Pd/Cu-free Heck and Sonogashira cross-coupling reaction by Co nanoparticles immobilized on magnetic chitosan as reusable catalyst

 

Pd/Cu-free Heck and Sonogashira cross-coupling reaction by Co nanoparticles immobilized on magnetic chitosan as reusable catalyst

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03377F, Paper
Abdol R. Hajipour, Fatemeh Rezaei, Zahra Khorsandi
Chitosan (CS) is a porous, self-standing, nanofibrillar microsphere that can be used as a metal carrier. Amino groups on CS enable to modulate cobalt coordination using a safe organic ligand (methyl salicylate).

Pd/Cu-free Heck and Sonogashira cross-coupling reaction by Co nanoparticles immobilized on magnetic chitosan as reusable catalyst

aDepartment of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
E-mail: haji@cc.iut.ac.ir
Fax: +98 311 391 2350
Tel: +98 311 391 3262
bDepartment of Neuroscience, University of Wisconsin, Medical School, Madison, USA
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC03377F

Department of Chemistry
Office : College of Chemistry, Isfahan University of Technology, Isfahan 84156, IR IranPhone : +98 311 391xxxxFax : +98 311 391xxxxWeb Site : Prof. Abdolreza Hajipour
EDUCATION:
1970-1974               High School, Shahpour high school, Kazerun, IR, Iran
1975-1979               B.S., Chemistry, Department of Chemistry, Isfahan University, Isfahan, I.R. Iran
1981-1983               M.S., Organic Chemistry, Synthesis, Shiraz University, Shiraz, I.R. Iran
Thesis Title: “Synthesis of 2,6,7,11-Tetraphenyl Isobenzofuran B Cyclobutadiene”
Advisor: Professor Habib Firouzabadi
1990-1994               Ph.D., Organic Chemistry, Wollongong University, Australia
Dissertation Title: “Asymmetric Synthesis of Chiral Amines and Benzazepine Alkaloids from Chiral Sulfoxides”
Advisor: Professor Stephen G. Pyne

POSITIONS:
09/94-11/98            Assistant Professor, Isfahan University of Technology
12/98-02/03            Associate Professor, Isfahan University of Technology
03/03-present        Professor, Isfahan University of Technology
02/01-03/02            Visiting Scientist, University of Wisconsin Medical School, Madison, WI
04/02-09/02            Associate Researcher, University of Wisconsin Medical School, Madison, WI
10/02-1/05              Associate Scientist, University of Wisconsin Medical School, Madison, WI
1/04 to present      Senior Scientist, University of Wisconsin Medical School, Madison, WI
 str1
Chitosan (CS) is a porous, self-standing, nanofibrillar microsphere that can be used as a metal carrier. Amino groups on CS enable to modulate cobalt coordination using a safe organic ligand (methyl salicylate). This catalyst efficiently promotes Heck cross-coupling of a large library of functional substrates under mild and sustainable conditions (polyethylene glycol as solvent at 80 °C in a short time (1 h)). The cobalt complex was also used as a heterogeneous, efficient, inexpensive, and green catalyst for Sonogashira cross-coupling reactions. The reactions of various aryl halides and phenylacetylene provided the corresponding products in moderate to good yields. More importantly, this phosphine, copper, and palladium-free catalyst was stable under the reaction conditions and could be easily reused using an external magnet for at least five successive runs without a discernible decrease in its catalytic activity.
Reaction yields were analyzed by gas chromatography (GC, BEIFEN-3420, detector type: FID, TCD equipped with Nukol™ capillary GC column, size × I.D. 30 m × 0.25 mm, df 0.25 μm). 2,3-Dimethylnaphthalene as was used as internal standard. The gas flow rate of 2 mL min-1; and oven temperature at 80 oC for 15 min and then increased to 170 oC.
str1
str2
General procedure for catalyst preparation The magnetic nanoparticles (MNPs) were prepared according to the method reported in literature64 based on the precipitation of magnetite nanoparticles from a mixture of iron(III) chloride and iron(II) sulfate by ammonia (25% solution in water). Subsequently, in a round-bottom flask equipped with a mechanical stirrer and condenser, a mixture of magnetic nanoparticles and sodium sulfate (20%, w/v) was added to a solution of chitosan (1%, w/v) in acetic acid (2%, w/v) under stirring. Stirring was continued for 1 h to obtain the aqueous suspension of MNPs/CS. Then, the magnetic nanoparticles were separated from the reaction mixture by an external permanent magnet, washed with ethanol and methanol several times, and dried under vacuum at 70 °C. For the preparation of supported methyl salicylate ligands, a solution of ethanol suspension of MNPs/CS (1.5 g per 10 mL) was added to methyl salicylate (6.5 mmol), and the mixture was stirred at 60 °C for 24 h. The final Co-MS@MNPs/CS was obtained as a brown solid by the addition of CoCl2·6H2O (4.2 mmol) dissolved in 10 mL of ethanol to disperse the mixture of MNPs/CS-MS (1.01 g) in ethanol (5 mL) and stirred at 60 °C for 18 h. The resulting complex was collected by an external permanent magnet, washed with ethanol (3 × 10 mL) to remove the unreacted materials, and finally dried in air (89% yield based on the amount of Co in the catalyst determined by ICP).
General procedure for the Heck reaction In a round-bottom flask equipped with a mechanical stirrer, a mixture of K3PO4 (4 eq.), olefin (1.1 mmol), and aryl halide (1 mmol) in PEG (3 mL) was added to 5 mg of catalyst (1.1 mol% of Co) and the flask was equipped with a condenser for refluxing. The abovementioned mixture was heated at 80 °C in an oil bath. The progress of the reaction was monitored by TLC (hexane/EtOAc, 80 : 20) and gas chromatography (GC). After the completion of the reaction, the mixture was diluted with dichloromethane and water. The organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography. The products were characterized by comparing their physical properties, such as m.p., IR, 1 H, and 13C NMR spectra, with those reported in literature
General procedure for Sonogashira reaction In a round-bottom flask equipped with a mechanical stirrer, phenyl acetylene (1.2 mmol), aryl halide (1.0 mmol), catalyst (10 mg), and KOH (2 eq.) in DMSO (3 mL) were stirred under an air atmosphere at 140 °C. The progress of the reaction was monitored using TLC and GC. After the completion of the reaction, the mixture was diluted with dichloromethane and water. The organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The product was isolated by column chromatography to afford the corresponding products in 55–80% yields. The products were characterized by comparing their physical properties, such as m.p, IR, 1 H, and 13C NMR spectra with those reported in literature.
////////////

Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

 

Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC03324E, Communication
Shrikant G. Pharande, Alma Rosa Corrales Escobosa, Rocio Gamez-Montano
An ultrasound accelerated, environmentally benign Ugi-azide based method was developed for the synthesis of 1,5-disubstituted tetrazoles under solvent and catalyst-free conditions.

Endogenous water-triggered and ultrasound accelerated synthesis of 1,5-disubstituted tetrazoles via a solvent and catalyst-free Ugi-azide reaction

 *Corresponding authors
aDepartamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, Guanajuato, México
E-mail: rociogm@ugto.mx
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC03324E,  http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC03324E?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

A novel, sustainable, endogenous water-triggered, environmentally friendly, high substrate scope, efficient, solvent-free and catalyst-free Ugi-azide based method for the synthesis of 1,5-disubstituted tetrazoles is described.
Shrikant Pharande

Shrikant Pharande

Doctoral student

Research experience

  • Apr 2014–Jun 2014, Research chemist
    TCG Lifesciences · pune
  • Mar 2012–Dec 2013, project assistant
    CSIR – National Chemical Laboratory, Pune · Organic Chemistry Division (NCL)
N-((1-(tert-butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl)aniline (4a)
Based on GP, 100 mg 4-Chlorobenzaldehyde (0.71 mmol), 0.065 cm3 aniline (0.71 mmol), 0.080 cm3 ter. Butyl isocyanide (0.71 mmol), and 0.093 cm3 TMS-azide (0.71 mmol) were reacted together to afford 237 mg (97%) as a white solid.
Melting range 144-145oC,
Rf = 0.45 (Hexane-AcOEt = 7/3 V/V),
1H NMR (500 MHz, CDCl3) δ 7.34 – 7.29 (m, 4H), 7.18 – 7.13 (m, 2H), 6.79 – 6.75 (m, 1H), 6.65 (d, J = 7.6 Hz, 2H), 6.11 (d, J = 6.2 Hz, 1H), 4.78 (d, J = 5.6 Hz, 1H), 1.71 (s, 9H);
13C NMR (126 MHz, CDCl3) δ 155.03, 145.54, 136.81, 134.71, 129.62, 129.43, 129.19, 119.64, 114.42, 61.95, 53.93, 30.29;
FT-IR (ATR) νmax/cm-1 3330.5, 3052.5, 2940.9, 1603.6, 1284.1;
HRMS (ESI+): m/z calcd. for C18H20ClN5 + 342.1480, found 342.1474
str1
str2

//////////////

Towards automation of chemical process route selection based on data mining

Graphical abstract: Towards automation of chemical process route selection based on data mining

A methodology for chemical routes development and evaluation on the basis of data-mining is presented. A section of the Reaxys database was converted into a network, which was used to plan hypothetical synthesis routes to convert a bio-waste feedstock, limonene, to a bulk intermediate, benzoic acid. The route evaluation considered process conditions and used multiple indicators, including exergy, E-factor, solvent score, reaction reliability and route redox efficiency, in a multi-criteria environmental sustainability evaluation. The proposed methodology is the first route evaluation based on data mining, explicitly using reaction conditions, and is amenable to full automation.

In the field of process and synthetic chemistry ‘clean synthesis’ has become one of the standard criteria for good, commercially viable synthesis routes. As a result synthetic and process chemists must be equipped with adequate methodologies for quantification of ‘cleanness’ or ‘greenness’ of alternative routes at the early phases of the development cycle. These new criteria, and the traditional criteria of cost, security of supply, health and safety (H&S), and risk, provide a balanced picture of sustainability of a future technology. Thus, there are two separate aspects to process chemistry: developing the chemistry and the process, and evaluating the overall process, which must occur in parallel. Evaluation of the proposed routes requires data. As data science rapidly evolves, chemistry will inevitably use more of the new tools of data mining and data analysis to automate the routine tasks, such as evaluation of process metrics. In this paper we show some initial results in automation of process evaluation based on deep data mining of process chemistry and multi-criteria decision making.

The evaluation of greenness is a mature field, with a large number of published and standardised approaches, of which many are adopted by industry. 1 However, all published methods are highly case-specific and rather labour-intensive. In the field of synthetic routes development one of the most exciting new areas is the potential for automation of synthesis planning using data mining.2 What has never been attempted before is to automate route generation and evaluation in a coherent methodology, which would aid process development at the early, data-lean, stages. For this we show how to automatically generate process options using a network representation of a section of Reaxys database,3 followed by their screening using multi-criteria decision making, see Fig. 1. As the methods mature and become commercially available, such integration and automation will produce significant savings of time, and would deliver a far more detailed view of the competing synthesis route options than is generally possible at the early stages of design.

To date, obtaining the data, assembling the network and finding potential synthesis routes can already be carried out in a fully automated fashion. Due to issues around data availability the connection to the analysis of the routes still has to be initiated manually, involving a data curation step. The subsequent analysis and multi-criteria decision making have been largely automated in this study. To our knowledge this is the first example of the analysis of synthesis routes generated from the network representation of Reaxys obtained through datamining, using reaction conditions and process data.

image file: c6gc02482c-f2.tif

Fig. 2 A section of a network of organic chemistry. Dots are species and arrows represent reactions.
  1. D. J. C. Constable, C. Jimenez-Gonzalez and A. Lapkin, in Green Chemistry Metrics, John Wiley & Sons, Ltd, Chichester, UK, 2009, pp. 228–247 
  2. S. Szymkuć, E. P. Gajewska, T. Klucznik, K. Molga, P. Dittwald, M. Startek, M. Bajczyk and B. A. Grzybowski, Angew. Chem., Int. Ed., 2016, 55, 5904–5937 
  3. Reed Elsevier Properties SA, Login – Reaxys Login Page [Internet], 2014 [accessed 2014 Jun 8]. Available from: https://www.reaxys.com/. Reaxys is a trademark, copyright owned by Relex Intellectual properties SA and used under licence.

