Unexpected C-C bond cleavage of epoxide motif: Rhodium(i)-catalyzed tandem heterocyclization/[4+1] cycloaddition of 1-(1-alkynyl)oxiranyl ketones

Article abstract of DOI:10.1039/c0cc05650b

A rhodium(i)-catalyzed tandem heterocyclization and formal [4+1] cycloaddition of 1-(1-alkynyl)oxiranyl ketones was developed, which provides a general, efficient and practical route to highly substituted furo[3,4-b]furan-3(2H)-ones, wherein the epoxide m

Full text of DOI:10.1039/c0cc05650b

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COMMUNICATION
Unexpected C–C bond cleavage of epoxide motif: Rhodium(I)-catalyzed
tandem heterocyclization/[4+1] cycloaddition of 1-(1-alkynyl)oxiranyl
ketonesw
Tao Wang, Cui-Hong Wang and Junliang Zhang*
Received 17th December 2010, Accepted 23rd March 2011
DOI: 10.1039/c0cc05650b
A rhodium(I)-catalyzed tandem heterocyclization and formal
[4+1] cycloaddition of 1-(1-alkynyl)oxiranyl ketones was
developed, which provides a general, efficient and practical route
to highly substituted furo[3,4-b]furan-3(2H)-ones, wherein the
epoxide motif undergo unexpected C–C bond cleavage rather
than the classical C–O bond cleavage.
to develop rhodium-catalyzed reactions,14 we became inter-
ested in the chemistry of 1-(1-alkynyl)oxiranyl ketones 1 (such
as 1a),15 which is readily available from the corresponding
2-(1-alkynyl)-alk-2-en-1-ones via stereoselective epoxidation.
It is envisaged that under the catalysis of rhodium complex,
ketone 1a might undergo a tandem heterocyclization and
formal [4+1] cycloaddition to produce bicyclic lactone 2a
via C–O bond cleavage of the epoxide motif. Herein we want
to document an efficient rhodium-catalyzed tandem hetero-
cyclization/formal [4+1] cycloaddition of 1-(1-alkynyl) oxiranyl
ketones via an unexpected C–C bond cleavage of epoxide
motif, which provides an rapid access to highly substituted
furo[3,4-b]furan-3(2H)-ones.
Transition metal-mediated C–C bond activation has received
much attention in recent years.1 There have been lots
of reports about metal-catalyzed C–C bond cleavage among
the small carbocyclic compounds such as cyclobutanes,2
cyclobutanones3 and their oxime derivatives,4 cyclobutanols,5
cyclobutenediones,6 cyclopropanes,1h,i,7 methylenecyclo-
propanes,1j,8 cyclopropanols,9 and cyclic 2-azidoalcohol
derivatives.10 In contrast, the metal-catalyzed selective C–C bond
cleavage of small heterocyclic compounds is rarely explored,11
since the carbon-heteroatom bond is easier to break.
We began our study by examining of (1-alkynyl)oxiranyl
ketone 1a with CO under the catalysis of various rhodium
catalysts (Table 1). The reaction did not occur (Table 1, entry 1)
under normal conditions (1 atm of CO (balloon), DCE, 70 1C)
using a [Rh(CO)2Cl]2 catalyst, which is the commonly used
and most effective catalyst in rhodium-catalyzed reactions.
Fortunately, it was found that the reaction proceeds smoothly
under the catalysis of 5 mol% of [RhCl(CO)(PPh3)2], affording
70% yield of furo[3,4-b]furan-3(2H)-one 3a rather than the
expected bicyclic lactone 2a after 12 h, indicating a novel
unexpected C–C bond cleavage of epoxide motif was involved
(Table 1, entry 2). Different solvents (Table 1, entries 3–5) and
silver salts (Table 1, entries 6–7) such as AgSbF6 and AgOTf
were further tested, but failed to improve the yield. The
reaction did not occur at lower temperature (Table 1, entry 8).
A mixture of CO/N2 (1/4) gas led to a trace amount of product
(Table 1, entries 8–9). The oftused catalyst [Rh(COD)Cl]2
itself failed to catalyze this reaction either (Table 1, entry
10). However, the combination of 1 : 1 ratio of [Rh(COD)Cl]2
with ligands S-Phos (L1), Ruphos (L2) or Davephos (L3)
resulted in excellent yields (Table 1, entries 11–13). Among
which S-phos (L1) derived rhodium catalyst gave a quantita-
tive yield. Interestingly, when the ratio of rhodium and L1 was
1 : 2, the reaction was slowed down, affording the desired
product in only 51% NMR yield (Table 1, entry 14).
