Gold(I)-catalyzed tandem rearrangement-nucleophilic substitution of α-acetoxy alkynyl oxiranes or aziridines: Efficient approach to furans and pyrroles

Article abstract of DOI:10.1002/ejoc.200901331

Highly substituted furans and pyrroles were efficiently formed by a new gold(I)-catalyzed tandem rearrangement-nucleophilic substitution of acetoxylated alkynyl oxiranes and aziridines in the presence of various nucleophiles.

Full text of DOI:10.1002/ejoc.200901331

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200901331
Gold(I)-Catalyzed Tandem Rearrangement–Nucleophilic Substitution of
α-Acetoxy Alkynyl Oxiranes or Aziridines: Efficient Approach to Furans and
Pyrroles
Aurélien Blanc,*[a] Aurélien Alix,[a] Jean-Marc Weibel,[a] and Patrick Pale*[a]
Keywords: Gold / Cyclization / Homogeneous catalysis / Oxygen heterocycles / Nitrogen heterocycles
Highly substituted furans and pyrroles were efficiently
formed by a new gold(I)-catalyzed tandem rearrangement–
nucleophilic substitution of acetoxylated alkynyl oxiranes
and aziridines in the presence of various nucleophiles.
Introduction
Gold catalysis[1] has revamped the chemistry of pro-
pargyl derivatives and especially that of propargyl esters.[2]
Gold coordination to the alkyne moiety of such compounds
usually induces rearrangements through internal 1,2- or
1,3-nucleophilic addition of the ester carbonyl group to the
Au-activated alkyne. Although gold salts have the reputa-
tion of being alkeno- and alkynophilic,[1,3] recent evidence
showed that oxophilicity could also play a key role in Au-
catalyzed reactions of alkynyl derivatives containing hetero-
atoms.[4] This duality was also highlighted by our own work
on the rearrangement of acyloxylated alkynyloxiranes into
divinyl ketones catalyzed by
a
gold(I) complex
(Scheme 1).[5] Moreover, recent theoretical mechanistic
studies of this reaction revealed only a slight stability differ-
ence between π– and σ–Au complexes of such substrates
(Scheme 1). These calculations also showed that both acti-
vations, that is, alkynophilicity and Lewis acid character of
gold, could be operative in this rearrangement.[6]
Scheme 1. Gold(I)-catalyzed rearrangement of acyloxylated alkynyl
oxiranes in divinyl ketones.
In parallel, we recently found that alkynyloxiranes could
also be rearranged into furans in the presence of an external
nucleophile and catalytic amounts of silver or gold salts.
This process occurred by nucleophile opening of the epox-
ide ring followed by a cyclization–elimination process
(Scheme 2).[7]
On the basis of our previous reports, we thought that
2,3,5-trisubstituted furans could also be produced from α-
acyloxylated αЈ-alkynyloxiranes and external nucleophiles
by gold catalysis through oxophilic and/or alkynophilic ac-
Scheme 2. Coinage metal-catalyzed transformation of alkynyl oxir-
anes into furans.
[a] Laboratoire de Synthèse et Réactivité Organiques, associé au
CNRS, Institut de Chimie, Université de Strasbourg,
4 rue Blaise Pascal, 67000 Strasbourg, France
Fax: +33-3-90241517
E-mail: ppale@unistra.fr
ablanc@unistra.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901331.
Scheme 3. Nucleophile-mediated furan formation in gold catalysis.
1644
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1644–1647

