12
Tetrahedron
Hz, 1H, NHBoc), 4.25-4.11 (m, 2H, OCH2CH3), 2.62-2.48
CHIRALPAK AD-H, hexane/iPrOH = 20/1, flow rate = 0.5
A
CCEPTED MANUSCRIPT
(m, 1H, CH2), 2.41-2.30 (m, 2H, CH2), 2.29-2.18 (m, 1H, CH2),
2.11-2.04 (m, 5H, CH2), 1.97-1.84 (m, 1H, CH2), 1.63-1.52 (m,
4H, CH2), 1.43 (s, 9H, C(CH3)3), 1.25 (t, J = 7.2 Hz, 3H,
OCH2CH3); 13C-NMR (100 MHz, CDCl3): δ 214.9, 170.0, 154.6,
135.6, 119.8, 86.3, 82.8, 79.7, 62.9, 61.7, 46.0, 39.1, 32.9, 29.0,
28.3, 25.5, 22.1, 21.3, 19.6, 14.0; HRMS (ESI): calcd. for
mL/min, λ = 210 nm, retention time; tR = 23.3 min (minor), 29.5
min (major); [α]24 43.7 (c 1.0, CHCl3, 91% ee).
D
4.9.8. Ethyl (1S)-1-((S)-1-((tert-
butoxycarbonyl)amino)-3-cyclohexylprop-2-yn-1-
yl)-2-oxocyclopentanecarboxylate
+
1H-NMR (400 MHz, CDCl3): δ 5.94 (br d, J = 10.0 Hz,
NHBoc), 4.95 (d, J = 10.0 Hz, 1H, CHNHBoc), 4.24-4.10 (m,
2H, OCH2CH3), 2.63-2.47 (m, 1H, CH2), 2.40-2.28 (m, 3H, CH2,
CHCH2), 2.26-2.15 (m, 1H, CH2), 2.11-1.99 (m, 1H, CH2), 1.96-
1.83 (m, 1H, CH2), 1.72-1.62 (m, 4H, Cy), 1.49-1.21 (m, 6H,
Cy), 1.43 (s, 9H, C(CH3)3), 1.24 (t, J = 7.2 Hz, 3H, OCH2CH3);
13C-NMR (100 MHz, CDCl3): δ 210.4, 170.1, 154.8, 89.2, 79.6,
77.2, 62.9, 61.7, 45.7, 39.1, 32.9, 32.5, 28.7, 28.3, 25.8, 24.6,
C22H31NNaO5 (M+Na)+: 412.2094, found: 412.2110; IR (neat):
3429, 2977, 2932, 1718, 1487, 1366, 1228, 1158, 1036 cm-1;
HPLC analysis: Daicel CHIRALPAK AD-H, hexane/iPrOH =
20/1, flow rate = 0.5 mL/min, λ = 226 nm, retention time; tR =
17.3 min (minor), 19.4 min (major); [α]2D3 54.8 (c 1.0, CHCl3,
94% ee).
4.9.5. Ethyl (1S)-1-((S,E)-1-((tert-
butoxycarbonyl)amino)-5-phenylpent-4-en-2-yn-1-
yl)- 2-oxocyclopentanecarboxylate
19.7, 14.0; HRMS (ESI): calcd. for C22H33NNaO5 (M+Na)+:
+
414.2251, found: 414.2260; IR (neat): 3430, 2977, 2930, 2854,
1750, 1720, 1489, 1366, 1228, 1159, 1036 cm-1; HPLC analysis:
Daicel CHIRALPAK IC, hexane/iPrOH = 20/1, flow rate = 0.5
mL/min, λ = 210 nm, retention time; tR = 30.8 min (minor), 58.8
1H-NMR (400 MHz, CDCl3): δ 7.38-7.25 (m, 5H, Ph), 6.89
(d, J = 16.4 Hz, 1H, PhCH=CH), 6.09 (dd, J = 16.4 Hz, 2.4 Hz,
1H, PhCH=CH), 6.04 (br d, J = 9.6 Hz, 1H, NHBoc), 5.15 (br d,
J = 9.6 Hz, 1H, CHNHBoc), 4.28-4.13 (m, 2H, OCH2CH3), 2.67-
2.51 (m, 1H, CH2), 2.45-2.23 (m, 3H, CH2) 2.14-2.04 (m, 1H,
CH2), 2.00-1.87 (m, 1H, CH2), 1.44 (s, 9H, C(CH3)3), 1.26 (t, J =
7.2 Hz, 3H, OCH2CH3); 13C-NMR (100 MHz, CDCl3): δ 214.9,
170.0, 154.7, 142.1, 135.9, 128.8, 128.7, 126.2, 107.2, 87.7, 83.7,
79.9, 62.8, 61.8, 46.2, 38.9, 32.9, 28.3, 19.6, 14.0; HRMS (ESI):
min (major); [α]23 44.0 (c 1.0, CHCl3, 95% ee).
