Enantioselective Synthesis of Octane-1,3,7-triol
J ournal of Natural Products, 1999, Vol. 62, No. 1 39
published method21 using 80% aqueous acetic acid or by the
following procedure:23 (S)-1,2-O-Isopropylidene-4-O-benzylbu-
tane-1,2,4-triol (31.4 g, 133 mmol) and freshly prepared strong
acidic cation exchanger Dowex 50 (H+ form) suspended in
MeOH (300 mL) were stirred at room temperature. Dowex
50 was replaced daily by fresh material. After 3 d, Dowex 50
was filtered off and the solvent was removed in vacuo. Flash
chromatography with Et2O-MeOH (15:1) yielded 48% of (R,S)-
and (S)-4-O-benzylbutane-1,2,4-triol: Rf 0.3 (Et2O); tR ) 2975;
99 (4), 67 (4); ESI-MS m/z 343 [M + H]+ (100), 360 [M + NH4]+
(20); MS/MS of m/z 343, 235 [M - C7H7OH]+ (100), 181 (60),
143 (40), 128 (38), 91 (35), 217 (20), 99 (12), 325 [M + H -
H2O]+ (5), 199 (5), 157 (5); anal. C 77.49%, H 8.92%, calcd for
C22H30O3, C 77.16%, H 8.83%.
(3R,7R,S)-, (3R,S,7R)-, a n d (7R,3R)-Oct a n e-1,3,7-t r iol
((3R,7R,S)-3, (3R,S,7R)-3, a n d (7R,3R)-3). A mixture of 20
(1.17 g, 3.42 mmol) and 120 mg of 10% Pd/C in 22 mL of EtOH
was hydrogenated26 at room temperature and 73 psi for 24 h.
The reaction mixture was filtered over Celite and concentrated
[R]25 +4.3° (c 2.50, CHCl3);37 1H NMR data were identical to
D
those in the literature;21 13C NMR (CDCl3, 100 MHz) δ 137.9
(CH2C(C5H5)), 128.4, 127.8, 127.7 (CH2C(C5H5)), 73.3 (CH2C6-
H5), 71.2 (C-2), 68.1 (C-1), 66.6 (C-4), 32.9 (C-3); EIMS m/z 91
(100), 107 (38), 65 (20), 79 (19), 92 (15), 178 [M - H2O]+ (1),
177 (1), 196 [M]+ (<1).
in vacuo (colorless, viscous liquid) (95%): (3R,7R,S)-3, [R]25
)
D
-3.6° (c 1.49, CHCl3); (3R,S,7R)-3, [R]25 ) -7.6° (c 2.79,
D
CHCl3); (7R,3R)-3, [R]25 ) -14.44° (c 5.76, CHCl3). All
D
spectral data (IR, H NMR, 13C NMR, LC-MS) corresponded
1
well with the data obtained for the natural product.
(3R,7R,S)-, (3R,S,7R)-, a n d (7R,3R)-Tr i-O-a cetylocta n e-
1,3,7-tr iol ((3R,7R,S)-4, (3R,S,7R)-4, a n d (7R,3R)-4). Acety-
lation of the triol was performed according to the literature.9
Dia-3 (17 mg, 0.1 mmol) and acetic anhydride (300 mg, 2.9
mmol) were dissolved in pyridine (200 mg, 2.5 mmol) and kept
overnight. The product was purified by preparative TLC with
Et2O (95%): Rf 0.73 (Et2O); tR 2496; IR (KBr) νmax 2920 (CH),
(R,S)- a n d (R)-1,2-Dich lor o-4-O-ben zylbu ta n -4-ol (r a c-
16 a n d (R)-16), (R,S)- a n d (S)-1-Ch lor o-4-O-ben zylbu ta n e-
2,4-d iol (r a c-17 a n d (S)-17), a n d (R,S)- a n d (R)-2-Ch lor o-
4-O-ben zylbu tan e-1,4-diol (r a c-18 an d (R)-18). Compounds
16-18 were prepared according to the published procedure.24
Separation of undesired 16 was achieved by flash chromatog-
raphy with pentane-Et2O (1:1) to give 43% of 17 and 18. IR
and 1H and 13C NMR data of 16-18 were identical to those
previously published.24 16: Rf 0.77 (pentane-Et2O (1:1)); tR
2404; EIMS m/z 91 (100), 65 (36), 79 (31), 92 (25), 89 (20), 77
(14), 127/125 (12), 107 (12), 234/232 [M]+ (1). 17: Rf 0.41
(pentane-Et2O (1:1)); tR 2648; EIMS m/z 91 (100), 107 (88),
65 (28), 92 (15), 77 (13), 55 (11), 214/216 [M]+ (1). 18: Rf 0.30
(pentane-Et2O (1:1)); tR 2744; EIMS m/z 91 (100), 107 (85),
92 (28), 65 (25), 79 (24), 77 (12), 55 (11), 214/216 [M]+ (1).
