Palladium(II)-catalyzed domino reaction of 2-(1-alkynyl)-2-alken-1-ones with nucleophiles: Scope, mechanism and synthetic application in the synthesis of 3,4-fused bicyclic tetrasubstituted furans

Article abstract of DOI:10.1002/adsc.200800715

Described herein is the development of a palladium(II)-catalyzed two- or three-component reaction of 2-(1-alkynyl)-2-alken-1-ones with nucleophiles and allylic chlorides. Various types of nucleophiles such as O-, N-, C-based nucleophiles and olefin-tether

Full text of DOI:10.1002/adsc.200800715

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DOI: 10.1002/adsc.200800715
Palladium(II)-Catalyzed Domino Reaction of 2-(1-Alkynyl)-2-
alken-1-ones with Nucleophiles: Scope, Mechanism and Synthetic
Application in the Synthesis of 3,4-Fused Bicyclic Tetrasubstituted
Furans
Yuanjing Xiaoa and Junliang Zhanga,b,*
a
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal
University, 3663 N. Zhongshan Road, Shanghai 200062, Peopleꢀs Republic of China
Fax : (+86)-021-6223-5039; e-mail: jlzhang@chem.ecnu.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, 354 Fenglin Road, Shanghai 200032, Peopleꢀs Republic of China
Received: November 19, 2008; Revised: January 21, 2009; Published online: February 18, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800715.
Abstract: Described herein is the development of a based nucleophiles were used, only the cross-cou-
palladium(II)-catalyzed two- or three-component re- pling reaction pathway was observed, in contrast,
action of 2-(1-alkynyl)-2-alken-1-ones with nucleo- both reaction pathways were observed when olefin-
philes and allylic chlorides. Various types of nucleo- tethered C-based nucleophiles were employed. The
philes such as O-, N-, C-based nucleophiles and product ratio is dependent on the length of the teth-
olefin-tethered O-, N-, C-based nucleophiles were in- ered chain. Furthermore, ring-closing metathesis
vestigated. The scope, mechanism and application of (RCM) of corresponding furans with C=C bonds
this Pd(II)-catalyzed domino reaction were studied. provides an easy method for the preparation of func-
In these transformations, the palladium catalyst ex- tionalized oxygen-heterocycles – 3,4-fused bicyclic
hibits a dual role, serving simultaneously as a Lewis furans. It is also noteworthy that allylic chloride can
acid and a transition metal. Two possible reaction be as an oxidant besides its well known function as
pathways (cross-coupling reaction vs. Heck reaction) an alkylating reagent.
from the same intermediate furanylpalladium species
were observed. The reaction pathway is dependent
on the property of the nucleophile and the length of Keywords: cyclization; domino reactions; fused ring
the tethered chain as well. When olefin-tethered O- systems; palladium; synthetic methods
Introduction
alkynyl or allenyl ketone substrates, 2-(1-alkynyl)-2-
alken-1-ones bearing carbonyl, alkynyl and alkenyl
As one of the most prominent classes of heterocyclic groups were less explored despite the fact that they
compounds, furans are important subunits in many are more readily accessible and more easily manipu-
natural products, pharmaceuticals,[1,2] and organic lated than those alkynyl or allenyl ketones.[12]
building blocks in organic synthesis.[3,4] It is thus not
In 2004, Larock and co-workers[13] reported the first
surprising that various new synthetic methods have example of an AuCl3-catalyzed cyclization of 2-(1-al-
been developed for the assembly of the furan ring.[5] kynyl)-2-alken-1-ones to afford highly substituted
It is believed that transition metal-catalyzed one- or furans efficiently [Eq. (1)]. Soon after, Yamamoto,[14a]
two-component reactions are the most general and Oh,[14b] and Liang[14c] developed CuBr-, PtCl2- or
powerful approaches, which include the cyclization of Bu4NAuCl4-catalyzed versions of this transformation
allenyl ketones,[6] 3-alkyn-1-ones,[6k,7] 1-(1-alkynyl)-cy- independently.
clopropyl ketones,[8] (Z)-2-en-4-yn-1-ols,[9] and/or cy-
Almost at the same time, Liu[15a] and Larock[15b] ob-
cloisomerization of cyclopropyl ketones[10]/cyclopro- served that electrophiles such as I2 can induce the cyc-
penyl ketones.[11] In contrast to the above-mentioned lization of 2-(1-alkynyl)-2-alken-1-ones with various
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nucleophiles leading to tetrasubstituted furans in synthesis of trisubstituted furans. It was then envi-
good to excellent yields [Eq. (2)]. sioned that 2-(1-alknyl)-2-alken-1-ones might react
During our study of furan synthesis, we realized that with nucleophiles and an allyl halide under the cataly-
route to efficiently synthesize tetrasubstituted sis of Pd(II) species, in which the Pd(II) species might
a
furans,[16] especially tetrasubstituted 3,4-fused bicyclic exhibit a dual role: as a Lewis acid and as a transition
furans,[17] is still a challenging topic as compared to the metal (Scheme 1). To the best of our knowledge, there
Scheme 1. Proposed reaction pathway for the reaction, in the first step the Pd(II) serves as a Lewis acid, and in subsequent
steps Pd(II) serves as a transition metal.
Table 1. Catalyst screening for the three-component Michael-addition/cycliza-
tion/cross-coupling reaction.[a]
[a]
Reaction was carried out with 1a (0.5 mmol) at room temperature.
Yields were determined by NMR using CH2Br2 as an internal standard,
[b]
isolated yields are shown in parentheses.
K2CO3 (2.0 equiv.) was used.
10 equiv. of allyl bromide was used instead of allyl chloride .
[c]
[d]
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Table 2. Coupling cyclization of 2-(1-alkynyl)-2-alken-1-ones
1a with O-, N-based nucleophiles 2b–2i.[a]
is only one example of PdACHTNUTRGENNG(U OAc)2 serving as a dual cat-
alyst.[18] Now, we will report a comprehensive study of
this multicomponent reaction[19,20] including scope,
mechanism and synthetic applications, together with a
novel cascade process[21] involving Michael addition/
cyclization/Heck reaction, which produces various 3,4-
fused bicyclic furans in moderate to good yields. It is
interesting to find that allylic chloride can play a dual
role as an alkylating reagent and as an oxidant (!).
