Atom- and step-economical nucleophilic arylation of azaaromatics via electrochemical oxidative cross C-C coupling reactions

 

Atom- and step-economical nucleophilic arylation of azaaromatics via electrochemical oxidative cross C-C coupling reactions

Green Chem., 2017, 19,2931-2935
DOI: 10.1039/C7GC00789B, Communication

O. N. Chupakhin, A. V. Shchepochkin, V. N. Charushin
A simple and efficient electrochemical method for the synthesis of asymmetrical bi(het)aryls through direct functionalization of the C(sp2)-H bond in azaaromatics with fragments of (hetero)aromatic nucleophiles has been developed.

From the journal:

Green Chemistry

Atom- and step-economical nucleophilic arylation of azaaromatics via electrochemical oxidative cross C–C coupling reactions

O. N. Chupakhin,*ab  A. V. Shchepochkinab  and  V. N. Charushinab 

*Corresponding authors

aInstitute of Organic Synthesis of the Russian Academy of Sciences, 22 S. Kovalevskoy Street, 620990 Ekaterinburg, Russia
E-mail: chupakhin@ios.uran.ru

bUral Federal University, 19 Mira Street, 620002 Ekaterinburg, Russia

Abstract

The synthesis of asymmetrical bi(het)aryls through direct functionalization of the C(sp2)–H bond in azaaromatics with fragments of (hetero)aromatic nucleophiles has first been carried out under electrochemical oxidative conditions. This versatile method for C–C bond formation between two aryl fragments can be realized under very mild potential-controlled oxidative conditions, and it does require neither incorporation of any halogen atoms or other leaving groups, nor the use of metal catalysts. The use of the electrochemical SHN methodology for modification of azaaromatic compounds has first been demonstrated.

   

9-(1H-Indol-3-yl)-10-methylacridinium tetrafluoroborate (3e) Red crystals, 189 mg (96%). M.p.: 192-193 °C. 1H NMR (500 MHz, [D6]DMSO): δ 12.44 (s, 1H), 8.80 (d, 2H, J=9.5 Hz), 8.43-8.39 (m, 4H), 8.14 (d, 1H, J=2.6 Hz), 7.90-7.86 (m, 2H), 7.70 (d, 1H, J=8.2 Hz), 7.32 (t, 1H, J=7.4 Hz), 7.17-7.10 (m, 2H), 4.88 (s, 3H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ 156.2, 141.2, 137.9, 136.5, 131.1, 130.5, 127.9, 127.1, 125.6, 122.9, 121.2, 119.0, 118.9, 112.7, 107.9, 38.6 ppm. Elem. Anal. Calcd. For C22H17N2BF4: C 66.69, H 4.33, N 7.07 Found: C 66.78, H 4.39, N 7.10.

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Catalytic carbonyl hydrosilylations via a titanocene borohydride-PMHS reagent system

Catalytic carbonyl hydrosilylations via a titanocene borohydride-PMHS reagent system

Catal. Sci. Technol., 2017, Advance Article

DOI: 10.1039/C7CY01088E, Paper

Godfred D. Fianu, Kyle C. Schipper, Robert A. Flowers II
Catalytic amounts of titanocene(III) borohydride, generated under mild conditions from commercially available titanocene dichloride, in concert with a stoichiometric hydride source is shown to effectively reduce aldehydes and ketones to their respective alcohols in aprotic media.

From the journal:

• Catalysis Science & Technology

Catalytic carbonyl hydrosilylations viaa titanocene borohydride–PMHS reagent system

Godfred D. Fianu,a  Kyle C. Schippera  and  Robert A. Flowers II*a 

 Author affiliations

*Corresponding authors

aDepartment of Chemistry, Lehigh University, Bethlehem, USA
E-mail: rof2@lehigh.edu

Abstract

Reduction of a wide range of aldehydes and ketones with catalytic amounts of titanocene borohydride in concert with a stoichiometric poly(methylhydrosiloxane) (PMHS) reductant is reported. Preliminary mechanistic studies demonstrate that the reaction is mediated by a reactive titanocene(III) complex, whose oxidation state remains constant throughout the reaction.

