(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.

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/

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

GERMANY....