Indium-mediated highly diastereoselective allenylation in aqueous medium: Total synthesis of (+)-goniofufurone

Article abstract of DOI:10.1039/a707881a

(+)-Goniofufurone was synthesized from D-glucurono-6,3-lactone via an indium-mediated highly regio- and diastereo-selective allenylation of carbonyl compounds in aqueous medium.

Full text of DOI:10.1039/a707881a

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Indium-mediated highly diastereoselective allenylation in aqueous medium:
total synthesis of (+)-goniofufurone
Xiang-Hui Yi, Yue Meng and Chao-Jun Li*
Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA
(+)-Goniofufurone was synthesized from D-glucurono-
OH
H
O
•
H
Br
6,3-lactone via an indium-mediated highly regio- and
diastereo-selective allenylation of carbonyl compounds in
aqueous medium.
H
O
H
O
H
H
H
O
O
O
HO
HO
The Asian trees of the genus Goniothalamus have long been
recognized as a potential source of chemotherapeutical agents.
The extracts and leaves of Goniothalamus have traditionally
been used for the treatment of edema and rheumatism,1 a pain
killer and a mosquito repellent,2 as well as used as an
abortifacient.3 Recently, from the constituents of these plants,
McLaughlin discovered a number of novel styryl lactones
which were found to possess moderate to significant cytotox-
icities against several human tumors. These findings have
attracted considerable biological and synthetic attention to these
styryl compounds. Among the key components in the extracts
are (+)-goniofufurone 14 and (+)-7-epi-goniofufurone 2.5 The
1
3
removal
Br
H
OH
O
O
H
HO
+
O
HO
couple
4
5
Scheme 1
OH
OH
H
H
H
H
O
O
H
H
H
O
O
O
O
HO
HO
Table 1 Diastereoselective allenylation of carbonyl compounds
H
1 (+)-Goniofufurone
2 (+)-7-epi-Goniofufurone
Carbonyl
Entry compound
Diastereo- Yield
selectivity (%)a
Product
absolute stereochemistry of (+)-goniofufurone was established
by Shing through the total synthesis of ent-(2)-1.6 Subse-
quently, several synthetic studies have been carried out on the
synthesis of 1.7–13
OH
HO
1
—
HO
CHO
57
•
The recent advances in Barbier–Grignard type carbon–
carbon bond formations in aqueous medium14 offer opportu-
nities to synthesize various heavily oxygenated biologically
important agents in a concise manner. Out continued interest in
metal mediated carbon–carbon bond formation in aqueous
media, particularly the synthetic application of these reactions,
drew our attention to these styryl compounds. Here we report a
highly regio- and diastereo-selective indium-mediated allenyl-
ation15,16 of carbonyl compounds in aqeuous medium, which
leads to a concise total synthesis of (+)-goniofufurone from a
readily available starting material. The retrosynthetic analysis
of (+)-goniofufurone is illustrated in Scheme 1.
Initially, the coupling between 1-phenyl-3-bromopropyne
and several carbohydrate substrates mediated by indium were
investigated in aqueous EtOH (Table 1). In each case, the
corresponding allenylation product was obtained with high
diastereoselectivity, favoring the syn diastereomer. The high
diastereoselectivity of this indium-mediated allenylation reac-
tion could be attributed to chelation control.17
The results of the allenylation study confirmed the key step
for the outlined synthesis. Thus, the commercially available
d-glucurono-6,3-lactone 5 was readily converted into the
corresponding bromo compound 6 based on the modification of
a literature procedure for synthesizing a related chloro deriva-
tive.18 Then allenylation of the compound with prop-2-ynyl
bromide 4, mediated by indium in aqueous EtOH, generated a
mixture of allenylation products (56%) in which the allene 7 is
the major component, together with debromination and re-
OH OH
OH
OH
HO
63b
(10:1)
2
CHO
•
HO
H
OH
OH
O
HO
OH
O
63b
(>10:1)
O
O
3
4
O
H
HO
H
•
H
O
OH
HO
Cl
Cl
HO
OH
O
O
O
(9:1)
(8:1)
72
O
H
O
HO
H
•
H
O
OH
HO
HO
OH
49b
O
5
O
HO
O
H
•
H
HO
a
The yields were those of the isolated major isomers after column
b
chromatograph on silica gel and were not optimized. Determined after
peracetylation. Conditions: stirred in 0.1 m aq. HCl–EtOH (1:9) overnight
at room temperature.
Chem. Commun., 1998
449

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H
O
H
Br
OH
O
the deprotected product which cyclized in situ giving the target
natural product in 44% yield over two steps. The spectroscopic
data and melting point of the target molecule synthesized by this
method are consistent with previous literature reports.7
In conclusion, (+)-goniofufurone has been synthesized in a
short sequence from d-glucurono-6,3-lactone using an indium-
mediated, highly regio- and diastereo-selective allene formation
in aqueous medium. The scope and application of the current
indium-mediated method to the syntheses of other carbo-
hydrates is presently under investigation.
O
O
H
HO
HO
i–iv
O
O
HO
HO
H
6
5
v
Br
Br
AcO
OAc
HO
OH
vi–viii
O
O
O
O
H
H
•
OAc OAc
HO
Notes and References
8
† E-mail: CJLi@Mailhost.Tcs.Tulane.Edu
7
ix, x
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OH
H
H
O
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O
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H
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1
Scheme 2 Reagents and conditions: i, acetone, H2SO4, room temp., 5 h,
86%; ii, Tf2O, Py, CH2Cl2, 240 °C, 94%; iii, LiBr, acetone, room temp., 1
h, 97%; iv, TFA–H2O (3:1), room temp., 4.5 h, 98%; v, 4, In, 0.1 m HCl–
EtOH (1:9), room temp., 14 h; vi, O3, MeOH, 278 °C, then DMS; vii,
NaBH4, MeOH, 210 °C, 30 min, then AcOH quench; viii, H2SO4, Ac2O,
room temp., 75% from 7; ix, Na2HSO3, Na2SO3, MeOH–H2O, room temp.,
3 h, quant.; x, HCl (g), MeOH, room temp., 2 d, 44% from 8
8 T. K. M. Shing, H. C. Tsui and Z. H. Zhou, J. Chem. Soc., Chem.
Commun., 1992, 810.
ductive elimination products. The allene 7 again shows a high
( > 10:1) syn diastereoselectivity (the desired isomer). Standard
ozonolysis of the allene compound in MeOH, followed by a
diastereoselective reduction with NaBH4, provided the corre-
sponding alcohol as the predominant product (de = 3:1). The
initial assignment of the stereochemistry for the reduction was
confirmed after completion of the total synthesis. Subsequent
reaction of the polyol with conc. H2SO4 in Ac2O generated the
peracetylation product 8 (ca. 75% from 7) which decomposed
on silica gel. Direct treatment of the peracetylation product with
Na2HSO3 and Na2SO3 in MeOH–H2O generated an a,b-
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1
unsaturated g-lactone, as shown by H NMR analysis of the
crude material. In order to remove the acetyl protecting groups,
the crude product was treated with HCl in MeOH resulting in
Received in Corvallis, OR, USA, 31st October 1997; 7/07881A
450
Chem. Commun., 1998