M. Bauer, U. Kazmaier
FULL PAPER
H), 8.32 (d, J = 1.8 Hz, 1 H) ppm. 13C NMR (125 MHz): δ =
16.8, 22.2, 27.2, 28.0, 29.3, 58.8, 73.1, 161.8 ppm. (E)-5a: 1H NMR
(500 MHz): δ = 0.91 (d, J = 6.8 Hz, 3 H), 0.92 (d, J = 6.8 Hz, 3
H), 1.22 (s, 3 H), 1.27 (s, 3 H), 2.14 (m, 1 H), 2.54 (s, 1 H), 2.90
(dd, J = 10.8, 2.3 Hz, 1 H), 6.42 (dd, J = 11.9, 10.8 Hz, 1 H), 7.92
(d, J = 11.9 Hz, 1 H) ppm. 13C NMR (125 MHz): δ = 16.6, 22.2,
27.0, 27.6, 28.9, 64.9, 72.6, 165.3 ppm. HRMS (CI): calcd. for
C8H18NO2 [M + H]+ 160.1337; found 160.1337. C8H17NO2
(159.23): C 60.35, H 10.76, N 8.80; found C 60.75, H 10.49, N
8.74.
that the solution started to reflux. After complete addition, the
reaction mixture was stirred for a further 10 min, before satd.
NH4Cl was added carefully. The layers were separated, and the
aqueous layer was extracted twice with Et2O. The combined or-
ganic layers were dried (Na2SO4) and concentrated in vacuo. Flash
chromatography (silica, Et2O) provided 8b (21.9 g, 89 mmol, 98%)
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as a yellow oil. = –30.2 (c = 1.0, CHCl3). H NMR (400 MHz):
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δ = 1.16 (s, 3 H), 1.17 (s, 3 H), 1.39 (d, J = 6.2 Hz, 3 H), 1.49 (s,
12 H), 1.60 (s, 3 H), 3.71 (d, J = 5.2 Hz, 1 H), 3.97 (br. s, 1 H),
5.86 (br. s, 1 H) ppm. 13C NMR (100 MHz): δ = 22.6, 24.6, 26.6,
27.7, 28.3, 29.3, 72.3, 73.4, 73.6, 81.5, 94.7, 155.6 ppm. HRMS
(CI): calcd. for C14H28NO4 [M + H]+ 274.2018; found 274.2005.
C14H27NO4 (273.37): C 61.51, H 9.96, N 5.12; found C 61.01, H
9.56, N 5.64.
(–)-(2S)-(Formylamino)-3-methyl-1,1-diphenyl-1-butanol (5b): Ac-
cording to GP 1, 5b was obtained from 4b[23] (543 mg, 1.86 mmol),
ethyl formate (7.4 mL, 92 mmol), and NEt3 (261 µL, 1.86 mmol)
after 24 h. Flash chromatography (silica, CH2Cl2/MeOH, 8:2) gave
rise to 5b as a colorless solid in 93% yield (491 mg, 1.73 mmol).
(–)-(4S)-3-(tert-Butoxycarbonyl)-4-(1-methoxy-1-methylethyl)-2,2-di-
methyloxazolidine (9a): A solution of 8a[20] (8.22 g, 31.7 mmol) in
dry DMF (30 mL) was cooled to 0 °C, before MeI (3.95 mL,
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M.p. 145–146 °C. = –97.7 (c = 0.9, CHCl3). The NMR spectra
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showed signals of the (Z)- and (E)-formamide in an (Z)/(E) ratio
1
of 86:14. (Z)-5a: H NMR (400 MHz): δ = 0.90 (d, J = 6.7 Hz, 3 63.4 mmol) and NaH (1.71 g, 43 mmol, 60 % suspension in oil)
H), 0.92 (d, J = 6.7 Hz, 3 H), 1.85 (qqd, J = 6.7, 6.7, 2.1 Hz, 1 H),
3.05 (s, 1 H), 5.05 (dd, J = 10.2, 2.1 Hz, 1 H), 6.21 (d, J = 10.2 Hz,
were added. The colorless suspension was stirred at room temp. for
2 h, before MeOH (5 mL) was added to quench the reaction. The
1 H), 7.18 (t, J = 7.4 Hz, 1 H), 7.21 (t, J = 7.4 Hz, 1 H), 7.28 (t, J solution was diluted with CH2Cl2 (100 mL) and washed twice with