D
4.9.9. Ethyl (1S)-1-((S)-1-((tert-
butoxycarbonyl)amino)-3-cyclopropylprop-2-yn-1-
yl)-2-oxocyclopentanecarboxylate
1H-NMR (400 MHz, CDCl3): δ 5.92 (br d, J = 8.8 Hz, 1H,
NHBoc), 4.90 (br d, J = 8.8 Hz, 1H, CHNHBoc), 4.23-4.10 (m,
2H, OCH2CH3), 2.59-2.46 (m, 1H, CH2), 2.35-2.16 (m, 3H,
CH2), 2.09-2.02 (m, 1H, CH2), 1.95-1.83 (m, 1H, CH2), 1.42 (s,
9H, C(CH3)3), 1.24 (t, J = 7.2 Hz, 3H, OCH2CH3), 1.21-1.13 (m,
1H, CH), 0.75-0.70 (m, 2H, CHCHH), 0.62-0.58 (m, 2H,
CHCHH); 13C-NMR (100 MHz, CDCl3): δ 214.9, 170.1, 154.7,
88.2, 79.6, 71.6, 62.9, 61.7, 45.6, 39.0, 32.8, 28.3, 19.6, 14.0,
calcd. for C24H29NNaO5 (M+Na)+: 434.1938, found: 434.1949;
+
IR (neat): 3426, 2978, 1717, 1489, 1367, 1319, 1298, 1229,
1158, 1036 cm-1; HPLC analysis: Daicel CHIRALPAK AD-3,
hexane/EtOH = 20/1, flow rate = 0.5 mL/min, λ = 254 nm,
retention time; tR = 29.9 min (major), 40.2 min (minor); [α]24 79.1
D
(c 1.0, CHCl3, 90% ee)
+
4.9.6. Ethyl (1S)-1-((S)-1-((tert-
butoxycarbonyl)amino)-oct-2-yn-1-yl)-2-
oxocyclopentanecarboxylate
8.22, 8.19, –0.7; HRMS (ESI): calcd. for C19H27NNaO5
(M+Na)+: 372.1781, found: 372.1789; IR (neat): 3429, 2978,
1717, 1488, 1367, 1229, 1158, 1030 cm-1; HPLC analysis: Daicel
CHIRALCEL OZ-H, hexane/iPrOH = 20/1, flow rate = 0.5
mL/min, λ = 210 nm, retention time; tR = 18.4 min (minor), 20.8
1H-NMR (400 MHz, CDCl3): 5.96 (br d, J = 8.8 Hz, 1H,
CHNHBoc), 4.94 (br d, J = 9.2 Hz, 1H, NHBoc), 4.24-4.10 (m,
2H, OCH2CH3), 2.63-2.48 (m, 1H, CH2), 2.36-2.32 (m, 2H, CH2),
2.29-2.01 (m, 2H, CH2), 2.12 (td, J = 7.2 Hz, 2.0 Hz, 2H, CH2),
1.96-1.86 (m, 1H, CH2), 1.48-1.43 (m, 2H, CH2), 1.43 (s, 9H,
C(CH3)3), 1.32-1.27 (m, 4H, CH2), 1.24 (t, J = 7.2 Hz, 3H,
OCH2CH3), 0.89 (t, J = 6.8 Hz, 3H, CH2CH2CH3); 13C-NMR
(100 MHz, CDCl3): δ 215.0, 170.1, 154.8, 85.2, 79.6, 76.5, 62.8,
61.7, 45.7, 39.0, 32.9, 30.9, 28.3, 28.2, 22.1, 19.6, 18.5, 14.0,
min (major); [α]25 39.4 (c 1.0, CHCl3, 93% ee).