Results and Discussion
Three-Component Michael Addition/Cyclization/
Cross-Coupling Reaction of 2-(1-Alkynyl)-2-alken-1-
ones with O-, N-, C-Based Nucleophiles and Allylic
Chloride: Allylic Chloride is Serving as a Crossing-
Coupling Reagent
The exploration was carried out by using (E)-3-ben-
zylidene-5-phenylpent-4-yn-2-one 1a, methanol 2a
and allyl chloride 3a as model substrates (Table 1).
After catalyst screening, we found that the cycliza-
tion/cross-coupling reaction of 1a with MeOH 2a
(4.0 equiv.), allyl chloride 3a (4.0 equiv.) in the pres-
ence of 5 mol% of PdCl2ACHTUNGTRNE(GNU CH3CN)2 and K2CO3
(4.0 equiv.) in CH3CN at room temperature gives the
product 4aaa in 75% isolated yield (Table 1, entry 3,
Standard Conditions). The reaction will afford the
product in a lower yield upon lowering the loading of
base, methanol or allyl chloride (Table 1, entries 4–6).
Use of the weaker Lewis acid PdBr
2ACHTUNGTRNEN(UNG CH3CN)2 [com-
pared to PdCl2A(CH3CN)2], generated via addition of
CHTUNGTRENNUNG
1.0 equivalent of KBr or using allyl bromide as cross-
coupling reagent instead of allyl chloride, gives the
expected product in lower yield, indicating that the
[a]
Unless otherwise specified, reactions were run with 1a
(0.5 mmol, 1.0 equiv.), nucleophiles (1.0 mmol, 2.0 equiv.)
in CH3CN (2 mL). Reported yields are of the isolated
product.
PdCl
(Table 1, entries 7 and 8). Other catalysts such as
PdCl2A(PPh3)2 (generated in the reaction by adding 20
mol% of PPh3) and Pd(PPh3)4 showed no catalytic ac-
tivity (Table 1, entries 1 and 2). We can then conclude
that PdCl2A(CH3CN)2 is a stronger Lewis acid than
PdBr2A(CH3CN)2, PdCl2A(PPh3)2 and Pd(PPh3)4. In addi-
2ACHTUNGTRENNUNG(CH3CN)2 indeed plays the role of a Lewis acid
CHTUNGTRENNUNG
[b]
Additional PdCl
24 h.
2ACHTNUGTREN(NUGN CH3CN)2 (5 mol%) was added after
AHCTUNGTRENNUNG
[c]
[d]
Used i-PrOH (6.0 equiv.) and allyl chloride (6.0 equiv.).
Additional 2.0 equiv. of allyl alcohol and allyl chloride
(4.0 equiv.) were added after 24 h.
The designation 4aba for the product indicates that the
reactants used were 1a, 2b, and 3a, respectively.
CHTUNGTRENNUNG
C
E
ACHTUNGTRENNUNG
[e]
tion, the allylpalladium dimer can also make this
transformation work but gives a relatively lower yield
(Table 1, entry 9). Thus, PdCl2ACHTNUTRGNEUNG(CH3CN)2 was chosen
as the catalyst for this transformation.
First, various O-, N-based nucleophiles were tested
to react with (E)-3-benzylidene-5-phenylpent-4-yn-2- secondary alcohol i-PrOH 2b with 1a gave a relatively
one 1a and allyl chloride 3a in the presence of a cata- lower yield (42%) and required a longer reaction
lytic amount of PdCl2ACHTNUGRTNEUNG(CH3CN)2, the results are listed time (Table 2, entry 1). This may be due to the steric
in Table 2. The scope of the O-based nucleophiles is effect of i-PrOH. Compared to other O-nucleophiles,
quite general. Besides methanol, other alcohols such the reaction with 3-butene-1-ol 2f affords the corre-
as isopropyl alcohol, benzyl alcohol, olefin-tethered sponding allyl-substituted furan 4afa in a relatively
alcohols, and phenol, can act as O-based nucleophiles higher yield (82%) (Table 2, entry 5), it is noteworthy
to give tetrasubstituted furans in moderate to excel- that no desired product was obtained, instead N,N-
lent yields (Table 2, entries 1–7). The reaction of the bisallyl-p-toluenesulfonamide was isolated, when N-
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Table 3. Scope of 2-(1-alkynyl)-2-alken-1-ones 1 and allyl chlorides 3.[a]
[a]
[b]
[c]
Unless otherwise noted, the reactions were performed under standard conditions.
Another portion of PdCl2A(CH3CN)2 (5 mol%) was added after 24 h.
Reaction conditions: MeOH (8.0 equiv.), allyl chloride (8.0 equiv.), K2CO3 (6.0 equiv.),
and PdCl2A(CH3CN)2 (10 mol%).
The designation 4aab for the product indicates that the reactants used were 1a, 2a,
and 3b, respectively.
CTHUNGTRENNUNG
CTHUNGTRENNUNG
[d]
allyl-p-toluenesulfonamide is used as the N-nucleo- tolerated in the present transformation including the
phile (Table 2, entry 8). ester group, which make it be a good candidate for
Next, we examined the reaction of a series of 2-(1- further organic transformations. (3) Various substitut-
alkynyl)-2-alken-1-ones 1 with various allyl chlorides ed 2-(1-alkynyl)-2-alken-1-ones 1 were examined and
3
and methanol 2a under standard conditions most of them except 1i react well to give good to ex-
(Table 3). It should be highlighted that: (1) the reac- cellent yields (Table 3, entry 10). (4) We were pleased
tion of 1a with substituted allylic chlorides such as to find that the cyclic enyne 1g can also be used as
3b–3d proceeds very well to afford the corresponding the substrate and that this reaction affords the corre-
highly functionalized furans in good yields (Table 3, sponding fused bicycle furan 4gaa in 57% yield under
entries 1–3). (2) Many functional groups are cleanly our conditions (Table 3, entry 9).
