Ph.D. THESIS ABSTRACT SYNTHESIS, STEREOCHEMISTRY AND ...

Radu Gropeanu – PhD Thesis Abstract
The unsymmetrical structure of the phenothiazine derivatives 8-10 was shown by the NMR
spectra. For example, the 1 H-NMR spectrum of 9 presents distinct 6 signals for the phenothiazine
protons, as well as the signal corresponding for the formyl proton (δ 3-CHO = 9.80 ppm, Figure
2).
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
I S
CHO
Figure 2. 1 H-NMR spectrum of 9 (CD3COCD3, 300 MHz, r.t.)
6.0
N
5.5
The 13 C-NMR spectrum of 9 presents two characteristic signals: one corresponding to C-I (δ C7
= 85.81 ppm) and one for the formyl group carbon atom (δ C3’ = 190.28 ppm).
2.2. PALLADIUM-CATALYZED CROSS-COUPLING REACTIONS OF HALO-
PHENOTHIAZINES
Halo-phenothiazines, as many other halo-derivatives, 35 undergo palladium-catalyzed
cross-coupling reactions. An extensively used method for the coupling of two Csp2 carbons is
represented by the Suzuki cross-coupling. 36 This reaction involves the interaction of one organic
halide and one organoboron compound, interaction mediated by Pd reduced species. This crosscoupling
reaction undergo in the presence of charged bases (Na2CO3, K2CO3, Na3PO4, KOH, and
alkoxides). 37,38
The synthesis of the phenothiazine boronic intermediates was previously described. 39
After generation of a mono or a double lithiated species by Li-Br exchange, an addition of
trimethylborate as electrophile, followed by the transesterification with pinacole, afforded the
phenothiazine mono- or bis-boronic esters (11a,b, 12, 13, Scheme 6). It was chosen the pinacole
ester due to their high stability. 40
In order to increase the selectivity, the reaction temperature was decreased. In the
synthesis of 15, despite the very good selectivity, the yield was not very good, after work-up
35 Poli, G.; Giambastiani, G.; Heumann, A. Tetrahedron 2000, 56, 5959.
36 Miyaura, N.; Suzuki, A. Chem. Rev.1995, 95, 2457.
37 Susuki, A. Acc. Chem. Res. 1982, 15, 178.
38 Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am. Chem. Soc. 1985, 107, 972.
39 Krämer, C.; Sailer, M.; Müller, T.J.J. Synthesis 2002, 1163.
40 Hoffmann, R.W.; Dresely, S. Synthesis 1988, 103.
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
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