Efficient synthesis of isoquinolines in water by a Pd-catalyzed tandem reaction of functionalized alkylnitriles with arylboronic acids
1,3-Diphenylisoquinoline (3a). Pale-yellow solid (103.5 mg, 92%),
mp 78-79 oC (lit.24, 73-74.5 oC). 24 J. D. Tovar and T. M. Swager, J. Org. Chem., 1999, 64, 6499
1H NMR (500 MHz, CDCl3) δ 8.25-8.23 (m, 2H), 8.15-8.14 (m, 1H), 8.09 (s, 1H), 7.95-7.93 (m, 1H), 7.84-7.83 (m, 2H), 7.70-7.67 (m, 1H), 7.59-7.50 (m, 6H), 7.44-7.40 (m, 1H);
13C NMR (125 MHz, CDCl3) δ 160.5, 150.3, 140.1, 139.8, 138.0, 130.4, 130.2, 128.8, 128.7, 128.6, 128.4, 127.7, 127.6, 127.2, 127.0, 126.0, 115.8.
|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|
|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|
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 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.
|Fig. 2 A section of a network of organic chemistry. Dots are species and arrows represent reactions.|
Professor of Sustainable Reaction Engineering
Fellow of Wolfson College
Catalytic Reaction Engineering
Sustainable Chemical Technologies
Office Phone: 330141
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)
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.
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.
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.
////////automation, chemical process, route selection, data mining
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
Jennifer Tsoung, Jane Panteleev, Matthias Tesch, and Mark Lautens
Org. Lett. 2014, 16, 110-113. DOI: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.
(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,
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;
calcd for C21H18F3N2 (M+H)+: 355.1422; found. 355.1419.
PhD graduate, organic chemistry
September 2010 – October 2015 (5 years 2 months)
June 2014 – August 2014 (3 months)Kyoto, Japan
Methodology project in asymmetric phase-transfer catalyzed alkylations.
May 2009 – August 2009 (4 months)Vancouver, Canada Area
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.
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
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
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.
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.
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
Department of Chemistry
Davenport Chemical Laboratories
80 St. George St.
University of Toronto
|Place and Date of Birth||Hamilton, Ontario, Canada||July 9, 1959|
|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|
|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
|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
///////Multicomponent, Multicatalyst Reactions, (MC)2R, Dibenzazepine Synthesis, Mark Lautens, University of Toronto , Toronto, Ontario, Jennifer Tsoung