Prof. Carsten Bolm

DR ANTHONY MELVIN CRASTO Ph.D ORGANIC CHEMISTRY

 

abstract graphic

(R)-(−)-2-[(5-oxido-5-phenyl-5λ4-isoquino[4,3-c][2,1]benzothiazin- 12-yl)amino]benzonitrile (4).

Copper-catalyzed cross-coupling between (S)-S-methyl-S-phenylsulfoximine (1) and 2-iodobenzonitrile (2) resulted in the discovery of an unprecedented one-pot triple arylation sequence to give (R)-(−)-2-[(5-oxido-5-phenyl-5λ4-isoquino[4,3-c][2,1]benzothiazin- 12-yl)amino]benzonitrile (4). Here, we describe the synthesis of the title compound (R)-4 and the elucidation of its structure by means of various techniques.

Carsten Bolm with wife and new baby Lewon, March 2009 (344 / 433)

Germany

Molbank 2014, 2014(3), M834; doi:10.3390/M834
http://www.mdpi.com/1422-8599/2014/3/M834

(R)-(−)-2-[(5-Oxido-5-phenyl-5λ4-isoquino[4,3-c][2,1]benzothiazin-12-yl)amino]benzonitrile

Marcus Frings, Iuliana Atodiresei and Carsten Bolm *
* Author to whom correspondence should be addressed; E-Mail: carsten.bolm@oc.rwth-aachen.de;
Fax: +29-241-80-92-391. http://bolm.oc.rwth-aachen.de/

Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany

 Carsten Bolm

   Dr. rer. nat., Professor of Organic Chemistry
Institut für Organische Chemie
RWTH Aachen University
Landoltweg 1
D-52074 Aachen, Germany
Tel.: + 49 241-80 94 675
FAX : + 49 241-80 92 391
e-mail: Carsten.Bolm@oc.RWTH-Aachen.de
http://bolm.oc.rwth-aachen.de/
Prof. Carsten Bolm
The combined organic phases were dried with
MgSO4 and filtered. After evaporation of solvents, the oily residue was subjected to column
chromatography (SiO2, n-pentane/EtOAc = 2/1). Product (R)-4 was isolated as a yellow solid.
Additionally, sulfoximine (S)-3 was separately obtained as a yellow oil (61% yield, 0.899 g, 3.51 mmol).
Yield: 23% (0.616 g, 1.34 mmol); mp = 211–212 °C (racemate: 263–265 °C); [α] = −57.7 (c = 0.6 g,
100 mL−1, CHCl3); 1H NMR (600 MHz, CDCl3): δ = 7.11 (ddd, J = 8.2 Hz, 7.1 Hz, 1.2 Hz, 1H, Ar-H),
7.25 (dd, J = 8.0 Hz, 1.1 Hz, 1H, Ar-H), 7.27 (td, J = 7.6 Hz, 1.0 Hz, 1H, Ar-H), 7.42–7.50 (m, 3H,
Ar-H), 7.50–7.58 (m, 3H, Ar-H), 7.70 (dd, J = 7.8 Hz, 1.5 Hz, 1H, Ar-H), 7.78 (ddd, J = 8.8 Hz, 7.5
Hz, 1.6 Hz, 1H, Ar-H), 7.87–7.90 (m, 2H, Ar-H), 8.07 (dd, J = 7.6 Hz, 1.6 Hz, 1H, Ar-H), 8.19–8.24
(m, 2H, Ar-H and NH), 8.50 (dd, J = 8.1 Hz, 1.5 Hz, 1H, Ar-H), 8.81 (d, J = 8.4 Hz, 1H, Ar-H) ppm;
13C NMR (150 MHz, CDCl3): δ = 103.4 (C), 105.5 (Ar-C), 116.9 (Ar-C), 117.5 (C), 118.4 (Ar-C),
120.3 (Ar-CH), 121.8 (Ar-CH), 122.3 (Ar-CH), 123.6 (Ar-CH), 123.8 (Ar-CH), 124.8 (Ar-CH), 125.9
(Ar-CH), 127.6 (Ar-CH), 127.7 (2 Ar-CH), 129.0 (2 Ar-CH), 132.0 (2 Ar-CH), 132.4 (Ar-CH), 132.5
(Ar-C), 132.8 (Ar-CH), 133.9 (Ar-CH), 141.7 (Ar-C), 144.0 (Ar-C), 144.2 (Ar-C), 148.0 (C), 153.2
(C) ppm; 1
H NMR [600 MHz, (CD3)2SO]: δ = 6.98 (ddd, J = 8.2 Hz, 7.2 Hz, 1.1 Hz, 1H, Ar-H), 7.11
(dd, J = 8.1 Hz, 0.8 Hz, 1H, Ar-H), 7.40 (ddd, J = 8.6 Hz, 7.2 Hz, 1.6 Hz, 1H, Ar-H), 7.53 (td, J = 7.7 Hz,
1.0 Hz, 1H, Ar-H), 7.56–7.60 (m, 2H, Ar-H), 7.60–7.64 (m, 1H, Ar-H), 7.67–7.73 (m, 2H, Ar-H), 7.80
(d, J = 8.0 Hz, 1H, Ar-H), 7.84–7.88 (m, 3H, Ar-H), 8.04 (dd, J = 7.8 Hz, 1.4 Hz, 1H, Ar-H), 8.12 (dd,
J = 7.7 Hz, 1.8 Hz, 1H, Ar-H), 8.18 (dd, J = 8.1 Hz, 1.5 Hz, 1H, Ar-H), 8.68 (dd, J = 7.5 Hz, 1.7 Hz,
1H, Ar-H), 10.51 (s, 1H, NH) ppm;
13C NMR [150 MHz, (CD3)2SO]: δ = 103.5 (C), 110.2 (Ar-C),
117.0 (Ar-C), 117.4 (C), 118.0 (Ar-C), 119.7 (Ar-CH), 122.6 (Ar-CH), 123.6 (Ar-CH), 124.5 (Ar-CH),
125.6 (Ar-CH), 126.2 (Ar-CH), 127.1 (2 Ar-CH), 127.3 (Ar-CH), 127.4 (Ar-CH), 129.3 (2 Ar-CH),
131.7 (Ar-C), 131.8 (Ar-CH), 132.2 (Ar-CH), 133.0 (Ar-CH), 133.1 (Ar-CH), 133.9 (Ar-CH), 141.9
(Ar-C), 143.7 (Ar-C), 144.0 (Ar-C), 147.4 (C), 155.6 (C) ppm;
IR (ATR): ν = 3640, 3258, 2324, 2221,
2020, 1980, 1936, 1601, 1572, 1546, 1515, 1484, 1459, 1422, 1376, 1333, 1277, 1241, 1206, 1149,
1092, 1038, 1009, 976, 844, 794, 754, 720, 681 cm−1; EI-MS: m/z (%) = 458 (100) [M]+, 410 (15), 381(22), 357 (9), 333 (62), 102 (6), 77 (12), 51 (10); CI-MS: m/z (%) = 499 (3) [M+C3H5]+, 487 (16)[M+C2H5]+
, 459 (100) [M+H]+, 358 (7); ESI-MS: m/z (%) = 939 (9) [2M+Na]+, 497 (8) [M+K]+, 481(24) [M+Na]+, 459 (42) [M+H]+, 358 (100); ESI-HRMS: m/z calcd for C28H19N4OS: 459.12741; found
459.12793 with ∆ = 1.14 ppm; anal. calcd for C28H18N4OS (458.54): C, 73.34; H, 3.96; N, 12.22;
found C, 73.44; H, 4.09; N, 12.30; HPLC: tr = 16.8 min [major], tr = 25.2 min [minor] (Chiralpak AD-H,
0.6 mL min−1, n-heptane/isopropanol = 60/40, λ = 230 nm, 20 °C); >99% ee.
Crystallographic data were collected with a Bruker Kappa APEX II CCD-diffractometer with
monochromatic Mo–Kα radiation (λ = 0.71073 Å) and a CCD detector. The structure was solved by
direct methods using SHELXS-97 and refined against F2 on all data by full-matrix least-squares
methods using SHELXL-97 [13,14].
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany

Prof. Carsten Bolm
Carsten Bolm was born in Braunschweig in 1960. He studied chemistry at the TU Braunschweig (Germany) and at the University of Wisconsin, Madison (USA). In 1987 he obtained his doctorate with Professor Reetz in Marburg (Germany). After postdoctoral training with Professor Sharpless at MIT, Cambridge (USA), Carsten Bolm worked in Basel (Switzerland) with Professor Giese to obtain his habilitation. In 1993 he became Professor of Organic Chemistry at the University of Marburg (Germany), and since 1996 he has a chair of Organic Chemistry at the RWTH Aachen (Germany).

GERMANY….

Leave a comment