contraction by Flash Vacuum Pyrolysis Marina Harras, Wolfgang Milius, R. Alan Aitken, Rainer Schobert J. Org. Chem. 2017, 82, 579–587. DOI: 10.1021/acs.joc.6b02586

Abstract: We report the syntheses of combretastatins D-2 and D-4, as well as a formal synthesis of combretastatin D-1 by a conceptually new route harnessing a ring-contracting flash vacuum pyrolytic extrusion of sulfur dioxide from the respective 16-membered sulfone precursors. Via flash vacuum pyrolysis even metaparacyclophanes as small and strained as the hitherto unknown oxa[1.5]metaparacyclophane could be prepared as a side product en route to combretastatin D-2 by synchronous extrusion of SO2 and CO2. Regioselective 5-endo-dig Electrophilic Iodocyclization of Enediynes: A Convenient Route to Iodo-Substituted Indenes and Cyclopenta-Fused Arenes Rakesh K. Saunthwal, Abhinandan K. Danodia, Monika Patel, Sushil Kumar, Akhilesh K. Verma Chem. Asian J. 2016, 11, 3001–3007. DOI: 10.1002/asia.201601085

Abstract: An efficient iodine-mediated regioselective tandem approach for the synthesis of symmetric and asymmetric iodo-substituted indenes and stereoselective cyclopenta [b]pyridine/thiophenes from easily accessible enediynes that proceeds by in situ formation of an iodonium intermediate followed by a regioselective 5-endo-dig cyclization has been described. The intramolecular electrophilic iodocyclization was selectively triggered by a distribution of electronic density along the alkyne bond. Subsequently, the iodo-substituted indenes were diversified by employing palladium-catalyzed cross-coupling reactions and the coupled products were further confirmed by X-ray crystallographic studies.

Issue10;March2017

International Society of Heterocyclic

Chemistry

ISHC

4

Hetero-Diels-Alder Approach to Bis(indolyl)methanes Carla Grosso, Ana L. Cardoso, Maria João Rodrigues, Cátia Marques, Luísa Barreira, Américo Lemos, Teresa M. D. V. Pinho e Melo Bioorg. Med. Chem. 2017, 25, 1122–1131. DOI: 10.1016/j.bmc.2016.12.028

Abstract: A novel synthetic approach to bis(indolyl)methanes has been established. Our one-pot synthetic strategy based on two consecutive hetero-Diels-Alder cycloaddition reactions of electrophilic conjugated nitrosoalkenes with indoles was extended to a range of new 1-hydroxyiminomethyl-bis(indolyl)methanes. Furthermore, a similar and broad range approach was applied to the synthesis of previously unknown 1-hydrazonomethyl-bis(indolyl)methanes. The biological evaluation of the new bis(indolyl)methanes as anti-cancer agents was investigated. One-Pot Synthesis of a-Ylidene d-Lactones from Functionalized Allylic Bromides in a Water-Isopropanol Medium Misael Ferreira, Tula B. Bisol, Henrique P. da Conceição, Theo V. C. Russo, Adailton J. Bortoluzzi, Marcus M. Sá Synthesis 2017, 49, 667–676. DOI: 10.1055/s-0036-1588078

R

Br

O

OMe

O

OEt

O

one-pot, µw-assisted

+

1. NaOH, iPrOH-H2O

2. NaOH (exc.)

3. NaBH4

4. HCl

R

O

O

R = Aryl, Alkyl11 examples

up to 62% yield Abstract: The one-pot microwave-assisted synthesis of a series of a-ylidene d-lactones from (Z)-2-(bromomethyl)-2-alkenoates (derived from Morita–Baylis–Hillman reaction) in an aqueous environment is reported. The protocol includes regioselective base-mediated allylation of ethyl acetoacetate with (Z)-2-(bromomethyl)-2-alkenoates followed by decarboxylative hydrolysis, carbonyl reduction of the keto carboxylate intermediate, and acid-mediated cyclization of the resulting d-hydroxy acid to furnish the a-ylidene d-lactones with good overall yields. The synthesis was also performed in the stepwise mode, which allowed the isolation and full characterization of each intermediate involved in the one-pot method. The main features of this efficient transformation include the fast reaction rates, the use of a benign aqueous medium, the use of inexpensive and readily available reagents, the production of nearly innocuous residues, and the requirement for a single work-up and purification stage at the end of the process.