4th EucheMs chemistry congress

Poster Session 1
s1014
chem. Listy 106, s587–s1425 (2012)
Poster session 1 - organic chemistry
P - 0 3 0 5
rutheniuM-CAtALyzed direCt C–h Bond
AryLAtionS of AreneS BeArinG reMovABLe
direCtinG GrouPS
e. dierS 1 , L. ACKerMAnn 1
1 Georg-August Universität Göttingen, Institut für Organische
und Biomolekulare Chemie, Göttingen, Germany
Transition-metal-catalyzed direct arylation reactions via
C–H bond cleavages constitute an economically and ecologically
benign alternative to conventional cross-coupling reactions. [1]
In recent years, we have reported on generally applicable,
site-selective direct arylations of various arenes using aryl
bromides, chlorides, tosylates and phenols as (pre)electrophiles. [2]
We disclosed the beneficial effect of carboxylic acids as additives
in ruthenium-catalyzed direct arylations [3] or direct alkylations
with unactivated alkyl halides. [4] This catalytic system showed a
broad scope, and the key C–H bond metalation was proposed to
proceed through a carboxylate-assisted mechanism. [3]
However, ruthenium-catalyzed C–H bond arylations of
arenes with aryl halides continue to lack generality, as illustrated
by their limitation to substrates that form five-membered
ruthenacycles. [1–3]
Recently, we devised first ruthenium-catalyzed direct
arylations of arenes via six-membered ruthenacycles that set the
stage for a removable directing group strategy. [5]
Herein, we present the development, and scope of this
transition-metal-catalyzed C–H bond functionalizations.
references:
1. a) L. Ackermann, Modern Arylation Methods, Wiley-VCH,
Weinheim, 2009;
b) L. Ackermann, R. Vicente, A. R. Kapdi, Angew. Chem.,
Int. Ed. 2009, 48, 9792–9826;
c) X. Chen, K. M. Engle, D.-H. Wang,J.-Q. Yu, Angew.
Chem. Int. Ed. 2009, 48, 5094; d) D. Alberico, M. Scott,
M. Lautens, Chem. Rev. 2007, 107, 174-238.
2. a) L. Ackermann, A. Althammer, S. Fenner, Angew. Chem.
Int. Ed. 2009, 48, 201–204.
b) L. Ackermann, S. Fenner, Chem. Commun. 2011, 47,
430–432.
c) L. Ackermann, A. V. Lygin, Org. Lett. 2011, 13,
3332–3335.
d) L. Ackermann, J. Pospech, H. K. Potukuchi, Org. Lett.
2012, 14, 2146–2149.
3. L. Ackermann, R. Vicente, A. Althammer, Org. Lett. 2008,
10, 2299–2302.
4. a) L. Ackermann, P. Novák, R. Vicente, N. Hofmann,
Angew. Chem. Int. Ed. 2009, 48, 6045–6048.
b) L. Ackermann, N. Hofmann, R. Vicente, Org. Lett.
2011, 13, 1845–1877.
5. L. Ackermann, E. Diers, A. Manvar, Org. Lett. 2012, 14,
1154–1157.
Keywords: C-H activation; Homogeneous catalysis;
Ruthenium; Sustainable Chemistry; Arenes;
4 th EucheMs chemistry congress
P - 0 3 0 6
SyntheSiS of A PhotoSenSitizer for
PhotodynAMiC therAPy
L. donAhue 1
1 Loyola University Chicago, Chemistry, Chicago IL, USA
A phenothiazine trimer (N-benzyl-3,7-diphenothiazinyl -
phenothiazine) was synthesized for use as a photosensitizer (PS)
in photodynamic therapy (PDT). Buchwald-Hartwig chemistry
utilizing a Pd catalyst and XPhos ligand resulted in the formation
of two new C-N bonds on the benzyl protected phenothiazine
base. PDT involves the use of a PS, light, and singlet oxygen to
destroy cancer cells. A PS can be administered to a patient, and
light of a specific wavelength directed to the cancer site using
optical fibers. The light excites the PS and energy is transferred
to oxygen to produce singlet oxygen or to nearby molecules to
produce radical species. The singlet oxygen and radicals damage
vital cellular organelles, and subsequently destroy cancer cells.
Highly conjugated photosensitizers will absorb longer
wavelengths (600 – 900 nm), and have the potential to destroy
cells of deeper tissue tumors.
Future work involves the deprotection of the phenothiazine
trimer, and subsequent attachment of a polyethylene glycol (PEG)
linker so that the PS is more soluble in aqueous media. The linker
will also allow attachment of a folic acid molecule to increase
selectivity to cancer cells. Receptor mediated endocytosis will
allow preferential uptake of the PS complex into cancer cells.
Cross-linked hemoglobin will also be complexed to the PS.
The final phase of the research involves testing the PS
complex to assess the killing potential using HeLa and
neuroblastoma cell cultures. A colorimetric MTT assay as well as
confocal microscopy will be utilized to confirm cell death. The
hypothesis is that the cells that have been folate restricted will
show the most uptake of PS-folate complex and the greatest
amount of cell death.
Keywords: Cross-coupling; Medicinal chemistry; Palladium;
P ligands; Singlet oxygen;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc