3376
Z. Guerrab et al. / Tetrahedron 63 (2007) 3367–3379
(58.7 mg, 97%) as a colorless oil. Rf¼0.36 (PE–EE 60:40).
Data for major endo-18e diastereomer: 1H NMR (300 MHz,
2
2
1H NMR (300 MHz, CDCl3) d: 4.04 (d, J¼11.5 Hz, 1H,
CDCl3) d: 3.94 (d, J¼11.4 Hz, 1H, CHaHbO), 3.87 (d,
CHaHbO), 3.90 (d, 2J¼11.5 Hz, 1H, CHaHbO), 2.52 (d,
2J¼11.4 Hz, 1H, CHaHbO), 2.55 (dd, 2J¼15.1 Hz,
3J¼6.3 Hz, 1H, CHaHb–CO), 2.27 (dd, 2J¼15.1 Hz,
3J¼4.4 Hz, 1H, CHaHb–CO), 2.2–1.9 (m, 4H, H-5, H-6,
2
3
2J¼15.1 Hz, 1H, CHaHb–CO), 2.30 (dd, J¼15.1 Hz, J¼
3
3
6.6 Hz, 1H, CHaHb–CO), 2.01 (td, J¼7.4 Hz, J¼6.6 Hz,
1H, H-4a), 1.88–1.98 (m, 1H, H-5), 1.40–1.70 (m, 5H, H-
6, H-7, and H-50), 1.32–1.18 (m, 6H, CH2CH2CH2), 0.89
2
3
4
and H-4a), 1.53 (ddd, J¼12.2 Hz, J¼6.3 Hz, J¼1.8 Hz,
2
1H, H-7), 1.30 (d, J¼12.2 Hz, 1H, H-70), 1.03 (s, 3H,
(t, J¼7.2 Hz, 3H, CH3). 13C NMR (75.5 MHz, CDCl3) d:
CH3), 0.95 (d, 3J¼6.3 Hz, 3H, CHCH3). 13C NMR
(75.5 MHz, CDCl3) d: 173.6 (C]O), 75.2 (CH2–O), 45.5
(C-7), 43.7 (C-5), 42.8 (C-4a), 41.3 (C-7a), 34.5 (C-4),
32.7 (C-6), 26.0 (CH3), 18.6 (CHCH3). GC–MS (EI) m/z:
168 (M+, 1), 110 (6), 96 (M+ꢁCH2–CO2–CH2, 41), 81
(100), 79 (12), 55 (14), 42 (32), 41 (89), 29 (17).50
3
174.2 (C]O), 74.0 (CH2–O), 45.0 (C-7a), 41.8 (C-4a),
39.0 (CH2), 35.6 (C-7), 34.9 (C-5), 34.8 (C-4), 27.0 (CH2),
25.1 (C-6), 18.7 (CH2–CH3), 14.4 (CH3). MS (EI) m/z:
196 (M+, 20), 168 (M+ꢁCO, 16), 165 (8), 124 (M+ꢁCH2–
CO2–CH2, 100), 109 (8), 95 (30), 94 (46), 81 (40), 67
(56), 41 (20).50 HRMS (EI): calcd for C12H20O2 [M+]:
196.1464; found: 196.1463.
1
Data for minor exo-18e diastereomer: H NMR (300 MHz,
2
CDCl3) d: 3.92 (d, J¼11.4 Hz, 1H, CHaHbO), 3.90 (d,
4.3.9.3.