Towards automation of chemical process route selection based on data mining

*Corresponding authors
aDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, UK
E-mail: aal35@cam.ac.uk
Green Chem., 2017,19, 140-152

DOI: 10.1039/C6GC02482C, http://pubs.rsc.org/en/Content/ArticleLanding/2017/GC/C6GC02482C?utm_medium=email&utm_campaign=pub-GC-vol-19-issue-1&utm_source=toc-alert#!divAbstract

Professor Alexei Lapkin, FRSC

Professor Alexei Lapkin FRSC

Professor of Sustainable Reaction Engineering

Fellow of Wolfson College

Catalytic Reaction Engineering

Sustainable Chemical Technologies

Office Phone: 330141

University of Cambridge
Image result for Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, UK

Biography:

MChem in Biochemistry, Novosibirsk State University, 1994

PhD in Chemical Engineering, University of Bath, 2000

Boreskov Institute of Catalysis, Novosibirsk, Russia (1994-1997)

University of Bath, Department of Chemical Engineering, Research Officer (1997-2000)

University of Bath, Department of Chemical Engineering, Lecturer-SL-Reader (2000-2009)

University of Warwick, School of Engineering, Professor of Engineering (2009-2013)

Research Interests

Reaction Engineering group

Our group is developing cleaner manufacturing processes within chemical and chemistry using industries. We are mainly focusing on liquid- and multi-phase catalytic and biochemical processes. Within the group we have pursued projects on developing functional materials for catalysts, adsorbents and reactors, design of multi-functional intensive reactors, modelling of reaction kinetics and integrated processes, linking reaction kinetics with computational fluid dynamics (CFD) and linking process modelling with life cycle assessment (LCA), integration of reactions and separation.

Public funding:

The group is currently involved in an EU project ‘RECOBA’ (http://www.spire2030.eu/recoba/), in which our group collaborates with Materials and Electronic Engineering at Cambridge to work on innovative measurement techniques for monitoring processes under reaction conditions.

We are involved in the EPSRC project on developing novel routes to platform and functional molecules from waste terpenes, led by University of Bath.

We are involved in “Dial a Molecule 2” network funded by EPSRC.

Keywords

  • Reaction Engineering
  • flow
  • sustainability
  • heterogeneous catalysis
  • catalysis

Key Publications

J. Zakrzhewski, A.P. Smalley, M. Kabeshov, A. Lapkin, M. Gaunt, Continuous flow synthesis and derivatization of aziridines via palladium-catalyzed C(sp3)-H activation, Angew. Chem. Int. Ed., 55 (2016) 8878-8883.

P. Yaseneva, P. Hodgson, J. Zakrzewski, S. Falss, R.E. Meadows, A.A. Lapkin, Continuous flow Buchwald-Hartwig amination of a pharmaceutical intermediate, React. Chem. Eng., 1 (2016) 229-238.

P. Yaseneva, D. Plaza, X. Fan, K. Loponov, A. Lapkin, Synthesis of the antimalarial API artemether in a flow reactor, Catal. Today, 239 (2015) 90-96.

N. Peremezhney, E. Hines, A. Lapkin, C. Connaughton, Combining Gaussian processes, mutual information and a generic algorithm for multi-targeted optimisation of expensive-to-evaluate functions, Engineering Optimisation, 46 (2014) 1593-1607.

P. Yaseneva, C.F. Marti, E. Palomares, X. Fan, T. Morgan,P.S. Perez, M. Ronning, F. Huang,T. Yuranova, L. Kiwi-Minsker, S. Derrouiche, A.A. Lapkin, Efficient reduction of bromates using carbon nanofibre supported catalysts: experimental and a comparative life cycle assessment study, Chem. Eng. J., 248 (2014) 230-241

K.N. Loponov, J. Lopes, M. Barlog, E.V. Astrova, A.V. Malkov, A.A. Lapkin, Optimization of a Scalable Photochemical Reactor for Reactions with Singlet Oxygen, Org.Process Res.Dev., 18 (2014) 1443-1454.

X. Fan, V. Sans, P. Yaseneva, D. Plaza, J.M.J. Williams, A.A. Lapkin, Facile Stoichiometric Reductions in Flow: an Example of Artemisinin, Org.Process Res.Dev., 16 (2012) 1039-1042.

M.V. Sotenko, M. Rebros, V.S. Sans, K.N. Loponov, M.G. Davidson, G. Stephens, A.A. Lapkin, Tandem transformation of glycerol to esters, J. Biotechnol., 162 (2012) 390-397.

A.A. Lapkin, A. Voutchkova, P. Anastas, A conceptual framework for description of complexity in intensive chemical processes, Chem. Eng. Processing. Process intensification, 50 (2011) 1027-1034.

Lapkin, A., Peters, M., Greiner, L., Chemat, S., Leonhard, K., Liauw, M. A. and Leitner, W., Screening of new solvents for artemisinin extraction process using ab-initio methodology, Green Chem., 12 (2010) 241-251.

