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 .

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)


(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.


Jennifer Tsoung

Jennifer Tsoung

Jennifer Tsoung

PhD graduate, organic chemistry

Department of Chemistry, University of Toronto



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


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.


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

Curriculum Vitae


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

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
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

Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material


Abstract Image

Efficient continuous Grignard and lithiation processes were developed to produce one of the key regulatory starting materials for the production of edivoxetine hydrochoride. For the Grignard process, organometallic reagent formation, Bouveault formylation, reduction, and workup steps were run in continuous stirred tank reactors (CSTRs). The lithiation utilized a hybrid approach where plug flow reactors (PFRs) were used for the metal halogen exchange and Bouveault formylation steps, while the reduction and workup steps were performed in CSTRs. Relative to traditional batch processing, both approaches offer significant advantages. Both processes were high-yielding and produced the product in high purity. The two main processes were directly compared from a number of perspectives including reagent and operational safety, fouling potential, process footprint, need for manual operation, and product yield and purity.

Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material

Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, United States
D&M Continuous Solutions, LLC, Greenwood, Indiana 46143, United States
Org. Process Res. Dev., Article ASAP

//////////Flow Grignard,  Lithiation, Screening Tools,  Development, Continuous Processes,  Benzyl Alcohol, Starting Material

Day 10 of the 2016 Doodle Fruit Games! Find out more at

MICONAZOLE NITRATE , Миконазол , ミコナゾール硝酸塩

New Drug Approvals

Miconazole            C18H14Cl4N2O    416.13             [22916478]

Miconazole Nitrate            C18H14Cl4N2O.HNO3              479.14             [22832877]

ミコナゾール硝酸塩 JP16
Miconazole Nitrate

C18H14Cl4N2O▪HNO3 : 479.14

click on above image for clear view



1D 1H, n/a spectrum for Miconazole


2D [1H,1H]-TOCSY, n/a spectrum for Miconazole


1D DEPT90, n/a spectrum for Miconazole

1D DEPT135

1D DEPT135, n/a spectrum for Miconazole

2D [1H,13C]-HSQC

2D [1H,13C]-HSQC, n/a spectrum for Miconazole

2D [1H,13C]-HMBC

2D [1H,13C]-HMBC, n/a spectrum for Miconazole

2D [1H,1H]-COSY

2D [1H,1H]-COSY, n/a spectrum for Miconazole

2D [1H,13C]-HMQC

2D [1H,13C]-HMQC, n/a spectrum for MiconazoleMiconazole is an imidazole antifungal agent, developed by Janssen Pharmaceutica, commonly applied topically to the skin or tomucous membranes to cure fungal infections. It works by inhibiting the synthesis of ergosterol, a critical component of fungal cell membranes. It can also be used against certain species of Leishmania protozoa which are a type of unicellular parasites that…

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Directed alkynylation of unactivated C(sp3)-H bonds with ethynylbenziodoxolones mediated by DTBP

Green Chemistry International

Directed alkynylation of unactivated C(sp3)-H bonds with ethynylbenziodoxolones mediated by DTBP

Green Chem., 2016, 18,4185-4188

DOI: 10.1039/C6GC01336H, Communication
Zhi-Fei Cheng, Yi-Si Feng, Chun Rong, Tao Xu, Peng-Fei Wang, Jun Xu, Jian-Jun Dai, Hua-Jian Xu
A general and efficient alkynylation of unactivated C(sp3)-H bonds under metal-free conditions was developed herein.

Directed alkynylation of unactivated C(sp3)–H bonds with ethynylbenziodoxolones mediated by DTBP

Zhi-Fei Cheng,a  Yi-Si Feng,*abc  Chun Rong,a  Tao Xu,a  Peng-Fei Wang,a  Jun Xu,a  Jian-Jun Daia and  Hua-Jian Xu*abc  
*Corresponding authors
aSchool of Chemistry and Chemical Engineering, School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, P. R. China
bAnhui Key Laboratory of Controllable Chemical Reaction and Material Chemical Engineering, Hefei 230009, P. R…

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