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)
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.
Jennifer Tsoung
Jennifer Tsoung
PhD graduate, organic chemistry
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
Education
University of Toronto
Doctor of Philosophy (PhD), Organic Chemistry
2010 – 2014
Activities and Societies: Pueblo Science executive member, Let’s Talk Science volunteer, International Chemistry Olympiad tutor
The University of British Columbia
Bachelor of Science (BSc), Chemistry
2005 – 2010
Activities and Societies: Undergraduate Chemistry Society (UCS) executive member, Science Undergraduate Society (SUS) executive member, Science Co-op Students Association (SCOOPS) president and founding member
port moody secondary
High school
Mark Nitz presents Jennifer Tsoung certificate for her CTFP award
Women in Chemistry group, 2015
Lautens Research Group :: Group Pictures
www.chem.utoronto.ca
July 2013
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