Lapkin, A. A. and Plucinski, P. K., Engineering factors for efficient flow processes in chemical industries, in Chemical reactions and processes under flow conditions, pp. 1- 43, Eds: Luis, S. V. and Garcia-Verdugo, E., Royal Society of Chemistry, Cambridge, 2010.

Iwan, A., Stephenson, H., Ketchie, W. C. and Lapkin, A. A., High temperature sequestration of CO2 using lithium zirconates, Chem. Eng. J., 146 (2009) 249-258.

Constable, D. J. C., Jimenez-Gonzalez, C. and Lapkin A., ‘Process metrics’, in Green chemistry metrics: measuring and monitoring sustainable processes, pp.  228- 247, Eds.: Lapkin, A. and Constable, D. J. C., Wiley-Blackwell, Chichester, 2008.

L.Torrente-Murciano, A.Lapkin, D.V. Bavykin, F.C. Walsh, K. Wilson, Highly selective Pd/titanate nanotubes catalysts for the double bond migration reaction, J. Catal., 245 (2007) 270-276.

A. Lapkin, P. Plucinski, Comparative assessment of technologies for extraction of artemisinin, J. Natural Prod., 69 (2006) 1653-1664.

D.V. Bavykin, A.A. Lapkin, S.T. Kolaczkowski, P.K. Plucinski, Selective oxidation of alcohols in a continuous multifunctional reactor: ruthenium oxide catalysed oxidation of benzyl alcohol, Applied Catal. A: General, 288 (2005) 165-174.

Image result for A. A. Lapkin

////////automation, chemical process,  route selection, data mining

Heck–Matsuda Reaction in Flow

Abstract Image

Product 3 was obtained as a mixture of diastereomers (58:42). The NMR data are consistent with literature precedent.20a

Major diastereomer: 1H NMR (300 MHz, CDCl3) δ (ppm) 7.25-7.28 (m, 2H), 7.14-7.17 (m, 2H), 5.14 (dd, 1H, J = 2.5, 5.8 Hz), 4.29 (t, 1H, J = 8.3 Hz), 3.79 (dd, 1H, J = 6.9, 8.4 Hz), 3.54-3.62 (m, 1H), 3.38 (s, 3H), 2.32 (dd, 1H, J = 7.7, 12.9 Hz), 2.04 (ddd, 1H, J = 5.1, 9.3, 13.1 Hz);

Minor diastereomer: 1H NMR (300 MHz, CDCl3) δ 7.25-7.28 (m, 4H), 5.16 (d, 1H, J = 4.4 Hz), 4.17 (t, 1H, J = 8.1 Hz), 3.72 (dd, 1H, J = 8.5, 9.7 Hz), 3.42 (s, 3H), 3.32-3.36 (m, 1H), 2.59 (ddd, 1H, J = 5.5, 10.3, 13.7 Hz), 1.91 (ddd, 1H, J = 2.4, 7.7, 10.2 Hz);

13C NMR (75 MHz, CDCl3) δ (ppm) 141.4, 140.0, 132.4, 132.3, 129.1, 128.7, 128.7, 128.5, 105.7, 105.4, 73.7, 73.0, 54.9, 54.7, 43.6, 42.1, 41.4, 41.1.

(20) (a) Oliveira, C. C.; Angnes, R. A.; Correia, C. R. D. J. Org. Chem. 2013, 78, 4373. (b) Oliveira, C. C.; Pfaltz, A.; Correia, C. R. D. Angew. Chem. Int. Ed. 2015, 54, 14036.

The optimization of a palladium-catalyzed Heck–Matsuda reaction using an optimization algorithm is presented. We modified and implemented the Nelder–Mead method in order to perform constrained optimizations in a multidimensional space. We illustrated the power of our modified algorithm through the optimization of a multivariable reaction involving the arylation of a deactivated olefin with an arenediazonium salt. The great flexibility of our optimization method allows to fine-tune experimental conditions according to three different objective functions: maximum yield, highest throughput, and lowest production cost. The beneficial properties of flow reactors associated with the power of intelligent algorithms for the fine-tuning of experimental parameters allowed the reaction to proceed in astonishingly simple conditions unable to promote the coupling through traditional batch chemistry.

