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2H), 3.82 (q, J¼6.3 Hz, 2H), 6.45 (br s, 1H), 7.14 (d, J¼
8.7 Hz, 2H), 7.30 (d, J¼8.7 Hz, 2H). 13C NMR (100 MHz,
CDCl3) d 28.3, 38.4, 63.7, 80.5, 118.9, 130.0, 133.1,
136.8, 152.9. MS (EI) m/z 237 (M+). Anal. Calcd for
C13H19NO3: C, 65.80; H, 8.07; N, 5.90. Found: C, 66.01;
H, 8.03; N, 5.88.
1H), 5.03 (br d, J¼8.1 Hz, 1H). 13C NMR (100 MHz,
CDCl3) d 17.6, 18.9, 28.3, 31.3, 52.0, 58.5, 79.8, 155.7,
172.9. MS (EI) m/z 231 (M+).
4.4.5. Boc–Phe–OMe (9e). A colorless liquid. [a]2D5 ꢁ6.0 (c
2.5, MeOH) [lit.17 [a]D20 ꢁ3.0 (c 2.0, MeOH)]. IR (neat)
cmꢁ1: 1716, 1746, 3368. 1H NMR (400 MHz, CDCl3)
d 1.41 (s, 9H), 2.97–3.16 (m, 2H), 3.70 (s, 3H), 4.52–4.65
(m, 1H), 5.03 (br d, J¼7.6 Hz, 1H), 7.11–7.24 (m, 2H),
7.27–7.31 (m, 3H). 13C NMR (100 MHz, CDCl3) d 28.3,
38.3, 52.2, 54.4, 79.9, 127.0, 128.5, 129.3, 136.0, 155.1,
172.3. MS (EI) m/z 279 (M+).
4.4. General procedure for the N-tert-butoxy-
carbonylation of amino acid esters 8 by 1
Method A: A solution of 1 (15 mmol) in DME (20 mL) was
added to a stirred suspension of amino acid ester hydrochlo-
ride 8 (5 mmol) in DME (10 mL), with stirring at room tem-
perature for overnight. After removing DME under reduced
pressure, the residue was dissolved in AcOEt, washed with
5% HCl solution (10 mLꢂ2) and brine (10 mL), dried
(MgSO4), and concentrated in vacuo. The residue was puri-
fied by flash column chromatography on silica gel to give 9.
Method B: A stirred mixture of 1 (15 mmol) and amino acid
alkyl ester hydrochloride (5 mmol) in Et2O (30 mL) was
refluxed for overnight. The reaction mixture was washed
with 5% HCl solution (10 mLꢂ2) and brine (10 mL), dried
over MgSO4 and then evaporated. The residue was purified
by flash column chromatography on silica gel to give 9.
Method C: A stirred mixture of 1 (10 mmol) and amino
acid alkyl ester hydrochloride (5 mmol) in acetonitrile
(30 mL) was stirred for 48 h. The reaction mixture was
washed with 5% HCl solution (10 mLꢂ2) and brine
(10 mL), dried over MgSO4 and then evaporated. The resi-
due was purified by flash column chromatography on silica
gel to give 9. Yields are shown in Table 3.
4.4.6. Boc–Pro–OMe (9f). A colorless liquid. [a]2D7 ꢁ54.5 (c
1.1, CH2Cl2) [lit.18 [a]D25 ꢁ52.47 (c 0.99, CH2Cl2)]. IR (neat)
cmꢁ1: 1702, 1752. 1H NMR (400 MHz, CDCl3, major/
minor) d 1.41/1.47 (2ꢂs, 9H), 1.85–2.03 (m, 3H), 2.14–
2.30 (m, 1H), 3.36–3.60 (m, 2H), 3.72 (s, 3H), 4.22/4.33
(dd, J¼8.5, 4.1 Hz, 0.6H/J¼8.7, 3.4 Hz, 0.4H). 13C NMR
(100 MHz, CDCl3, major/minor) d 23.6/24.2, 28.2/28.3,
30.8/29.8, 46.2/46.5, 51.8/52.0, 59.0/58.6, 79.7, 153.7/
154.3, 173.7/173.4. MS (EI) m/z 229 (M+).
4.4.7. Boc–Glu(OEt)–OEt (9g). A colorless needles. Mp
46–47 ꢀC (pentane). [a]D27 ꢁ18.2 (c 1.3, Acetone) [lit.19
mp 46–47 ꢀC, [a]D ꢁ16.4 (c 1.0, Acetone)]. IR (KBr)
cmꢁ1: 1682, 1694, 1732, 3352. 1H NMR (400 MHz,
CDCl3) d 1.26 (t, J¼7.1 Hz, 3H), 1.29 (t, J¼7.1 Hz, 3H),
1.44 (s, 9H), 1.88–2.01 (m, 1H), 2.12–2.24 (m, 1H), 2.30–
2.44 (m, 2H), 4.14 (q, J¼7.1 Hz, 2H), 4.20 (q, J¼7.1 Hz,
2H), 4.23–4.37 (m, 1H), 5.12 (br d, J¼7.6 Hz, 1H). 13C
NMR (100 MHz, CDCl3) d 14.1, 14.1, 27.7, 28.2, 30.3,
52.9, 60.6, 61.4, 79.9, 155.5, 172.2, 172.7. MS (EI) m/z
304 (M++1).
