4th EucheMs chemistry congress

Poster Session 2
s1302
chem. Listy 106, s257–s1425 (2012)
Poster session 2 - organic chemistry
P - 0 8 7 8
towArdS the SyntheSiS of APiCuLAren A: An
APPLiCAtion of new MethodoLoGy to
ConStruCt 2,6-Anti-tetrAhydroPyrAn rinGS
S. S. ChuA 1 , A. ALni 1 , t. P. Loh 1
1 Nanyang Technological University, Chemistry and Biological
Chemistry, Singapore, Singapore
Since the isolation [1] and the subsequent structural
elucidation [2] of Apicularen A, 1, by Hofle and co-workers, the
molecule has been an intriguing molecule to the chemical society.
Its wondrous biological properties [3] place Apicularen A as a
potential candidate for anticancer drug target and the delicate
architecture of the molecule are two major factors that motivate
many synthetic chemists to construct Apicularen A. The first total
synthesis successfully reported by De Brabander and co-workers [4]
and there are hitherto 11 total syntheses and numerous formal
syntheses for this interesting molecule found in the literature.
Our group also became interested and jumped onto the
bandwagon in the attempt to construct the molecule. We embarked
on our synthetic study with commercially available
2,6-dihydroxybenzoic acid and effected a hetero-Diels-Alder to
obtain intermediate 2. We then applied a new methodology
recently developed in our group, [5] which involves
Mukaiyama-Michael addition of silyl enol ether that is catalyzed
by indium trichloride (InCl ), to dihydropyranone at ambient
3
temperature to yield the desired, 2,6-anti-tetrahydropyran
intermediate 3 with high diastereoselectivity.In conclusion, we
managed to demonstrate the applicability of the methodology
developed and the total synthesis of Apicularen A is currently still
underway.
references:
1. Kunze, B.; Jansen, R.; Sasse, F.; Hofle, G.; Reichenbach,
H. J. Antibiot. 1998, 51, 1075.
2. Jansen, R.; Kunze, B.; Reichenbach, H.; Hofle, G.
Eur. J. Org. Chem. 2000, 6, 913.
3. Boyd, M. R.; Farina, C.; Belfiore, P.; Gagliardi, S.; Kim, J. W.;
Hayakawa, Y.; Beutler, J. A.; McKee, T. C.; Bowman, B. J.;
Bowman, E. J. J. Pharmacol.Exp. Ther. 2001, 297, 114.
4. a) Bhattacharjee, A.; Seguil, O. R.; De Brabander, J. K.
Tetrahedron Lett. 2000, 41, 8069.
b) Bhattacharjee, A.; De Brabander, J. K. Tetrahedron Lett.
2001, 42, 1217.
5. Chua, S.-S.; Alni, A.; Chan, L.-T. J.; Yamane, M.; Loh, T.-P.
Tetrahedron 2011, 67, 5079.
Keywords: Synthetic methods; Total synthesis; Michael
addition; Indium;
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SynthetiC And MeChAniStiC StudieS on
niCKeL-CAtALyzed C–C Bond forMAtionS
APPLyinG weLL-defined niCKeL CoMPLexeS
Modified By tridentAte o,n,o'-LiGAndS
C. inoue 1 , S. enthALer 1
4 th EucheMs chemistry congress
1Technical University Berlin, Department of Chemistry,
Berlin, Germany
Nowadays nickel-catalyzed carbon–carbon bond formations
have been extensively developed, and have been used in synthesis
of fine chemicals and natural products. In contrast to well
established sp2 –sp2 cross coupling reactions, sp3 –sp3 cross
coupling reactions are more challenging tasks, because of the
several problems, e.g., β–hydride elimination. [1] One option to
overcome these problems is the design and fine-tuning of the
catalyst, which has been demonstrated in a number of studies.
Nevertheless, the development of novel ligands is still requested
for improving the catalyst performance. Furthermore the
understanding of the underlying reaction mechanism is also
important to advance these reactions.
Recently we studied the abilities of octahedral nickel
complexes containing O,N,O?–ligands in coordination chemistry
and catalysis. [2] Moreover, the octahedral nickel complexes were
successfully applied as pre-catalyst in cross coupling reactions.
Hence, we report herein the synthesis and characterization of
square planar nickel complexes modified by tridentate O,N,O?–
ligands and a phosphane as an additional ligand, which can be a
useful probe (e.g., NMR). Moreover, the capability of the
complexes were investigated in C(sp2 )–C(sp3 ) cross coupling
reactions of aryl halides with zinc reagents and experiments to
shed light on the underlying reaction mechanism were performed.
references:
1. a) R. Jana, T. P. Pathak, M. S. Sigman, Chem. Rev., 2011,
111, 1417;
b) X. Hu, Chem. Sci., 2011, 2, 1867.
2. a) C. I. Someya, S. Inoue, E. Irran, S. Krackl, S. Enthaler,
Eur. J. Inorg. Chem. 2011, 2691;
b) C. I. Someya, S. Inoue, E. Irran, S. Krackl, S. Enthaler,
Eur. J. Inorg. Chem. 2012, 1269.
Keywords: Homogeneous catalysis; C-C coupling; Nickel;
Tridentate ligands; Reaction mechanisms;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc