Acylation of Alkyl Halides and Amino Aldehydes with Phosphane Oxide
FULL PAPER
H), 1.81 (dddd, J ϭ 13.4, 9.3, 6.7, 5.7 Hz, 1 H, 3-HЈ), 2.28 (ddd, N(CH2CHCH2)2], 7.12Ϫ7.30 (m, 5 H, H arom.) ppm. 13C NMR
J ϭ 15.6, 9.0, 6.7 Hz, 1 H, 2-H), 2.33 (ddd, J ϭ 15.6, 9.3, 6.4 Hz, (100 MHz, CDCl3, δ ϭ 77 ppm): δ ϭ 35.7 (t, C-4), 36.7 (t, C-2),
1 H, 2-HЈ), 3.46 (dd, J ϭ 9.9, 5.9 Hz, 1 H, 5-H), 3.49 (dd, J ϭ 9.9, 51.2 (q, OMe), 2 ϫ 52.5 [2 ϫ t, N(CH2CHCH2)2], 58.4 (d, C-3), 2
5.8 Hz, 1 H, 5-HЈ), 3.66 (s, 3 H, OCH3), 7.33Ϫ7.45 (m, 6 H,
TBDPS), 7.68Ϫ7.62 (m, 4 H, TBDPS) ppm. 13C NMR (100 MHz,
CDCl3, δ ϭ 77.0 ppm): δ ϭ 16.5 (CH3), 19.3 (tBu), 26.9 (tBu), 28.4
ϫ 116.4 [2 ϫ t, N(CH2CHCH2)2], 128.3, 2 ϫ 128.6, 128.7, 129.2
(5 ϫ d, C arom.), 2 ϫ 137.2 [2 ϫ d, N(CH2CHCH2)2], 139.6 (s, C
arom.), 172.7 (s, C-1) ppm. HRMS (C17H23NO2): calcd. 274.1807
(C-3), 31.8 (C-2), 35.2 (C-4), 51.4 (OMe), 68.5 (C-4), 127.6, 129.5, 2 [M ϩ H]ϩ, found 274.1813.
ϫ 133.9, 2 ϫ 135.6 (6 ϫ TBDPS), 174.3 (s, COOMe) ppm. HRMS
Methyl (2R,3S)-3-[(Benzyloxycarbonyl)amino]-2-hydroxy-4-phenyl-
(C23H32O3NaSi): calcd. [M ϩ Na]ϩ 407.2018, found 407.2023.
butyrate (35): By treatment of phosphane oxide 27 (56 mg,
0.1 mmol) in dichloromethane prepared according to general pro-
cedure, the title compound 35 (33.3 mg, 97 µmol, 97%) was ob-
tained. The diastereomeric ratio was determined by 1H NMR
sprectroscopy to be 8:1 in favour of the 2R,3S- over the 2S,3S-iso-
mer.
Methyl (3S)-3-[(Benzyloxycarbonyl)amino]-4-phenylbutyrate (31):
Phosphane oxide 27 (70 mg, 0.125 mmol) in THF (3 mL) under
nitrogen was treated with potassium tert-butoxide (1.1 equiv.) in
THF (2 mL/mmol) at 0 °C. After 15 min, the solution was concen-
trated in an ice-bath under reduced pressure to a volume of appoxi-
mately 1 mL. The intermediate ketene acetal was treated with an
aqueous solution of 1 HCl until the pH value was adjusted to 5.
The mixture was extracted with dichloromethane and the combined
organic layers were dried (MgSO4) and purified by column chroma-
tography to give the title compound 31 (27 mg, 0.083 mmol, 66%).
Spectroscopic data of 31 were in accordance with those reported
before.[36] Colorless oil. [α]2D0 ϭ Ϫ15.2 (CHCl3, c ϭ 1.0). HRMS
(C19H21NO4): calcd. 350.1368 [M ϩ Na]ϩ, found 350.1374.
(2R,3S)-35:[12] Colorless crystals, m.p. 97 °C (CH2Cl2). [α]2D3 ϭ ϩ7.9
(CHCl3, c ϭ 1.0). 1H NMR (400 MHz, CDCl3, TMS, δ ϭ 0 ppm):
δ ϭ 2.89 (dd, J ϭ 13.2, 7.1 Hz, 1 H, 4-HЈ), 2.97 (dd, J ϭ 13.2,
8.9 Hz, 1 H, 4-H), 3.16 (br. s, 1 H, OH), 3.70 (s, 3 H, OMe), 4.08
(d, J ϭ 1.8 Hz, 1 H, 2-H), 4.33 (dddd, J ϭ 8.9, 8.0, 7.1, 1.8 Hz, 1
H, 3-H), 5.04 (s, 2 H, PhCH2O), 5.09 (d, J ϭ 8.0 Hz, 1 H, NH),
7.38Ϫ7.20 (m, 10 H, H arom.) ppm. 13C NMR (100 MHz, CDCl3,
CDCl3, δ ϭ 77 ppm): δ ϭ 38.3 (t, C-4), 52.9 (q, OMe), 54.7 (d, C-
3), 66.8 (t, PhCH2O), 70.1 (d, C-2), 126.7, 127.9, 128.1, 128.5,
128.6, 129.4 (10 ϫ d, C arom.), 136.3, 137.2 (2 ϫ s, C arom.),
155.7 (s, NCO2), 174.1 (s, C-1) ppm. HRMS (C19H21NO5): calcd.