/////////

Multicomponent-Multicatalyst Reactions (MC)2R: Efficient Dibenzazepine Synthesis

Multicomponent-Multicatalyst Reactions (MC)2R: Efficient Dibenzazepine Synthesis
Jennifer Tsoung, Jane Panteleev, Matthias Tesch, and Mark Lautens

Org. Lett. 2014, 16, 110-113. DOI:10.1021/ol4030925 .

http://pubs.acs.org/doi/abs/10.1021/ol4030925

A RhI/Pd0 catalyst system was applied to the multicomponent synthesis of aza-dibenzazepines from vinylpyridines, arylboronic acids, and amines in a domino process with no intermediate isolation or purification.

5-(p-tolyl)-3-(trifluoromethyl)-10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepine (4a)

STR1

1H NMR
(400 MHz, CDCl3) δ 8.66 (d, J = 1.1 Hz, 1H), 7.97 (d, J = 1.8 Hz, 1H), 7.43 – 7.38 (m, 1H), 7.38 – 7.29
(m, 3H), 6.98 (d, J = 8.4 Hz, 2H), 6.57 – 6.51 (m, 2H), 3.33 – 3.21 (m, 2H), 3.09 – 2.99 (m, 2H), 2.26 (s,
3H);

13C NMR (101 MHz, CDCl3) δ 161.7 (q, J = 1.3 Hz), 145.8, 143.6, 143.4 (q, J = 4.0 Hz), 139.7,
139.5, 134.9 (q, J = 3.5 Hz), 130.3, 130.0, 129.9, 128.9, 128.2, 127.7, 125.3 (q, J = 33.1 Hz), 123.4 (q, J =
272.5 Hz), 114.0 (2), 35.9, 29.0, 20.4;

19F NMR (377 MHz, CDCl3) δ -62.0;

IR (NaCl, neat): 3063, 3028,
2926, 2862, 1616, 1506, 1489, 1456, 1435, 1429, 1410, 1339, 1319, 1296, 1267, 1240, 1207, 1165, 1128,
1086, 1036, 978, 947, 930, 910, 895, 808, 772, 756, 737, 721, 704, 687, 664, 646, 627 cm-1;

HRMS (ESI):
calcd for C21H18F3N2 (M+H)+: 355.1422; found. 355.1419.

STR1

Jennifer Tsoung

Jennifer Tsoung

Jennifer Tsoung

PhD graduate, organic chemistry

Department of Chemistry, University of Toronto

Experience

PhD

University of Toronto

September 2010 – October 2015 (5 years 2 months)

Research Intern

Kyoto University

June 2014 – August 2014 (3 months)Kyoto, Japan

Methodology project in asymmetric phase-transfer catalyzed alkylations.

Co-op student

Angiotech

May 2009 – August 2009 (4 months)Vancouver, Canada Area

Formulation chemistry

Co-op student

Boehringer Ingelheim

January 2008 – August 2008 (8 months)Montreal, Canada Area

On two hit-to-lead teams working to synthesize analogues of hit compounds for HIV research.

Publications

Diastereoselective Friedel−Crafts Alkylation of Hydronaphthalenes(Link)

The Journal of Organic Chemistry

September 27, 2011

An efficient and versatile synthesis of chiral tetralins has been developed using both inter- and intramolecular Friedel-Crafts alkylation as a key step. The readily available hydronaphthalene substrates were prepared via a highly enantioselective metal-catalyzed ring opening of meso-oxabicyclic alkenes followed by hydrogenation. A wide variety of complex tetracyclic compounds have been isolated…more

One-Pot Synthesis of Chiral Dihydrobenzofuran Framework via Rh/Pd Catlaysis

Organic Letters

October 12, 2012

A one-pot synthesis of the chiral dihydrobenzofuran framework is described. The method utilizes Rh-catalyzed asymmetric ring opening (ARO) and Pd-catalyzed C-O coupling to furnish the product in excellent enantioselectivity without isolation of intermediates. Systematic metal-ligand studies were carried out to investigate the compatibility of each catalytic system using product enantiopurity as an…more

Rh/Pd Catalysis with Chiral and Achiral Ligands: Domino Synthesis of Aza-Dihydrodibenzoxepines(Link)

Angew. Chem. Int. Ed

July 19, 2013

A game of dominoes: A synthetic route to aza-dihydrodibenzoxepines is described, through the combination of a Rh-catalyzed arylation and a Pd-catalyzed C-O coupling in a single pot. For the first time, the ability to incorporate a chiral and an achiral ligand in a two-component, two-metal transformation is achieved, giving the products in moderate to good yields, with excellent enantioselectivities.

Multicomponent-multicatalyst reactions (MC)(2)R: efficient dibenzazepine synthesis.

