Gold(l)-catalyzed formation of furans by a Claisen type rearrangement of ynenyl allyl ethers

Article abstract of DOI:10.3762/bjoc.7.100

A series of ynenyl allyl ethers were rearranged into polysubstituted furans in the presence of a gold(I) catalyst. It is proposed that the transformation involves a Claisen-type rearrangement that allows the efficient creation of quaternary centers under mild experimental conditions.

Full text of DOI:10.3762/bjoc.7.100

Gold(I)-catalyzed formation of furans by a Claisen-
type rearrangement of ynenyl allyl ethers
Florin M. Istrate and Fabien Gagosz*
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 878–885.
Département de Chimie, UMR 7652, CNRS/Ecole Polytechnique,
91128 Palaiseau, France
doi:10.3762/bjoc.7.100
Received: 20 April 2011
Accepted: 08 June 2011
Published: 29 June 2011
Email:
Fabien Gagosz* - gagosz@dcso.polytechnique.fr
* Corresponding author
This article is part of the Thematic Series "Gold catalysis for organic
synthesis".
Keywords:
Claisen rearrangement; furans; gold-catalysis; quaternary centers
Guest Editor: F. D. Toste
© 2011 Istrate and Gagosz; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
A series of ynenyl allyl ethers were rearranged into polysubstituted furans in the presence of a gold(I) catalyst. It is proposed that
the transformation involves a Claisen-type rearrangement that allows the efficient creation of quaternary centers under mild experi-
mental conditions.
Findings
Furans represent an important class of heteroaromatic com- The various alkynyl and allenyl compounds presented in
pounds, which are found in a large number of natural products, Scheme 1 have thus proved to be suitable precursors for the for-
in synthetic biologically active substances and also in flavor mation of polysubstituted furans in the presence of a gold(I) or
chemicals [1,2]. Consequently, many efforts have been devoted a gold(III) catalyst [17-44].
to the development of synthetic methods which allow a rapid,
efficient, and selective access to the furan motif [3-6]. Recently, We report herein our own investigations in this field which have
several new strategies that involve a metal-mediated cycliza- led to the development of a new procedure for the synthesis of
tion of an allene or an alkyne derivative with an oxygen func- polysubstituted furans by a gold-catalyzed cycloisomerization
tionality have appeared in the literature [7]. Among the tran- of ynenyl allyl ethers [45-48].
sition metals that are commonly employed in these transforma-
tions (viz. Cu, Ag, Pd and Au), gold has proven to be particu- In the course of our work on the development of new gold-
larly suitable given the strong π Lewis acidic property of catalyzed transformations [49-51], we recently found that a
cationic gold species and their ability to activate alkynes and series of ynenyl allyl tosylamides 1 (X = NTs) could be
allenes towards the addition of oxygen functionalities [8-16]. converted under mild experimental conditions into functional-
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Beilstein J. Org. Chem. 2011, 7, 878–885.
Scheme 1: Alkynyl and allenyl substrates in gold-catalyzed formation of furans.
ized pyrroles 3 (X = NTs) in the presence of a gold(I) catalyst shift (2 → 4 → 5). Based on these initial findings, we envis-
(Scheme 2) [52]. In contrast to Fürstners observations for the aged that an analogous transformation could be employed for
rearrangement of allyl pent-4-ynyl ethers [53,54], the results the synthesis of substituted furans 3 (X = O) from ynenyl allyl
obtained during this study strongly suggested that no allyl ethers 1 (X = O) (Scheme 2). The proof that a similar reaction
cation was formed during the reaction. The substitution pattern can take place via an analogous pathway using oxygen- instead
of the pyrroles thus obtained point toward the involvement of a of nitrogen-derivatives would therefore support our initial
more concerted aza-Claisen-type rearrangement mechanism (2 mechanistic proposal and would broaden the scope of this new
→ 3) and tend to exclude the possibility of a simple N to C allyl gold-catalyzed Claisen-type rearrangement [55-62].
Scheme 2: Synthetic approach to functionalized furans.
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Beilstein J. Org. Chem. 2011, 7, 878–885.
Moreover this synthetic approach to furans would be particu-
larly interesting for several reasons:
• The required ynenyl allyl ether substrates are easily accessible
via various methods (see Supporting Information File 1 for
more details),
• the Claisen-type rearrangement would allow the formation of
two new C–O and C–C bonds in a single step,
Figure 1: Natural products possessing a 2-butenylfuran motif.
• the reaction would allow the easy formation of quaternary
centers and the introduction of a variety of other substituents on
the side chain (when R4 ≠ H and R5 ≠ H),
Thus, a wide range of ynenyl allyl ethers 6a–s was synthesized
(see Supporting Information File 1) and reacted under the
• and the reaction could be particularly useful for the prepar- conditions that were found to be optimal for the analogous for-
ation of 2-butenylfurans, whose motif can be found in a variety mation of pyrroles from ynenyl allyl tosylamides, that is,
of natural products, such as rubifolide [63], curzerene [64] or 2 mol % of the gold catalyst {[(p-CF3-C6H4)3P]-Au-NTf2} [66]
pumiloxide [65] (Figure 1).
in dichloromethane at room temperature (Table 1).
Table 1: Scope of the gold(I)-catalyzed formation of furans.a
entry
1
substrate
product
conversionb
100%
yieldc
18%
(75%d)
6a
7a
7b
39%
(86%d)
2
3
6be
100%
100%
59%
(82%d)
6c
6d
7c
7d
81%
(92%d)
4
100%
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Beilstein J. Org. Chem. 2011, 7, 878–885.
Table 1: Scope of the gold(I)-catalyzed formation of furans.a (continued)
5
6
6ef
7e
100%
100%
66%
71%
6f
7f
7
6g
7g
100%
63%
8
9
6h
7h
100%
100%
quant.
quant.
6i
7i
10
6j
7j
100%
78%
11
12
6k
7k
100%
100%
78%
17%
6l
7l
881

