I. Reile et al. / Tetrahedron 67 (2011) 5942e5948
5947
1 mmol), (þ)-diethyl tartrate (270
m
l, 1.6 mmol), 3-benzyl-2-
4.10. Cyclization of the mixture of 18O labeled 2-benzyl-2-
hydroxy-pentanedioic acids 4c into 18O labeled 2-benzyl-5-
oxo-tetrahydrofuran-2-carboxylic acid 2d and unlabeled
acid 2
hydroxy-cyclopent-2-en-1-one (188 mg, 1 mmol) solution in
1.8 ml of DCM and di-18O-tert-butyl hydroperoxide 5 (1.6 ml,
1.56 M, 1.5 mmol) and quenching the reaction with 6 ml of H2O
followed by 1.2 ml of 30% NaOH solution in brine gave, after ex-
traction and purification, a mixture of di-18O labeled 2-benzyl-2-
hydroxy-pentanedioic acids 4a and 4b (149 mg, 61%) as a yellow
Using the general procedure for the cyclization of 18O labeled 2-
benzyl-2-hydroxy-pentanedioic acids with 18O labeled 2-benzyl-2-
hydroxy-pentanedioic acids 4c (4 mg, 0.018 mmol) and 0.5 ml of
toluene gave a mixture of 18O labeled 2-benzyl-5-oxo-tetrahydro-
furan-2-carboxylic acid 2d and unlabeled 2-benzyl-5-oxo-tetrahy-
drofuran-2-carboxylic acid 2 (8 mg) as a light brown solid, mp
oil: 1H NMR (400 MHz, CD3OD)
d
¼7.29e7.19 (m, 5H, Ph), 3.08 and
2.92 (2d, J¼13.5 Hz, 2H, PheCH2e), 2.56e2.46 and 2.26e2.12 (m,
2H, H3), 2.56e2.46 and 2.00e1.91 (m, 2H, H4); 13C NMR (100 MHz,
CD3OD)
d
¼177.684 (C1eOOH), 177.658 (C1e18OOH), 177.090
(C5eOOH), 177.065 (C5e18OOH), 137.49 (s), 131.48 (o), 128.94 (m),
127.66 (p), 78.30 (C2), 46.49 (PheCH2e), 35.33 (C3), 29.77 (C4); LC/
MS/MS (ESI): m/z (%)¼243 (2.6, [MꢀH]ꢀ), 241 (100, [MꢀH]ꢀ), 239
(4.5, [MꢀH]ꢀ), 237 (0.8, [MꢀH]ꢀ); Fragments of 241 (ESI): m/z (%)¼
223 (100), 221 (36.3), 219 (0.9), 179 (0.9), 177 (10.6), 175 (9.1), 131
(6.3).
103e105 ꢁC: 1H NMR (400 MHz, CDCl3)
d
¼7.99 (s, 1H; COOH),
7.24e7.11 (m, 5H, Ph), 3.32 and 3.08 (2d, J¼14.4 Hz, 2H, PheCH2e),
2.46e2.37 and 2.25e2.16 (m, 2H; H3), 2.46e2.37 and 2.11e2.00 (m,
2H, H4); 13C NMR (100 MHz, CDCl3)
d
¼176.06 (C1eOOH), 175.927
(C5eO), 175.889 (C5e18O), 133.68 (s), 130.74 (o), 128.79 (m), 127.75
(p), 86.14 (C2), 42.26 (PheCH2e), 30.07 (C3), 28.11 (C4); IR: 3032,
2925, 1784, 1750, 1714, 1496, 1456, 1419, 1192, 1042, 931, 699 cmꢀ1
;
4.8. Cyclization of the mixture of di-18O labeled 2-benzyl-2-
hydroxy-pentanedioic acids 4a and 4b into 18O labeled 2-
benzyl-5-oxo-tetrahydrofuran-2-carboxylic acids 2a, 2b,
and 2c
LC/MS/MS (ESI): m/z (%)¼221 (95.5, [MꢀH]ꢀ), 219 (100, [MꢀH]ꢀ);
Fragments of 221 (ESI): m/z (%)¼177 (5.1), 175 (100), 131 (37.7).
