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ELVETICA
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ACTA – Vol. 88 (2005)
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(+)-(1S,2R)-6 (708.1 mg, 95%) with a cis/trans (=(1S,2R)/(1R,2R)) ratio of 88 :12 (1H-NMR). ½aꢃD23 =+10.7
(c=1.09, MeOH; 99.1% ee4)). 1H-NMR (H,H-COSY, H,C-COSY, DEPT; CDCl3, 300 MHz): cis-6: 0.88 (t,
J=6.3, Me(5’’)); 1.09–2.03 (m, 7 CH2, HꢁC(2)); 1.33 (s, MeꢁC(2’)); 3.25 (s, HꢁC(5)); 3.88–3.99 (m, 2
CH2O); trans-6: 0.88 (t, J=6.3, Me(5’’)); 1.09–2.32 (m, 7 CH2, HꢁC(2)); 1.33 (s, MeꢁC(2’)); 3.22 (s, Hꢁ
C(5)); 3.88–3.99 (m, 2 CH2O). 13C-NMR (H,C-COSY, DEPT; CDCl3, 75 MHz): cis-6: 14.0 (q, Me(5’’)); 22.5
(t, C(4’’)); 24.2 (q, MeꢁC(2’)); 24.7, 27.1, 27.6, 29.2, 31.9, 38.5 (6t, CH2); 36.5 (d, C(2)); 61.9 (d, C(5)); 64.3,
64.6 (CH2O); 69.3 (C(1)); 110.0 (C(2’)). trans-6: 14.0 (q, Me(5’’)); 22.5 (t, C(4’’)); 24.3 (q, MeꢁC(2’)); 24.6,
24.9, 25.6, 28.9, 32.1, 38.3 (6t, CH2); 35.8 (d, C(2)); 62.2 (d, C(5)); 64.3, 64.8 (CH2O); 69.4 (C(1)); 110.17
(C(2’)). GC/MS (injector temp. 2508 temp. program: 508 for 1 min, heating at a rate of 208/min, 2508 for 10
min): tR 10.34 ((1’R)-5), 11.1 ((+)-(1S,2R)-65)). HR-EI-MS: 254.1855 (M+, C15H26Oþ3 ; calc. 254.1882). Anal.
calc. for C15H26O3 (254.37): C 70.83, H 10.30; found: C 70.58, H 10.29.
(ꢁ)-(1R,2S)-2-[(2-Methyl-1,3-dioxolan-2-yl)methyl]-1-pentyl-6-oxabicyclo[3.1.0]hexane ((ꢁ)-(1R,2S)-6).
As described for (+)-(1S,2R)-6, from (ꢁ)-(1’S)-5. ½aꢃ2D2 =ꢁ12.5 (c=1.08, MeOH; 98.7% ee4)).
(+)-(2S,3R)-3-(2-Oxopropyl)-2-pentylcyclopentanone (=(2S,3R)-Magnolione®; (+)-(2S,3R)-1). Under Ar,
(Ph3C)BF4 (28.0 mg, 0.09 mmol) was added to a cold (08) soln. of (+)-(1S,2R)-6 (391.3 mg, 1.538 mmol; contain-
ing (1R,2R)-6) in dry CH2Cl2 (50 ml). The resulting deep red soln. was stirred at 08 for 4 h (GC/MS: complete
conversion). Sat. aq. NaHCO3 soln. (60 ml) was then added. The mixture was stirred for 1 h at r.t., and extracted
with Et2O (3×100 ml). The combined org. layers were washed with brine (1×100 ml) and evaporated. A soln. of
the residue in petroleum ether/Et2O 7:3 was filtered through a pad of silica gel, and the filtrate was evaporated.
The resultant pale yellow oil was dissolved in 50% aq. AcOH (10 ml) and the soln. stirred at r.t. for 2 h (TLC
(petroleum ether/Et2O 7 :3; phosphomolybdic acid): complete conversion; Rf 0.15). The mixture was treated
with sat. aq. K2CO3 soln. until pH 8–10 was reached and extracted with Et2O (3×50 ml). The combined org.
phase was dried (Na2SO4), and evaporated and the crude product subjected to FC (silica gel, pentane/Et2O
7 :3) and bulb-to-bulb distillation: (+)-(2S,3R)-1/(2R,3R)-1 (140.4 mg, 43% over both steps) as a colorless oil
with a cis/trans (=2S,3R)/(2R,3R)) ratio 78 :22 (GC). The isomers were separated by prep. HPLC silica gel
(5 m; 21×250 mm), hexane/i-PrOH 95 :5, flow 20 ml/min, det. at 254 nm; tR 9 ((+)-(2S,3R)-1), 10 (2R,3R)-1)
to afford (2R,3R)-Magnolione® ((2R,3R)-1; trans/cis 98 :2 by GC/MS) and (2S,3R)-Magnolione® ((+)-(2S,
3R)-1; cis/trans 91:9 by GC/MS).