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Table 4. Carbon-based nucleophiles 2j and 2k were examined under standard condi-
tions.[a]
[a]
Unless otherwise specified, reactions were carried out under standard conditions.
Another 0.5 equiv. of dimethyl malonate was added after 12 h.
[b]
After studying O- and N-based nucleophiles, we nate 2l was used as the C-based nucleophile
turned our attention to the case of C-based nucleo- (Scheme 2). The expected cross-coupling product, the
philes such as malonates and malononitrile,[22] the re- allyl-substituted furan 4ala was isolated in a trace
sults are summarized in Table 4. As expected, the re- amount, whereas a novel 6-membered carbocycle, the
action occurred smoothly to give tetrasubstituted 3,4-fused bicyclic furan 5al, was harvested in 50%
furans with polyfunctional groups in moderate to ex- yield. When the reaction was performed at 458C with
cellent yields when dimethyl malonate 2j and substi- three equivalents of allyl chloride 3a, a slightly higher
tuted allyl chlorides were used, respectively (Table 4, yield (63%) could be obtained. The structure of 5al
entries 1–5). On the other hand, the reaction with ma- was further confirmed by single-crystal X-ray diffrac-
lononitrile failed to produce the corresponding cross- tion analysis (Figure l).[23] Thus, a novel palladium-
coupling product (Table 4, entry 6).
catalyzed two-component domino process involving
Michael addition/cyclization/Heck reaction was ex-
plored. In this novel cascade process, two carbon-
À
Two-Component Michael Addition/Cyclization/Heck
Reaction of 2-(1-Alkynyl)-2-alken-1-ones with Olefin- single operative step. Furthermore, allyl chloride is
carbon bonds and one C O bond are formed in a
Tethered C-Based Nucleophiles: Allyl Chloride is
Serving as an Oxidant
not serving as a cross-coupling reagent but, instead, as
an oxidant, since two hydrogen atoms are lacking on
comparing the starting materials 1a and 2l with the
It is surprising but also quite interesting to observe a product 5al. To evaluate the scope of this novel cata-
different reaction pattern when dimethyl 2-allylmalo- lytic cascade process and in order to get seven- or
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Scheme 2. Coupling cyclization reaction of 1a with olefin-tethered C-based nucleophiles.
which allyl chloride serves as a cross-coupling reagent.
Thus, if we can find an oxidant to replace the allyl
chloride which plays as the oxidant role, the reaction
will become much cleaner and give a higher yield of
5al. Thus, (E)-3-benzylidene-5-phenylpent-4-yn-2-one
1a and dimethyl 2-allylmalonate 2l were selected as
representative substrates for optimization of reaction
conditions (Table 5). In this domino process, the key
problem that needs to be solved is to find an appro-
priate oxidant that enables the conversion of Pd(0)
into Pd(II) and thus accomplishes the catalytic cycle.
To increase the yield, many oft-used oxidants such as
O2,[25] benzoquinone/MnO2,[26] the a-halocarbonyl
compound desyl chloride,[27] and CuCl2 were tested.[28]
Unfortunately, all of these oxidants as well as addi-
tives such as LiCl, (n-Bu)4NCl [could stabilize the
Pd(0) complex and not convert it into Pd black[29]
were not suitable for the present transformation.
Among these oxidants, allyl chloride is the only work-
ing oxidant for this transformation (Table 5, entries 1
]
Figure 1. ORTEP depiction of compound 5al.
eight-membered carbocyclic 3,4-fused bicyclic furans, and 2). The desired product 5al was obtained in 63%
another two 2-substituted malonate derivatives with isolated yield when the reaction was carried out in
longer tether chains, dimethyl 2-(but-3-enyl)malonate CH3CN at 458C for 36 h with allyl chloride
2m and dimethyl 2-(pent-4-enyl)malonate 2n were (3.0 equiv.) and K2CO3(4.0 equiv.). Other changes,
prepared according to known procedures,[24] and sub- such as lowering the amount of the base or use of dif-
sequently subjected to the optimized reaction condi- ferent solvent or base, lead to a lower yield or no
tions, respectively. The results show that the selectivi- product at all (Table 5, entries 1–18).
ty depends much on the length of the tethered chain.
To further explore the scope of this transformation,
When 2l was employed, the two-component domino a variety of 2-(1-alkynyl)-2-alken-1-ones 1 were exam-
reaction ran prior to the three-component process to ined and the results are listed in Table 6. It is shown
give the 3,4-fused bicyclic 5al as the major product. In that: (1) alkynes containing aryl groups afford rela-
contrast, in the case of dimethyl 2-(pent-4-enyl)malo- tively higher yields than those with alkyl groups
nate 2n with a longer chain, the three-component (Table 6, compare entries 1–4 with entry 5); (2) the
cross-coupling reaction is predominant to yield 4ana reaction of those substrates with alkynes bearing an
(46%) as the major product. Moreover, the reaction electron-rich aryl ring requires a longer reaction time
gave the two-component product 5am as the major and gives relatively lower yields (Table 6, compare en-
product (56%) and the three-component cross-cou- tries 1 and 2 with entries 3 and 4); (3) it is surprising
pling product 4ama (12%) as minor product in the that the reaction mixture became very complicated
case of 2m.
and no product was isolated when cyclic substrate 1g
It is obvious that a better yield of the two-compo- was treated with 2l (Table 6, entry 6).
nent product 5al will be formed if the competitive
three-component reaction can be suppressed, in
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Table 5. Screening reaction conditions for Pd(II)-catalyzed
double cyclization of 1a with 2l.[a]
Table 6. Cascade two-component reaction of 1 with dimethyl
2-allylmalonate 2l under the standard conditions[a]
Entry Different from standard conditions
Yield[b]
1
2
3
4
5
6
7
8
r.t.
50%
40%
K2CO3 (2 equiv.)
no base
under O2 protection
same as entry 4, LiCl (1.0 equiv.)
same as entry 4, (n-Bu)4NCl (1.0 equiv.)
1,4-benzoquinone (1.0 equiv.)
1,4-benzoquinone (0.1equiv.), MnO2
(1.0 equiv.)