Godfred Fianu

Lehigh University , Bethlehem · Department of Chemistry

Robert A Flowers

Danser Distinguished Faculty Chair in Chemistry and Deputy Provost for Faculty Affairs

Lehigh University , Bethlehem · Department of Chemistry

Lehigh University

Department of Chemistry

Bethlehem, United States

Phenyl methanol (2-c)
Phenyl methanol (2-c) was prepared from benzaldehyde (1-c) by the procedure outlined
in GP1. NMR analysis showed 100% conversion in 1 hour. 86% isolated yield of alcohol
product was obtained after complete workup.

1H NMR (400 MHz, CDCl3) δ 7.37 – 7.26 (m,5H), 4.59 (s, 2H), 2.99 (s, 1H).

13C NMR (101 MHz, CDCl3) δ 140.92, 128.56, 127.60, 127.07,77.52, 77.20, 76.88, 65.04.

 

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NaBH4, twin screw technology (i.e., granulator, melt extruder, etc.) to yield the desired product in a continuous manner

In this work the application of green chemistry principles such as process intensification and the replacement of reagents and solvents to more benign alternatives were coupled with the advantages of continuous manufacturing. The reduction of lipophilic aromatic aldehydes using an aqueous alkaline solution of NaBH4 was achieved by means of mechanical shearing and kneading provided by a custom-made batch reactor at the lab scale and a twin screw extruder at the kilo scale. The process was run continuously for 17 min to yield 1.41 kg of product (89% purity). The benefits of running the process in a continuous manner instead a conventional fed-batch mode were discussed in terms of both environmental and economic factors.

Screwing NaBH4 through a Barrel without a Bang: A Kneaded Alternative to Fed-Batch Carbonyl Reductions

Valerio Isoni* , Ken Mendoza, Eleen Lim, and Soo Khean Teoh

Institute of Chemical and Engineering Sciences, 1 Pesek Road, 627833, Jurong Island, Singapore

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00107

 

http://pubs.acs.org/doi/suppl/10.1021/acs.oprd.7b00107

*E-mail: isoniva@ices.a-star.edu.sg.

 

 

Institute of Chemical and Engineering Sciences, 1 Pesek Road, 627833, Jurong Island, Singapore

The chemical industry has been a major part of the Singapore economy for many years, based on a strong foundation as a major oil refining centre with a long history, and strategically placed at the heart of the Asia - Pacific region. In recent years the pharmaceuticals industry has also seen major growth, so that chemistry and chemical engineering science now make a very significant contribution to Singapore's economy.

In order to strengthen this position and to foster future development to grow from dependence solely on manufacturing to secure a more knowledge dependant, high tech research and development based business environment, Agency for Science, Technology and Research (A*STAR) and Economic Development Board (EDB) looked at how to bolster the local science and technology base. As a result, the Institute of Chemical and Engineering Sciences (ICES) came into being, to provide highly trained R&D manpower, to establish a strong science base and to develop technology and infrastructure to support future growth.

Starting from a small centre in the National University of Singapore (NUS), ICES was established as an autonomous national research institute under A*STAR on October 1st 2002. Since that time, we have grown rapidly. We have established world leading laboratories, pilot facilities, and the necessary infrastructure to carry out a world class research programme in chemistry and chemical engineering sciences. We have the capability to cover the range of activities from exploratory research to process development, optimisation and problem solving. We can go from very small lab scale right to kg and pilot scale in one organisation, with all of the necessary skills directly at hand and integrated into a project oriented environment.

 

 

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Iridium-catalyzed highly efficient chemoselective reduction of aldehydes in water using formic acid as the hydrogen source

Iridium-catalyzed highly efficient chemoselective reduction of aldehydes in water using formic acid as the hydrogen source

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC01289F, Paper

Zhanhui Yang, Zhongpeng Zhu, Renshi Luo, Xiang Qiu, Ji-tian Liu, Jing-Kui Yang, Weiping Tang
A highly efficient iridium catalyst is developed for the chemoselective reduction of aldehydes to alcohols in water, using formic acid as a reductant.