= 7.4 Hz, 2 H), 7.32 (t, J = 7.4 Hz, 2 H, 8Ј-H), 7.46 (d, J = 7.4 Hz,
2 H), 7.48 (d, J = 7.4 Hz, 2 H), 8.06 (d, J = 1.7 Hz, 1 H) ppm. 13C
NMR (100 MHz): δ = 17.6, 22.8, 28.7, 56.6, 82.0, 125.1, 125.3,
126.9, 127.1, 128.45, 128.47, 145.2, 145.9, 161.3 ppm. (E)-5a: 1H
NMR (400 MHz, selected signals): δ = 2.01 (qqd, J = 6.8, 6.8,
H2O. The combined organic layers were dried (Na2SO4) and con-
centrated in vacuo. Flash chromatography (silica, hexanes/Et2O,
9:1) gave rise to 9a (6.41 g, 23.5 mmol, 75%) as a colorless oil,
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which crystallized on standing. M.p. 53–55 °C. = –5.1 (c = 0.7,
D
CHCl3). 1H NMR (400 MHz): δ = 1.12 (s, 3 H), 1.17 (s, 3 H), 1.47
1.4 Hz, 1 H), 3.03 (s, 1 H), 4.06 (dd, J = 10.7, 1.4 Hz, 1 H), 7.70 (s, 9 H), 1.48 (s, 3 H), 1.59 (s, 3 H), 3.20 (s, 3 H), 3.85 (dd, J = 9.2,
(d, J = 11.9 Hz, 1 H) ppm. 13C NMR (100 MHz, selected signals):
δ = 17.0 (C-5), 22.4, 28.1, 62.8, 81.5, 125.43, 125.48, 127.25, 127.28,
6.4 Hz, 1 H), 4.05 (br. s, 1 H), 4.13 (d, J = 9.2 Hz, 1 H) ppm. 13C
NMR (100 MHz): δ = 21.0, 23.2, 24.4, 26.8, 28.3, 49.4, 62.6, 64.2,
128.55, 128.59, 144.3, 145.0, 164.7 ppm. HRMS (CI): calcd. for 77.4, 80.1 ppm. HRMS (CI): calcd. for C14H28NO4 [M + H]+
C18H22NO2 [M + H]+ 284.1650; found 284.1644. C18H21NO2
(283.37): calcd. C 76.30, H 7.47, N 4.94; found C 75.90, H 7.42, N
4.84.
274.2018; found 274.2032. C14H27NO4 (273.37): calcd. C 61.51, H
9.96, N 5.12; found C 61.46, H 9.76, N 5.10.
(–)-(4S,5R)-3-(tert-Butoxycarbonyl)-4-(1-methoxy-1-methylethyl)-
(–)-(3S)-3-Isocyano-2,4-dimethyl-2-pentanol (6a): According to GP 2,2,5-trimethyloxazolidine (9b): Methyl ether 9b was obtained from
2b, 6a was obtained from 5a (1.04 g, 6.53 mmol), NEt3 (2.29 mL,
16.3 mmol), and POCl3 (0.6 mL, 6.55 mmol) after flash chromatog-
raphy (silica, Et2O) as a colorless oil in 91% yield (836 mg,
8b (10.9 g, 40.0 mmol), NaH (2.16 g, 54.0 mmol), and MeI
(5.0 mL, 80.0 mmol) in analogy to ether 9a as a colorless oil. Yield:
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76% (8.70 g, 30.3 mmol).
= –7.6 (c = 1, CHCl3). 1H NMR
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5.92 mmol). = –23.6 (c = 0.9, CHCl3). H NMR (500 MHz): δ
(500 MHz): δ = 1.13 (s, 3 H, 9-H), 1.14 (s, 3 H), 1.29 (d, J = 6.6 Hz,
D
= 1.05 (d, J = 6.5 Hz, 3 H), 1.07 (d, J = 6.5 Hz, 3 H), 1.30 (s, 3
3 H), 1.46 (s, 9 H), 1.52 (s, 3 H), 1.60 (s, 3 H), 3.18 (s, 3 H), 3.81
H), 1.34 (s, 3 H), 1.93 (s, 1 H), 2.09 (m, 1 H), 3.37 (dt, J = 4.5, (br. s, 1 H), 4.41 (qd, J = 6.6, 1.5 Hz, 1 H) ppm. 13C NMR
2.4 Hz, 1 H) ppm. 13C NMR (125 MHz): δ = 17.0, 22.5, 26.0, 27.8,
27.4, 70.7 (t, J = 5.4 Hz), 71.9, 157.3 (t, J = 5.2 Hz) ppm. HRMS
(CI): calcd. for C8H16NO [M + H]+ 142.1232; found 142.1232.
