7056 J . Org. Chem., Vol. 62, No. 20, 1997
Notes
(R)-Meth yl 2-((ter t-bu toxyca r bon yl)a m in o)p en ta n oa te
(4). The general procedure gave 0.22 g (80%): Rf, 0.30 (9:1
system A); tR 3.70 min (120 °C, 20 psi, N-Ac >99% ee, N-Boc
formation of small amounts of hydrolysis products. The
lower yield for entry 5 reflects the greater stability of the
benzamide. The peracetylated GlcNAc in entry 6 was
converted into the Boc derivative 12 in good yield with
loss only of the highly labile anomeric acetate group.
Lowering the temperature to -20 °C did not allow the
anomeric acetate to survive: the acetamide and anomeric
acetate were cleaved at the same rate. The correspond-
ing methyl glycoside required forcing conditions to achieve
acylation, and some decomposition occurred. The hy-
drolysis step went smoothly, however, and a good yield
of methyl 3,4,6-tri-O-acetyl-2-(N-(tert-butoxycarbony-
l)amino)-2-deoxy-R-D-glucopyranoside (13) resulted.
>99% ee); [R]22 ) -5.72° (c ) 2.08, CHCl3); 1H NMR δ 0.87 (t,
D
3H, J ) 7.3 Hz), 1.30-1.80 (m, 4H), 1.38 (s, 9H), 3.68 (s, 3H),
4.20-4.30 (m, 1H), 4.98 (br d, 1H, J ) 8.3Hz); 13C NMR δ 13.6,
18.6, 28.2, 34.8, 52.1, 53.2, 79.7, 155.3, 173.5; HRMS calcd for
C
11H22NO4 (M + H+) 232.1549, found 232.1546.
N-(ter t-Bu toxyca r bon yl)-D-leu cin e Meth yl Ester (5). The
general procedure gave 0.24 g (91%): Rf 0.39 (9:1 system A); tR
4.58 min (120 °C, 20 psi, N-Ac 98.9% ee, N-Boc 99.0% ee); [R]22
D
) +4.21° (c ) 2.40, CHCl3); 1H NMR δ 1.80-1.90 (m, 6H), 1.30-
1.80 (m, 3H), 1.36 (s, 9H), 3.65 (s, 3H), 4.15-4.30 (m, 1H), 4.93
(br d, 1H, J ) 8.6Hz); 13C NMR δ 21.7, 22.7, 24.6, 28.2, 41.6,
51.8, 52.0, 79.6, 155.3, 173.9; HRMS calcd for C12H23NO4 (M +
H+) 246.1705, found 246.1703.
(R)-Meth yl 2-((ter t-bu toxyca r bon yl)a m in o)-3-eth ylp en -
ta n oa te (6). The general procedure gave 54 mg (93%): Rf 0.33
(9:1 system A); tR 2.41 min (145 °C, 20 psi, N-Ac 96.9% ee, N-Boc
96.9% ee); [R]22D)-14.1° (c ) 1.08, CHCl3); 1H NMR δ 0.60-1.00
(m, 6H), 1.20-1.70 (m, 5H), 1.40 (s, 9H), 3.68 (s, 3H), 4.30-
4.40 (m, 1H), 4.91 (br d, 1H, J ) 8.3Hz); 13C NMR δ 21.7, 22.7,
24.6, 28.2, 41.6, 51.8, 52.0, 79.6, 155.3, 173.9; HRMS calcd for
The convenient conversion of amides into useful N-Boc
derivatives under mild conditions has been demonstrated
and will facilitate the synthesis of amines and amino
acids. Amide-forming preparations such as the Beck-
mann rearrangement,18 the Ritter reaction,19 and others
may become more useful entries into syntheses. Their
mild cleavage should allow amides themselves more use
as versatile protecting groups. Work is currently under-
way to extend these methods to the preparation of
benzylcarbamates from amides.20
C
13H26NO4 (M + H+): 260.1862, found 260.1855.
