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doi.org/10.1002/ejoc.202001532
of Mg (20.8 mmol, 513 mg) in abs. Et2O (30 mL) and the solution
was stirred under reflux for 3 h. The freshly prepared Grignard
solution was slowly added over 15 min to a suspension of CuCl
Conversion of Oxoester 1c with enol acetate 2a: CeCl3 ·7 H2O
(4.00 μmol, 1.50 mg) was added to a solution of β-oxoester 1c
(410 μmol, 100 mg) and enol acetate 2a (0.61 mmol, 98.0 mg) in
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°
°
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5
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(0.52 mmol, 52 mg) in abs. THF (50 mL) at À 78 C and the reaction
TFE (1 mL) and the resulting reaction mixture was stirred at 30 C
mixture was stirred for 1.5 h at this temperature. A solution of 2-
methyl-2-cyclopenten-1-on (27, 10.4 mmol, 1.00 g) and TMSCl
(13.5 mmol, 1.47 g, 1.70 mL) in abs. THF (5 mL) was then within
15 min added to the reaction mixture and it was stirred for another
for 18 h. The solvent was evaporated and the residue purified by
column chromatography (SiO2, hexanes/MTBE/CH2Cl2 6:2:1) to
yield the 1,4-diketone 3b (129 μmol, 47.0 mg, 32%, Rf =0.41) as a
colorless oil in the first fraction. Secondly, the lactone 4b
(163 μmol, 62.0 mg, 40%, Rf =0.27) was eluted as a colorless oil. As
a third fraction, the lactone 4c (57.8 μmol, 22.0 mg, 14%, Rf =0.23)
was obtained as colorless oil.
°
16 h at À 78 C. The solution was hydrolyzed with hydrochloric acid
(1 mol/L, 10 mL) and the aqueous layer was extracted with MTBE
(3×10 mL). The combined organic layers were dried (MgSO4) and
filtered through SiO2 (5 cm, MTBE). The solvent was evaporated and
the residue was purified by column chromatography (SiO2,
hexanes/MTBE 8:1) to yield compound 28 (998 mg, 5.73 mmol,
55%, Rf =0.20) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ=1.04 (d,
J=6.9 Hz, 3H), 1.89–2.05 (m, 1H), 2.17–2.39 (m, 3H), 2.49–2.63 (m,
1H), 2.81 (td, J=12.0 Hz, J=5.6 Hz, 1H), 7.22–7.30 (m, 3H), 7.33–7.40
(m, 2H) ppm. C12H14O (174.24 g/mol). The relative configuration was
established by the following NOE experiments to be trans:
Irradiation at δ=1.04 ppm (2-Me) led to a positive signal at δ=
2.81 ppm (3-H) in the NOE difference spectrum. All other data were
in accordance with the literature.[22]
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(3R*,5R*,6R*)-Ethyl 6-methyl-2-oxo-3-(2-oxo-2-phenyl)-5-phenyl-
tetrahydropyran-3-carboxylate (4b): 1H NMR (500 MHz, CDCl3): δ=
3
3
1.18 (d, J=6.2 Hz, 3H; 6-Me), 1.32 (t, J=7.1 Hz, 3H; Et), 2.23 (dd,
2J=14.6 Hz, Jeq,ax =7.2 Hz, 1H; 4-Heq), 2.82 (dd, J=14.6 Hz, Jax,ax
=
3
2
3
11.5 Hz, 1H; 4-Hax), 3.20 (td, 3Jax,ax =11.1 Hz, 3Jax,eq =7.2 Hz, 1H; 5-Hax),
3.77 (d, 2J=18.2 Hz, 1H; 3-CHH), 3.92 (d, 2J=18.2 Hz, 1H; 3-CHH),
4.27–4.36 (m, 2H; Et), 4.87 (dq, 3Jax,ax =11.1 Hz, 3J=6.2 Hz, 1H; 6-Hax),
7.23–7.27 (m, 3H; 5-Ph), 7.30–7.34 (m, 2H; 5-Ph), 7.43–7.47 (m, 2H;
m-PhCO), 7.54–7.58 (m, 1H; p-PhCO), 7.95–7.98 (m, 2H; o-PhCO)
