PAPER
Modular Synthesis of Chiral N-Protected b-Seleno Amines and Amides
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13C NMR (CDCl3, 100 MHz): d = 155.6, 136.4, 129.7, 128.9, 126.1,
1H NMR (CDCl3, 400 MHz): d = 7.51–7.49 (m, 2 H), 7.26–7.20 (m,
79.1, 55.2, 37.5, 30.8, 28.3, 19.4, 17.8.
3 H), 5.73 (d, J = 8.4 Hz, 1 H), 4.03–3.96 (m, 1 H), 3.18 (dd,
1J = 12.4 Hz, 2J = 6.0 Hz, 1 H), 3.09 (dd, 1J = 12.4 Hz, 2J = 4.8 Hz,
1 H), 1.89 (oct, J = 7.2 Hz, 1 H), 1.12 (s, 9 H), 0.90 (d, J = 6.8 Hz,
3 H), 0.89 (d, J = 6.8 Hz, 3 H).
HRMS: m/z calcd for C16H25NO2SNa: 318.1504; found: 318.1498.
Synthesis of Chiral b-Seleno Amine 4
Under an argon atmosphere, the lithium diselenide was generated
by reaction of elemental selenium (1.1 mmol) in a mixture of THF
(8 mL) and Super-hydride (1.1 mmol). After stirring for 30 min, the
N-acyl oxazolidinone (2a; 1 mmol) was added to the mixture and
the resulting solution was stirred for 48 h under reflux. The mixture
was quenched with sat. NH4Cl (10 mL), extracted with CH2Cl2
(3 × 15 mL) and the combined organic fractions were collected,
dried over MgSO4, and filtered. Purification of the crude product by
column chromatography (hexane–EtOAc, 90:10) furnished the de-
sired b-seleno amide 4.
13C NMR (CDCl3, 100 MHz): d = 177.6, 132.4, 130.1, 129.0, 126.8,
53.5, 38.6, 31.8, 31.4, 27.3, 19.3, 18.2.
HRMS: m/z calcd for C16H25NOSeNa: 350.0999; found: 350.0993.
(S)-2,2,2-Trifluoro-N-[3-methyl-1-(phenylthio)butan-2-yl]acet-
amide (6d)
Yield: 87%; [a]D20 +4 (c 3, CH2Cl2).
1H NMR (CDCl3, 400 MHz): d = 7.53–7.51 (m, 2 H), 7.27–7.25 (m,
3 H), 6.49 (d, J = 7.6 Hz, 1 H), 4.01–3.94 (m, 1 H), 3.11–3.05 (m,
2 H), 1.94 (oct, J = 6.4 Hz, 1 H), 0.90 (d, J = 6.8 Hz, 3 H), 0.90 (d,
J = 6.8 Hz, 3 H).
13C NMR (CDCl3, 100 MHz): d = 156.9 (q, J = 146.8 Hz), 133.2,
132.8, 129.2, 127.6, 115.7 (q, J = 1146.0 Hz), 55.4, 31.5, 30.7, 19.0,
18.0.
Yield: 57%.
1H NMR (CDCl3, 300 MHz): d = 4.80 (d, J = 9.2 Hz, 1 H), 3.67–
3.60 (m, 1 H), 3.17–3.12 (m, 2 H), 1.97–1.78 (m, 1 H), 1.44 (s,
9 H), 0.92 (t, J = 7.6 Hz, 6 H).
13C NMR (CDCl3, 75 MHz): d = 156.7, 79.1, 56.3, 34.5, 31.2, 28.4,
19.4, 17.7.
HRMS: m/z calcd for C13H16F3NOSeNa: 362.0247; found:
362.0241.
HRMS: m/z calcd for C20H40N2O4Se2Na: 555.1216; found:
555.1210.
(S)-N-[3-Methyl-1-(phenylthio)butan-2-yl]-4-nitrobenzamide
(6e)
Synthesis of Chiral b-Seleno Amides 6; General Procedure
Compound 3a (10 mmol) was treated with TFA (5 mL) in CH2Cl2
(30 mL) and stirred for 4 h to remove the Boc group. The organic
solvent was evaporated, CH2Cl2 (10 mL) was added and evaporat-
ed. The residue was used in the next step without any further puri-
fication.
Yield: 77%; [a]D20 +69 (c 3, CH2Cl2).
1H NMR (CDCl3, 400 MHz): d = 8.16 (d, J = 8.8 Hz, 2 H), 7.67 (d,
J = 8.8 Hz, 2 H), 7.52–7.50 (m, 2 H), 7.21–7.20 (m, 3 H), 6.34 (d,
J = 8.8 Hz, 1 H), 4.25–4.18 (m, 1 H), 3.27 (dd, 1J = 13.0 Hz,
2J = 4.4 Hz, 1 H), 3.22 (dd, J = 13.0 Hz, J = 6.4 Hz, 1 H), 2.03
(oct, J = 6.4 Hz, 1 H), 0.98 (d, J = 6.8 Hz, 3 H), 0.97 (d, J = 6.8 Hz,
3 H).
1
2
The seleno amine 5 (1 mmol) obtained above, was stirred with
CH2Cl2 (8 mL) and K2CO3 (2.4 mmol) under argon atmosphere.