366.1317 [M ϩ Na]ϩ, found 366.1326.
Methyl (3S)-3-Dibenzylamino-4-phenylbutyrate (32): Phosphane ox-
ide 28 (95 mg, 0.157 mmol) in 3 mL THF under nitrogen was
treated with potassium tert-butoxide (1.1 equiv.) in THF (2 mL/
mmol) at 0 °C. After 15 min, the solution was concentrated in an
ice-bath under reduced pressure to a volume of appoximately 1 mL.
The intermediate ketene acetal was treated with with an aqueous
solution of 1 HCl until the pH value was adjusted to 5. The
mixture was extracted with dichloromethane and the combined or-
ganic layers were dried (MgSO4) and purified by column chroma-
tography to give the title compound 32 (55 mg, 0.147 mmol, 93%).
Methyl (2S,3S)-3-Dibenzylamino-2-hydroxy-4-phenylbutyrate (37):
By treatment of phosphane oxide 28 (60.6 mg, 0.1 mmol) in di-
chloromethane prepared according to general procedure, the title
compound 37 (35.4 mg, 91 µmol, 91%) was obtained as pure anti-
configured isomer. Colorless oil. [α]2D0 ϭ ϩ35.8 (CHCl3, c ϭ 1.0).
1H NMR (400 MHz, CDCl3, TMS, δ ϭ 0 ppm): δ ϭ 2.80 (dd, J ϭ
13.9, 7.6 Hz, 1 H, 4-HЈ), 3.02 (dd, J ϭ 13.9, 7.0 Hz, 1 H, 4-H),
3.12 (br. s, 1 H, OH), 3.41 (ddd, J ϭ 7.6, 7.0, 2.5 Hz, 1 H, 3-H),
3.51 (s, 3 H, OMe), 3.65 [d, J ϭ 14.0 Hz, 2 H, N(CH2Ph)Ј], 3.81
[d, J ϭ 14.0 Hz, 2 H, N(CH2Ph)], 4.49 (br. s, 1 H, 2-H), 7.28Ϫ7.04
(m, 15 H, H arom.) ppm. 13C NMR (100 MHz, CDCl3, CDCl3,
δ ϭ 77 ppm): δ ϭ 32.0 (t, C-4), 52.3 (q, OMe), 54.6 [2 ϫ t,
N(CH2Ph)2], 62.2 (d, C-3), 69.7 (d, C-2), 126.1, 126.9, 128.0, 128.1,
128.8, 129.5 (15 ϫ d, C arom.), 139.6, 139.0 (3 ϫ s, C arom.), 174.9
(s, C-1) ppm. HRMS (C25H27NO3): calcd. 390.2069 [M ϩ H]ϩ,
found 390.2082. The material was subjected to the hydrogenation
conditions (Pd/C, H2) described in ref.[20] in order to prove its stere-
ochemical purity. The analytical and spectroscopic data of the hy-
drochloride of methyl (2S,3S)-3-amino-2-hydroxy-4-phenylbutano-
ate were identical with those reported in the literature.[20]
1
Colorless oil. [α]2D0 ϭ Ϫ1.5 (CHCl3, c ϭ 1.0). H NMR (400 MHz,
TMS, δ ϭ 0 ppm): δ ϭ 2.31 (dd, J ϭ 14.1, 6.0 Hz, 1 H, 2-HЈ), 2.53
(dd, J ϭ 13.4, 8.9 Hz, 1 H, 4-HЈ), 2.62 (dd, J ϭ 14.1, 8.7 Hz, 1 H,
2-H), 3.10 (dd, J ϭ 13.4, 5.6 Hz, 1 H, 4-H), 3.43 (dddd, J ϭ 8.9,
8.7, 6.0, 5.6 Hz, 1 H, 3-H), 3.58 [d, J ϭ 13.7 Hz, 2 H, N(CH2Ph)Ј],
3.54 (s, 3 H, OMe), 3.73 [d, J ϭ 13.7 Hz, 2 H, N(CH2Ph)],
7.04Ϫ7.29 (m, 15 H, H arom.) ppm. 13C NMR (100 MHz, CDCl3,
δ ϭ 77 ppm): δ ϭ 35.8 (t, C-2), 36.1 (t, C-4), 51.3 (q, OMe), 53.4
[2 ϫ t, N(CH2Ph)2], 57.6 (d, C-3), 126.1, 126.9, 128.1, 128.3, 128.9,
129.3 (15 ϫ d, C arom.), 139.4, 139.5 (3 ϫ s, C arom.), 172.7 (s,
C-1) ppm. HRMS (C25H27NO2): calcd. 374.2120 [M ϩ H]ϩ,
found 374.2108.
