7924 J . Org. Chem., Vol. 62, No. 23, 1997
Pepito and Dittmer
column chromatography (1:2 Et2O/hexanes on recycled silica
gel) (0.440 g, 1.69 mmol, 63%): [R]23D -8.2 (c 1.73, CHCl3); 1H
NMR δ 0.9 (t, 3 H, J ) 6.9), 1.5-1.6 (m, 5 H), 2.9-3.0 (m, 1
H), 5.0 (s and d, 2 H, overlapping peaks), 5.2 (dd, 1 H, J )
10.2, 1.8), 5.6-5.7 (m, 1 H), 7.2-7.5 (m, 10 H); 13C NMR δ
14.1, 19.1, 38.3, 58.5, 63.5, 115.6, 126.8, 127.3, 127.5, 128.3,
141.2.
CH2Cl2 (150 mL) was treated with imidazole (3.17 g, 46.2
mmol), TBDMSCl (8.79 g, 58.3 mmol), and 4-DMAP (236 mg,
1.92 mmol) to give crude silyl ether as a thick, yellow oil (8.31
g, 31.4 mmol, 82%): [R]21.5 -29.7 (c 1.08, CHCl3); 1H NMR δ
D
0.10 (s, 3 H), 0.11 (s, 3 H), 0.9 (s, 9 H), 3.1 (m, 1 H), 3.8
(overlapping signals, 2 H), 3.9 (dd, 1 H, J ) 12.0, 3.0), 7.3-
7.4 (m, 5 H); 13C NMR δ -5.3, 18.4, 25.9, 55.9, 62.8, 63.0, 125.7,
128.1, 128.4, 137.2.
(2S,3S)-1-(Tr ip h en ylm eth yl)-3-m eth yl-2-a zir id in eca r -
boxylic Acid Meth yl Ester .12e,30 A procedure reported for
the 2R,3R isomer was followed.31 The 2S,3S ester was purified
by trituration with hexanes and recrystallization from
A solution of the silyl ether (1.01 g, 3.83 mmol) in MeOH
(10.0 mL) was heated to reflux with NaN3 (0.760 g, 11.5 mmol),
NH4Cl (0.309 g, 5.75 mmol), and H2O (1.60 mL) to yield a
mixture of isomeric azido alcohols with one isomer predomi-
nating, presumably the 3-azido-3-phenyl derivative (1.11 g,
MeOH: mp 101-102 °C [lit.30a mp 103-107 °C]; [R]24 -98.6
D
(c 1.04, CHCl3) [lit. for 2R,3R isomer31 [R]20 +98 (c 1.04,
D
CHCl3); [R]23D for 2S,3S isomer30a -79.7 (c 1.1, THF)]; 1H NMR
δ 1.4 (d, 3 H, J ) 5.4), 1.6-1.7 (m, 1 H), 1.9 (d, 1 H, J ) 6.4),
3.7 (s, 3 H), 7.2-7.5 (m, 15 H); 13C NMR δ 13.3, 34.8, 35.9,
51.8, 75.0, 126.8, 127.6, 129.3, 143.9, 170.7.
3.63 mmol, 94%): [R]22 -98.3 (c 1.02, CHC13); 1H NMR δ
D
0.078 (s, 3 H), 0.09 (s, 3 H), 0.91 (s, 9 H), 2.5 (br s, 1 H, OH),
3.6-3.8 (m, 2 H), 3.8 (br d, 1 H, J ) 3.6), 4.6 (d, 1 H, J ) 7.1),
7.3 (m, 5 H); 13C NMR δ -5.5, -5.4, 18.3, 25.8, 63.2, 66.6, 73.7,
127.8, 128.5, 128.7, 136.3; HRMS (FAB) m/z calcd for
C15H26N3O2Si(MH+) 308.1794, found 308.1791.
(2S ,3S )-1-(Tr ip h e n ylm e t h yl)-3-m e t h yl-2-a zir id in e -
m eth a n ol.19b The reduction of (2S,3S)-1-(triphenylmethyl)-
3-methyl-2-aziridinecarboxylic acid methyl ester was done
according to a procedure described by Deyrup and Moyer.25
The ester (3.69 g, 10.3 mmol) was added to a suspension of
LiA1H4 (0.64 g, 19.2 mmol) in Et2O (82 mL) and stirred for 3
h. The reaction was worked up by addition of H2O (6.4 mL)
and 15% aqueous NaOH (2.0 mL). The resulting suspension
was filtered, the residue washed generously with Et2O, and
the solvent removed by evaporation. Crystallization of the
aziridinemethanol was done with hexanes/CH2Cl2 (19:1) to
yield white crystals (2.85 g, 8.66 mmol, 84.4%): mp 112-113
°C [lit.19b mp 86-88 °C; lit.19c 110-112 °C]; [R]23D +16.7 (c 1.02,
CHCl3) [lit.19b [R]D +16.5 (c 1.06, CHCl3)]; IR (KBr) 3430 (br),
The mixture of azido alcohols (1.11 g, 3.62 mmol) in toluene
(5.00 mL) was treated with PPh3 (1.03 g, 3.90 mmol) in toluene
(10.0 mL) to yield the aziridine, purified by column chroma-
tography (1:9 EtOAc-hexanes, then 1:4 EtOAc-hexanes), as
a yellow oil (0.732 g, 2.78 mmol, 85%): [R]24 +49.0 (c 1.02,
D
CHCl3); 1H NMR δ 0.09 (s, 3 H), 0.10 (s, 3 H), 0.9 (s, 9 H), 1.8
(br s, 1 H), 2.2 (br s, 1 H) 2.9 (d, 1 H, J ) 2.3), 3.9 (d, 2 H, J
) 1.9), 7.3 (m, 5 H); 13C NMR δ -5.4, 18.3, 25.9, 42.2, 61.4,
125.8, 126.8, 128.3, 140.1; HRMS (FAB) m/z calcd for
C15H26NOSi (MH+) 264.1784; found 264.1777.
