One pot rhodium catalyzed, base and solvent-free synthesis of 2-(bromomethyl)furan derivatives and synthesis of Hashmi phenol through platinum catalyzed cascade cyclization

Article abstract of DOI:10.1016/j.tetlet.2012.12.108

A novel rhodium catalyzed one pot synthetic strategy was developed to construct fused furan scaffolds via in situ generation of dicarbonyl iodonium ylide and its application to the synthesis of Hashmi phenol is described.

Full text of DOI:10.1016/j.tetlet.2012.12.108

Tetrahedron Letters 54 (2013) 1507–1509
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Tetrahedron Letters
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One pot rhodium catalyzed, base and solvent-free synthesis
of 2-(bromomethyl)furan derivatives and synthesis of Hashmi phenol through
platinum catalyzed cascade cyclization
⇑
Mahalingam Sivaraman, Doraiswamy Muralidharan, Paramasivan T. Perumal
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel rhodium catalyzed one pot synthetic strategy was developed to construct fused furan scaffolds
via in situ generation of dicarbonyl iodonium ylide and its application to the synthesis of Hashmi phenol
is described.
Received 16 November 2012
Revised 21 December 2012
Accepted 24 December 2012
Available online 3 January 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Dicarbonyl iodonium ylide
Cycloaddition
Rhodium
Hashmi phenol
Fused furan derivatives are found to be the core structure in
numerous natural products and pharmaceutical scaffolds
(Fig. 1).1 Because of the wide range of biological activities and
pharmaceutical applications, organic chemists are interested in
the synthesis of this privileged structure.2 Many synthetic ap-
proaches to this skeleton have been disclosed in the literature, of
particular value is transition metal catalyzed cyclization of alkyne.3
Although these methods offer some advantages, typically they re-
quire the preparation of starting materials. Therefore, there is still
scope for the development of new methods, especially one pot
reaction which do not require starting material preparation. 1,3-
Dicarbonyl iodonium ylide is relatively stable which is equivalent
to the carbene precursors and a safe alternative to the diazo com-
pounds.4 The ylide behaves as an excellent 1,3-dipole and under-
goes [3+2]-cycloadditon with suitable acceptors to provide a
wide range of five-membered heterocycles.4c,5 From previous re-
ports we observed the interesting chemistry of ylide with phenyl
acetylenes, ketenes, nitriles, isocyanates, isothiocyanates, dienes,
and carbodiimides leading to five-membered fused heterocy-
cles.4–6
ylide and to functionalize C–Br bond further. To test this strategy
first we chose the known 5,5-dimethyl-1,3-cyclohexanedione phe-
nyliodonium ylide (1a0) as a substrate, which is easily synthesized
by condensation of PhI(OAc)2 with dimedone under basic condi-
tion.7 Rh2(OAc)4 catalyzed reaction of 1a0 and propargyl bromide
(2) under the solvent-free condition leads to 2-(bromomethyl)-
6,7-dihydro-6,6-dimethylbenzofuran-4(5H)-one (3a) with an iso-
lated yield of 53% (Scheme 1).
OH
OH
HO
HO
OH
O
3
HO
O
O
R
O
O
OCH3
O
Tyrolobibenzyl A (R = H)
Tyrolobibenzyl A (R = OH)
Egonol
We were interested in the one pot and cascade reactions to
develop
a green approach to avoid the toxic waste to the
HO
O
OH
environment. So we planned an one pot synthesis of 2-
(bromomethyl)furans directly through the [3+2]-cycloaddition of
1,3-cyclic diketones and propargyl bromide without isolation of
H
HO
O
O
Fischerisin A
Frondosin B
⇑
Corresponding author.
E-mail address: ptperumal@gmail.com (P.T. Perumal).
Figure 1. Fused furan containing natural products.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.108