Epoxides, the highly strained three membered ethers, have
been extensively used as building blocks in organic synthesis.
However, the dominant chemistry of epoxides is ring opening
via C–O bond cleavage.12 For example, alkynyl oxirane
scaffold has been reported by Murakami and co-workers to
react with arylboronic acids in the presence of rhodium
catalyst leading to a-allenols via the C–O bond cleavage.13i
The metal-catalyzed carbonylation of simple epoxide with
CO generally undergo a C–O bond insertion to afford
b-lactones.13 Recently, Liu and his co-workers have explored
a very impressive Co2(CO)8-mediated tandem [5+1]/[2+2+1]
cycloadditions of cis-epoxy eneynes, leading to tricyclic
d-lactones in high yields, in which the ring opening of epoxide
mode is still C–O bond cleavage.13h Very recently, we also
developed a rhodium-catalyzed tandem carbonylative cycliza-
tion reaction of 1-(1-alkynyl)cyclopropyl ketones to afford
highly substituted 5, 6-dihydro-cyclopenta[c]furan-4-ones.14a
During this study and as a continuation of our ongoing efforts
Shanghai Key Laboratory of Green Chemistry and Chemical
Processes, Department of Chemistry, East China Normal University,
3663 N. Zhongshan Road, Shanghai 200062, P.R. China.
E-mail: jlzhang@chem.ecnu.edu.cn; Fax: (+86) 21-6223-5039
w Electronic supplementary information (ESI) available: All experi-
mental procedure, data, and spectra of 1H and13 C NMR. CCDC
796889. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c0cc05650b
Under the optimal reaction conditions, a wide variety of
1-(1-alkynyl)oxiranyl ketones 1 were examined and the results
are summarized in Table 2. The ketone substituent R1 can be
either an aromatic or alkyl group. For those substrates with
aromatic R1, the reactions normally gave the corresponding
c
5578 Chem. Commun., 2011, 47, 5578–5580
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Table 1 Optimization of reaction conditionsa
(Table 2, entries 12–15), in which the relatively lower yields
resulted from the air sensitivity of the products during the
purification by column chromatography. Substituent R2 on
the epoxide moiety can be either aromatic or styryl group,
producing the corresponding products in moderate to excellent
yields (Table 2, entries 1–4). For example, the reaction of ketone
1e with a styryl group proceeded smoothly to afford 3e in 58%
yield (Table 2, entry 4), which can readily undergo further
functional group transformation. Substituent R3 groups on the
alkyne moiety can be aromatic, alkenyl and alkyl groups and
moderate to excellent yields of the products can be obtained in
the reactions (Table 2, entries 5–10 and 13–14).
Synthetic applications of the products were showcased by
the conversion of the representative 3a and 3m (Scheme 1).
Treatment of 3a and 3m by 1.1 equiv. of m-CPBA in DCE at
r.t. gave the corresponding tetrasubstituted furans 4a and 4m
in 86% and 83% yields, respectively. Interestingly, 3a can be
oxidized by the air slowly and the presence of 2,6-lutidine can
accelerate this transformation due to the enole form which will
make the whole system be more electron-rich.17 It is note-
worthy that on treatment of 3a with LDA followed by PhNTf2
in THF, a tetrasubstituted furan-3-yl triflate 6 could be
obtained rather than the corresponding heterobicyclic
furo[3,4-b]furan-3-yl triflate. Although we can see a new dot
in the TLC plate during the reaction, attempts to isolate this
intermediate failed as it was quickly to be oxidized by air
during the work-up.17 Product 6 can also be obtained in
excellent yield by an alternative more simple operation
(Tf2O, Et3N, and cat. DMAP). The structure of 4m was
established by spectroscopic analysis and further confirmed
by single-crystal X-ray analysis.16 2,3-Dihydrofuro[3,4-b]furan-
3-ol 5 can be obtained in 80% yield from 3a by LiAlH4
reduction in THF.