HRMS (ESI): calcd for C12H12O4 [MþH]þ 221.0808; found 221.0813.
HRMS (ESI): calcd for C12H12O318O [MþH]þ 223.0851; found
223.0855.
Using the general procedure for the cyclization of 18O labeled 2-
benzyl-2-hydroxy-pentanedioic acids with the mixture of di-18O
labeled 2-benzyl-2-hydroxy-pentanedioic acids 4a and 4b (39 mg,
0.162 mmol) and 2 ml of toluene gave a mixture of 18O labeled 2-
benzyl-5-oxo-tetrahydrofuran-2-carboxylic acids 2a, 2b, and 2c
(34 mg, 100%) as yellow oil that solidified at cooling into the
yellowish-white crystals, mp 106e108 ꢁC: 1H NMR (400 MHz,
4.11. Oxidation of C2 18O labeled 3-benzyl-2-hydroxycyclop-
ent-2-enone 1b with tert-butyl hydroperoxide
Using the general procedure for the oxidation of 3-benzyl-2-
hydroxy-cyclopent-2-en-1-ones 1 with tert-butyl hydroperoxide
i
ꢀ
CDCl3, 244 K)
d
¼9.48 (s, 1H, COOH), 7.35e7.29 (m, 5H, Ph), 3.42 and
with 2.5 ml of DCM, 39 mg of MS 4 A powder, Ti(O Pr)4 (116
ml,
3.16 (2d, J¼14.4 Hz, 2H, PheCH2e), 2.58e2.48 and 2.40e2.28 (m,
0.391 mmol), (þ)-diethyl tartrate (109
m
l, 0.625 mmol), C2 18O la-
beled 3-benzyl-2-hydroxy-cyclopent-2-en-1-one 1b (86 mg,
0.391 mmol) solution in 0.8 ml of DCM and tert-butyl hydroper-
2H, H3), 2.58e2.48 and 2.23e2.11 (m, 2H, H4); 13C NMR (100 MHz,
CDCl3, 244 K)
d
¼176.901 (C1eOOH), 176.878 (C1e18OOH), 176.524
(C5eO), 176.486 (C5e18O), 133.33 (s), 130.67 (o), 128.72 (m), 127.67
(p), 85.90 (C2), 41.73 (PheCH2e), 30.00 (C3), 28.05 (C4); IR: 3059,
1769, 1734, 1707, 1496, 1462, 1408, 1178, 1033, 919, 709 cmꢀ1; LC/
MS/MS (ESI): m/z (%)¼223 (100, [MꢀH]ꢀ), 221 (35.7, [MꢀH]ꢀ), 219
(2.3, [MꢀH]ꢀ); Fragments of 223 (ESI): m/z (%)¼179 (7.6), 177 (98.1),
175 (79.5), 131 (100). HRMS (ESI): calcd for C12H12O4 [MþH]þ
221.0808; found 221.0798. HRMS (ESI): calcd for C12H12O318O
[MþH]þ 223.0851; found 223.0840. HRMS (ESI): calcd for
C12H12O218O2 [MþH]þ 225.0893; found 225.0881.
oxide (160 ml, 6.15M in decane, 0.977 mmol) and quenching the
reaction with 2.34 ml of H2O followed by 0.5 ml of 30% NaOH so-
lution in brine gave, after extraction an purification, 18O labeled 2-
benzyl-2-hydroxy-pentanedioic acid 4d (27 mg, 29%) as a yellowish
oil: 1H NMR (400 MHz, CD3OD)
d
¼7.29e6.19 (m, 5H, Ph), 3.08 and
2.92 (2d, J¼13.5 Hz, 2H, PheCH2e), 2.54e2.46 and 2.27e2.13 (m,
2H, H3), 2.54e2.46 and 2.01e1.90 (m, 1H, H4); 13C NMR (100 MHz,
CD3OD)
d
¼177.688 (C1eOOH), 177.662 (C1e18OOH), 177.08
(C5eOOH), 137.49 (s), 131.48 (o), 128.94 (m), 127.66 (p), 78.32(C2),
46.49 (PheCH2e), 35.33 (C3), 29.78 (C4); LC/MS/MS (ESI): m/z (%)¼
239 (100, [MꢀH]ꢀ), 237 (20.8, [MꢀH]ꢀ); Fragments of 239 (ESI): m/
z (%)¼221 (100), 219 (13.5), 177 (11.5), 175 (4.2), 131 (5.1).