The aziridine (0.217 g, 0.824 mmol) was converted to the
N-Boc derivative by treatment with (Boc)2O (0.463 g, 2.06
mmol) in CH2Cl2 (4.0 mL) and a catalytic amount of 4-DMAP
(30.5 mg, 0.247 mmol). The crude product was purified by
column chromatography (0-5% EtOAc-hexanes) to yield the
1
1480 (s), 1438 (s), 1058 (m), 1024 (s) cm-1; H NMR δ 1.3 (d,
3 H, J ) 6.0), 1.4 (m, 1 H), 1.8 (m, 1 H), 3.7-3.9 (m, 2 H),
7.2-7.6 (m, 15 H) [lit.19b 1H NMR (CDCl3) δ 1.3 (m, 3 H), 1.4
(m, 1 H), 1.7 (m, 1 H), 3.8 (m, 2 H), 7.1-7.5 (m, 15 H)]; 13C
NMR δ 13.5, 30.9, 36.2, 61.2, 74.5, 126.7, 127.5, 129.3, 144.6.
(2S ,3S )-1-(Tr ip h e n ylm e t h yl)-3-m e t h yl-2-a zir id in e -
m eth yl p-Tolu en esu lfon a te (9). The aziridinemethanol
above (0.502 g, 1.52 mmol) was treated with NEt3 (0.265 mL,
1.90 mmol), 4-DMAP (3.71 mg, 0.03 mmol), and tosyl chloride
(0.32 g, 1.67 mmol) in CH2Cl2 (ca. 15 mL) to give 9 as colorless
crystals (0.72 g, 1.48 mmol, 97.4%) after recrystallization from
N-Boc aziridine silyl ether as a thick liquid (0.256 g, 0.705
1
mmol, 86%): [R]22 -48.8 (c 1.04, CHCl3); H NMR δ 0.09 (s,
D
3 H), 0.1 (s, 3 H), 0.9 (s, 9 H), 1.4 (s, 9 H), 2.8 (m, 1 H), 3.5 (d,
1 H, J ) 3.1), 3.9 (dd, 1 H, J ) 11.5, 3.7), 4.0 (dd, 1 H, J )
11.6, 3.3), 7.3 (m, 5 H); 13C NMR δ -5.2, 18.2, 25.9, 28.0, 41.6,
46.6, 60.4, 81.0, 126.8, 127.7, 128.4, 136.6, 157.0; HRMS (FAB)
m/z calcd for C20H33NNaO3Si (MNa+) 386.2127, found 386.2119.
The N-Boc-aziridine silyl ether (0.774 g, 60% GC purity, 1.28
mmol) was dissolved in THF (4.0 mL) and treated with tetra-
n-butylammonium fluoride in THF (2.43 mL, 1.0 M in THF,
2.43 mmol) to yield the aziridinemethanol, purified by column
chromatography (1:4 EtOAc-hexanes) (0.299 g, 1.26 mmol,
99%): 1H NMR δ 1.3 (s, 9 H), 2.8 (dd, 1 H, J ) 9.1, 4.3) 2.9
(m, 1 H), 3.4 (d, 1 H, J ) 3.1), 3.6 (m, 1 H), 4.1 (m, 1 H), 7.3-
7.4 (m, 5 H); 13C NMR δ 27.9, 42.0, 47.0, 62.0, 82.0, 126.6,
127.9, 128.4, 128.5, 161.0. The proton NMR spectrum is
comparable to that for the known N-(p-toluenesulfonyl) deriv-
ative:19b δ 4.3, 4.2 (each ddd, CH2O) 4.0 (d, J ) 4.4, C3-H),
3.1 (ddd, C2-H). The general procedure for tosylation was
followed. Aziridinemethanol (0.299 g, 1.26 mmol) in CH2Cl2
(1.50 mL) was treated with Ts2O (0.496 g, 1.46 mmol) and
4-DMAP (3.10 mg, 0.0243 mmol). The tosylate 11 was purified
by column chromatography (0-20% EtOAc-hexanes) and
isolated as a white powder (0.260 g, 0.643 mmol, 52%): mp
CH2Cl2-MeOH: mp 149.5-151 °C; [R]23 -40.5 (c 1.05,
D
1
CHCl3); H NMR δ 1.2 (d, 3 H, J ) 5.4), 1.2 (m, 1 H), 1.4 (m,
1 H), 2.4 (s, 3 H), 4.1 (dd, 1 H, J ) 10.2, 7.45), 4.4 (dd,1 H, J
) 10, 5.2), 7.2-7.5 (m, 17 H), 7.7 (d, 2 H, J ) 8.2); 13C NMR
δ 13.4, 21.6, 30.9, 32.9, 69.7, 74.4, 126.7, 127.5, 127.8, 129.2,
129.8, 133.1, 144.2, 144.7. Anal. Calcd for C30H29O3NS: C,
74.50; H, 6.04; N, 2.90. Found: C, 74.36; H, 6.05; N, 2.84.
