A. H. L. Machado et al. / Tetrahedron Letters 50 (2009) 1222–1225
1225
OBn
OBn
OBn
A
B
BnO
OH
BnO
O
BnO
BnO
OH
20
21
22
C, D
OBn
OBn
OBn
E
F
BnO
O
O
BnO
O
O
24
19
23
OMe
G
OH
Amazonian Shrub (Faramea guianensis)
in vitro leishmanicidal activity
HO
25
OMe
Scheme 2. Reagents and conditions: (A) Allyl bromide, K2CO3, acetone, 60 °C, 15 h, 77%; (B) 230 °C, 1 h, 80%; (C) 1,2-dibromoethane, K2CO3, acetone, 60 °C, 38 h; D) 50%
aqueous NaOH, n-Bu4NHSO4, benzene, 1 h, 80%; (E) 4 mol % Grubbs-2 Ru-catalyst, toluene (0.020 M), 60 °C, 10 min; (F) 1 equiv of 2, 10 mol % Pd(OAc)2, 4 equiv 2,6-di-t-butyl-
4-methylpyridine, EtOH, 55 °C, 20 min, 50% (over two steps) (G) H2, 6 equiv Pd(OH)2, THF/MeOH, 25 °C, 5 h, 65%.
in 80% yield. Next, the vinyl ether function was introduced using
1,2-dibromoethane, followed by base elimination under phase
transference catalysis to give diene 23 in 80% yield (two steps).
Ring-closing metathesis of diene 23 using 4 mol % of the Grubbs-
2 catalyst furnished the desired 4H-chromene 19 in 90% yield after
flash chromatography. The 4H-chromene 19 proved to be a rather
unstable compound, and was used just after its purification by col-
umn chromatography. With the 4H-chromene 19 in hand, we car-
ried out the Heck arylation using arenediazonium salt 2a by
applying conditions as shown in Table 3, entry 4. After some exper-
imentation, the desired Heck adduct 24 was obtained in two steps
(RCM and Heck arylation) in 50% yield.
Due to the structural similarities between Heck adduct 24 and
natural product 25, a flavan isolated by Sauvain et al. from the
Amazonian shrub (Faramea guianensis),16 we submitted 24 to a cat-
alytic hydrogenation-hydrogenolysis reaction to get the natural
product 25 in 65% yield (Scheme 2). This compound displays signif-
icant in vitro leishmanicidal activity.
In summary, the Heck arylation of cyclic and acyclic enol ethers
using arenediazonium tetrafluoroborates proved to be a viable
alternative for the construction of acetophenones, aryl dihydrofu-
ran, aryl dihydropyrans, and aryl benzopyrans (chromenes) with
high regiocontrol in moderate to excellent yields. The synthesis
of 2H-chromene 24 opened up the way for the total synthesis of
the natural flavan 25 possessing leishmanicidal activity. Studies
are under way to apply the Heck–Matsuda arylation to the synthe-
sis of other flavonoids and cathecins.
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Acknowledgments
We are indebted to FAPESP, CNPq, and CAPES for the financial
support. We also thank Prof. Fábio C. Gozzo and Alexandre F.
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