Organic Letters

January 13, 2014

A Rh(I)/Pd(0) catalyst system was applied to the multicomponent synthesis of aza-dibenzazepines from vinylpyridines, arylboronic acids, and amines in a domino process with no intermediate isolation or purification.

Formation of substituted oxa- and azarhodacyclobutanes.

Chemistry – A European Journal

December 6, 2013

The preparation of substituted oxa- and azarhodacyclobutanes is reported. After exchange of ethylene with a variety of unsymmetrically and symmetrically substituted alkenes, the corresponding rhodium-olefin complexes were oxidized with H2O2 and PhINTs (Ts=p-toluenesulfonyl) to yield the substituted oxa- and azarhodacyclobutanes, respectively. Oxarhodacyclobutanes could be prepared with excellent…more

Women in Chemistry group, 2015

Lautens Research Group :: Group Pictures

Mark Lautens , O.C.

University Professor
J. Bryan Jones Distinguished Professor
AstraZeneca Professor of Organic Chemistry
NSERC/Merck-Frosst Industrial Research Chair


Department of Chemistry
Davenport Chemical Laboratories
80 St. George St.
University of Toronto
Toronto, Ontario
M5S 3H6

Tel: (416) 978-6083
Fax: (416) 946-8185
E-Mail: mlautens@chem.utoronto.ca

Curriculum Vitae

Personal

Place and Date of Birth Hamilton, Ontario, Canada July 9, 1959

Education

Harvard University NSERC PDF with D. A. Evans 1985 – 1987
University of Wisconsin-Madison Ph.D. with B. M. Trost 1985
University of Guelph B.Sc. – Distinction 1981

Academic Positions

J. Bryan Jones Distinguished Professor University of Toronto 2013 – 2018
University Professor University of Toronto 2012 – present
NSERC/Merck Frosst Industrial Research Chair NSERC/Merck Frosst 2003 – 2013
AstraZeneca Professor of Organic Synthesis University of Toronto 1998 – present
Professor University of Toronto 1995 – 1998
Associate Professor University of Toronto 1992 – 1995
Assistant Professor University of Toronto 1987 – 1992

Awards & Honors

University of Toronto Alumni Faculty Award University of Toronto 2016
CIC Catalysis Award CSC 2016
Officer of the Order of Canada Governor General 2014
Killam Research Fellowship Canada Council for the Arts 2013-2015
CIC Medal Chemical Institute of Canada 2013
Fellow of the Royal Society of UK Royal Society of Chemistry 2011
Pedler Award Royal Society of Chemistry 2011
Senior Scientist Award Alexander von Humboldt Foundation
Berlin, Aachen and Gottingen
2009-2014
Visiting Professor University of Berlin 2009
Visiting Professor Université de Marseilles 2008
ICIQ Summer School ICIQ Tarragona, Spain 2008
Attilio Corbella Summer School Professor Italian Chemical Society 2007
Arthur C. Cope Scholar Award American Chemical Society 2006
Alfred Bader Award Canadian Society for Chemistry 2006
R. U. Lemieux Award Canadian Society for Chemistry 2004
Solvias Prize Solvias AG 2002
Fellow of the Royal Society of Canada Royal Society of Canada 2001

Areas of Research Interest and Expertise

  • new synthetic methods
  • metal catalyzed cycloaddition and annulation reactions
  • asymmetric catalysis with focus on rhodium, nickel and palladium catalysts
  • cyclopropane synthesis and reactions
  • hydrometallation reactions
  • reactions of organosilicon and organotin compounds
  • fragmentation reactions
  • new routes to medicinally/biologically interesting compounds
  • heterocycle synthesis using metal catalysts

///////Multicomponent, Multicatalyst Reactions,  (MC)2R,  Dibenzazepine Synthesis, Mark Lautens, University of Toronto , Toronto, Ontario, Jennifer Tsoung

2-Bromo-1,4-benzenedimethanol

(2-bromo-4-hydroxymethylphenyl)methanol.png

(2-bromo-4-hydroxymethylphenyl)methanol;

 CAS 89980-92-7; 

2-Bromo-1,4-benzenedimethanol;

Molecular Formula: C8H9BrO2
Molecular Weight: 217.05986 g/mol

(2-Bromo-4-hydroxymethylphenyl)methanol (3).