(2S)-N-(Tr ip h en ylm eth yl)-3-bu ten -2-a m in e (10). Tel-
lurium (0.26 g, 2.07 mmol) was reduced by NaBH4 (0.19 g, 5.00
mmol) in DMF (8.0 mL) as described in the general procedure.
Tosylate 9 (0.50 g, 1.04 mmol) in DMF (2.0 mL) was added
and the mixture stirred for 24 h. The crude product was
passed through a plug of silica gel with elution by hexanes to
give allylamine 10 as a clear, viscous liquid (0.28 g, 0.94 mmol,
91.1%) that was crystallized from MeOH: mp 61-62 °C;
[R]23.5 -33.7 (c 1.04, CHCl3); 1H NMR δ 0.6 (d, 3 H, J ) 6.6),
D
1.3 (d, 1 H, J ) 2.1), 3.1 (m, 1 H), 4.8 (d, 1 H, J ) 10), 5.0 (d,
1 H, J ) 17), 5.6 (ddd, 1 H, J ) 17, 10, 6.1), 7.1-7.7 (m, 15 H);
13C NMR δ 23.0, 51.0, 71.5, 111.6, 126.2, 127.7, 128.9, 144.2,
147.1. Anal. Calcd for C23H23N: C, 88.13; H, 7.40; N, 4.47.
Found: C, 88.08; H, 7.39; N, 4.41.
1
82-83 °C; H NMR δ 1.3 (s, 9 H), 2.4 (s, 3 H), 3.00 (m, 1 H),
3.4 (d, 1 H, J ) 3.0), 4.1 (dd, 1 H, J ) 11.2, 5.6), 4.4 (dd, 1 H,
J ) 11.2, 4.7), 7.2 (m, 2 H), 7.3 (m, 5 H), 7.8 (d, 2 H, J ) 8.2);
13C NMR δ 21.6, 27.7, 41.3, 44.0, 68.4, 81.9, 127.1, 128.0, 128.3,
128.4, 128.5, 129.9, 130.0, 145.1, 158.4.
(2R*,3R*)-1-(ter t-Bu tyloxyca r bon yl)-3-p h en yl-2-a zir i-
d in em eth a n ol p-Tolu en esu lfon a te (11). The N-Boc-aziri-
dinemethanol was prepared according to a procedure described
by Ziegler and Belema.19f The analogous cis-3-[4-(methyl-
thio)phenyl]aziridinemethanol has been described recently.32
(2S,3S)-3-Phenyloxiranemethanol23a (5.78 g, 38.5 mmol) in
The tosylate was treated with telluride ion (tellurium,
rongalite, 1.0 N aqueous NaOH) under phase-transfer condi-
tions [Adogen 464 (1 drop), distilled water (0.5 mL), toluene
(2.5 mL)]. The reaction was stirred with a magnetic stirrer
for 1 week. A mixture of unidentified compounds was ob-
tained.
p-Tolu en esu lfon a te Ester (12) of Eth yl (2S,3S)-1-(ter t-
Bu tyloxyca r bon yl)-r-h yd r oxy-2-a zir id in em eth a n e-3-ca r -
boxyla te. The tert-butyldimethylsilyl ether of ethyl (2S,3S)-
1-(tert-butyloxycarbonyl)-R-hydroxyaziridinemethane-3-car-
boxylate was prepared in the same way as the 2R,3R methyl
ester.19f Ethyl (2R,3S)-R-hydroxyoxiranemethane-2-carboxy-
(30) (a) Okawa, K.; Nakajima, K. Biopolymers 1981, 20, 1811-1821.
(b) Willems, J . G. H.; Dommerholt, F. J .; Hammink, J . B.; Vaarhorst,
A. M.; Thijs, L.; Zwanenburg, B. Tetrahedron Lett. 1995, 36, 603-606.
(31) Wakimiya, T.; Shimbo, K.; Shiba, T.; Nakajima, K., Neya, M.;
Okawa, K. Bull. Chem. Soc. J pn. 1982, 55, 3878-3881.
(32) Davis, F. A.; Zhou, P. Tetrahedron Lett. 1994, 35, 7525-7528.