D
4.9.10. Ethyl (1S)-1-((S)-1-((tert-
butoxycarbonyl)amino)-4,4-dimethylpent-2-yn-1-
yl)-2-oxocyclopentanecarboxylate
1H-NMR (400 MHz, CDCl3): δ 5.90 (br d, J = 10.0 Hz, 1H,
NHBoc), 4.93 (br d, J = 10.0 Hz, 1H, CHNHBoc), 4.23-4.10 (m,
2H, OCH2CH3), 2.64-2.47 (m, 1H, CH2), 2.40-2.27 (m, 2H, CH2),
2.23-2.14 (m, 1H, CH2), 2.11-2.02 (m, 1H, CH2), 1.96-1.83 (m,
1H, CH2), 1.43 (s, 9H, OC(CH3)3), 1.25 (t, J = 7.2 Hz, 3H,
OCH2CH3), 1.16 (s, 9H, CC(CH3)3); 13C-NMR (100 MHz,
CDCl3): δ 214.8, 170.1, 154.7, 93.3, 79.6, 75.2, 63.0, 61.6, 45.6,
39.2, 32.9, 30.8, 28.3, 27.2, 19.6, 14.0; HRMS (ESI): calcd. for
13.9; HRMS (ESI): calcd. for C21H33NNaO5 (M+Na)+:
+
402.2251, found: 402.2253; IR (neat): 3429, 2961, 2932, 1750,
1720, 1489, 1228, 1159 cm-1; HPLC analysis: Daicel
CHIRALPAK IC, hexane/iPrOH = 10/1, flow rate = 0.5 mL/min,
λ = 210 nm, retention time; tR = 21.3 min (minor), 37.3 min
(major); [α]25 35.4 (c 1.0, CHCl3, 92% ee).
C20H31NNaO5 (M+Na)+: 388.2094, found: 388.2105; IR (neat):
D
+
3430, 2970, 1719, 1489, 1366, 1321, 1299, 1227, 1159, 1036 cm-
1; HPLC analysis: Daicel CHIRALCEL OZ-H, hexane/iPrOH =
50/1, flow rate = 0.5 mL/min, λ = 209 nm, retention time; tR =
12.1 min (minor), 16.6 min (major); [α]2D4 42.2 (c 1.0, CHCl3,
95% ee).
4.9.7. Ethyl (1S)-1-((S)-1-((tert-
butoxycarbonyl)amino)-5-phenylpent-2-yn-1-yl)-2-
oxocyclopentanecarboxylate
1H-NMR (400 MHz, CDCl3): δ 7.30-7.26 (m, 2H, Ph), 7.22-
7.16 (m, 3H, Ph), 5.96 (br d, J = 10.0 Hz, 1H, NHBoc), 4.90 (br
d, J = 10.0 Hz, 1H, CHNHBoc), 4.22-4.07 (m, 2H, OCH2CH3),
2.76 (t, J = 7.2 Hz, 2H, PhCH2CH2), 2.49-2.44 (m, 2H,
PhCH2CH2), 2.44-2.36 (m, 1H, CH2), 2.28-2.22 (m, 1H, CH2),
2.15-2.07 (m, 1H, CH2), 2.00-1.76 (m, 3H, CH2), 1.42 (s, 9H,
C(CH3)3), 1.22 (t, J = 7.2 Hz, 3H, OCH2CH3); 13C-NMR (100
MHz, CDCl3): δ 215.1, 170.1, 154.7, 140.3, 128.4, 128.3, 126.2,
84.2, 79.6, 77.3, 62.7, 61.7, 45.6, 38.8, 34.5, 32.7, 28.3, 20.4,
4.9.11. Ethyl 1-(1-((tert-butoxycarbonyl)amino)-3-
phenylprop-2-yn-1-yl)-2-oxocyclohexanecarboxylate
1H-NMR (400 MHz, CDCl3): δ 7.41-7.35 (m, 2H, Ph), 7.31-
7.25 (m, 3H, Ph), 5.89 (br d, J = 10.4 Hz, 1H, NHBoc), 4.97 (br
d, J = 10.4 Hz, 1H, CHNHBoc), 4.22 (qd, J = 7.2 Hz, 1.2 Hz, 2H,
OCH2CH3), 2.69-2.56 (m, 1H, CH2), 2.58-2.48 (m, 2H, CH2),
2.11 (td, J = 13.2 Hz, 3.2 Hz, 1H, CH2), 2.06-2.00 (m, 1H, CH2),
1.86 (app d, J = 13.2 Hz, 1H, CH2), 1.72-1.51 (m, 2H, CH2), 1.42
(s, 9H, C(CH3)3), 1.29 (t, J = 7.2 Hz, 3H, OCH2CH3); 13C-NMR
19.6, 13.9; HRMS (ESI): calcd. for C24H31NNaO5 (M+Na)+:
+
436.2094, found: 436.2108; IR (neat): 3427, 2977, 1716, 1487,
1366, 1319, 1299, 1226, 1155, 1033 cm-1; HPLC analysis: Daicel