PAPER
Synthesis of Caprolactam Derivatives
4073
1H NMR (400 MHz, CDCl3): d = 7.20–7.50 (m, 5 H), 6.08 (d,
J = 5.6 Hz, 1 H), 4.78 (d, J = 14.4 Hz, 1 H), 4.51 (d, J = 14.4 Hz,
1 H), 4.44 (m, 1 H), 3.50 (m, 1 H), 3.38 (m, 1 H), 3.25 (d,
J = 14.4 Hz, 1 H), 2.16 (m, 2 H), 2.11 (m, 1 H), 1.80 (m, 1 H), 1.60
(m, 1 H), 1.47 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 172.9, 155.2, 136.7, 128.8 (2C),
128.2 (2C), 127.8, 79.6, 68.5, 54.1, 53.0, 51.9, 36.9, 30.4, 28.4 (3C).
1H NMR (400 MHz, DMSO-d6): d = 7.40 (m, 1 H), 6.37 (d, J =
6.4 Hz, 1 H), 4.58 (d, J = 4.4 Hz, 1 H), 4.06 (m, 1 H), 3.72 (m, 1 H),
3.29 (m, 1 H, overlapped with DMSO), 3.01 (m, 1 H), 1.45–1.99
(m, 4 H), 1.38 (s, 9 H).
13C NMR (100 MHz, DMSO-d6): d = 174.3, 155.0, 78.4, 64.1, 52.9,
45.6, 34.7, 28.6 (3C), 25.4.
MS (ESI): m/z (%) = 389 (100) [2M + H – Boc]+, 267 (50) [M +
MS (ESI): m/z (%) = 707 (8) [2M + K]+, 335 (90) [M + H]+.
Na]+.
(2S,5R)-4 or (2S,5S)-4 isomers were determined on the basis of 1H
NMR signals at d = 4.32 (m, 5-H), 4.22 (d, J = 14.4 Hz, 7-N-CH2-
Ar-p-OMe) and 5.04 (d, J = 14.4 Hz, 7-N-CH2-Ar-p-OMe) ppm or
at d = 4.36 (m, 5-H), 4.42 (d, J = 14.4 Hz, 7-N-CH2-Ar-p-OMe) and
4.61 (d, J = 14.4 Hz, 7-N-CH2-Ar-p-OMe) ppm.
Pure (2S,5S)-2
Obtained from AD-mix-a dihydroxylation (22% total yield) after
the 1st batch recrystallization (MeOH–EtOAc; recrystallization
yield of the 1st batch: ~40%).
1H NMR (400 MHz, DMSO-d6): d = 7.73 (m, 1 H), 6.37 (d, J =
6.8 Hz, 1 H), 4.92 (d, J = 4.4 Hz, 1 H), 4.01 (m, 1 H), 3.25 (m, 1 H),
3.07 (m, 1 H), 2.97 (m, 1 H), 1.99 (m, 1 H), 1.75 (m, 1 H), 1.50 (m,
2 H), 1.37 (s, 9 H).
(2S,5R)-4 from AD-Mix-b Dihydroxylation or from Shi Epoxi-
dation
Purified by repeated silica gel chromatography (CH2Cl2–MeOH,
100:0→98:2).
13C NMR (100 MHz, DMSO-d6): d = 174.5, 154.9, 78.7, 69.5, 53.2,
1H NMR (400 MHz, CDCl3): d = 7.19 (d, J = 8.8 Hz, 2 H), 6.85 (d,
J = 8.8 Hz, 2 H), 6.06 (m, 1 H), 5.04 (d, J = 14.4 Hz, 1 H), 4.32 (m,
1 H), 4.22 (d, J = 14.4 Hz, 1 H), 3.97 (m, 1 H), 3.79 (s, 3 H), 3.54
(d, J = 15.2 Hz, 1 H), 3.39 (dd, J = 5.2, 15.6 Hz, 1 H), 1.94 (m,
2 H), 1.82 (m, 1 H), 1.67 (m, 1 H), 1.54 (m, 1 H), 1.45 (s, 9 H).
48.0, 36.9, 29.9, 28.7 (3C).
MS (ESI): m/z (%) = 389 (100) [2M + H – Boc]+, 267 (15) [M +
Na]+, 245 (10) [M + H]+.
2 from 4 by CAN
13C NMR (100 MHz, CDCl3): d = 172.9, 159.3, 155.2, 129.6 (2C),
129.2, 114.2 (2C), 79.5, 65.6, 55.2, 53.2, 52.5, 51.4, 34.9, 28.4 (3C),
26.7.