1
1720 (CdO), 1360, (OCOCH3), 1230, 1010; H NMR (CDCl3,
400 MHz) δ 4.97 (1H, m, C-7H), 4.87 (1H, m, C-3H), 4.08 (2H,
t, J ) 6.5 Hz, C-1H2), 2.04 (6H, s, COCH3), 2.02 (3H, s,
COCH3), 1.86 (2H, m, C-2H2), 1.25-1.72 (6H, m, C-4H2, C-5H2,
C-6H2), 1.20 (3H, d, J ) 6 Hz, C-8H); 13C NMR (CDCl3, 100
MHz) δ 170.9, 170.6, 170.5 (3 CH3CO), 70.9 (C-3), 70.6 (C-7),
60.8 (C-1), 35.6 (C-2), 34.0 (C-6), 33.1 (C-4), 19.8 (C-8), 21.1
(C-5), 21.3, 21.1, 20.8 (3 CH3CO); EIMS m/z 43 (100), 99 (74),
93 (60), 81 (56), 108 [M - 3AcOH]+ (55), 79 (48), 54 (41), 67
(39), 117 (34), 126 (17), 159 (15), 171 (6), 168 [M - 2AcOH]+
(6), 185 (5), 213 (2), [M]+ (<1); anal. C 57.93%, H 8.51%, calcd
for C14H24O6, C 58.32%, H 8.39%.
(R,S)- a n d (S)-1,2-Ep oxy-4-O-ben zylbu ta n -4-ol (r a c-19
a n d (S)-19). The mixture of monochloro alcohols was con-
verted to the oxirane as described.24 The residue was purified
by flash chromatography with pentane-Et2O (1:1) (99%): Rf
0.42 (pentane-Et2O (1:1)); tR 2138; [R]25 -13.9° (c 2.75,
D
Ack n ow led gm en t. This work was supported by the Deut-
sche Forschungsgemeinschaft, Bonn (Schw 634/1-1 and Schw
634/1-2). The support of Dr. P. Brunerie, Pernod Ricard, Centre
de Recherche, Cre´teil, France, who kindly provided apples cv.
Peau de Chien, is greatly acknowledged. We thank B. Pink
and M. Lazarus for the NMR, B. Boss for chiral GC measure-
ments, and E. Richling for the HPLC-MS analysis.
CHCl3);24,38 spectral data (IR, 1H NMR, 13C NMR) were as
previously reported;24 EIMS m/z 91 (100), 107 (28), 105 (21),
79 (20), 65 (12), 177 [M]+ (6), 159 [M - H2O]+ (5), 150 (4), 132
(4), 147 (3).
(3R,7R,S)-, (3R,S,7R)-, a n d (3R,7R)-1,7-Di-O-ben zyloc-
ta n e-1,3,7-tr iol ((3R,7R,S)-20, (3R,S,7R)-20, a n d (3R,7R)-
20). (3R,7R,S)-20 was prepared from (R,S)-12 and (S)-19,
(3R,S,7R)-20 was synthesized from (R)-12 and (R,S)-19, and
(3R,7R)-20 was prepared from (R)-12 and (S)-19 by the
following modified procedure:26,28 Magnesium (0.35 g, 14.4
mmol) and (R,S)-12 or (R)-12 (2.76 g, 11.4 mmol) were
dissolved in 10 mL of absolute Et2O, and the solution was
gently warmed until reaction commenced. The reaction
Refer en ces a n d Notes
(1) Frankenfeld, J . W.; Karel, M.; Labuza, T. P.; Sinskey, A. J . United
States Patent, 3,806,615, Apr 23, 1974.
(2) Wright, D. L.; Frankenfeld, J . W. United States Patent, 3,836,672,
Sep 17, 1974.
(3) Frankenfeld, J . W.; Mohan, R. R.; Squibb, R. L. United States Patent,
3,773,518, Nov 20, 1973.
(4) Frankenfeld, J . W.; Karel, M.; Labuza, T. P. United States Patent,
3,732,112, May 8, 1973.