From the journal:

Green Chemistry

Iridium-catalyzed highly efficient chemoselective reduction of aldehydes in water using formic acid as the hydrogen source

Zhanhui Yang,ab  Zhongpeng Zhu,ac  Renshi Luo,ad  Xiang Qiu,a  Ji-tian Liu,a  Jing-Kui Yangc  and Weiping Tang*ae 

*Corresponding authors

aSchool of Pharmacy, University of Wisconsin–Madison, Madison, USA
E-mail: weiping.tang@wisc.edu

bFaculty of Science, Beijing University of Chemical Technology, Beijing, P. R. China

cSchool of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China

dSchool of Pharmacy, Gannan Medical University, Ganzhou, P. R. China

eDepartment of Chemistry, University of Wisconsin–Madison, Madison, USA

Abstract

A water-soluble highly efficient iridium catalyst is developed for the chemoselective reduction of aldehydes to alcohols in water. The reduction uses formic acid as the traceless reducing agent and water as a solvent. It can be carried out in air without the need for inert atmosphere protection. The products can be purified by simple extraction without any column chromatography. The catalyst loading can be as low as 0.005 mol% and the turn-over frequency (TOF) is as high as 73800 mol mol−1 h−1. A wide variety of functional groups, such as electron-rich or deficient (hetero)arenes and alkenes, alkyloxy groups, halogens, phenols, ketones, esters, carboxylic acids, cyano, and nitro groups, are all well tolerated, indicating excellent chemoselectivity.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC01289F?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

4-Methoxybenzyl alcohol (2a)2 . Yellowish oil. Yield: 273 mg, 99%.

1H NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 4.52 (s, 2H), 3.76 (s, 3H).

13C NMR (101 MHz, CDCl3) δ 159.07, 133.23, 128.63, 113.89, 64.73, 55.30, 55.26.

Zhanhui Yang

School of Pharmacy, University of Wisconsin–Madison, Madison, USA
E-mail:weiping.tang@wisc.edu

School of Pharmacy
UNIVERSITY OF WISCONSIN - MADISON

Beijing University of Chemical... , Beijing

Organic Chemistry, Green Chemistry, Catalysis

PhD student

Beijing University of Chemical Technology

Organic Chemistry

Beijing, China

School of Pharmacy, University of Wisconsin–Madison, Madison, USA

4-Methoxybenzyl alcohol

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Efficient and Stereoselective Syntheses of Isomerically Pure 4-Aminotetrahydro-2H-thiopyran 1-Oxide Derivatives

 

trans-4-Aminotetrahydro-2H-thiopyran 1-Oxide Methanesulfonate (trans-3d-MsOH)

Compound ...................afforded trans-3d-MsOH (20 g, 68%) as a white crystalline solid.

1H NMR (300 MHz, DMSO-d6) δ 1.60–1.76 (2H, m), 2.16–2.29 (2H, m), 2.31 (3H, s), 2.68–2.81 (2H, m), 3.13–3.23 (2H, m), 3.27–3.35 (1H, m), 7.86 (3H, brs).

 

13C NMR (75 MHz, D2O) δ 24.98, 38.51, 46.18, 46.84.

 

LCMS m/z calcd for C5H11NOS: 133.06, found 134.1 [M + H].

 

Anal. Calcd for C6H15NO4S2: C, 31.43; H, 6.59; N, 6.11. Found: C, 31.62; H, 6.48; N, 6.19. mp 214–216 °C.

 

cis-4-Aminotetrahydro-2H-thiopyran 1-Oxide Hydrochloride (cis-4d-HCl)

A mixture of .................... to afford cis-4d-HCl (22.5 g, 62%) as a white crystalline solid.

