(2S)-2-(2,2,2-Trifluoroacetamido)-N-[1-(3,4-dihydroquinolin-
1(2H)-yl)-4-iodo-1-oxopent-4-en-2-yl]-3-phenylpropanamide (10s).
Iodine (66.2 mg, 0.26 mmol) dissolved in Et2O (1 mL) was
added to a solution of 10p (100 mg, 0.13 mmol, 91% ds) in
Et2O (2 mL). After stirring for 30 min a saturated KF solution
(2 mL) and ethyl acetate (5 mL) were added. After vigorous
stirring for 2 h the aqueous layer was removed and the organic
layer was filtrated and dried (Na2SO4). After evaporation of the
solvent, the crude product was purified by flash chromatography
(hexanes/ethyl acetate 3 : 1) to yield 10s (70.9 mg, 0.12 mmol, 91%,
91% ds). HPLC (Reprosil, hexanes/iPrOH 95 : 5, 1 mL min-1): tR
(9%) = 11.45 min, tR (91%) = 13.55 min. Major diastereomer;
1H-NMR (500 MHz, DMSO-d6, 353 K): d 9.15 (d, J = 8.5 Hz,
1H, TFANH), 8.55 (d, J = 8.0 Hz, 1H, NH), 7.49 (d, J =
7.5 Hz, 1H, ArH), 7.26–7.25 (m, 4H, ArH), 7.21–7.16 (m,
3H, ArH), 7.13 (td, J = 7.5, 1.5 Hz, 1H, ArH), 6.11 (d, J =
1.0 Hz, 1H, C CH2), 5.71 (d, J = 1.0 Hz, 1H, C CH2),
5.24–5.19 (m, 1H, CH), 4.71–4.66 (m, 1H, TFANHCH), 4.00–
3.95 (m, 1H, NCH2), 3.51–3.45 (m, 1H, NCH2), 3.10 (dd, J =
14.0, 5.0 Hz, 1H, PhCH2), 2.96 (dd, J = 14.0, 10.0 Hz, 1H,
PhCH2), 2.77–2.72 (m, 2H, CH2C CH2, NCH2CH2CH2), 2.69–
2.60 (m, 2H, CH2C CH2, NCH2CH2CH2)), 2.02–1.94 (m, 1H,
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NCH2CH2), 1.89–1.81 (m, 1H, NCH2CH2); 13C-NMR (125 MHz,
2
DMSO-d6, 353 K): d 169.2 (CO), 168.8 (CO), 155.6 (q, JC,F
=
36.4 Hz, CF3CO), 137.9 (ArC), 136.5 (ArC), 132.5 (ArC), 128.6
(2 ArCH), 128.4 (C CH2), 127.9 (ArCH), 127.5 (2 ArCH), 125.9
(ArCH), 125.5 (ArCH), 124.8 (ArCH), 123.9 (ArCH), 115.3 (q,
1JC,F = 286.5 Hz, CF3), 104.2 (C CH2), 54.2 (TFANHCH),
48.9 (CH), 47.1 (CH2C CH2), 42.9 (NCH2), 36.7 (PhCH2), 25.5
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1
peaks); H-NMR (500 MHz, DMSO-d6, 353 K): d 8.25 (d, J =
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7.0 Hz, 1H, NH), 7.44 (d, J = 7.5 Hz, 1H, ArH), 6.12 (d, J =
1.0 Hz, 1H, C CH2), 5.73 (d, J = 1.0 Hz, 1H, C CH2); 13C-
NMR (125 MHz, DMSO-d6, 353 K): d 128.5 (2 ArCH), 53.9
(TFANHCH), 49.2 (CH), 36.3 (PhCH2), 25.5 (NCH2CH2CH2).
HRMS (CI) m/z calcd for C25H26F3N3O3I [M+H]+ 600.0971.
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Acknowledgements
This work was supported by the Deutschen Forschungsgemein-
schaft (Ka880/6 and Ka880/8) and the Fonds der Chemischen
Industrie. Dr Swarup Datta thanks the Alexander von Humboldt
Foundation for a postdoctoral fellowship.
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