ppm. 13C{1H} NMR (125 MHz, CDCl3): δ=14.15 (CH3), 19.93 (CH3),
38.79 (CH2), 46.51 (CH2), 46.74 (CH), 51.49 (C), 62.85 (CH2), 79.85
(CH), 127.55 (CH), 128.12 (2 CH), 128.20 (2 CH), 128.79 (2 CH), 129.07
(2 CH), 133.68 (CH), 136.45 (C), 140.49 (C), 169.91 (C), 171.45 (C),
Ethyl
trans-3-Methyl-4-phenyl-2-cyclopentanone-1-carboxylate
(1c): A solution of compound 28 (4.40 mmol, 768 mg) in abs. THF
(2 mL) was added to a suspension of NaH (60% dispersion in
mineral oil, 8.85 mmol, 354 mg) and diethyl carbonate (22.0 mmol,
2.60 g, 2.70 mL) in abs. THF (30 mL) and the mixture was stirred for
6 h under reflux. It was then hydrolyzed with hydrochloric acid
(1 mol/L, 15 mL), the layers were separated and the aqueous layer
was extracted with MTBE (3×10 mL). The combined organic layers
were dried (MgSO4) and filtered. The solvent was evaporated and
the residue was purified by column chromatography (SiO2,
hexanes/MTBE 8:1) to yield compound 1c (994 mg, 4.04 mmol,
91%, Rf =0.27) as a mixture of two diastereomers (A/B 70:30) as a
~
196.52 (C) ppm. IR (ATR): n=3063 (w), 3030 (w), 2982 (w), 2936 (w),
2254 (w), 1740 (s) 1722 (vs), 1686 (s), 1597 (w), 1582 (w), 1496 (w),
1449 (m), 1404 (w), 1383 (w), 1350 (w), 1322 (w), 1254 (w), 1193 (m),
1137 (w), 1079 (w), 1053 (w), 1021 (w), 1001 (w), 957 (w), 910 (m),
860 (w), 754 (w), 729 (m), 701 (m), 689 (m), 647 (w), 617 (w), 576
(w), 554 (w) cmÀ 1. MS (EI, 70 eV): m/z (%) 380 (13) [M+], 306 (8), 260
(13), 249 (6), 231 (3), 214 (2), 196 (2), 185 (3), 156 (3), 144 (12), 130
(5), 128 (7), 117 (6), 105 (8), 104 (100). HRMS (EI, 70 eV): calcd.
380.1618 (for C23H24O5); found 380.1622 [M+]. C23H24O5 (380.44 g/
mol). The relative trans-configuration at C-5 and C-6 was deter-
mined by the following NOE experiment: Irradiation at δ=
1.18 ppm (6-Me) led to a positive signal at δ=3.20 ppm (5-H) in the
NOE difference spectrum. The relative configuration at C-3 was
determined by irradiation at δ=3.20 ppm (5-Hax) which led to a
positive signal at δ=3.77 and 3.92 ppm (3-CH2) in the NOE
difference spectrum.
1
yellow oil. An enol-tautomer was not observed. H NMR (500 MHz,
CDCl3), isomer A: δ=1.06 (d, J=6.9 Hz, 3H; 3-Me), 1.31 (t, J=7.1 Hz,
3H; Et), 2.36–2.47 (m, 2H; 3-H, 5-H), 2.56 (ddd, J=13.3 Hz, J=8.4 Hz,
J=6.1 Hz, 1H; 5-H), 2.77 (td, J=12.3 Hz, J=6.0 Hz, 1H; 4-H), 3.31
(dd, J=11.6 Hz, J=8.4 Hz, 1H; 1-H), 4.18–4.28 (m, 2H; Et), 7.24–7.31
(m, 3H; Ph), 7.34–7.39 (m, 2H; Ph) ppm; isomer B: δ=1.09 (d, J=
6.9 Hz, 3H; 3-Me), 1.31 (t, J=7.1 Hz, 3H; Et), 2.18 (ddd, J=13.4 Hz,
J=11.7 Hz, J=9.5 Hz, 1H; 5-H), 2.34–2.42 (m, 1H; 3-H), 2.65 (ddd,
J=13.4 Hz, J=6.7 Hz, J=1.9 Hz, 1H; 5-H), 3.18 (td, J=11.9 Hz, J=
6.7 Hz, 1H; 4-H), 3.49–3.55 (m, 1H; 1-H), 4.18–4.28 (m, 2H; Et), 7.21–
7.28 (m, 3H; Ph), 7.30–7.36 (m, 2H; Ph) ppm. 13C{1H} NMR (125 MHz,
CDCl3), isomer A: δ=12.27 (CH3), 14.32 (CH3), 33.61 (CH2), 48.51
(CH), 51.59 (CH), 55.02 (CH), 61.65 (CH2), 127.21 (CH), 127.31 (2 CH),
128.97 (2 CH), 141.28 (C), 169.47 (C), 211.61 (C) ppm; isomer B: δ=