Beilstein J. Org. Chem. 2011, 7, 878–885.
Table 1: Scope of the gold(I)-catalyzed formation of furans.a (continued)
13
14
6m
6n
7m
7n
100%
100%
77%
80%
15
16
17
18
19
6o
6p
6q
6r
7o
7p
7q
7r
100%
100%
100%
>84%g
>62%g
90%
82%
86%
73%
36%
6s
7s
aReaction conditions: 0.1 M of substrate in DCM with 2 mol % of (p-CF3-C6H4)3P-Au-NTf2 at rt for 10 minutes. bConversion of the substrate deter-
mined by 1H NMR of the crude mixture. cIsolated yields. dYields determined by 1H NMR of the crude mixture (with 1,3,5-trimethoxybenzene as an
internal reference). eZ/E ratio ≈ 1/3. fZ/E ratio ≈ 1/2.6. gReaction time: 40 minutes.
Under these conditions, we observed the rapid formation quite challenging due to their high volatility (entries 1–4).
(usually less than 10 minutes) of the expected furans. The allyl These reactions were therefore performed in deuterated
(6a), crotyl (6b), prenyl (6c) and geranyl (6d) derivatives were dichloromethane and their yields assessed by 1H NMR spec-
readily cycloisomerized in the presence of the gold catalyst, but troscopy with 1,3,5-trimethoxybenzene as an internal reference
the isolation of the corresponding furans 7a–d proved to be (75–92%). All the examples presented in entries 2–19 are in
882

Beilstein J. Org. Chem. 2011, 7, 878–885.
agreement with the postulated Claisen-type rearrangement since Substrates 6n–q, which possess either a phenyl or a longer
only the exclusive formation of branched products of type 3 was alkyl chain, were indeed efficiently converted into
observed. Indeed, a linear product of type 5 resulting from an O compounds 7n–q (80–90%, entries 14–17). However, limited
to C shift of the allylic moiety could not be detected, whatever reactivity was observed with ethers 6r–s, which could not be
substrate was used [67]. Substrates 6b and 6e, which were used completely converted into the corresponding furans 7r–s
as a mixture of Z/E isomers, each afforded a single product, i.e., (entries 18–19).
the furans 7b and 7e, respectively (entries 2 and 5). The cycloi-
somerization of compounds 6f, 6g, 6o, 6q and 6s, which pos- A mechanistic proposal for the formation of furans 7a–s is
sess an exocyclic allyl moiety, furnished the corresponding presented in Scheme 3. It is based on the results shown in
furans 7f, 7g, 7o, 7q and 7s in moderate to quantitative yields entries 2–19 (Table 1), which support the involvement of a
(entries 6, 7, 15, 17 and 19). It is also worth noting that an gold-catalyzed Claisen-type rearrangement as the key step of
increase in the substitution at the terminus of the allylic the transformation.
moieties of the substrates (monosubstitution in the case of 6b,
disubstitution for 6c–s) did not notably influence the conver- The gold(I) activation of the alkyne moiety in substrate 6 could
sion, the rate or the yield of the reaction, even though the steric promote the nucleophilic addition of the oxygen atom, and lead
hindrance of the postulated Claisen intermediate 2 would have to the formation of the cationic vinyl gold intermediate 8. A
increased. This behavior strongly contrasts with the generally subsequent Claisen-type rearrangement would furnish the inter-
less efficient Claisen reactions of similarly substituted mediate 9. The loss of a proton to allow aromatization of the
substrates and consequently allows the easy creation of a new system, followed by a protodemetalation step would finally give
quaternary center for the disubstituted substrates 6c–s (entries furan 7.
3–19). Interestingly substrates 6h–m, which possess an extra
substituent at the allylic position of the ynenyl fragment, also In summary, we have developed a new gold(I)-catalyzed forma-
easily rearranged to afford the expected furans 7h–m in good to tion of polysubstituted furans, which is characterized by its effi-
quantitative yields (entries 8–13). A large variety of substituents ciency, the mild conditions employed and the easy formation of
were tolerated including primary, secondary or tertiary alkyl quaternary centers. The selectivity observed in the structure of
groups and even a vinyl or a phenyl group. However, a poor the final product is in agreement with the postulated Claisen-
yield (17%) was obtained when compound 6l was used as the type rearrangement. Further studies related to the development
substrate, due to the facile polymerization of the corresponding of an asymmetric version of this new gold(I)-catalyzed process
vinylfuran 7l (entry 12). Substituents other than a simple methyl and its application to the synthesis of natural products are
group could be introduced at position C(3) of the furans. underway.
Scheme 3: Mechanistic proposal.
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