1H NMR (400 MHz, DMSO-d6) δ 1.81–2.00 (2H, m), 2.06–2.24 (2H, m), 2.73 (2H, td, J = 13.6, 3.2 Hz), 2.90–3.01 (2H, m), 3.21 (1H, brs), 8.19 (3H, brs).

 

13C NMR (75 MHz, D2O) δ 19.80, 42.94, 47.34.

 

LCMS m/z calcd for C5H11NOS: 133.06, found 134.1 [M + H]. Anal. Calcd for C5H12NClOS: C, 35.39; H, 7.13; N, 8.26. Found: C, 35.28; H, 6.87; N, 8.26. mp 230–232 °C.

 

Efficient and Stereoselective Syntheses of Isomerically Pure 4-Aminotetrahydro-2H-thiopyran 1-Oxide Derivatives

Ryo Mizojiri*† , Kazuaki Takami†, Tatsuya Ito‡, Hiroyuki Maeda‡, Mitsuhisa Yamano‡, and Tetsuji Kawamoto*†

† Research, Takeda Pharmaceutical Company Ltd., Fujisawa, Kanagawa 251-8555, Japan

‡ Pharmaceutical Sciences, Takeda Pharmaceutical Company Ltd., Yodogawa-ku, Osaka 532-8686, Japan

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00147

 

*E-mail: ryo.mizojiri@takeda.com. Phone: +81-466-32-1058 (R.M.)., *E-mail: tetsuji.kawamoto@takeda.com. Phone: +81-466-32-1193 (T.K.).

http://pubs.acs.org/doi/suppl/10.1021/acs.oprd.7b00147

Efficient and stereoselective syntheses of isomerically pure 4-aminotetrahydro-2H-thiopyran 1-oxide derivatives have successfully been achieved. Isomerically pure (4-nitrophenyl)sulfonyltetrahydro-2H-thiopyran 1-oxides were identified by X-ray crystallographic analyses, and isomerically pure sulfoxide derivatives were characterized by 1H NMR. An oxidation reaction of tert-butyl(4-nitrophenyl)sulfonyl(tetrahydro-2H-thiopyran-4-yl)carbamate with Oxone provided steric control, affording its trans sulfoxide with high efficiency and selectivity. From the obtained trans sulfoxide derivatives, cis sulfoxide derivatives were synthesized conveniently by a hydrogen chloride catalyzed isomerization.

 

Tropylium salts as efficient organic Lewis acid catalysts for acetalization and transacetalization reactions in batch and flow

Tropylium salts as efficient organic Lewis acid catalysts for acetalization and transacetalization reactions in batch and flow

Green Chem., 2017, Advance Article
DOI: 10.1039/C7GC01519D, Communication

D. J. M. Lyons, R. D. Crocker, D. Enders, T. V. Nguyen
Tropylium salts were reported as organic-Lewis acids to efficiently catalyze acetalization reactions in batch and flow.

• 
• From the journal:
  

  Green Chemistry

Tropylium salts as efficient organic Lewis acid catalysts for acetalization and transacetalization reactions in batch and flow

 

D. J. M. Lyons,a  R. D. Crocker,a  D. Endersb  and  T. V. Nguyen*a 

Author affiliations

*Corresponding authors

aSchool of Chemistry, University of New South Wales, NSW 2052 Sydney, Australia
E-mail:t.v.nguyen@unsw.edu.au

bInstitute of Organic Chemistry, RWTH Aachen University, Aachen D52074, Germany

Abstract

Acetalization reactions play significant roles in the synthetically important masking chemistry of carbonyl compounds. Herein we demonstrate for the first time that tropylium salts can act as organic Lewis acid catalysts to facilitate acetalization and transacetalization reactions of a wide range of aldehyde substrates. This metal-free method works efficiently in both batch and flow conditions, prompting further future applications of tropylium organocatalysts in green synthesis.

http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C7GC01519D?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

1-(Diethoxymethyl)-4-methylbenzene (4a):