0
0
0
0
0
0
[a]
Reactions were carried out with 1 (0.25 mmol) under
standard conditions.
Isolated yield.
[b]
9
CuCl2 (1.1 equiv.)
0
10
11
12
13
14
15[c]
16
17
2-chloro-1,2-diphenylethanone
K3PO4·3H2O was used instead of K2CO3
K2HPO4 was used instead of K2CO3
Cs2CO3 was used instead of K2CO3
Na2CO3 was used instead of K2CO3
NMP was used instead of CH3CN
DMF was used instead of CH3CN
0
0
0
28%
0
0
8%
0
dures.[30] Then, we examined the reaction of 1a with
dimethyl 2-allylmalonate 2l under standard conditions
using 2-(naphthalen-1-y1-methyl)allyl chloride 6 in-
stead of allyl chloride as oxidant reagent [Eq. (3)].
We were pleased to find that the reaction proceeds
smoothly under standard conditions to afford the de-
sired product, the 3,4-fused bicyclic furan 5al in 69%
yield along with 2-methylallylnaphthalene 7 derived
from 6 in 76% isolated yield.
Pd
(CH3CN)2
Pd(dba)2 was used instead of PdCl2
(CH3CN)2
ACHTUNGTRENNUNG(OAc)2 was used instead of PdCl2
ACHTUNGTRENNUNG
18
G
0
ACHTUNGTRENNUNG
[a]
Unless otherwise stated, reaction were carried out with
According to the above control experiment result,
1a (0.5 mmol), 2l (1.0 mmol), base (2.0 mmol), catalyst (5
mol%), oxidant and additives in solvent (2 mL) at room two plausible mechanisms, a Pd(II) (Scheme 3) and a
temperature for 36 h.
Yield of the isolated product.
NMP=1-methyl-2-pyrrolidinone.
Pd(0) [Pd(II) as the precursor] catalytic cycle
(Scheme 4), are proposed, respectively. In the Pd(II)
catalytic cycle (Scheme 3), the Pd(II) catalyst plays a
dual role as a Lewis acid and transition metal to facil-
itate the nucleophilic addition step and the subse-
quent cyclization step[18,20] to afford a key intermedi-
ate, the furanyl-palladium 8, which would undergo
[b]
[c]
Mechanism Insights
In order to clarify where allyl chloride goes after the two possible pathways. One is the intermolecular
reaction, a 2-substituted allyl chloride, 1-[2-(chloro- cross-coupling reaction with allyl chloride via regio-
methyl)allyl]naphthalene 6, was prepared from the selctive insertion of the double bond of allyl chloride
À
commercially available 1-bromethylnaphthalene and into the C Pd bond of intermediate 8, followed by b-
prop-2-yn-1-ol in two steps according to known proce- halide elimination to afford the allyl-substituted tetra-
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Scheme 3. Proposed Pd(II) catalytic cycle.
Scheme 4. Proposed Pd(0) catalytic cycle.
substituted furan 4[31] and regenerate PdCl2 (path a). bond followed by b-H elimination to afford furan 5
The other one is the intramolecular Heck reaction via and generate 14. Subsequent reductive elimination
the intramolecular regioselective insertion of the would regenerate Pd(0).
double bond followed by b-H elimination to afford
Some further control experiments were then per-
tetrasubstitued furan 5 and generate an allyl chloride- formed in order to find out which mechanism is more
coordinated intermediate (CH2CHCH2Cl)HPdCl in reasonable. The coupling cyclization reaction of 1a
the presence of excess allylic chloride. The with dimethyl butene-3-yl-1-malonate 2m under dif-
(CH2CHCH2Cl)HPdCl intermediate would not under- ferent concentrations of allyl chloride catalyzed by
go reductive elimination to generate Pd(0) under the PdCl
basic conditions,[32] instead, a regioselective addition
reaction followed by b-halide elimination to regener-
ate PdCl2 (path b) occurs.
2ACHTUNGERTN(NUNG CH3CN)2 was investigated in detail (Scheme 5).
In the Pd(0)-catalyzed cycle (Scheme 4),[20] Pd(0)
could be generated from Pd(II) in the presence of
base and nucleophiles.[33] The oxidative addition of
allyl chloride with Pd(0) generates allylpalladium
chloride 11 which may also facilitate both the nucleo-
philic addition step and the cyclization step to afford
a furanyl allyl-palladium intermediate 12, which could
also undergo subsequently two possible pathways.
One is the direct reductive elimination to give the
cross-coupling product 4 and regenerate Pd(0). The
other is the intramolecular Heck reaction via the in-
tramolecular regioselective insertion of the double different concentration of allyl chloride 3a.
Scheme 5. Coupling cyclization reaction of 1a with 2m under
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The results showed that with the increasing concen- Table 7. Ring-closing metathesis of allyl-substituted furans
catalyzed by Grubbsꢀ catalyst (II).[a]
tration of allyl chloride, the ratio of 5am/4ama is be-
coming lower. However, treatment of 1a and dimethyl
2-allylmalonate 2l with a stoichiometric amount of al-
lylpalladium chloride dimer under the basic condi-
tions makes the reaction very complicated to give the
desired 5al in only 5% isolated yield (caculated based
on 1a), the main isolated product was dimethyl 2,2-di-
allylmalonate 16 in 52% yield {calculated based on 2l
[Eq. (4)]}. Although these results cannot exclude the
Pd(0) catalytic cycle exclusively, we prefer the Pd(II)
catalytic cycle (Scheme 3) as the more reasonable
possible mechanism for this cascade transformation.