Efficient Approach to Furans and Pyrroles
tivation. Such a route would be a convenient alternative to der these conditions, ethanol, butyl alcohol, and 2-propanol
the rearrangement of α-acyloxylated βЈ-alkynyloxiranes de- gave furans 2b–d in 86, 83, and 82% yield, respectively
scribed by Liang[8] (Scheme 3).
(Table 2, Entries 3–5). In the presence of tert-butyl alcohol,
the rapid formation of furan 2e was detected but degrada-
tion occurred, which led to polar products (Table 2, En-
try 6). Ten equivalents of allyl alcohol was required to ob-
tain a reasonable yield of furan 2f (Table 2, Entry 7). In
contrast, treatment of 1a with benzyl alcohol resulted in
the formation of benzyloxy furan 2g in high yield (Table 2,
Entry 8). With the perspective to induce the formation of
highly substituted phenols through a cascade reaction, sim-
ilar to the report of Hashmi,[10] we tried to introduce a pro-
pargyl moiety adjacent to the furan. Epoxyalkyne 1a was
thus submitted to the reaction conditions in the presence of
propargyl alcohol. Unfortunately, mostly degradation prod-
ucts were observed (Table 2, Entry 9). Nevertheless, with
protected 3-trimethylsilylprop-2-yn-1-ol, furan 2i was ob-
tained in 41% yield (Table 2, Entry 10). Interestingly, eth-
anethiol and benzyl thiol proved fully compatible with the
gold catalyst, despite their coordination ability. They acted
as alcohols, leading to the corresponding thio-substituted
furans 2j,k in good yields (Table 2, Entries 11 and 12). In
contrast, amines failed as nucleophiles, and starting materi-
als were mostly recovered, probably due to their strong co-
ordination to gold (Table 2, Entries 13 and 14).
Results and Discussion
In the present study, we report that gold(I) catalyzes an
efficient tandem rearrangement–nucleophilic substitution[9]
of α-acetoxyalkynyl oxiranes mediated by various nucleo-
philes to afford furans. We also extended this chemistry to
the corresponding aziridines, which gave pyrroles.
In order to establish the most appropriate reaction condi-
tions, we subjected readily available (3-acetoxyprop-1-ynyl)-
oxirane[5] 1a to a series of gold catalysts in the presence
of methanol in dichloromethane (Table 1). Treating 1a with
5 mol-% of gold(I) chloride slowly provided the expected
furan 2a bearing a methoxy group, although in only 45%
yield due to some decomposition (Table 1, Entry 1). AuCl3
significantly improved the rate of the reaction, as 2a was
obtained in only 1 h in 76% yield (Table 1, Entry 2). Using
the more cationic gold complex Ph3PAuSbF6 formed in
situ, 2a was formed in a fast and very clean reaction in
excellent isolated yield (Table 1, Entry 3). Other
counteranions did not improve this transformation
(Table 1, Entries 4 and 5). Control experiments revealed
that silver hexafluoroantimonate also catalyzed the same re-
action but to a lesser extent[7b] (Table 1, Entry 6) and that
triphenylphosphanylgold chloride alone was totally ineffec-
tive (Table 1, Entry 7).
Table 2. Scope of the nucleophiles used in the gold(I)-catalyzed
rearrangement of 1a into furans.
Table 1. Screening of catalysts for the transformation of acetoxyl-
ated alkynyloxiranes 1a.
Entry
Catalyst
Time [h]
Yield [%][a]
1
2
3
4
5
6
7
AuCl
AuCl3
PPh3AuCl/AgSbF6
PPh3AuCl/AgNTf2
PPh3AuCl/AgOTf
AgSbF6
15
1
0.25
0.5
0.25
20
45[b]
76
95
74
85
50[c]
[d]
PPh3AuCl
20
–
[a] Yield of isolated pure product. [b] Degradation of the starting
material occurred. [c] 35% of the starting material was recovered.
[d] No conversion.
Various representative nucleophiles, such as alcohols,
thiols, and amines were then engaged in the transformation
of 1a (Table 2). In each case, we adjusted the amount of
nucleophile used. For methanol, 2 equivalents was enough,
although the efficiency of the reaction was slightly affected,
[a] Yield of isolated pure product. [b] Degradation occurred leading
to unidentified byproducts. [c] Calculated yield on a nonseparable
mixture of 2k and benzyl thiol. [d] No conversion.
With these results in hand, we examined the scope of this
but 5 equivalents gave the same yield than an excess of gold(I)-catalyzed tandem rearrangement–nucleophilic sub-
methanol (Table 2, Entries 1 and 2 vs. Table 1, Entry 3). stitution on various alkynyloxiranes (Table 3). Compounds
Screening more hindered alcohols showed that 10 equiva- 3a,b were previously rearranged into divinyl ketones in the
lents of nucleophile were necessary to keep high yields. Un- presence of Ph3PAuSbF6,[5] but addition of a nucleophile
Eur. J. Org. Chem. 2010, 1644–1647
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1645