Prepared according to the general procedure from p-tolualdehyde and triethylorthoformate to yield the title compound as a colourless oil (99 mg, 0.50 mmol, quant. yield). 4a

1 H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 7.9 Hz, 2H), 5.50 (s, 1H), 3.59 (ddq, J = 35.4, 9.5, 7.1 Hz, 4H), 2.37 (s, 3H), 1.25 (t, J = 7.1 Hz, 6H) ppm;

13C NMR (101 MHz, CDCl3) δ 138.0, 136.3, 128.9, 126.64, 101.7, 61.0, 21.3, 15.3 ppm;

IR (KBr) 2973, 2880, 2327, 2102, 1909, 1740, 1448 cm-1 ;

ESI-MS Anal. Calcd. for 217.1199 C12H18O2Na, found 217.1195

1H NMR

1 H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 7.9 Hz, 2H), 5.50 (s, 1H), 3.59 (ddq, J = 35.4, 9.5, 7.1 Hz, 4H), 2.37 (s, 3H), 1.25 (t, J = 7.1 Hz, 6H) ppm;

13c nmr

13C NMR (101 MHz, CDCl3) δ 138.0, 136.3, 128.9, 126.64, 101.7, 61.0, 21.3, 15.3 ppm;

School of Chemistry

Science

Vinh Nguyen

BE (Hon 1, UNSW), Ph.D (ANU), MRACI CChem

Lecturer and DECRA fellow

Contact details

Phone: +61-2-9385 6167
Email: t.v.nguyen@unsw.edu.au

Office

Room 217 Dalton Building (F12)

School of Chemistry - UNSW

Research Group Website

Vinh Nguyen's group website

• Biographical Details
• Research interests
• Selected publications

• Interested in joining the group?
• Group website

 

Biographical Details

Dr. Vinh Nguyen (also known as: Thanh Vinh Nguyen or Thanh V. Nguyen on academic publication) was born in Vietnam. After high school, he went to Sydney, Australia to study industrial chemistry at University of New South Wales. He then moved to undertake his PhD in organic chemistry with Professor Michael Sherburn at the Australian National University, Canberra. He had worked to develop new synthetic methodologies for application in natural product synthesis and worked on the design and synthesis of enormoussynthetic host molecules for drug-delivery modelling. After graduating in 2010, he came to work on organocatalysis in Professor Dieter Enders group at the Institute of Organic Chemistry, RWTH Aachen, Germany under the auspices of an Alexander von Humboldt Postdoctoral Fellowship.  In June 2013, he moved to Curtin University (Perth, Australia) to start his own independent research group. In June 2015, he moved again to UNSW (Sydney) to take up a Lecturer/DECRA fellow position at the School of Chemistry. His current research interests are organocatalysis, aromatic cation activation, synthesis of naturally occurring and bioactive compounds, asymmetric synthesis and medicinal chemistry.

Selected Awards and Academic Achievements

• 2016: The 2016 Athel Beckwith Lectureship from RACI Organic Chemistry Division
• 2015-2018: ARC Discovery Early Career Researcher Award (DECRA)
• 2014: Thieme Chemistry Journal Award for outstanding early career academics.
• 2011 – 2013: Alexander von Humboldt Postdoctoral Fellowship (RWTH Aachen, Germany).
• 2005: The Era Polymer Prize for “The Best Honor Research Thesis” in Industrial Chemistry – UNSW
• 2000: Silver medal in the 32nd International Chemistry Olympiad in Copenhagen, Denmark

Research interests

Nguyen’s group focuses their research on development of new synthetic methodologies in organic chemistry, organocatalysis and natural product synthesis.

Aromatic Cation Activation:

A new method for the nucleophilic substitution of alcohols and carboxylic acids and other substrates using aromatic tropylium cation activation has been developed. It demonstrates, for the first time, the synthetic potential of tropylium cations in promoting chemical transformations. (http://pubs.acs.org/doi/abs/10.1021/ol5003972).

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