HRMS (ESI): m/z [M + H]+ calcd for C19H29N2O5: 365.2076; found:
365.2075.
Compound 4 (100 mg, 0.275 mmol) was dissolved in MeCN–H2O
(9:1, 15 mL) and the solution was cooled to –10 °C. CAN (603 mg,
1.1 mmol) was added and the reaction was stirred at –10 °C for
30 min and then at 0 °C overnight. When the reaction was complete,
sat. aq NaHCO3 (10 mL) was added and the mixture was extracted
with CH2Cl2 (3 × 20 mL), dried over anhydrous Na2SO4, filtered
and evaporated. The residue was purified by silica gel chromatog-
raphy (MeOH–EtOAc, 98:2→90:10) to afford 2 (51 mg, 76%), in
which the diastereomeric ratio of the (2S,5R)-2 and (2S,5S)-2 iso-
mers were the same as those of the (2S,5R)-4 and (2S,5S)-4 isomers.
Pure (2S,5R)-2 and (2S,5S)-2 isomers were recrystallized (MeOH–
EtOAc) as above (the 1st batch recrystallization yields from AD-
mix-a dihydroxylation, AD-mix-b dihydroxylation, and Shi epoxi-
dation were ~40%, 60% and ~37%, respectively).
(2S,5S)-4 from AD-Mix-a Dihydroxylation
Purified by repeated silica gel chromatography (CH2Cl2–MeOH,
100:0→98:2).
1H NMR (400 MHz, CDCl3): d = 7.15 (d, J = 8.4 Hz, 2 H), 6.82 (d,
J = 8.4 Hz, 2 H), 6.03 (m, 1 H), 4.61 (d, J = 14.4 Hz, 1 H), 4.42 (d,
J = 14.4 Hz, 1 H), 4.36 (m, 1 H), 3.76 (s, 3 H), 3.44–3.19 (m, 3 H),
~2.60 (br s, 1 H), 2.09 (m, 2 H), 1.72 (m, 1 H), 1.56 (m, 1 H), 1.42
(s, 9 H).
13C NMR (100 MHz, CDCl3): d = 172.7, 159.3, 155.2, 129.6 (2C),
128.9, 114.2 (2C), 79.5, 68.4, 55.2, 54.1, 53.0, 51.3, 36.8, 30.3, 28.4
(3C).
Supporting Information for this article is available online at
MS (ESI): m/z (%) = 751.3 (20) [2M + Na]+, 629.3 (70) [2M + H –
Boc]+, 387.1 (75) [M + Na]+, 465.1 (75) [M + H]+, 265.1 (100) [M
+ H – Boc]+.
Acknowledgment
This work was supported by the National Basic Research Program
of China (2007CB914504).
(2S,5R)/(2S,5S)-2-[(tert-Butoxycarbonyl)amino]-5-hydroxy-
caprolactam (2) and (2S,5R)/(2S,5S)-2-[(tert-Butoxycarbon-
yl)amino]-5-hydroxy-N-benzylcaprolactam (3)
References
Compound 10 (300 mg, 0.82 mmol) was dissolved in EtOH (50 mL)
and treated with 10% Pd/C (86 mg) under H2. The reaction was
heated at reflux overnight and then cooled to r.t., filtered and evap-
orated. The crude product was purified by gradient silica gel column
chromatography (CH2Cl2–MeOH, 98:2→95:5) to afford 2 (110 mg,
55.0%) and 3 (100 mg, 37%). The (2S,5R)-2 and (2S,5S)-2 isomers
were assigned according to the 1H NMR signals at d = 4.60 (m, 5-
H) and 7.40 (s, 7-NH) ppm, or at d = 4.92 (m, 5-H) and 7.76 (s, 7-
NH) ppm. All the spectroscopic data for pure (2S,5R)-2 and pure
(2S,5S)-2 were in accord with their corresponding reported data.5,7b
(1) (a) Quinoa, E.; Adamczeski, M.; Crews, P.; Bakus, G. J.
J. Org. Chem. 1986, 51, 4494. (b)Adamczeski, M.; Quinoa,
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Pure (2S,5R)-2
Obtained from AD-mix-b dihydroxylation (33% total yield) or Shi
epoxidation (20% total yield) after the 1st batch recrystallization
(MeOH–EtOAc; recrystallization yield of the 1st batch: 60% and
~37%, respectively).
Synthesis 2010, No. 23, 4068–4074 © Thieme Stuttgart · New York