A. Blanc, A. Alix, J.-M. Weibel, P. Pale
SHORT COMMUNICATION
led to completely different issues. Indeed, in the presence of converted into pyrroles 6 (75%) and 7 (67%) in the presence
methanol, α-methoxyfurans 4a,b were rapidly obtained in of methanol or ethanol, respectively (Scheme 4).
high yields of 85 and 92%, respectively (Table 3, Entries 1
and 2) and it is noteworthy that no trace of other products
Conclusions
could be detected. Similarly, alkynyloxirane 3c generated α-
methoxyfuran 4c in good yield (Table 3, Entry 3). Even sub-
strate 3d bearing an o-nitrophenyl group attached to the
propargylic position provided methoxyfuran 4d, although
in modest yield and with a longer reaction time (Table 3,
Entry 4).
In conclusion, we have reported a novel Au-catalyzed
cascade reaction of acetoxylated alkynyloxiranes and -azir-
idines. This cascade allows various highly substituted furans
and pyrroles carrying different alkoxy or alkylthio groups
at the α-position to be produced. Several mechanistic path-
ways can be considered such as 1,2-acyl migration concomi-
tant with oxirane opening, followed by nucleophilic substi-
tution, cyclization, and elimination (Scheme 5). Further
studies, including calculations and detailed investigations
into the mechanism of this reaction, are in progress in our
laboratory.
Table 3. Scope of the gold(I)-catalyzed tandem rearrangement–
nucleophilic substitution of alkynyloxiranes to furans in the pres-
ence of methanol.
Experimental Section
General Procedure for Preparation of α-Substituted Furans or Pyr-
roles: Alkynyloxirane or alkynylaziridine (0.2 mmol in 1 mL of
CH2Cl2) was added to a stirred solution of premixed Ph3PAuCl
(0.05 mmol) and AgOTf (0.05 mmol) in CH2Cl2/MeOH (9:1, 1 mL)
or in CH2Cl2 (1 mL) containing the corresponding nucleophile (5
or 10 equiv.) at 0 °C or room temperature. The reaction was moni-
tored by thin-layer chromatography until completion. The reaction
mixture was filtered throughout a pad of silica gel with CH2Cl2.
Solvents were removed in vacuo, and the crude residue was purified
by flash chromatography.
Supporting Information (see footnote on the first page of this arti-
cle): Selected experimental procedures and spectroscopic data.
Acknowledgments
[a] Yield of isolated pure product.
The authors thank the Centre National de la Recherche Sci-
entifique (CNRS) and the French Ministry of Research for finan-
cial support.
We then sought to extend the tandem reaction to analo-
gous aziridine compounds that would give highly substi-
tuted pyrroles.[11] As expected, acyloxylated alkynylazirid-
ine 5, synthesized in 41% yield from the corresponding en-
yne by using the procedure of Andersson,[12] was efficiently
[1] For selected reviews on gold chemistry, see: a) P. Belmont, E.
Parker, Eur. J. Org. Chem. 2009, 6075–6089; b) J. Muzart, Tet-
rahedron 2008, 64, 5815–5849; c) Z. Li, C. Brouwer, C. He,
Chem. Rev. 2008, 108, 3239–3265; d) A. Arcadi, Chem. Rev.
2008, 108, 3266–3325; e) E. Jiménez-Nunez, A. M. Echavarren,
Chem. Rev. 2008, 108, 3326–3350; f) D. J. Gorin, B. D. Sherry,
F. D. Toste, Chem. Rev. 2008, 108, 3351–3378; g) A. S. K.
Hashmi, M. Rudolph, Chem. Soc. Rev. 2008, 37, 1766–1775;
h) V. Michelet, P. Y. Toullec, J.-P. Genêt, Angew. Chem. Int. Ed.
2008, 47, 4268–4315; i) A. Fürstner, P. W. Davies, Angew.
Chem. Int. Ed. 2007, 46, 3410–3449; j) A. S. K. Hashmi, Chem.
Rev. 2007, 107, 3180–3211; k) E. Jiménez-Núñez, A. M. Echav-
arren, Chem. Commun. 2007, 333–346; l) A. S. K. Hashmi, G. J.
Hutchings, Angew. Chem. Int. Ed. 2006, 45, 7896–7936; m) C.
Bruneau, Angew. Chem. Int. Ed. 2005, 44, 2328–2334; n) C.
Scheme 4. Gold(I)-catalyzed rearrangement of alkynylaziridines
into pyrroles in the presence of alcohols.
Scheme 5. Proposed mechanistic pathway.
1646
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1644–1647