12.72 (CH3), 14.30 (CH3), 33.74 (CH2), 49.18 (CH), 51.41 (CH), 53.68
(CH), 61.71 (CH2), 127.19 (CH), 127.31 (2 CH), 128.95 (2 CH), 141.89
(3S*,5R*,6R*)-Ethyl 6-methyl-2-oxo-3-(2-oxo-2-phenyl)-5-phenyl-
tetrahydropyran-3-carboxylate (4c): H NMR (500 MHz, CDCl3): δ=
1
3
3
1.28 (d, J=6.3 Hz, 3H; 6-Me), 1.37 (t, J=7.1 Hz, 3H; CH3CH2OCO),
2.16 (dd, 2J=13.8 Hz, 3Jeq,ax =3.7 Hz, 1H; 4-Heq), 2.51 (dd, 2J=13.5 Hz,
3Jax,ax =13.5 Hz, 1H; 4-Hax), 3.15 (ddd, Jax,ax =13.8 Hz, Jax,ax =10.6 Hz,
3
3
3Jax,eq =3.6 Hz, 1H; 5-Hax), 3.63 (d, J=18.6 Hz, 1H; 3-CHH), 4.13 (d,
2
2J=18.6 Hz, 1H; 3-CHH), 4.29 (dq, 2J=10.7 Hz, 3J=7.1 Hz, 1H;
CH3CHHOCO), 4.37 (dq, 2J=10.7 Hz, 3J=7.1 Hz, 1H; CH3CHHOCO),
3
3
5.08 (dq, Jax,ax =10.8 Hz, J=6.3 Hz, 1H; 6-Hax), 7.17–7.20 (m, 2H; 5-
Ph), 7.24–7.28 (m, 1H; 5-Ph), 7.30–7.34 (m, 2H; 5-Ph), 7.46–7.50 (m,
2H; m-PhCO), 7.57–7.62 (m, 1H; p-PhCO), 7.98–8.01 (m, 2H; o-PhCO)
ppm. 13C{1H} NMR (125 MHz, CDCl3): δ=14.31 (CH3), 20.14 (CH3),
38.30 (CH2), 45.08 (CH), 45.72 (CH2), 51.59 (C), 62.53 (CH2), 81.54
(CH), 127.73 (CH), 127.82 (2 CH), 128.31 (2 CH), 128.87 (2 CH), 129.13
(2 CH), 133.91 (CH), 136.29 (C) 139.99 (C), 169.96 (C), 171.48 (C),
~
(C), 169.37 (C), 211.28 (C) ppm. IR (ATR): n=3030 (w), 2976 (w),
2932 (w), 2874 (w), 2360 (w), 1753 (m), 1720 (vs), 1602 (w), 1497
(w), 1454 (w), 1393 (w), 1370 (w), 1332 (w), 1290 (w), 1247 (w), 1200
(w), 1147 (w), 1047 (w), 1013 (w), 954 (w), 921 (w), 887 (w), 861 (w),
811 (w), 759 (w), 700 (s), 669 (w), 609 (w) cmÀ 1. MS (EI, 70 eV): m/z
(%) 246 (77) [M+], 231 (84), 228 (91), 200 (68), 199 (48), 185 (72),
173 (47), 172 (33), 171 (14), 157 (19), 155 (43), 145 (96), 144 (59),
143 (19),132 (14), 131 (21), 129 (38), 128 (23), 118 (94), 117 (100),
115 (95), 105 (45), 103 (23), 101 (12), 91 (83), 78 (15), 77 (26), 73
(18), 65 (12), 55 (76), 51 (11). HRMS (EI, 70 eV): calcd. 246.1250 (for
C15H18O3); found 246.1245 [M+]. C15H18O3 (246.31 g/mol). The
relative configuration of both diastereoisomers was established by
a NOE experiments to be trans: Irradiation at δ=1.06 ppm (3-Me,
isomer A) and δ=1.09 ppm (3-Me, isomer B) led to a positive signal
at δ=2.77 ppm (4-H, isomer A) and δ=3.18 ppm (4-H, isomer B) in
the NOE difference spectra.
~
197.11 (C) ppm. IR (ATR): n=3063 (w), 3030 (w), 2980 (w), 2933 (w),
2873 (w), 1740 (s) 1722 (vs), 1683 (s), 1597 (w), 1582 (w), 1496 (w),
1449 (m), 1403 (w), 1382 (w), 1354 (w), 1317 (w), 1272 (w), 1207 (s),
1124 (w), 1082 (w), 1024 (w), 1001 (w), 991 (w), 956 (w), 940 (w),
913 (w), 860 (w), 759 (m), 701 (w), 690 (w), 576 (w), 556 (w) cmÀ 1
.
MS (EI, 70 eV): m/z (%) 380 (13) [M+], 306 (7), 260 (15), 249 (24), 214
(5), 202 (3), 185 (11), 184 (4),156 (5), 144 (13), 130 (6), 128 (9), 105
(7), 104 (100). HRMS (EI, 70 eV): calcd. 380.1618 (for C23H24O5); found
380.1634 [M+]. C23H24O5 (380.44 g/mol). The relative trans-config-
uration at C-5 and C-6 was determined by the following NOE
Eur. J. Org. Chem. 2021, 907–914
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