Synthetic Application in Syntheses of 3,4-Fused
Bicyclic Furans via Ring-Closing Metathesis of
Three-Component Products
Ring-closing metathesis (RCM), one of the most pow-
erful methods for the construction of a wide variety
of complex molecules with multiple functional groups,
has emerged as an effective strategy in organic syn-
thesis.[34] It occurred to us that the two terminal ole-
fins of the obtained allyl-substituted furans (4aea–
4aha, 4ama, 4ana) might undergo a ring-closing
metathesisACHTUNGTRENNUNG(RCM) reaction to construct a new ring. To
the best of our knowledge, only few reports concern-
ing the synthesis of 3,4-fused fully substituted furans
have been published.[17] It is well documented that
seven-, eight-, and nine-membered heterocyclic ring
systems are characteristic structural frameworks of
various natural products.[35] To demonstrate the syn-
thetic utility of the obtained allyl-substituted furans,
we examined their RCM reaction catalyzed by the
commercially available second generation Grubbs cat-
alyst. The results are summarized in Table 7. Initially,
allyl-substituted furan 4afa was chosen as model sub-
strate for screening the RCM reaction conditions. It
was pleasing to find that the RCM reaction of allyl-
substituted furan 4afa under highly diluted concentra-
tion proceeds smoothly in refluxing DCE to afford
the corresponding 9-membered oxygen fused furan
15afa in 70% yield (Table 7, entry 2). The reaction
proceeds very slowly and 4afa could not be consumed
completely after 72 h at room temperature. Similar re-
sults were obtained when Grubbs catalyst (II) (5
[a]
[b]
Reactions run with 4 (0.25 mmol scale) in ClCH2CH2Cl
(40 mL).
Isolated yield.
mol%) was employed even if the reaction was carried 4aga and 4aha give the corresponding 8-, 10- and 11-
out in refluxing DCE. Under these conditions, the membered oxygen fused furans 15aea, 15aga and
RCM reactions of other allyl-substituted furans 4aea, 15aha in moderate to good yields, respectively
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Table 8. Synthesis of [5,9]-bicycles via a two-step strategy.[a,b]
[a]
[b]
[c]
The first step was run with 1a (0.5 mmol scale) in CH3CN (2.0 mL).
The second step was run with 4 (0.25 mmol) in ClCH2CH2Cl (40 mL).
Isolated yields.
(Table 7, entries 1, 3, and 4). With respect to the en- ing nine- to eleven-membered rings in moderate to
larged 11-membered oxygen heterocyclic fused furan good yields.
15aha, the reaction affords a mixture of two insepara-
ble E/Z isomers (Table 7, entry 4). Interestingly, the
RCM reactions of the corresponding allyl substituted Conclusions
furans 4ama, 4ana derived from carbon-based nucleo-
philes failed to yield the desired bicyclic products. In summary, we have developed a Pd(II)-catalyzed
Only decomposed products were obtained according domino reaction of 2-(1-alkynyl)-2-alken-1-ones with
1
to H NMR spectroscopy.
nucleophiles for the preparation of tetrasubstituted
Encouraged by the above successful results, this ex- furans. Its advantage is clear in some aspects: (1) it
pedient access to nine-membered oxygen fused furans provides an efficient route to cyclic 3,4-fused tetrasub-
via a two-step operation was examined with respect stituted furans via a two-component cascade double
to other substrates. First, we evaluated the scope of cyclization and tetrasubstituted furans via a three-
the coupling cyclization of 1 with 3-butene-1-ol 2f component cascade reaction; the type of nucleophiles
under the standard conditions, subsequently, the and the length of the tethered chain affect the effi-
RCM reaction of the resulting allyl-substituted furans ciency of two-component reaction. (2) It is easy to in-
4 was executed to afford nine-membered oxygen-het- troduce various substituents to the furan ring by the
erocyclic fused furans 15. As shown in Table 8, this appropriate choice of 2-(1-alkynyl)-2-alken-1-ones,
easy access to nine-membered fused furans can be nucleophiles and chlorides. (3) Ring-closing metathe-
successfully extended to a variety of 2-(1-alkynyl)-2- sis reactions of allyl-substituted tetrasubstituted
alken-1-ones 1. Both the three-component Michael furans provide an efficient route to synthesize 3,4-
addition/cyclization/cross-coupling reaction and the fused bicyclic furans; (4) Some control reactions for
subsequent ring-closing metathesis reaction proceed- mechanistic studies showed that this domino reaction
ed uneventfully to furnish the desired product under proceeds via a Pd(II) catalytic cycle. (5) Allyl chloride
standard conditions. The results in Table 7 and can act as an oxidant besides its well known behav-
Table 8 show that this new strategy provides an easy iour as an alkylating reagent.
access to functionalized fused bicyclic furans contain-
626
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Adv. Synth. Catal. 2009, 351, 617 – 629

Palladium(II)-Catalyzed Domino Reaction of 2-(1-Alkynyl)-2-alken-1-ones
FULL PAPERS
in: Chemistry of Heterocyclic Compounds in Flavours
and Aromas, (Ed.: G. Vernin), Ellis Horwood, Chiches-
ter, 1982, pp 161–165.
Experimental Section
The starting materials, 2-(1-alkynyl)-alken-1-ones 1, were
prepared according to known procedures.[13,15b] For prepara-
tive procedures and spectroscopic data for all new com-
pounds, see the Supporting Information.
[3] a) B. H. Lipshutz, Chem. Rev. 1986, 86, 795; b) R. Be-
nassi, in: Comprehensive Heterocyclic Chemistry II,
(Eds.: A. R. Katritzky, C. W. Rees, E. F. V. Scriven),
Pergamon: Oxford, 1996; Vol. 2, pp 259–295; c) H.
Heaney, J. S. Ahn, in: Comprehensive Heterocyclic
Chemistry II, (Eds.: A. R. Katritzky, C. W. Rees,
E. F. V. Scriven), Pergamon, Oxford, 1996, Vol. 2,
pp 297–357; d) W. Friedrichsen, in: Comprehensive
Heterocyclic Chemistry II, (Eds.: A. R. Katritzky, C. W.
Rees, E. F. V. Scriven), Pergamon, Oxford, 1996; Vol.
2, pp 351–393; e) B. A. Keay, P. W. Dibble, in: Compre-
hensive Heterocyclic Chemistry II, (Eds.: A. R. Katritz-
ky, C. W. Rees, E. F. V. Scriven), Pergamon, Oxford,
1996, Vol. 2, pp 395–436; f) Comprehensive Organic
Synthesis, (Eds.: B. M. Trost, I. Fleming), Pergamon,
Oxford, 1991.
