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Helvetica Chimica Acta Vol. 87 (2004)
frequencies on dilution, 1 H, OH); 1.29, 1.09 (2s, 3 H, Me(17)); 0.86 (3 H), 0.81 (6 H) (2s, Me(18), Me(19),
.
Me(20)). 13C-NMR: Table. EI-MS (70 eV): 252 (8, M ), 237 (100).
8a-Hydroxy-13,14,15,16-tetranorlabdan-12-al ( [(1R,2R,4aS,8aS)-Decahydro-2-hydroxy-2,5,5,8a-tetra-
methylnaphthalen-1-yl]ethanal; open-chain form of lactol 13): 1H NMR: 9.72 (ill-resolved q, w1/2 4.5,
HÀCO); remaining signals undistinguishable from those of the lactol. 13C-NMR: 203.6 (C(12)); 72.9 (C(8));
55.8 (C(9)); 55.5 (C(5)); 44.2 (C(7)); 41.6 (C(3)); 40.0 (C(1)); 38.0 (C(10)); 33.1 (C(18)); 33.0 (C(4)); 30.8
(C(11)); 23.6 (C(17)); 21.3 (C(19)); 20.3 (C(6)); 18.2 (C(2)); 15.5 (C(20)).
9. Reaction of Acetate 9 with Peracetic Acid: Bis(8a,12-epoxy-13,14,15,16-tetranorlabdan-12-yl) Peroxide
((3aR,3'aR,5aS,5'aS,9aS,9'aS,9bR,9'bR)-2,2'-Dioxybis[dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]fur-
an]; 14). To a stirred soln. of (12S)-9 (2.7 g, 9.2 mmol) in AcOEt (10 ml) at 158 was added dropwise AcOOH
(3.7 g, 18.4mmol). After 2 h stirring at 15 8, H2O was added, and the resulting mixture was extracted with Et2O.
The combined org. layer was washed with 10% aq. Na2CO3 soln., H2O, and brine, dried (Na2SO4), and
evaporated and the crude white solid (2.4g) subjected to HPLC analysis: peroxide 14 (15%), hydroperoxide 12
(50%), and sclareolide (3; 30%). Peroxide 14 (mixture of stereoisomers) was isolated by FC (hexane/Et2O
95 :5).
When the same experiment was run at 458, the product (2.3 g) was (by HPLC, 1H- and 13C-NMR) a ca. 3 :1
mixture of 3 and 12 (the (12R)-epimer being the most abundant).
Data of 14 (mixture of 12,12'-stereoisomers): Solid. 1H-NMR (400 MHz): 5.76, 5.73, 5.66 (d (J 6.4), t (J
5.9), t (J 5.9), HÀC(12,12')); 1.29, 1.27, 1.13 (3s, Me(17,17')); 0.86, 0.82 (s, br. s, Me(18,18'), Me(19,19'),
Me(20,20')). 13C-NMR: 107.5, 106.1, 105.7 (C(12,12')); 83.8, 81.9, 81.7 (C(8,8')); 60.0, 59.7, 57.2 (C(9,9')); 56.9,
56.9, 56.8 (C(5,5'); 42.3 (C(3,3')); 40.1, 39.9, 39.8 (C(7,7')); 39.6, 39.6, 39.5 (C(1,1')); 36.1, 36.0, 35.9 (C(10,10'));
33.4, 33.4, 32.9 (C(4,4')); 33.0 (C(18,18')); 28.3, 27.7, 27.5 (C(11,11')); 23.4, 23.2, 22.9 (C(17,17')); 20.9 (C(19,19'));
20.9, 20.7, 20.3 (C(6,6')); 18.2 (C(2,2')); 15.1, 15.0 (C(20,20')). LSI-MS (35 keV; 3-nitrobenzyl alcohol matrix):
503 (46, [M H] ), 525 (13, [M Na] ), 1027 (10, [M M Na] ).
