1934
L. Ferrié et al.
LETTER
Mes
N
N Mes
b
OTBS
=[Ru] cat A
Cl
Cl
i-PrO
Ru
COOH
97%
Me
8
OAc
TBSO
Me
TBSO
Me
OAc
c
e
f
OH
OTBS
OTBS
d
a
COOMe
89%
Me
92%
90%
82%
77%
Me
Me
O
11
9
6
7
10
COOMe
OTBS
O
O
OH
O
O
HO
Me
OTBS
g
i
h
TBSO
HO
Me
COOMe
Me
80%
84%
73%
COOMe
Me
COOMe
Me
O
O
15
12
14
13
O
O
O
COOMe
OH
COOH
OH
O
O
O
HO
HO
m
O
O
O
O
j
k
l
Me
Me
Me
Me
76%
72%
95%
58%
16
17
18
Me
Me
O
Me
Me
O
O
O
O
O
O
O
colletodiol
Scheme 2 a) TBSCl (1.05 equiv), Et3N (2 equiv), DMAP (0.2 equiv), CH2Cl2, 24 h, r.t.; b) [Ru] cat A (3 mol%), acrylic acid (3 equiv),
CH2Cl2; c) O3, CH2Cl2, –78 °C; then Et3N (2 equiv), r.t., 2 h; d) allylMgCl, 30 min, THF, –20 °C; then in situ Ac2O (5 equiv), pyridine (5 equiv),
8 h, r.t.; e) [Ru] cat A (3 mol%), methyl acrylate (5 equiv), CH2Cl2; f) DBU (1.1 equiv), DME 16 h, r.t.; g) modified AD-mix b, OsO4 (2 mol%),
(DHQD)2PHAL (4 mol%), MeSO2NH2 (1 equiv), K3Fe(CN)6 (3 equiv), K2CO3 (3 equiv), t-BuOH–H2O; h) PPTS (1.2 equiv), MeOH, 24 h,
r.t.; then dimethoxypropane (10 equiv) and p-toluenesulfonic acid (5 mol%); i) 2,4,6-trichlorobenzoyl chloride (1.7 equiv), Et3N (3 equiv),
carboxylic acid 8 (1.5 equiv) in Et2O, 2 h, r.t., filtration and evaporation of the solvent, then addition of 14 in toluene, 90 °C, 3.5 h; j) TBAF
(5 equiv), PhCOOH (5 equiv), THF–H2O, 96 h, r.t.; k) LiOH (1.2 equiv), THF–H2O, 16 h; l) DCC (5 equiv), DMAP (5 equiv), CH2Cl2, reflux,
12 h; m) Dowex 50W-8H+ resin, MeOH, reflux, 8 h.
compound 9 was first treated with allylmagnesium PhCO2H, THF–H2O, 96 h), the hydroxy ester 16 was iso-
chloride in THF at –20 °C and after 30 minutes, the inter- lated in 95% yield and then saponified [LiOH, 1.2 equiv),
mediate alkoxide was trapped in situ by addition of acetic THF–H2O, 16 h, r.t.] to produce the hydroxy acid 17 in
anhydride (3 equiv) and pyridine (3 equiv).
82% yield. Following the known procedure for
macrolactonization8 (DCC/DMAP/CH2Cl2, reflux), 17
was transformed to 18 in 58% yield and then, this macro-
lactone was deprotected (Dowex 50W-8H+, MeOH, re-
flux) in 76% yield, to afford colletodiol (1) as pure white
crystals. The spectral and physical data for the isolated
material were in accordance with the data reported in the
literature (1H NMR, 13C NMR, IR, optical rotation and
melting point).14
The homoallylic acetate 1011 was isolated as a 60:40 mix-
ture of two diastereoisomers in 82% yield. The transfor-
mation of 10 into diene 12 was achieved in two steps. The
first step is a cross-metathesis performed between com-
pound 10 and methyl acrylate (3 equiv) in the presence of
the Grubbs–Hoveyda catalyst (3 mol%) in CH2Cl2 at
room temperature. After 70 hours, the unsaturated ester
1111 was isolated in 77% yield. The second step is the
acetate elimination using DBU (1.1 equiv) in DME (r.t., The synthesis of colletodiol was achieved in 12 steps from
16 h) which produced diene 12 in 90% yield. The Sharp- (R)-(–)-4-penten-2-ol (6) with an overall yield of 7%.
less dihydroxylation12 applied to 12 using (DHQD)2-
PHAL yielded regioselectively diol 13 accompanied by
References
the regioisomer 13¢13 in a ratio of 10:1. After separation of
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230.
(2) Powell, J. W.; Whalley, W. B. J. Chem. Soc. C 1969, 911.
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5497. (b) MacMillan, J.; Simpson, T. J. J. Chem. Soc.,
Perkin Trans. 1 1973, 1487.
the two regioisomers 13 and 13¢ by chromatography, 13
was isolated in 73% yield. The monoprotected triol 13
was directly subjected to a deprotection–protection step
[PPTS (1.2 equiv) in the presence of MeOH, 24 hours,
room temperature; then dimethoxypropane (10 equiv) and
p-toluenesulfonic acid (5 mol%)] to produce selectively
the five-membered ring acetonide 14 in 80% yield.
(4) Gurusiddaiah, S.; Ronald, R. C. Antimicrob. Agents
Chemother. 1981, 19, 153.
(5) Hunter, T. J.; O’Doherty, G. A. Org. Lett. 2002, 4, 4447.
(6) Seidel, W.; Seebach, D. Tetrahedon Lett. 1982, 23, 159.
(7) (a) Tsutsui, H.; Mitsunobu, O. Tetrahedron Lett. 1984, 25,
2159. (b) Tsutsui, H.; Mitsunobu, O. Tetrahedron Lett.
1984, 25, 2163.
Having synthesized the two main fragments of colleto-
diol, esterification of the carboxylic acid 8 by alcohol 14
using 2,4,6-trichlorobenzoyl chloride (DMAP, toluene,
90 °C, 3 h) furnished ester 15 in 84% yield. After depro-
tection of the hydroxy group present in 15 (TBAF,
Synlett 2005, No. 12, 1933–1935 © Thieme Stuttgart · New York