(5) Akedo, M.; Sinskey, A. J .; Gomez, R. J . Food Sci. 1977, 42, 699-706.
(6) Dymsza, H. A. Fed Proc. 1975, 34, 2167-2170.
(7) Brule´, G. Ann. Technol. Agric. 1973, 22, 45-58.
(8) Yajima, I.; Yanai, T.; Nakamura, M.; Sakakibara, H.; Hayashi, K.
Agric. Biol. Chem. 1984, 48, 849-855.
(9) Schwab, W.; Scheller, G.; Gerlach, D.; Schreier, P. Phytochemistry
1989, 28, 157-160.
(10) Beuerle, T.; Schreier, P.; Schwab, W. Nat. Prod. Lett. 1997, 10, 119-
124.
mixture was refluxed for 1 h and then cooled to -78 °C.
A
solution of Li2CuCl4 (2.53 mL of 0.1 M) in THF was introduced
into the reaction mixture. After a further 1 h of stirring, (R,S)-
19 or (S)-19 (1.35 g, 7.58 mmol) in 15 mL of absolute Et2O
was added dropwise. The mixture was stirred at -78 °C for
an additional 3 h and was then allowed to warm to room
temperature overnight. The reaction mixture was quenched
with cold (0 °C) saturated aqueous NH4Cl (50 mL). The
organic layer was separated, and the aqueous layer was
extracted 3× with 25 mL of Et2O. The combined organic layer
was dried (Na2SO4) and concentrated. The residue was
purified by flash chromatography with pentane-Et2O (6:4) on
silica gel (62%): Rf 0.45 (pentane-Et2O (6:4)); tR 2672 (DB-5);
(11) Beuerle, T.; Schreier, P.; Brunerie, P.; Bicchi, C.; Schwab, W.
Phytochemistry 1996, 43, 145-149.
(12) Berger, R. G.; Dettweiler, G. R.; Drawert, F. Dt. Lebensm.-Rundschau
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(13) Beuerle, T.; Schwab, W. Phytochemistry 1997, 45, 1153-1155.
(14) Taber, D. F.; Amedio, J . J .; Raman, K. J . Org. Chem. 1988, 53, 2984-
2990.
(3R,7R,S)-20, [R]25D +5.6° (c 2.85, CHCl3); (3R,S,7R)-20, [R]25
D
-13.0° (c 3.52, CHCl3); (3R,7R)-20, [R]25D -5.5° (c 3.92, CHCl3);
IR (KBr) νmax 3425 (OH), 3040 (CdCH), 3010 (CdCH), 2910
(CH), 2840 (CH), 1440, 1360, 1190, 1080 (C-O), 720, 690; 1H
NMR (CDCl3, 400 MHz) δ 7.26-7.35 (10H, m, C6H5), 4.44-
4.59 (4H, m, CH2-C6H5), 3.81 (1H, m, C-7H), 3.62-3.75 (2H,
m, C-1H2), 3.52 (1H, m, C-3H), 1.74 (2H, m, C-2H2), 1.30-
1.65 (6H, m, C-4H, C-5H, C-6H), 1.20 (3H, d, J ) 6.3 Hz,
C-8H); 13C NMR (CDCl3, 100 MHz) δ 139.2 and 138.0 (OCH2-
C(C5H5)), 127.0-128.4 (OCH2C(C5H5)) 74.8 and 73.3 (OCH2-
C6H5), 71.2 (C-7), 70.3 (C-3), 69.2 (C-1), 37.5 (C-2), 36.6 (C-4),
36.5 (C-6), 21.5 (C-8), 19.8 (C-5); EIMS m/z 91 (100), 92 (13),
65 (13), 107 (9), 109 (7), 79 (7), 77 (6), 55 (5), 110 (4), 105 (4),
(15) Tsuji, J .; Nagashima, H.; Nemoto, H. Org. Synth. 1984, 62, 9-13.
(16) Tsuji, J . Synthesis 1984, 369-384.
(17) The changed stereochemical descriptor at C-7 is due to the changing
substituent priorities according to the Cahn-Ingold-Prelog system,
not to an inversion of stereochemistry.
(18) Na´jera, C.; Yus, M.; Seebach, D. Helv. Chim. Acta 1984, 67, 289-
300.
(19) Voss, G.; Gerlach, H. Helv. Chim. Acta 1983, 66, 2294-2307.
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(21) Martin, J . C.; Smee, D. F.; Verdeyden, J . P. H. J . Org. Chem. 1985,
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