7a-Benzylhexahydrocyclopenta[c]pyran-
2J¼11.4 Hz, 1H, CHaHbO), 2.49 (dd, 2J¼14.6 Hz,
3J¼6.6 Hz, 1H, CHaHb–CO), 2.25 (dd, 2J¼14.6 Hz,
3J¼9.6 Hz, 1H, CHaHb–CO), 2.15–1.9 (m, 4H, H-5, H-6,
and H-4a), 1.70 (dd, 2J¼13.2 Hz, 3J¼6.3 Hz, 1H, H-7),
1.20 (m, 1H, H-70), 1.12 (s, 3H, CH3), 0.84 (d, 3J¼10.7 Hz,
3H, CHCH3). 13C NMR (75.5 MHz, CDCl3) d: 172.5
(C]O), 75.8 (CH2–O), 47.2 (C-7), 42.4 (C-4a), 42.2 (C-5),
42.1 (C-7a), 34.9 (C-4), 33.4 (C-6), 26.8 (CH3), 19.3
(CHCH3). GC–MS (EI) m/z: 96 (M+ꢁCH2–CO2–CH2, 32),
81 (97), 79 (10), 53 (16), 41 (100), 29 (11), 18 (4).50
3(1H)-one 18b. According to TP.7 above, hydrogenation
of d-lactone 17b (100 mg, 0.44 mmol) gave lactone 18b
(96.5 mg, 96%) as a light brown oil. Rf ¼0.53 (EE). IR
(CHCl3 solution): 2950, 1740, 1600, 1490, 1450, 1380,
1280, 1220, 1050, 820, 760, 700 cmꢁ1
.
1H NMR
(300 MHz, CDCl3) d: 7.32–7.19 (m, 5H, Ar–H), 4.11 (d,
2J¼11.5 Hz, 1H, CHaHbO), 3.85 (d, 2J¼11.5 Hz, 1H,
2
3
CHaHbO), 2.57 (dd, J¼14.9 Hz, J¼6.5 Hz, 1H, CHaHb–
2
3
CO), 2.32 (dd, J¼14.9 Hz, J¼7.7 Hz, 1H, CHaHb–CO),
3
3
2.21 (td, J¼7.7 Hz, J¼6.8 Hz, H-4a), 2.00–1.95 (m, 1H,
H-5), 1.90–1.75 (m, 1H, H-50), 1.7–1.50 (m, 2H, H-6),
1.40–1.30 (m, 2H, H-7). 13C NMR (75.5 MHz, CDCl3) d:
173.7 (C]O), 137.7 (Ar–Cipso), 130.7 (2ꢂAr–Cortho),
128.7 (2ꢂAr–Cmeta), 127.1 (Ar–Cpara), 72.8 (CH2–O),
46.2 (C-7a), 44.3 (CH2Ph), 41.8 (C-4a), 35.1, 35.0, and
4.3.9.6.
7a-Propylhexahydrocyclopenta[c]pyran-
3(1H)-one 18g. According to TP.7 above, hydrogenation
of d-lactone 17c (80 mg, 0.45 mmol) gave lactone 18g
(80.6 mg, 99%) as an oil. Rf¼0.20 (PE–EE 60:40). IR
(CHCl3 solution): 2960, 1750, 1450, 1390, 1300, 1200,
1
34.9 (3CH2: C-4, C-5, and/or C-7), 25.0 (C-6). MS (EI)
1100, 940 cmꢁ1. H NMR (300 MHz, CDCl3) d: 4.02 (d,
´
m/z: 230 (M+, 45), 170 (20), 139 (M+ꢁBn, 96), 129 (16),
115 (16), 95 (32), 91 (Bn+, 100), 81 (24), 67 (48), 41 (16).
HRMS (EI): calcd for C15H18O2 [M+]: 230.1307; found:
230.1305.
2J¼11.5 Hz, 1H, CHaHbO), 3.90 (d, 2J¼11.5 Hz, 1H,
CHaHbO), 2.52 (d, 2J¼15.0 Hz, 1H, CHaHb–CO), 2.29
(dd, 2J¼15.0 Hz, 3J¼6.6 Hz, 1H, CHaHb–CO), 2.03 (td,
3
3J¼7.7 Hz, J¼6.6 Hz, 1H, H-4a), 1.86–1.96 (m, 1H, H-
5), 1.45–1.70 (m, 4H, H-6, H-7, and H-50), 1.24–1.40 (m,
3
4.3.9.4.
7a-Methylhexahydrocyclopenta[c]pyran-
5H, CH2CH2 and H-70), 0.89 (t, J¼7.1 Hz, 3H, CH3). 13C
3(1H)-one 18d. According to TP.7 above, hydrogenation
of d-lactone 17d (100 mg, 0.66 mmol) gave lactone 18d
(98.8 mg, 98%) as a colorless oil. Rf¼0.26 (PE–EE 60:40).