10. Reaction of Oxy Ketone 4 with Peracetic Acid. Powdered (12R)-4 (2.8 g, 10 mmol) was impregnated with
a small part of a 8-g (40 mmol) amount of AcOOH. A reaction was not long in starting as evidenced by the rapid
rise in temp. While stirring gently, the remainder of the AcOOH was then added at a rate such that the temp. was
maintained at 50 558. About 5 min after the end of the addition, the temp. fell and, because the mixture was
nearly solid, stirring was stopped. The mixture was kept overnight at r.t. and then partitioned between H2O
(50 ml) and Et2O (50 ml). The org. layer was washed with 10% aq. Na2SO3 soln., 10% aq. Na2CO3 soln., and
1
brine, dried (Na2SO4), and evaporated; white solid (2.1 g) consisting (by HPLC, H- and 13C-NMR) of a ca.
70 :30 mixture of sclareolide (3) and hydroperoxide 12 (the (12R)-epimer being the most abundant).
11. Eliminative Coupling of Acetate 9: Bis(8a,12-epoxy-13,14,15,16-tetranorlabdan-12-yl) Ether
((3aR,3'aR,5aS,5'aS,9aS,9'aS,9bR,9'bR)-2,2'-oxybis[dodecahydro-3a,6,6,9a-tetramethylnaphtho[2,1-b]furan];
16). Crude freshly prepared (12S)- or (12R)-9 (0.9 g, 3 mmol) was set aside at r.t. in a stoppered flask. The
evolution of this chemical was observed every second day by 1H-NMR. As the days went by, the typical signals of
9 were vanishing; after ca. 20 days, they ceased to be detectable. FC (hexane/Et2O 9 :1) of the solid flask content
(0.75 g) gave (12R,12'R)-16 as a white solid (0.6 g). (12S,12'S)- and (12R,12'S)-16 were tentatively identified by
NMR in the product prior to FC.
Data of (12R,12'R)-16: Solid. M.p. 1688 ([26]: m.p. 160 1768 after chromatography before recrystalliza-
tion). IR (KBr): 2925, 2860, 2843, 1461, 1381, 1337, 1219, 1130, 1073, 1042, 999, 965, 945, 886; the spectrum
matched the one presented by Stoll and Hinder [26]. 1H-NMR: 5.43 (q, J 6.0, 5.4, 2 H, HÀC(12,12')); 1.22
(s, 6 H, Me(17,17')); 0.86 (12 H), 0.92 (6 H) (2s, Me(18,18'), Me(19,19'), Me(20,20')). 13C-NMR: Table. EI-MS
.
(70 eV): 486 (0.2, M ), 191 (100). HR-MS: 486.40425 (C32H54O3 ; calc. 486.40730).
Data of (12S,12'S)-16: 1H-NMR (distinctive signals): 5.39 (d, J 6.0, 2 H, HÀC(12,12')). 13C-NMR
(distinctive signals): 100.3 (C(12,12')); 82.6 (C(8,8')).
Data of (12R,12'S)-16: 1H-NMR (distinctive signals): 5.34( d, J 5.6, 1 H, HÀC(12')); 5.25 (q, J 6.0, 5.2,
1 H, HÀC(12)). 13CNMR (distinctive signals): 102.4(C(12)); 101.9 (C(12 ')); 82.5 (C(8')); 81.5 (C(8)).
12. Hydrolysis of Lactol Anhydride 16. A soln. of lactol anhydride 16 (0.5 g, 1.0 mmol) in 1,4-dioxane
(20 ml) was treated with 10% H2SO4 soln. (7 ml) and heated at 458 for two days. The solvent was evaporated,
and Et2O was added. The mixture was washed with 10% aq. Na2CO3 soln., H2O, and brine, dried (Na2SO4), and
evaporated and the residual waxy solid (0.4g) subjected to FC: unreacted 16 (0.2 g, 0.4mmol; with pentane/
Et2O 9 :1 ! 4:1) and 13 as epimer mixture (0.15 g, 0.6 mmol; with pentane/Et2O 1 :1 from the last fractions).
13. Hydrolysis of Acetate 9. To a soln. of (12S)-9 (1.0 g, 3.4mmol) in AcOEt (5 ml) were added AcOH
(1.5 ml) and H2O (0.5 ml). The reaction at r.t. was monitored by 1H-NMR. After 20 h, ca. 90% of 9 was
hydrolyzed into lactol 13. The remaining acetate 9 was epimerized but no lactol anhydride 16 could be detected.