The corresponding acyl chloride (1.1 mmol) was added and the so-
lution was stirred at r.t. for 24 h. The mixture was quenched with
sat. NH4Cl (15 mL) and extracted with CH2Cl2 (3 × 20 mL) and the
combined organic fractions were collected, dried over MgSO4, and
evaporated. The crude material was purified by column chromatog-
raphy to give the desired products 6a–g.
13C NMR (CDCl3, 100 MHz): d = 165.1, 149.2, 140.0, 132.6, 129.2,
127.9, 127.2, 123.5, 55.4, 31.7, 31.3, 19.2, 18.6.
HRMS: m/z calcd for C18H20N2O3SeNa: 415.0537; found:
415.0531.
(S)-2-Chloro-N-[3-methyl-1-(phenylthio)butan-2-yl]benz-
amide (6f)
Yield: 77%; [a]D20 +58 (c 3, CH2Cl2).
(S)-N-[3-Methyl-1-(phenylthio)butan-2-yl]acetamide (6a)
Yield: 93%; [a]D20 +8 (c 3, CH2Cl2).
1H NMR (CDCl3, 400 MHz): d = 7.52–7.50 (m, 2 H), 7.24–7.22 (m,
3 H), 5.65 (d, J = 8.4 Hz, 1 H), 4.04–3.97 (m, 1 H), 3.13–3.09 (m,
2 H), 2.21 (s, 3 H), 1.88 (oct, J = 6.8 Hz, 1 H), 0.89 (d, J = 6.4 Hz,
6 H).
1H NMR (CDCl3, 400 MHz): d = 7.54–7.49 (m, 3 H), 7.37–7.20 (m,
6 H), 6.26 (d, J = 8.8 Hz, 1 H), 4.26–4.20 (m, 1 H), 3.24–3.15 (m,
2 H), 2.01 (oct, J = 6.8 Hz, 1 H), 0.98 (d, J = 6.8 Hz, 3 H), 0.97 (d,
J = 6.8 Hz, 3 H).
13C NMR (CDCl3, 100 MHz): d = 166.1, 135.1, 132.9, 131.8, 131.0,
130.0, 130.0, 129.1, 127.0, 126.9, 55.0, 31.7, 31.4, 19.4, 18.2.
13C NMR (CDCl3, 100 MHz): d = 173.2, 132.5, 130.1, 129.0, 126.9,
54.0, 31.6, 31.3, 29.5, 19.2, 18.2.
HRMS: m/z calcd for C18H20ClNOSeNa: 404.0296; found:
404.0296.
HRMS: m/z calcd for C13H19NOSeNa: 308.0530; found: 308.0524.
(S)-4-Methyl-N-[3-methyl-1-(phenylthio)butan-2-yl]benz-
amide (6g)
(S)-N-[3-Methyl-1-(phenylthio)butan-2-yl]propionamide (6b)
Yield: 81%; [a]D20 +5 (c 3, CH2Cl2).
1H NMR (CDCl3, 400 MHz): d = 7.52–7.50 (m, 2 H), 7.24–7.22 (m,
3 H), 5.65 (d, J = 8.4 Hz, 1 H), 4.04–3.97 (m, 1 H), 3.13–3.09 (m,
2 H), 2.13–2.02 (m, 2 H), 1.88 (oct, J = 6.8 Hz, 1 H), 1.07 (t, J = 7.6
Hz, 3 H), 0.89 (d, J = 6.4 Hz, 6 H).
Yield: 77%; [a]D20 +73 (c 3, CH2Cl2).
1H NMR (CDCl3, 400 MHz): d = 7.52–7.50 (m, 4 H), 7.24–7.14 (m,
5 H), 6.22 (d, J = 8.8 Hz, 1 H), 4.25–4.18 (m, 1 H), 3.26–3.17 (m,
2 H), 2.36 (s, 3 H), 2.00 (oct, J = 6.8 Hz, 1 H), 0.95 (d, J = 6.6 Hz,
3 H), 0.94 (d, J = 6.6 Hz, 3 H).
13C NMR (CDCl3, 100 MHz): d = 167.0, 141.6, 132.7, 131.6, 130.0,
129.0, 126.9, 126.7, 54.6, 31.8, 31.6, 21.3, 19.3, 18.5.
13C NMR (CDCl3, 100 MHz): d = 173.2, 132.5, 130.1, 129.0, 126.9,
54.0, 31.6, 31.3, 29.5, 19.2, 18.2, 9.2.
HRMS: m/z calcd for C14H21NOSeNa: 322.0686; found: 322.0680.
HRMS: m/z calcd for C19H23NOSeNa: 384.0843; found: 384.0837.
(S)-N-[3-Methyl-1-(phenylthio)butan-2-yl]pivalamide (6c)
Yield: 89%; [a]D20 +21 (c 3, CH2Cl2).
Synthesis 2008, No. 8, 1262–1268 © Thieme Stuttgart · New York