Anal. HPLC (silica gel (Eurosphere 80-5, 5 m, 5×250 mm), hexane/i-PrOH 95 :5, flow 0.5 ml/min, det. at
280 nm): tR 17.68 ((+)-(2S,3R)-1), 19.50 ((2R,3R)-1). GC (injector temp. 2008; temp. program: 1608 for 15
min, heating at a rate of 108/min, 1808 for 10 min): tR 15.5 ((2R,3R)-1), 16.7 ((+)-(2S,3R)-1). ½aꢃ2D5 =+43.9
(c=1.14, MeOH; 99.1% ee4); cis/trans 78 :226)). 1H-NMR (H,H-COSY, H,C-COSY, DEPT; CDCl3, 500
MHz): cis-(2S,3R): 0.85–0.88 (m, Me(5’’)); 1.11–1.41 (m, 3 CH2, HaꢁC(4)); 1.48–1.60 (m, HbꢁC(4)); 1.68–
1.75 (m, HaꢁC(1’’)); 1.96–2.04 (m, HbꢁC(1’’)); 2.08–2.38 (m, 1 CH2, HaꢁC(1’), HꢁC(2)); 2.16 (s, MeC=O);
2.42–2.49 (m, HbꢁC(1’)); 2.81–2.87 (m, HꢁC(3)); trans-(2R,3R): 0.85–0.88 (m, Me(5’’)); 1.21–1.41 (m, 3
CH2, HaꢁC(4)); 1.48–1.60 (m, 1 CH2); 1.68–1.75 (m, HꢁC(2)); 2.08–2.38 (m, 1 CH2, HbꢁC(4), HꢁC(3));
2.17 (s, MeC=O); 2.42–2.49 (m, HaꢁC(1’)); 2.74 (dd, J=16.9, 4.0, HbꢁC(1’)). 13C-NMR (H,C-COSY, DEPT;
CDCl3, 75 MHz): cis-(2S,3R): 14.0 (q, Me(5’’)); 22.4 (t, C(4’’)); 24.8, 25.7, 27.1 (3t, CH2); 30.4, (q, MeC=O);
31.8 (t, CH2); 34.36 (d, C(3)); 35.2 (t, C(5)); 42.7 (t, C(1’)); 52.4 (d, C(2)); 207.4 (C(2’)=O); 219.60, (C(1)=
O); trans-(2R,3R): 14.00 (q, Me(5’’)); 22.42 (t, C(4’’)); 26.38, 27.37, 27.88 (3t, CH2); 30.48 (q, MeC=O); 32.06
(t, CH2); 36.91, (d, C(3)); 37.72 (t, C(5)); 48.40 (t, C(1’)); 54.16 (d, C(2)); 207.42 (C(2’)=O); 219.84 (C(1)=
O). GC/MS (injector temp. 2508; temp. program: 508 for 1 min, heating at a rate of 208/min, 2508 for 10
min): tR 10.06 ((2R,3R)-1), 10.14 ((+)-(2S,3R)-1). HR-EI-MS: 210.1624 (M+, C13H22O2þ; calc. 210.1620). Anal.
calc. for C13H22O2 (210.31): C 74.245, H 10.54; found: C 74.24, H 10.72.
(ꢁ)-(2R,3S)-3-(2-Oxopropyl)-2-pentylcyclopentanone (=(2R,3S)-Magnolione®; (ꢁ)-(2R,3S)-1). As descri-
bed for (+)-(2S,3R)-1, from (ꢁ)-(1R,2S)-6. Prep. HPLC gave (2S,3S)-Magnolione® ((2S,3S)-1; trans/cis 98 :2 by
GC/MS) and (2R,3S)-Magnolione® ((ꢁ)-(2R,3S)-1; cis/trans by GC/MS). ½aꢃD23 =ꢁ37.0 (c=0.96, MeOH; 98.7%
ee4); cis/trans (=(2R,3S)/(2S,3S)) 66 :347)). ½aꢃD23 =ꢁ43.6 (c=1.33, CHCl3 ; 98.7% ee; cis/trans 53 :477)) ([7]:
½aꢃ2D0 =+22.0, CHCl3; 76% ee, (2S,3S)-6 (trans)).
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The cis- and trans-isomer were not separated.
The cis/trans-isomer (=(2S,3R)/(2R,3R)) ratio was determined by GC analysis immediately before meas-
urement of the optical rotation.
The cis/trans-isomer (=(2R,3S)/(2S,3S)) ratio was determined by GC analysis immediately before measure-
ment of the optical activity.
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