General Procedure for the Pd(II)-Catalyzed Domino
Reaction of 2-(1-Alkynyl)-alken-1-ones 1 with
Nucleophiles using Allyl Chloride as Oxidant or
Cross-Coupling Reagent
PdCl2ACHTUNGTRENNUNG(CH3CN)2 (6.0 mg, 0.025 mmol) was added to a mix-
ture of 1 (0.5 mmol), nucleophile (1.0 mmol, 2.0 equiv.), allyl
chloride (1.5–2.0 mmol, 3.0–4.0 equiv.) in CH3CN (2.0–
4.0 mL) followed by addition of solid K2CO3(2.0 mmol,
4.0 equiv.) as the base. The reaction mixture was stirred at
room temperature or 458C until 1 was consumed completely
as determined by TLC analysis. The reaction mixture was
filtered and the filtrate was concentrated under vacuum.
The residue was purified by column chromatography on
silica gel (petroleum ether/Et2O=10:1–100:1) to give de-
sired product 4 or 5.
[4] a) E. J. Corey, X.-M. Cheng, The Logic of Chemical
Synthesis, John Wiley, New York, 1989; b) K. C. Nico-
laou, E. J. Sorensen, Classics in Total Synthesis, VCH,
Weinheim, 1996.
[5] For reviews, see: a) X. L. Hou, H. Y. Cheung, T. Y.
Hon, P. L. Kwan, T. H. Lo, S. Y. T. Tong, H. N. C.
Wong, Tetrahedron 1998, 54, 1955; b) B. A. Keay,
Chem. Soc. Rev. 1999, 28. 209; c) T. L. Gilchrist, J.
Chem. Soc. Perkin Trans. 1 1999, 2849; d) S. Cacchi, J.
Organomet. Chem. 1999, 576, 42; e) X. L. Hou, Z.
Yang, K. S. Yeung, H. N. C. Wong, in: Progress in Het-
erocyclic Chemistry, Vol. 19, (Eds.: G. W. Gribble, J. A.
Joule), Pergamon, Oxford, 2008, p 176; f) S. F. Kirsch,
Org. Biomol. Chem. 2006, 4, 2076.
[6] a) J. A. Marshall, E. D. Robinson, J. Org. Chem. 1990,
55, 3450; b) J. A. Marshall, G. S. Bartley, J. Org. Chem.
1994, 59, 7169; c) J. A. Marshall, E. M. Wallace, J. Org.
Chem. 1995, 60, 796; d) A. S. K. Hashmi, Angew.
Chem. 1995, 107. 1749; Angew. Chem. Int. Ed. Engl.
1995, 34, 1581; e) A. S. K. Hashmi, T. L. Ruppert, T.
Knofel, J. W. Bats, J. Org. Chem. 1997, 62, 7295;
f) A. S. K. Hashmi, L. Schwarz, J. H. Choi, T. M. Frost,
Angew. Chem. 2000, 112, 2382; Angew. Chem. Int. Ed.
2000, 39, 2285; g) S. Ma, L. Li, Org. Lett. 2000, 2, 941;
h) S. Ma, Z. Yu, Angew. Chem. 2002, 114, 1853; Angew.
Chem. Int. Ed. 2002, 41, 1775; i) S. Ma, ; J. Zhang, L.
Lu, Chem. Eur. J. 2003, 9, 2447; j) J. T. Kim, A. V.
Kel’in, V. Gevorgyan, Angew. Chem. 2003, 115, 102;
Angew. Chem. Int. Ed. 2003, 42, 98; k) A. W. Sromek,
A. V. Kel’in, V. Gevorgyan, Angew. Chem. 2004, 116,
2330; Angew. Chem. Int. Ed. 2004, 43, 2280; l) M. H.
Suhre, M. Reif, S. F. Kirsch, Org. Lett. 2005, 7, 3925;
m) A. W. Sromek, M. Rubina, V. Gevorgyan, J. Am.
Chem. Soc. 2005, 127, 10500; n) A. Dudnik, V. Ge-
vorgyan, Angew. Chem. 2007, 119, 5287; Angew. Chem.
Int. Ed. 2007, 46, 5195; o) T. Schwier, A. W. Sromek,
D. M. L. Yap, D. Chernyak, V. Gevorgyan, J. Am.
Chem. Soc. 2007, 129, 9868.
General Procedure for Ring-Closing Metathesis
Reaction of Allyl-Substituted Furans 4 Catalyzed by
Second Generation Grubbsꢀ Catalyst
To a solution of allyl-substituted furan 4(0.25 mmol) in dry
CH2ClCH2Cl (40 mL), second generation Grubbsꢀ catalyst
(21.2 mg, 10 mol%) was added at room temperature under
N2 protection, the mixture was then stirred at reflux. After 4
was consumed completely as determined by TLC analysis.
The reaction mixture was concentrated under vacuum and
the residue was purified by column chromatography on
silica gel (petroleum ether/Et2O=10:1–100:1) to give the
desired product 15.
Acknowledgements
This work was supported by 973 program (2009CB825300),
NSFC (20702015), Shanghai Shuguang Program (07SG27),
Shanghai Pujiang Program (07pj14039) and Shanghai Lead-
ing Academic Discipline Project (B409).
References
[1] a) M. V. Sargent, F. M. Dean, in: Comprehensive Heter-
ocyclic Chemistry, Vol. 4, (Eds.: A. R. Katrizky, C. W.
Rees), Pergamon Press, New York, 1984, pp 599–656;
D. M. X. Donnelly, M. J. Meegan, in: Comprehensive
Heterocyclic Chemistry, Vol. 4, (Eds.: A. R. Katrizky,
C. W. Rees), Pergamon Press, New York, 1984, pp 657–
712; b) Natural Products Chemistry, (Ed.: K. Naka-
nishi), Kodansha, Toyko, 1974, pp 392–403; c) M. Ship-
man, Contemp. Org. Synth. 1995, 2, 1.
[7] a) Y. Fukuda, H. Shiragami, K. Utimoto, H. Nozaki, J.