4.4.1. Boc–Met–OMe (9a). A colorless liquid. [a]2D6 ꢁ34.0
(c 2.6, MeOH) [lit.15 [a]Damb ꢁ34.0 (c 1.0, MeOH)]. IR (neat)
cmꢁ1: 1715, 1745, 3359. 1H NMR (400 MHz, CDCl3) d 1.45
(s, 9H), 1.84–1.99 (m, 1H), 2.08–2.18 (m, 1H), 2.10 (s, 3H),
2.54 (t, J¼7.6 Hz, 2H), 3.76 (s, 3H), 4.34–4.46 (br, 1H),
5.08–5.20 (br, 1H). 13C NMR (100 MHz, CDCl3) d 15.4,
28.3, 30.0, 32.2, 52.4, 52.7, 80.0, 155.3, 172.8. MS (EI)
m/z 263 (M+).
4.4.8. Boc–Ser–OMe (9h). A colorless liquid. [a]2D6 +9.1 (c
1.3, CHCl3) [lit.20 [a]D20 +9.0 (c 1.0, CHCl3)]. IR (neat)
cmꢁ1: 1717, 1747, 3399. 1H NMR (400 MHz, CDCl3)
1.45 (s, 9H), 3.08 (br s, 1H), 3.78 (s, 3H), 3.87–3.90 (m,
1H), 3.95–3.97 (m, 1H), 4.38 (br s, 1H), 5.59 (br, 1H). 13C
NMR (100 MHz, CDCl3) d 28.2, 52.5, 55.6, 63.2, 80.2,
155.8, 171.4. MS (EI) m/z 220 (M++1).
4.4.2. Boc–Ala–OEt (9b). A colorless liquid. [a]2D6 ꢁ39.8 (c
2.5, MeOH) [lit.16 [a]D ꢁ42.5 (c 1.0, MeOH)]. IR (neat)
cmꢁ1: 1715, 1738, 3367. 1H NMR (400 MHz, CDCl3)
d 1.28 (t, J¼7.0 Hz, 3H), 1.38 (d, J¼7.2 Hz, 3H), 1.45 (s,
9H), 4.20 (q, J¼7.1 Hz, 2H), 4.23–4.36 (m, 1H), 5.10 (br
s, 1H). 13C NMR (100 MHz, CDCl3) d 14.1, 18.6, 28.3,
31.1, 49.2, 61.2, 79.7, 155.1, 173.3. MS (EI) m/z 217 (M+).
4.4.9. Boc–Cys–OMe (9i). A colorless liquid. [a]2D6 +27.5 (c
1.0, CHCl3) [lit.21 [a]D21 +28.5 (c 318 mM, CHCl3)]. IR
(neat) cmꢁ1: 1712, 1747, 3368. 1H NMR (400 MHz,
CDCl3) d 1.46 (s, 9H), 1.84 (br s, 1H), 2.95–2.99 (m, 2H),
3.79 (s, 3H), 4.61–4.80 (br s, 1H), 5.45 (br s, 1H). 13C
NMR (100 MHz, CDCl3) d 27.3, 28.2, 52.6, 54.8, 80.3,
155.1, 170.8. MS (EI) m/z 235 (M+).
4.4.3. Boc–Leu–OEt (9c). A colorless liquid. [a]2D5 ꢁ34.6 (c
2.3, MeOH) [lit.17 [a]D ꢁ37.0 (c 1.0, MeOH)]. IR (neat)
cmꢁ1: 1716, 1740, 3365. 1H NMR (400 MHz, CDCl3)
d 0.94 (dd, J¼6.5, 3.1 Hz, 6H), 1.28 (t, J¼7.1 Hz, 3H),
1.44 (s, 9H), 1.48–1.78 (m, 3H), 4.18 0 (q, J¼7.2 Hz, 2H),
4.24–4.33 (m, 1H), 4.90 (br s, 1H). 13C NMR (100 MHz,
CDCl3) d 14.3, 21.9, 22.8, 24.8, 28.3, 41.9, 52.1, 61.1,
79.7, 155.4, 173.5. MS (EI) m/z 260 (M++1).
4.4.10. Boc–Tyr–OMe (9j). Colorless prisms. Mp 102–
104 ꢀC (Et2O–hexane), [a]D27 +12.0 (c 2.2, EtOH) [lit.31
mp 101–103 ꢀC, [a]D25 +10.6 (c 2, EtOH)]. IR (KBr) cmꢁ1
:
1690, 1716, 1761, 3389. 1H NMR (400 MHz, CDCl3)
d 1.42 (s, 9H), 2.91–3.07 (m, 2H), 3.71 (s, 3H), 4.47–4.60
(m, 1H), 5.04 (br d, J¼8.1 Hz, 1H), 6.55 (br s, 1H), 6.72
(d, J¼8.1 Hz, 2H), 6.95 (d, J¼8.6 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d 28.3, 37.5, 52.3, 54.6, 80.3, 115.5,
127.3, 130.3, 155.2, 155.4, 172.7. MS (EI) m/z 295 (M+).
4.4.4. Boc–Val–OMe (9d). A colorless liquid. [a]2D5 ꢁ21.9
(c 2.2, MeOH) [lit.15 [a]aDmb ꢁ22.7 (c 2.0, MeOH)]. IR
(neat) cmꢁ1: 1715, 1746, 3369. 1H NMR (400 MHz,
CDCl3) d 0.93 (dd, J¼25.8, 7.0 Hz, 6H), 1.45 (s, 9H),
2.06–2.16 (m, 1H), 3.74 (s, 3H), 4.22 (dd, J¼9.2, 4.8 Hz,
4.4.11. Boc–Tyr(Boc)–OMe (10). Colorless needles. Mp
90–91 ꢀC (hexane). [a]2D0 ꢁ0.6 (c 2.3, MeOH). IR (KBr)