To a solution of commercially available 2-bromoterephthalic acid (2) (575 g, 2.34 mol) in THF (5.75 L), a THF solution of BH3 (1.0 M, 5.86 L) was added at 0 °C dropwise for 2.5 h, and the mixture was stirred for 1 h at 0 °C. The mixture was gradually warmed up to 35 °C over 3.5 h. The reaction mixture was cooled to 0 °C and quenched by dropwise addition of MeOH (1.15 L) over 30 min. Then, the mixture was concentrated in vacuo. The residue was dissolved in MeOH (1.72 L), and then water (10.3 L) was added; the mixture was then stirred at 0 °C for 30 min. The off-white solid was filtered and washed with water (1.15 L × 3) and heptanes (2.30 L) to obtain 3 (426 g, 84%) as a white crystal;

mp 108–109 °C;

1H NMR (400 MHz, DMSO-d6) δ: 4.47 (2H, d, J = 5.6 Hz), 4.49 (2H, d, J = 5.4 Hz), 5.29 (1H, t, J = 5.6 Hz), 5.39 (1H, t, J = 5.4 Hz), 7.31 (1H, d, J = 7.8 Hz), 7.47 (1H, d, J = 7.8 Hz), 7.48–7.49 (1H, m);

13C NMR (100 MHz, DMSO-d6) δ: 61.9, 62.5, 120.8, 125.5, 127.9, 129.7, 139.1, 143.4;

HRMS (EI) calcd for C8H9BrO2 [M]+ 215.9786, found 215.9787.

1H NMR

1H NMR (400 MHz, DMSO-d6) δ: 4.47 (2H, d, J = 5.6 Hz), 4.49 (2H, d, J = 5.4 Hz), 5.29 (1H, t, J = 5.6 Hz), 5.39 (1H, t, J = 5.4 Hz), 7.31 (1H, d, J = 7.8 Hz), 7.47 (1H, d, J = 7.8 Hz), 7.48–7.49 (1H, m); 

13C NMR

13C NMR (100 MHz, DMSO-d6) δ: 61.9, 62.5, 120.8, 125.5, 127.9, 129.7, 139.1, 143.4;

MASS PREDICT

1H/13C PREDICT

J. Org. Chem.201681 (5), pp 2148–2153

DOI: 10.1021/acs.joc.5b02734

///////////c1(cc(c(cc1)CO)Br)CO

Copper catalysed alkynylation of tertiary amines with CaC2 via sp3 C-H activation

 

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC00872K, Communication
Siew Ping Teong, Dingyi Yu, Yin Ngai Sum, Yugen Zhang
A mild and easy-to-handle protocol to produce propargylamines with a terminal alkyne through sp3 C-H bond activation and C-C coupling of tertiary amines and calcium carbide has been developed.

 

Copper catalysed alkynylation of tertiary amines with CaC2 via sp3 C–H activation

*Corresponding authors
aInstitute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore
E-mail: ygzhang@ibn.a-star.edu.sg
Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC00872K

A mild and easy-to-handle protocol to produce propargylamines with a terminal alkyne through catalytic cross-coupling of tertiary amines and calcium carbide has been developed. The reaction proceeds via sp3 C–H bond activation and C–C coupling. Good to excellent yields were obtained for the corresponding propargylamines with both alkyl and aryl substitutions. The development of these functionalized propargylamines with a terminal alkyne group will offer a wider application for the synthesis of natural or pharmaceutical products due to their unique sp C–H reactivity.
STR1
N-methyl-N-(prop-2-yn-1-yl)cyclohexanamine (3a) This compound was prepared according to general procedure and isolated by column chromatography (ethyl acetate/hexane = 1/8) to give the product as a light yellow liquid (139 mg, 92%). 1H NMR (400 MHz, CDCl3) δ 3.42 (d, J = 2.4 Hz, 2H, CH2), 2.39 – 2.31 (m, 1H, CH), 2.35 (s, 3H, CH3), 2.19 (t, J = 2.5 Hz, 1H, C≡CH), 1.92 – 1.90 (m, 2H, CH2), 1.78 – 1.75 (m, 2H, CH2), 1.62 – 1.59 (m, 1H, CH2), 1.31 – 1.08 (m, 5H, CH2); 13C NMR (101 MHz, CDCl3) δ 79.8, 72.6, 60.7, 42.9, 38.5, 29.8, 26.0, 25.5; HRMS (EI) m/z calcd. for C 10 H 17 N 151.1361; found 151.1358
STR1
STR1

/////Copper catalysed alkynylation,  tertiary amines,  CaC2,  sp3 C-H activation