Org. Chem. 1991, 56, 5816; b) A. V. Kel’in, V. Gevorgy-
an, J. Org. Chem. 2002, 67, 95.
[2] G. Vernin, in: Chemistry of HeteroACTHNUTRGNEUNGcyclic Compounds in
Flavours and Aromas, (Ed.: G. Vernin), Ellis Horwood,
Chichester, 1982, pp 74–85; G. Vernin, C. Parknanyi,
[8] J. Zhang, H. G. Schmalz, Angew. Chem. 2006, 118,
6856; Angew. Chem. Int. Ed. 2006, 45, 6704.
Adv. Synth. Catal. 2009, 351, 617 – 629
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
627

Yuanjing Xiao and Junliang Zhang
FULL PAPERS
[9] Y. H. Liu, F. Song, Z. Song, M. Liu, ; B. Yan, Org. Lett.
2005, 7, 5409.
[10] a) S. Ma, J. Zhang, Angew. Chem. 2003, 115, 193;
Angew. Chem. Int. Ed. 2003, 42, 183; b) S. Ma, L. Lu, J.
Zhang, J. Am. Chem. Soc. 2004, 126, 9645.
[11] a) A. Padwa, J. M. Kassir, S. L. Xu, J. Org. Chem. 1991,
56, 6971; b) S. Ma, J. Zhang, J. Am. Chem. Soc. 2003,
125, 12386.
[12] M. W. Miller, C. R. Johnson, J. Org. Chem. 1997, 62,
1582.
1996, 96, 137; e) P. J. Parsons, C. S. Penkett and A. J.
Shell, Chem. Rev.1996, 96, 195; f) H. Pellissier, Tetrahe-
dron 2006, 62, 2143; g) H. Pellissier, Tetrahedron 2006,
62, 1619; h) L. F. Tietze, G. Brasche, K. Gercke,
Domino Reactions in Organic Synthesis, Wiley-VCH,
Weinheim, 2006, p 672; i) Metal Catalyzed Cascade Re-
actions, (Ed: T. J. J. Mꢃller), Springer, Berlin, Heidel-
berg. Top. Organomet. Chem. 2006, Vol 19; j) K. C.
Nicolaou, D. J. Edmonds, P. G. Bulger, Angew. Chem.
2006, 118, 7292; Angew. Chem. Int. Ed. 2006, 45, 7134;
k) D. M. D’Souza, T. J. J. Mꢃller, Chem. Soc. Rev. 2007,
36, 1095; l) S. F. Kirsch, Synthesis 2008, 3183.
[13] T. Yao, X. Zhang, R. C. Larock, J. Am. Chem. Soc.
2004, 126, 11164.
[14] a) N. T. Patil, H. Wu, Y. Yamamoto, J. Org. Chem.
2005, 70, 4531; b) C. Oh, V. Reddy, A. Kim, C. Rhim,
Tetrahedron Lett. 2006, 47, 5307; c) X. Liu, Z. Pan, X.
Shu, X. Duan, Y. liang, Synlett 2006, 12, 1962.
[15] a) Y. H. Liu, S. Zhou, Org. Lett. 2005, 7, 4609; b) T.
Yao, X. Zhang, R. C. Larock, J. Org. Chem. 2005,
70,7679.
[16] For selected recent examples see: a) R. Sanz, D.
Miguel, A. Martinez, J. M. Alvarez-Gutierrez, F. Rodri-
guez, Org. Lett. 2007, 9, 727; b) V. Cadierno, J.
Gimeno, N. Nebra, Adv. Synth. Catal, 2007, 349, 382;
c) I. Yavari, A. Mokhtarporyani-Sanandaj, L. Morad,
A. Mirzaei, Tetrahedron 2008, 64, 5221; d) X. Feng, Z.
Tan, D. Chen, Y. Shen, C. Guo, J. Xiang, C. Zhu, Tetra-
hedron Lett. 2008, 49, 4110; e) Z. Chai, Z. Xie, X. Liu,
G. Zhao, J. Wang, J. Org. Chem. 2008, 73, 2947.
[17] a) M. Suzuki, H. Ohtaka, Y. Kameya, N. Hamanaka, R.
Noyori, J. Org. Chem. 1989, 54, 5292; b) M. E. Price,
N. E. Schore, J. Org. Chem. 1989, 54, 2777; c) Y. Siquot,
P. Frere, T. Nozdryn, J. Cousseau, M. Salle, M. Jubauct,
J. Orduna, J. Carin, A. Corguesa, Tetrahedron Lett,
1997, 38, 1919; d) G. Zhang, X. Huang, G. Li, L.
Zhang, J. Am. Chem. Soc. 2008, 130, 1814.
[22] The reaction of 2-(1-alkynyl)-2-alken-1-ones with 1, 3-
diketones as C-based nucleophiles readily affords 4H-
pyrans under basic reaction conditions, see: X. Yu, H.
Ren, Y. Xiao, J. Zhang, Chem. Eur. J. 2008, 14, 8481,
and unpublished results.
[23] X-ray data for compound 5al: C26H24O5, MW=416.45,
triclinic, space group-1, Mo-Ka, final R indices [I>
2s(I)], R1=0.0384, wR2=0.0980, a=9.4172(3) ꢅ, b=
9.4598(3) ꢅ, c=11.1284(2) ꢅ, a=93.5100(10)o, b=
107.1180(10)o, g=95.7700(10)o, V=1058.48(6) ꢅ3, T=
123(2) K, Z=2, reflections collected/unique: 24662/
3689 (Rint =0.0199), number of observations [I>2s(I)]
3289, parameters 288. CCDC 698140 contains the sup-
plementary crystallographic data for this paper. These
data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[24] S. Ma, B. Xu, Bukuo. Ni, J. Org. Chem. 2000, 65, 8532.
[25] For selected recent examples see: a) K. Akiyama, K.
Wakabayashi, K. Mikami, Adv. Synth. Catal. 2005,
347,1569; b) K. S. Yoo, C. H. Yoon, R. K. Mishra, Y. C.