(S)-Meth yl 2-((ter t-Bu toxyca r bon yl)a m in o)-2-cyclop en -
tyleth a n oa te eth a n oa te (7). The general procedure gave 68
mg (93%): Rf 0.43 (9:1 system A); tR 4.12 min (120 °C, 20 psi,
N-Ac 95.9% ee, N-Boc 95.9% ee); [R]22D ) +7.0° (c ) 1.36, CHCl3);
1H NMR δ 1.20-1.70 (m, 8H), 1.39 (s, 9H), 2.10-2.20 (m, 1H),
3.68 (s, 3H), 4.20-4.30 (m, 1H), 4.90-5.00 (br, 1H); 13C NMR δ
24.1, 25.2, 28.2, 28.8, 42.6, 52.0, 56.4, 79.7, 155.5, 173.3; HRMS
calcd for C13H24NO4 (M + H+) 258.1705, found 258.1703.
N-(ter t-Bu toxyca r bon yl)-D-leu cin e Eth yl Ester (8). The
general procedure gave 0.24 g (86%): Rf 0.55 (9:1 system A); tR
3.52 min (120 °C, 20 psi, N-Ac 97.4% ee, N-Boc 97.8% ee); [R]22
D
) -11.6° (c ) 2.43, CHCl3); 1H NMR δ 0.79 (d, 3H, J ) 6.9Hz),
0.86 (d, 3H, J ) 6.9Hz), 1.84 (t, 3H, J ) 7.1Hz), 1.35 (s, 9H),
2.00-2.10 (m, 1H), 4.10-4.20 (m, 3H), 5.01 (br d, 1H, J ) 8.0
Hz); 13C NMR δ 14.1, 17.4, 18.8, 28.1, 31.2, 58.3, 60.9, 79.4, 155.5,
172.2; HRMS calcd for C12H24NO4 (M + H+): 246.1705, found
246.1712.
Exp er im en ta l Section
Gen er a l Meth od s. 1H and 13C NMR spectra were recorded
on a General Electric QE-300 spectrometer at 300.15 and 75.48
MHz, respectively, in CDCl3, and the shifts are reported in ppm
downfield from TMS. High-resolution mass spectra were ob-
tained using a J EOL J MS-SX102A spectrometer. Chiral capil-
lary GC was performed on a Chrompack Chirasil-L-Val column
(25 m). For TLC, system A was (petroleum ether:ethyl acetate),
system B was (CHCl3:acetone). DMAP was crystallized from
toluene and THF was distilled from sodium/benzophenone before
use. Other unspecified reagents were from commercial sources
and used as obtained.
(2S,4E)-Meth yl 2-((ter t-Bu toxycar bon yl)am in o)-6-O-(ter t-
bu tyld im eth ylsilyl)h ex-4-en eoa te (9). (S)-Methyl 2-aceta-
mido-6-O-(tert-butyldimethylsilyl)hex-4-eneoate (0.20 g, 0.63
mmol) and N,N-dimethyl-4-aminopyridine (14 mg, 0.13 mmol)
were dissolved in THF (1.6 mL). Di-tert-butyl dicarbonate (0.29
mL, 1.30 mmol) was added, and the mixture was stirred at rt
for 8 h. MeOH (4 mL) was added, and the mixture was treated
with hydrazine (79 µL, 2.5 mmol) for 8 h. The reaction mixture
was poured into CH2Cl2, washed with 1 N HCl, CuSO4, and
NaHCO3, dried (MgSO4), and evaporated. Chromatography on
silica gave 0.22g of pure 9 (93%): Rf 0.31 (9:1 system A); tR 3.61
N-(ter t-Bu toxyca r bon yl)-L-va lin e Meth yl Ester (3). Gen -
er a l P r oced u r e. N-Acetyl-L-valine methyl ester (0.2 g, 1.15
mmol) and N,N-dimethyl-4-aminopyridine (28 mg, 0.23 mmol)
was dissolved in THF (4 mL). Di-tert-butyl dicarbonate (0.53
mL, 2.30 mmol) was added, and the mixture was heated to reflux
for 4 h. After the solution was cooled to room temperature,
MeOH (4 mL) and hydrazine (0.14 mL, 4.6 mmol) were added
and the mixture was stirred at rt for 4 h. The reaction mixture
was poured into CH2Cl2, washed with 1 N HCl, CuSO4, and
NaHCO3, dried (MgSO4), and evaporated. Chromatography on
silica gave 0.24 g of pure 3 (92%): Rf, 0.33 (9:1 system A); tR
min (180 °C, 30 psi, N-Ac 98.8% ee, N-Boc 99.4% ee); [R]22
)
D
+17.4° (c ) 2.21, CHCl3); 1H NMR δ -0.02 (s, 6H), 0.82 (s, 9H),
1.35 (s, 9H), 2.30-2.50 (m, 2H), 3.64 (s, 3H), 4.04 (d, 2H, J )
4.4Hz), 4.20-4.30 (m, 1H), 5.00 (br d, 1H, J ) 8.0Hz), 5.40-
5.60 (m, 2H); 13C NMR δ 18.2, 25.8, 28.2, 32.1, 32.3, 35.0, 52.0,
52.9, 63.2, 79.6, 123.9, 133.8, 155.0, 172.4; HRMS calcd for
C
18H36NO5 (M + H+): 374.2363, found 374.2355.