Methyl (3S)-3-Diallylamino-4-phenylbutyrate (33): Phosphane ox-
ide 29 (168 mg, 0.33 mmol) in 4 mL THF under nitrogen was
treated with potassium tert-butoxide (1.1 equiv.) in THF (2 mL/
mmol) at 0 °C. After 15 min, the solution was concentrated in an
ice-bath under reduced pressure to a volume of appoximately 1 mL.
The intermediate ketene acetal was treated with an aqueous solu-
tion of 1 HCl until the pH value was adjusted to 5. The mixture
was extracted with dichloromethane and the combined organic lay-
ers were dried (MgSO4) and purified by column chromatography
to give the title compound 33 (80 mg, 0.293 mmol, 88%). Colorless
oil. [α]2D0 ϭ Ϫ28.2 (CHCl3, c ϭ 1.0). 1H NMR (400 MHz, TMS,
δ ϭ 0 ppm): δ ϭ 2.27 (dd, J ϭ 14.3, 5.9 Hz, 1 H, 2-HЈ), 2.39 (dd,
J ϭ 13.3, 9.2 Hz, 1 H, 4-HЈ), 2.45 (dd, J ϭ 14.3, 9.2 Hz, 1 H, 2-
Methyl (2S,3S)-3-Diallylamino-2-hydroxy-4-phenylbutyrate (38): By
treatment of phosphane oxide 29 (50.5 mg, 0.1 mmol) in dichloro-
methane prepared according to general procedure, the title com-
pound 38 (26 mg, 90 µmol, 90%) was obtained as pure anti-config-
ured isomer. Colorless oil. [α]2D0 ϭ ϩ7.6 (CHCl3, c ϭ 1.0). 1H NMR
(400 MHz, CDCl3, TMS ϭ 0 ppm): δ ϭ 2.81 (dd, J ϭ 13.8, 8.2 Hz,
1 H, 4-HЈ), 2.87 (dd, J ϭ 13.8, 6.3 Hz, 1 H, 4-H), 3.13 [dddd, J ϭ
14.4, 6.9, 1.2, 1.2 Hz, 2 H, N(CH2CHCH2)2Ј], 3.19 [dddd, J ϭ 14.4,
5.7, 1.5, 1.5 Hz, 2 H, N(CH2CHCH2)2], 3.26 (br. s, 1 H, OH), 3.59
(s, 3 H, OMe), 3.46 (ddd, J ϭ 8.2, 6.3, 3.6 Hz, 1 H, 3-H), 5.16Ϫ5.08
H), 2.93 (dd, J ϭ 13.3, 5.1 Hz, 1 H, 4-H), 3.03 [dddd, J ϭ 14.3, [m, 4 H, N(CH2CHCH2)2], 4.24 (br. s, 1 H, 2-H), 5.73 [dddd, J ϭ
7.1, 1.2, 1.2 Hz, 2 H, N(CH2CHCH2)2Ј], 3.23 [dddd, J ϭ 14.3, 5.2, 17.1, 10.2, 6.9, 5.7 Hz, 2 H, N(CH2CHCH2)2], 7.28Ϫ7.15 (m, 5 H,
1.7, 1.7 Hz, 2 H, N(CH2CHCH2)2], 3.51 (dddd, J ϭ 9.2, 9.2, 5.9,
5.1 Hz, H, 3-H), 3.58 (s, H, OMe), 5.19 [m,
N(CH2CHCH2)2], 5.72 [dddd, J ϭ 17.2, 10.1, 7.1, 5.2 Hz, 2 H,
H arom.) ppm. 13C NMR (100 MHz, CDCl3, CDCl3, δ ϭ 77 ppm):
H, δ ϭ 31.9 (t, C-4), 52.1 (q, OMe), 2 ϫ 53.7 [2 ϫ t, N(CH2CHCH2)2],
63.6 (d, C-3), 70.6 (d, C-2), 2 ϫ 117.0 [2 ϫ t, N(CH2CHCH2)2],
1
3
4
Eur. J. Org. Chem. 2004, 1149Ϫ1160
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1157