Jung, S. W. Yi, K. W. Jung, J. Am. Chem. Soc. 2006,
128, 16384; c) K. S. Yoo, C. P. Park, C. H. Yoon, S. Sa-
kaguchi, J. OꢀNeill, K. W. Jung, Org. Lett, 2007, 9, 3933;
d) For a review, see: E. M. Beccalli, G. Broggini, M.
Martinelli, S. Sottocornola, Chem. Rev. 2007, 107, 5318.
[26] For selected recent examples, see: a) J. D. Crowley,
K. D. Hanni, A. L. Lee, D. A. Leigh, J. Am. Chem. Soc.
2007, 129, 12092; b) J. Lindh, P.-A. Enquist, A. Pilotti,
P. Nilsson, M. Larhed, J. Org. Chem, 2007, 72, 7957;
c) R. Giri, N. Maugel, J. Li, D. Wang, S. Breazzano, L.
Saunders, J. Yu, J. Am. Chem. Soc. 2007, 129, 3510;
d) C. Peng, Y. Wang, J. Wang, J. Am. Chem. Soc. 2008,
130, 1566.
[27] For selected recent examples see: a) A. Lei, X. Zhang,
Org. Lett, 2002, 4, 2285; b) Y. Zhao, H. Wang, X. Hou,
Y. Hu, A. Lei, H. Zhang, L. Zhu, J. Am. Chem. Soc.
2006, 128, 15048; c) Y. Zhao, L. Jin, P. Li, A. Lei, J.
Am. Chem. Soc. 2008, 130, 9429.
[28] a) C. Liu, X. wang, T. Pei, R. A. Widenhoefer, Chem.
Eur. J. 2004, 10, 6343; b) Z. Wang, S. Sugiarti, C. Mo-
rales, C. Jensen, D. Morales-Morales, Inorg. Chim. Acta
2006, 359, 1923; c)14d.
[29] W. Liu, Y. Xie, Y. Liang, J. Li, Synthesis 2006, 860.
[30] a) J. G. Duboudin, B. Jousseaume, A. Saux, J. Organo-
met. Chem, 1979, 168, 1; b) M. Frederick Hawthorne, J.
Am. Chem. Soc. 1960, 82, 1886.
[31] For the Pd-catalyzed allylation-cyclization reactions,
see: a) Y. Wakabayashi, Y. Fukuda, H. Shiragami, K.
Utimoto, H. Nozaki, Tetrahedron 1985, 41, 3655; b) M.
[18] PdACHTUNGTRENNUNG(OAc)2 acts as both a Lewis acid and a transition
metal, see: N. Asao, T. Nogami, K. Takahashi, Y. Yam-
mamoto, J. Am. Chem. Soc. 2002, 124, 764.
[19] For recent reviews, see: a) A. Dçmling, Curr. Opin.
Chem. Biol. 2002, 6, 306; b) R. V. A. Orru, M. de
Greef, Synthesis 2003, 1471; c) C. Hulme, V. Gore,
Curr. Med. Chem. 2003, 10, 51; d) J. Zhu, Eur. J. Org.
Chem. 2003, 1133; e) V. Nair, C. Rajesh, A. U. Vinod,
S. Bindu, A. R. Sreekanth, J. S. Mathen, L. Balagopal,
Acc. Chem. Res. 2003, 36, 899; f) D. J. Ramꢂn, M. Yus,
Angew. Chem. 2005, 117, 1628; Angew. Chem. Int. Ed.
2005, 44, 1602; g) A. Dondoni, A. Massi, Acc. Chem.
Res. 2006, 39, 451; h) A. Dçmling, Chem. Rev. 2006,
106, 17; i) D. M. D’Souza, T. J. J. Mꢃller, Chem. Soc.
Rev. 2007, 36, 1095; j) T. J. J. Mꢃller, in: Topics in Or-
ganometallic Chemistry (Ed. T. J. J. Mꢃller), Springer,
Berlin, 2006, Vol. 19, pp 149; k) Multicomponent Reac-
tions, (Eds.: J. Zhu, H. Bienaymꢄ), Wiley-VCH, Wein-
heim, 2005.
[20] Part of this work has been published in the preliminary
communication, see: Y. Xiao, J. Zhang, Angew. Chem.
2008, 120, 1929; Angew. Chem. Int. Ed. 2008, 47, 1903.
[21] For reviews, see: a) L. F. Tietze, U. Beifuss, Angew.
Chem. 1993, 105, 137; Angew. Chem. Int. Ed. Engl.
1993, 32, 131; b) R. A. Bunce, Tetrahedron Tetrahedron.
1995, 51, 13103; c) L. F. Tietze, Chem. Rev. 1996, 96,
115; d) S. E. Denmark, A. Thorarensen, Chem. Rev.
628
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 617 – 629

Palladium(II)-Catalyzed Domino Reaction of 2-(1-Alkynyl)-2-alken-1-ones
FULL PAPERS
Kimura, K. Fugami, S. Tanaka, Y. Tamaru, J. Org.
Chem, 1992, 57, 6377; c) see refs.[6g,7a]
K. Ohe, S. Uemura, J. Org. Chem, 1999, 64, 6750; c) T.
Nishimura, K. Ohe, S. Uemura, J. Am. Chem. Soc.
1999, 121, 2645.
[32] See the catalytic cycle of Heck reaction: a) F. Alonso,
I. P. Beletskaya, M. Yus, Tetrahedron 2005, 61, 11771;
b) S. Brase, A. de. Meijere, Metal-Catalyzed Cross-Cou-
pling Reactions, Wiley, Chichester, 1998, pp 99–166.
[33] a) T. Nishimura, T. Onoue, K. Ohe, S. Uemura, Tetra-
hedron. Lett, 1998, 39, 6011; b) T. Nishimura, T. Onoue,
[34] For reviews, see: a) M. Schuster, S. Blechert, Angew.
Chem. 1997, 109, 2124; Angew. Chem. Int. Ed. Engl.
1997, 36, 2036; b) R. Grubbs, S. Chang, Tetrahedron
1998, 54, 4413.
[35] D. J. Faulkner, Nat. Prod. Rep. 1986, 3, 1.
Adv. Synth. Catal. 2009, 351, 617 – 629
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
629