2.89 min (120 °C, 20 psi, N-Ac >99% ee, N-Boc >99% ee)21; [R]22
D
N-(ter t-Bu toxyca r bon yl)-L-leu cin e Meth yl Ester (en t-5).
1
) +12.9° (c ) 2.43, CHCl3) H NMR δ 0.79 (d, 3H, J ) 6.9Hz),
N-Acetamido-L-valine benzyl ester (0.20 g, 0.8 mmol) and N,N-
dimethyl-4-aminopyridine (18 mg, 0.16 mmol) was dissolved in
THF (2 mL). Di-tert-butyl dicarbonate (0.37 mL, 1.60 mmol) was
added, and the mixture was heated at reflux for 6 h. The
mixture was cooled to rt, MeOH (2 mL) and hydrazine (0.1 mL,
3.2 mmol) were added, and the mixture was stirred for 3 h. The
reaction mixture was poured into CH2Cl2, washed with 1 N HCl,
CuSO4, and NaHCO3, dried (MgSO4), and evaporated. Chro-
matography on silica gave 0.17 g of pure en t-5 (88%): tR 2.53
0.85 (d, 3H, J ) 6.8Hz), 1.34 (s, 9H), 2.00-2.10 (m, 1H), 4.12 (s,
3H), 4.10-4.20 (m, 3H), 5.02 (br d, 1H, J ) 8.5Hz); 13C NMR δ
17.4, 18.8, 28.1, 31.1, 51.8, 58.3, 79.5, 155.5, 172.7; HRMS calcd
for C11H22NO4 (M + H+) 232.1549, found 232.1543.
(18) For a review, see: Gawley, R. E. Org. React. 1988, 35, 1.
(19) For a review, see: Krimen, L. I.; Cota, D. J . Org. React. 1969,
17, 213.
(20) In several trials, the commercially available dibenzyl dicarbon-
ate (Cbz2O) gave only dibenzyl carbonate, the product of catalytic
decomposition of the reagent by benzyl oxide released by the first
acylation event. Trapping agents did not improve the reaction. In an
effort to use a bulkier leaving group, the mixed dicarbonate benzyl
tert-butyl dicarbonate (14) was prepared from sodium tert-butoxide,
carbon dioxide, and benzyl chloroformate. Acylation of O-acetyl-N-
benzoyl-L-serine benzyl ester gave a 4:1 mixture of the Cbz imide to
the Boc imide. Please see Supporting Information.
min (140 °C, 20 psi, N-Ac >99% ee, N-Boc 99.3% ee); [R]22
)
D
-4.21° (c ) 1.56, CHCl3). Other characterization data were
identical to those of 5.
N-(ter t-Bu toxycar bon yl)-L-m eth ion in e Meth yl Ester (10).
N-Benzamido-L-methionine methyl ester (0.31 g, 1.15 mmol) and
N,N-dimethyl-4-aminopyridine (28 mg, 0.23 mmol) was dissolved
in THF (3 mL). Di-tert-butyl dicarbonate (0.53 mL, 2.30 mmol)
was added, and the mixture was stirred at rt for 7 h. MeOH (3
mL) was added, and the mixture was cooled to 0 °C and treated
(21) All GC samples were of crude material before purification by
column chromatography.