4.9. Oxidation of C1 18O labeled 3-benzyl-2-hydroxycyclopent-
2-enone 1a with tert-butyl hydroperoxide
Using the general procedure for the oxidation of 3-benzyl-2-
hydroxy-cyclopent-2-en-1-one 1 with tert-butyl hydroperoxide
4.12. Cyclization of the mixture of 18O labeled 2-benzyl-2-
hydroxy-pentanedioic acid 4d into 18O labeled 2-benzyl-5-
oxo-tetrahydrofuran-2-carboxylic acid 2e
i
ꢀ
with 1.5 ml of DCM, 15 mg of MS 4 A powder, Ti(O Pr)4 (75
0.25 mmol), (þ)-diethyl tartrate (67.5
l, 0.4 mmol), C1 18O labeled
3-benzyl-2-hydroxy-cyclopent-2-en-1-one 1a (47 mg, 0.25 mmol)
solution in 0.5 ml of DCM and tert-butyl hydroperoxide (90 l,
ml,
m
m
Using the general procedure for the cyclization of 18O labeled 2-
benzyl-2-hydroxy-pentanedioic acids with 18O labeled 2-benzyl-2-
hydroxy-pentanedioic acid 4d (11 mg, 0.046 mmol) and 1.0 ml of
toluene gave 18O labeled 2-benzyl-5-oxo-tetrahydrofuran-2-
carboxylic acid 2e (19 mg) as white crystals, mp 107e110 ꢁC: 1H
6.8M in decane, 0.6 mmol) and quenching the reaction with
1.25 ml of H2O followed by 0.3 ml of 30% NaOH solution in brine
gave, after extraction and purification, a mixture of 18O labeled 2-
benzyl-2-hydroxy-pentanedioic acids 4c (10 mg, 17%) as a light
brown oil: 1H NMR (400 MHz, CD3OD)
d
¼7.30e7.17 (m, 5H, Ph),
NMR (800 MHz, CDCl3, 248 K)
d
¼10.39 (s, 1H, COOH), 7.26e7.19 (m,
3.08 and 2.92 (2d, J¼13.5 Hz, 2H, PheCH2e), 2.51e2.46 and
5H, Ph), 3.33 and 3.08 (2d, J¼14.5 Hz, 1H, PheCH2e), 2.46e2.40 and
2.26e2.12 (m, 2H, H3), 2.51e2.46 and 2.01e1.91 (m, 2H, H4); 13C
2.26e2.22 (m, 2H, H3), 2.46e2.40 and 2.11e2.05 (m, 2H, H4); 13C
NMR (100 MHz, CD3OD)
d
¼177.72 (C1eOOH), 177.096 (C5eOOH),
NMR (200 MHz, CDCl3, 248 K)
d
¼176.780 (C1eOOH), 176.757
177.071 (C5e18OOH), 137.50 (s), 131.48 (o), 128.94 (m), 127.65 (p),
78.34 (C2), 46.49 (PheCH2e), 35.34 (C3), 29.78 (C4); LC/MS/MS
(ESI): m/z (%)¼239 (100, [MꢀH]ꢀ), 237 (9.8, [MꢀH]ꢀ); Fragments
of 239 (ESI): m/z (%)¼221 (100), 219 (93.8), 177 (2.9), 175 (31.9),
131 (12.8).
(C1e18OOH), 176.28 (C5eO), 133.46 (s), 130.70 (o), 128.75 (m),
127.71 (p), 85.98 (C2), 41.97 (PheCH2e), 30.04 (C3), 28.06 (C4); IR:
3060, 1769, 1497, 1461, 1421, 1180, 1042, 946, 706 cmꢀ1; LC/MS/MS
(ESI): m/z (%)¼221 (100, [MꢀH]ꢀ), 219 (26.0, [MꢀH]ꢀ); Fragments
of 221 (ESI): m/z (%)¼177 (100), 175 (51.3), 131 (69.7). HRMS (ESI):