1508
M. Sivaraman et al. / Tetrahedron Letters 54 (2013) 1507–1509
Table 2
O
O
Substrate scope of the reaction
IPh
Br
5 mol% Rh2(OAc)4
O
O
O
O
Br
1 mol% Rh2(OAC)4
PhI(OAC)2
Br
1a'
2
3a, 53%
1 equiv
10 equiv
R1
R2
O
R1
R2
O
Br
Scheme 1. Reaction of iodonium ylide (1a0) and propargyl bromide.
1
3
Entry R1
R2
Product
% Yielda (Time)b
With this encouraging result we examined the one pot reaction
of dimidone (1a), propargyl bromide (10 equiv), PhI(OAc)2
(1.1 equiv), K2CO3 (1.1 equiv), and Rh2(OAc)4 (10 mol %) and ob-
tained 3a in 65% yield (Table 1, entry 1). When the reaction was
carried out in the absence of base, we observed a slight increase
in the yield from 65% to 67% (Table 1, entry 2). The reaction when
performed in the absence of either Rh2(OAc)4 or PhI(OAc)2, was
found to be inefficient (Table 1, entries 3 and 4). On further optimi-
zation of reaction conditions, we found that only 2 equiv of prop-
argyl bromide, 1.1 equiv of PhI(OAc)2, and 1 mol % Rh2(OAc)4
were enough for this effective transformation to yield 76% of 3a
(Table 1, entry 8). When the reaction was carried out in the pres-
ence of PhI(CF3CO2)2 instead of PhI(OAc)2 we got a reduced yield
(30%, Table 1, entry 9), and the Cu(acac)2 catalyzed reaction also
yielded only 37% (Table 1, entry 10). Finally we achieved an one
pot rhodium catalyzed base and solvent free in situ generation of
dicarbonyl iodonium ylide which with propargyl bromide lead to
the 2-(bromomethyl)furan derivatives. Product 3a is unequivocally
confirmed by 1D and 2D NMR techniques. After confirmation of the
product and optimum reaction conditions (Table 1, entry 8) in
hand, we examined the scope of this transformation and the re-
sults are presented in Table 2.
1
2
3
4
5
6
7
8
9
CH3
CH3
CH3
H
C6H5
4-CH3O–C6H4
3,5-(CH3O)2–C6H3
3,4,5-(CH3O)3–C6H2
4-Br–C6H4
4-Cl–C6H4
2,6-Cl2–C6H3
4-F–C6H4
3a
3b
3c
3d
3e
3f
3g
3h
3i
76 (1.0)
78 (1.0)
56 (1.5)
54 (2.0)
67 (1.5)
70 (1.0)
72 (1.0)
52 (2.0)
65 (1.5)
66 (1.5)
72 (1.0)
H
H
H
H
H
H
H
H
H
H
10
11
12
3j
3k
4,4-dimethylcyclohexane-1,3-dione 3l, 3l0 (1:1) 80 (1.0)
a
Isolated yield.
Time in hour.
b
O
O
Rh
IPh
RhLn
Rh(II)
PhI(OAC)2
1a
O
O
Br
PhI
5
4
Plausible reaction pathways are summarized for the formation
of 2-(bromomethyl)furans in Scheme 2, wherein the in situ gener-
ated iodonium ylide serves as the source of initial carbene (or carb-
enoid), which is transferred to the triple bond of propargyl bromide
via rhodium complexes 4 and 5. The formation of 3a may involve a
[3+2]-cycloaddition of the carbenoid mechanism (path A), which is
already well documented.4c,5 And also, we are not omitting the
possibility of cyclopropenation followed by cyclization (path B).8
path B
path A
O
O
Br
Br
O
O
Scheme 2. Plausible reaction mechanism for 3a.
Table 1
O
O
BnNH2
CH2Cl2
Optimization of reaction conditions of 3a
Bn
N
eq 1
3a
3a
O
O
O
O
Br
Conditionsa
6, 92%
O
Br
O
1a
3a
2
O
1 Acetone/water
2 NaH,DMF
O
eq 2
Entry Catalyst
(mol %)
Additives (equiv)
Yieldb
(%)
Time
(min)
O
Br
7, 86%
1
Rh2(OAc)4 (10) PhI(OAc)2 (1.1) + K2CO3
(1.1)
Rh2(OAc)4 (10) PhI(OAc)2 (1.1)
65
30
O
O
5 mol% PtCl2
acetone, 50 o
2
3
4
5
67
—
—
71
73
73
76
30
37
30
120
120
60
60
60
60
120
120
C
—
PhI(OAc)2 (1.1)
—
7
O
O
eq 3
Rh2(OAc)4 (10)
Rh2(OAc)4 (5)
Rh2(OAc)4 (1)
Rh2(OAc)4 (1)
Rh2(OAc)4 (1)
Rh2(OAc)4 (1)
Cu(acac)2 (1)
PhI(OAc)2 (1.1)
PhI(OAc)2 (1.1)
PhI(OAc)2 (1.1)
PhI(OAc)2 (1.1)
PhI(CF3CO2)2 (1.1)
PhI(OAc)2 (1.1)
OH
6
7c
8d
9d
10d
8, 83%
O
5 mol% PtCl2
aq. acetone, 50 o
O
O
C
7
eq 4
a One equivalent of dimedone, 10 equiv of propargyl bromide at room temperature,
unless otherwise mentioned.
O
OH
b
Isolated yield.
Five equivalents of propargyl bromide.
Two equivalents of propargyl bromide.
9, 62%
8, 10%
c
d
Scheme 3. Chemical transformation of 2-(bromomethyl)furans.