(125 MHz): δ = 21.0, 22.9, 23.6, 27.8, 28.3, 30.1, 49.2, 70.2, 72.9,
77.4, 79.9, 95.5, 154.0 ppm. HRMS (CI): calcd. for C15H30NO4 [M
+ H]+ 288.2175; found 288.2169. C15H29NO4 (287.40): C 62.69, H
10.17, N 4.87; found C 62.38, H 10.05, N 5.03.
(–)-(2S)-2-Isocyano-3-methyl-1,1-diphenyl-1-butanol (6b): Accord-
ing to GP 2b, 6b was obtained from 5b (220 mg, 77.6 µmol), NEt3
(273 µL, 1.94 mmol), and POCl3 (73 µL, 77.6 µmol) after flash
(–)-(2S)-2-Amino-3-methoxy-3-methyl-1-butanol Hydrochloride
(10a): According to GP 3, 10a was obtained from 9a (6.37 g,
23.3 mmol) and AcCl (4.14 mL, 58.3 mmol) as a colorless, hygro-
chromatography (silica, hexanes/EtOAc, 9:1) as colorless needles in
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97% yield (200 mg, 75.4 µmol).
= –33.8 (c = 0.2, CHCl3). 1H
scopic powder in 93% yield (3.77 g, 22.2 mmol). M.p. 135°°C (de-
D
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NMR (500 MHz): δ = 1.00 (d, J = 6.7 Hz, 3 H), 1.06 (d, J = 6.7 Hz,
3 H), 1.73 (m, 1 H), 2.66 (s, 1 H), 4.53 (d, J = 1.2 Hz, 1 H), 7.20–
comp.).
= –20.1 (c = 0.8, MeOH). 1H NMR (500 MHz, [D6]
D
DMSO): δ = 1.12 (s, 3 H), 1.17 (s, 3 H), 3.06 (dd, J = 7.4, 3.7 Hz,
7.42 (m, 8 H), 7.54 (d, J = 7.8 Hz, 2 H) ppm. 13C NMR (125 MHz): 1 H), 3.10 (s, 3 H), 3.51 (ddd, J = 11.4, 7.4, 4.2 Hz, 1 H), 3.66
δ = 17.0, 22.5, 27.6, 67.3 (t, J = 5.3 Hz), 79.7, 125.3, 125.9, 127.3,
127.7, 128.5, 128.6, 142.3, 145.0, 159.0 (t, J = 4.5 Hz) ppm. HPLC
(OD-H, hexane/iPrOH, 90:10, 0.5 mL/min): tR[(S)-2b] = 9.30 min.
HRMS (CI): calcd. for C18H20NO [M + H]+ 266.1544; found
266.1523. C18H19NO (265.35): calcd. C 81.48, H 7.22, N 5.28;
found C 80.99, H 7.20, N 5.24.
(ddd, J = 11.4, 3.8, 3.7 Hz, 1 H), 5.37 (dd, J = 4.2, 3.8 Hz, 1 H),
7.95 (br. s, 3 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 20.1,
21.7, 48.6, 58.4, 59.5, 73.8 ppm. HRMS (CI): calcd. for C6H16NO2
[M – Cl]+ 134.1181; found 134.1191. C6H16ClNO2 (169.65): calcd.
C 42.48, H 9.51, N 8.26; found C 42.79, H 9.02, N 8.16.
(–)-(2R,3S)-3-Amino-4-methoxy-4-methyl-2-pentanol Hydrochlo-
ride: (10b): According to GP 3, 10b was obtained from 9b (7.19 g,
25.0 mmol) and AcCl (4.44 mL, 62.5 mmol) as a colorless, hygro-
scopic powder in 94% yield (4.33 g, 23.6 mmol). M.p. 108–110 °C.
(–)-(4S,5R)-3-(tert-Butoxycarbonyl)-4-(1-hydroxy-1-methylethyl)-
2,2,5-trimethyloxazolidine (8b): A solution of MeI (14.9 mL,
240 mmol) was added slowly to Mg filings (4.86 g, 200 mmol) in
Et2O (200 mL). After complete consumption of the Mg, 7b[19]
(21.9 g, 80 mmol) in dry Et2O (80 mL) was added at such a rate
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= –1.1 (c = 0.8, MeOH). H NMR (500 MHz, CDCl3): δ = 1.30
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(s, 3 H), 1.31 (s, 3 H), 1.44 (d, J = 6.5 Hz, 3 H), 3.08 (m, 1 H),
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Eur. J. Org. Chem. 2009, 2360–2366