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

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