M. Sivaraman et al. / Tetrahedron Letters 54 (2013) 1507–1509
1509
We planned further transformation of 2-(bromomethyl)furans
(3a), where the presence of the C–Br bond provided an easy access
to other useful organic scaffolds. The product 3a is easily aminated
by treatment with BnNH2 in CH2Cl2 at room temperature to afford
6 in 92% yield (Scheme 3, Eq. 1).9 The product 3a when treated
with acetone and water followed by propargylation led to 6,7-
dihydro-6,6-dimethyl-2-((prop-2-ynyloxy)methyl)benzofuran-
4(5H)-one (7) with overall yield 86% (Scheme 3, Eq. 2).9,10 From the
literature review we found that the ring transformation of 2-
((prop-2-ynyloxy)methyl)furan lead to the Hashmi phenol.10,11
To examine this, we have chosen PtCl2 as the catalyst for this trans-
formation. Treatment of 7 with 5 mol % of PtCl2 in acetone at 50 °C
affords 7,8-dihydro-9-hydroxy-7,7-dimethylnaphtho[2,3-c]furan-
5(1H,3H,6H)-one (Hashmi phenol, 8), isolated yield 83% (Scheme 3,
Eq. 3). The treatment of 7 with 5 mol % of PtCl2 in aq acetone at
50 °C afforded 62% of hydrated product 9 along with 10% of 8
(Scheme 3, Eq. 4).
In conclusion, we have developed a facile one pot, base and sol-
vent-free pathway for the synthesis of 2-(bromomethyl)furans di-
rectly from in situ generated 1,3-dicarbonyl iodonium ylide. This
reaction involves readily available starting materials, high atom-
economy, low catalyst loading, and tolerates a wide scope of sub-
strates to afford medium to good yield. The product 3a is a useful
key intermediate in the synthesis of furoscrobiculin B12 and further
transformation of 3a is also achieved. Subsequent research will fo-
cus on application of this methodology to access five-membered
heterocycles.
7, 8, 9) associated with this article can be found, in the online ver-
sion, at http://dx.doi.org/10.1016/j.tetlet.2012.12.108.
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13
and scanned copies of 1H and C NMR of compound 3a–l, 3l0, 6,