Efficient Approach to Furans and Pyrroles
Aubert, O. Buisine, M. Malacria, Chem. Rev. 2002, 102, 813–
Ji, X.-Y. Shu, J. Chen, S.-C. Zhao, Z.-J. Zheng, X.-Y. Liu, Y.-
M. Liang, Org. Biomol. Chem. 2009, 7, 2501–2505.
[9] For references on direct nucleophilic substitutions catalyzed by
gold(III), see: a) M. Georgy, V. Boucard, J.-M. Campagne, J.
Am. Chem. Soc. 2005, 127, 14180–14181; b) V. Terrason, S.
Marque, M. Gregory, J.-M. Campagne, D. Prim, Adv. Synth.
Catal. 2006, 348, 2063–2067; c) M. Georgy, V. Boucard, O.
Debleds, C. Dal Zotto, J.-M. Campagne, Tetrahedron 2009, 65,
1758–1766; d) T. H. Haug, T. Harschneck, A. Duschek, C.-U.
Lee, J. T. Binder, H. Menz, S. F. Kirsch, J. Organomet. Chem.
2009, 694, 510–514.
834.
[2]
a) J. Marco-Contelles, E. Soriano, Chem. Eur. J. 2007, 13,
1350–1357; b) A. Correa, N. Marion, L. Fensterbank, M. Mal-
acria, S. P. Nolan, L. Cavallo, Angew. Chem. Int. Ed. 2008, 47,
718–721; c) N. Marion, S. P. Nolan, Angew. Chem. Int. Ed.
2007, 46, 2750–2752.
a) D. J. Gorin, F. D. Toste, Nature 2007, 446, 395–403; b) P.
Pyykkö, Angew. Chem. Int. Ed. 2004, 43, 4412–4456; c) P. S.
Bagus, Y. S. Lee, K. S. Pitzer, Chem. Phys. Lett. 1975, 33, 408–
411.
a) T. Jin, Y. Yamamoto, Org. Lett. 2008, 10, 3137–3139; b) L.-
Z. Dai, M. Shi, Chem. Eur. J. 2008, 14, 7011–7018; c) L.-Z.
Dai, M.-J. Qi, Y.-L. Shi, X.-G. Liu, M. Shi, Org. Lett. 2007, 9,
3191–3194; d) T. Jin, Y. Yamamoto, Org. Lett. 2007, 9, 5259–
5262; e) Y. Yamamoto, J. Org. Chem. 2007, 72, 7817–7831.
[3]
[4]
[10] A. S. K. Hashmi, P. Haufe, C. Schmid, A. Rivas Nass, W. Frey,
Chem. Eur. J. 2006, 12, 5376–5382.
[11] For selected references on the synthesis of substituted pyrroles
catalyzed by gold, see: a) D.-D. Chen, X.-L. Hou, L.-X. Dai,
Tetrahedron Lett. 2009, 50, 6944–6946; b) R. Surmont, G.
Verniest, N. De Kimpe, Org. Lett. 2009, 11, 2920–2923; c) P. W.
Davies, N. Martin, Org. Lett. 2009, 11, 2293–2296; d) H. M.
Peng, J. Zhao, X. Li, Adv. Synth. Catal. 2009, 351, 1371–1377;
e) X.-Z. Shu, X.-Y. Liu, H.-Q. Xiao, K.-G. Ji, L.-N. Guo, Y.-
M. Liang, Adv. Synth. Catal. 2008, 350, 243–248; f) F. M. Istr-
ate, F. Gagosz, Org. Lett. 2007, 9, 3181–3184; g) D. J. Gorin,
N. R. Davis, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 11260–
11261.
[5] M.-C. Cordonnier, A. Blanc, P. Pale, Org. Lett. 2008, 10, 1569–
1572.
[6] A. G. Pérez, C. S. López, J. Marco-Contelles, O. N. Faza, E.
Soriano, A. R. de Lera, J. Org. Chem. 2009, 74, 2982–2991.
[7] a) A. Blanc, K. Tenbrink, J.-M. Weibel, P. Pale, J. Org. Chem.
2009, 74, 4360–4363; b) A. Blanc, K. Tenbrink, J.-M. Weibel,
P. Pale, J. Org. Chem. 2009, 74, 5342–5348.
[8] a) X.-Y. Shu, X.-M. Liu, H.-Q. Xiao, K.-G. Ji, L.-N. Guo, C.-
Z. Qi, Y.-M. Liang, Adv. Synth. Catal. 2007, 349, 2493–2498;
b) K.-E. Ji, Y.-W. Shen, X.-Z. Shu, H.-Q. Xiao, Y.-J. Bian, Y.-
M. Liang, Adv. Synth. Catal. 2008, 350, 1275–1280; c) K.-G.
[12] M. J. Södergren, D. A. Alonso, A. V. Bedekar, P. G. Andersson,
Tetrahedron Lett. 1997, 38, 6897–6900.
Received: November 19, 2009
Published Online: February 11, 2010
Eur. J. Org. Chem. 2010, 1644–1647
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1647