NMR (75.5 MHz, CDCl3) d: 174.0 (C]O), 73.6 (CH2–O),
44.7 (C-7a), 41.5 (C-4a), 41.4 (CH2–CH2CH3), 35.3 (C-7),
34.6 (C-5), 34.5 (C-4), 24.8 (C-6), 17.7 (CH2–CH3), 14.8
(CH3). MS (EI) m/z: 182 (M+, 12), 164 (3), 151 (6), 123
(9), 110 (M+ꢁCH2–CO2–CH2, 100), 95 (16), 81 (35), 67
(87).50 HRMS (EI): calcd for C11H18O2 [M+]: 182.1307;
found: 182.1309.
IR (neat): 2940, 1740, 1280, 1050 cmꢁ1
.
1H NMR
2
(300 MHz, CDCl3) d: 3.96 (d, J¼11.4 Hz, 1H, CHaHbO),
2
2
3.90 (d, J¼11.4 Hz, 1H, CHaHbO), 2.55 (dd, J¼15.1 Hz,
3J¼6.3 Hz, 1H, CHaHb–CO), 2.26 (dd, 2J¼15.1 Hz,
3J¼5.9 Hz, 1H, CHaHb–CO), 1.90–2.20 (m, 2H, H-5 and
H-4a), 1.20–1.70 (m, 5H, H-50, H-6, and H-7), 1.06 (s, 3H,
CH3). 13C NMR (75.5 MHz, CDCl3) d: 173.7 (C]O),
75.3 (CH2–O), 42.5 (C-4a), 41.3 (C-7a), 37.7 (C-7), 34.9
(C-5), 34.5 (C-4), 25.9 (CH3), 24.7 (C-6). MS (EI) m/z:
154 (M+, 1), 96 (6), 82 (M+ꢁCH2–CO2–CH2, 100), 67 (6),
53 (19), 39 (72), 27 (29).50 Anal. Calcd for C9H14O2: C,
70.10; H, 9.15; found: C, 69.56; H, 9.14.
4.3.10. Synthesis of bicyclic d-lactones 20 and 21.
4.3.10.1. Ethyl 1-benzyl-2-oxocyclohexanecarboxylate
8. Rf¼0.40 (PE–EE 70:30). IR (neat): 3068, 3063, 3029,
1
2941, 1713, 1496, 1453, 1187 cmꢁ1. H NMR (300 MHz,
3
CDCl3) d: 7.12–7.34 (m, 5H, Ar–H), 4.09 (q, J¼7.1 Hz,
2
2H, OCH2CH3), 3.31 (d, J¼13.7 Hz, 1H, CHaHbPh), 2.88
2
(d, J¼13.7 Hz, 1H, CHaHbPh), 2.43 (m, 3H, H-3 and H-
6), 2.01 (m, 1H, H-60), 1.57 (m, 4H, H-4 and H-5), 1.17 (t,
3J¼7.1 Hz, 3H, CH2CH3). 13C NMR (75.5 MHz, CDCl3)
d: 215.0 (C]O), 171.0 (O–C]O), 136.7 (Ar–Cipso), 130.4
(2ꢂAr–Cortho), 128.8 (2ꢂAr–Cmeta), 126.7 (Ar–Cpara),
62.2 (C-1), 61.2 (OCH2CH3), 41.3 (C-3), 40.5 (C-6), 36.0
(CH2Ph), 27.6 (C-5), 22.6 (C-4), 14.0 (CH3).
4.3.9.5. 6,7a-Dimethylhexahydrocyclopenta[c]pyran-
3(1H)-one 18e. According to TP.7 above, hydrogenation
of d-lactone 17e (200 mg, 1.2 mmol) gave lactone 18e
(198.2 mg, 98%) as a colorless oil. GC (100 ꢀC+10 ꢀC/
min): endo–exo¼80:20; endo (443 s), exo (452 s). Rf¼0.30
(PE–EE 60:40). IR (neat): 2970, 1750, 1450, 1050, 850,
810 cmꢁ1. Anal. Calcd for C10H16O2: C, 71.39; H, 9.59;
found: C, 71.52; H, 9.84.
4.3.10.2. Ethyl 1-benzyl-(2,2-ethylenedioxy)cyclohex-
anecarboxylate 9. With a procedure similar to TP.1 above,