Entry Conditions
T (h) Yield (%)b
1
[{Rh(CO)2Cl}2], DCE
12
12
24
18
12
NR
78(70)
o5
2
3
4
5
[RhCl(CO)(PPh3)2], DCE
[RhCl(CO)(PPh3)2], THF
[RhCl(CO)(PPh3)2], CH3CN
[RhCl(CO)(PPh3)2], Toluene
10
NR
6
7
[RhCl(CO)(PPh3)2]/AgSbF6 (1 : 1), DCE 10
[RhCl(CO)(PPh3)2]/AgOTf (1 : 1), DCE 10
21
o5
8c
9d
10
11
12
13
14
[RhCl(CO)(PPh3)2], DCE
[RhCl(CO)(PPh3)2], DCE
[Rh(COD)Cl]2, DCE
[Rh(COD)Cl]2/L1, (1 : 1), DCE
[Rh(COD)Cl]2/L2(1 : 1), DCE
[Rh(COD)Cl]2/L3 (1 : 1), DCE
[Rh(COD)Cl]2/L1(1 : 2), DCE
24
36
12
11
13
40
36
NR
o5
NR
100(99)
98(90)
99(94)
51
a
Unless otherwise noted, reactions were performed with 0.4 mmol of
b
1a and 5.0 mol% of catalysts in DCE at 70 1C. NMR yield, the
c
d
number in the parentheses is the isolated yield. 60 1C. 1 atm of
mixture gas (CO/N2 = 1 : 4) was used.
Table 2 Scope of 1-(1-alkynyl)oxiranyl ketones 1a
Two plausible reaction pathways are depicted in Scheme 2.
In path I, chemoselective oxidative addition of the C–C bond
of epoxy motif of 1-(1-alkynyl)oxiranyl ketone 1 would generate
rhodaoxetane IA, which would undergo a rapid cycloisomeri-
zation to form intermediate ID. Insertion of carbon monoxide
generates fused furan derivative rhoda-pyranone IE, followed
by reductive elimination to furnish the heterobicyclic product
3 and regenerate the rhodium catalyst. An alternative pathway
is shown as path II, The rhodium(I) coordination of the
triple bond of 1 enhances the electrophilicity of alkyne.
Subsequent nucleophilic attack of the carbonyl oxygen to
Entry R1/R2/R3 (1)
T (h) Yieldb of Product (%)
1
Ph/4-MeOC6H4/Ph (1b)
12
17
22
13
11
3b (72)
3c (91)
3d (81)
3e (58)
3f (95)
3g (86)
3h (90)
3i (69)
3j (88)
3k (79)
3l (98)
3m (86)
3n (67)
3o (58)
3p (61)
2
3
4
Ph/4-ClC6H4/Ph (1c)
Ph/1-naphthyl/Ph (1d)
Ph/styryl/Ph (1e)
5
Ph/Ph/4-MeOC6H4 (1f)
6
Ph/Ph/3,5-(CF3)2C6H4 (1g) 40
7
8
Ph/Ph/1-naphthyl (1h)
Ph/Ph/n-Bu (1i)
40
48
11
16
17
18
36
42
36
9
Ph/Ph/Cyclohexenyl (1j)
4-MeOC6H4/Ph/Ph (1k)
4-ClC6H4/Ph/Ph (1l)
Me/Ph/ Ph (1m)
Me/Ph/4-MeOC6H4 (1n)
Me/Ph/cyclohexenyl (1o)
Me/4-ClC6H4/Ph (1p)
10
11
12c
13c
14c
15c
a
Unless otherwise noted, reactions were performed with 0.4 mmol of 1
and 5.0 mol% of [Rh(COD)Cl]2/L1(1 : 1) in the presence of 1 atm of
b
c
CO (balloon) in DCE at 70 1C. Isolated yields. 10.0 mol% of
[Rh(COD)Cl]2/L3 were used.
cycloadducts in good to excellent yields (Table 2, entries 1–11);
for alkyl-substituted substrates, the reactions required higher
catalyst loading (10 mol% of 1 : 1 ratio of [Rh(COD)Cl]2/L3)
Scheme 1 Synthetic applications of representative 3a and 3m.
Chem. Commun., 2011, 47, 5578–5580 5579
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Scheme 2 Plausible mechanism.
the rhodium (I)-activated alkyne would form the oxonium-
containing vinyl-rhodium intermediate IB, which would then
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In summary, we have demonstrated a rhodium(I)-catalyzed
tandem heterocyclization and formal [4+1] cycloaddition
reaction of 1-(1-alkynyl)oxiranyl ketones, leading to highly
substituted furo[3,4-b]furan-3(2H)-ones in moderate to excellent
yields. It is noteworthy that this reaction represents the first
example of rhodium-catalyzed C–C bond cleavage of epoxide
instead of the well known C–O bond cleavage process. This
new approach can be successfully extended to construct other
various heterobicyclic frameworks. Further studies on the
reaction scope, mechanism, and synthetic applications of this
new process are being pursued in this lab.
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This research was supported by the NSFC (20972054),
Ministry of Education of China, STCSM (08dj1400100) and
973 Program (2009CB825300).
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5580 Chem. Commun., 2011, 47, 5578–5580
This journal is The Royal Society of Chemistry 2011