Communications
DOI: 10.1002/anie.200902248
Gold Catalysis
Evolution of Propargyl Ethers into Allylgold Cations in the Cyclization
of Enynes**
Eloꢀsa Jimꢁnez-Nfflæez, Mihai Raducan, Thorsten Lauterbach, Kian Molawi, Cꢁsar R. Solorio,
and Antonio M. Echavarren*
Table 1: Gold(I)-catalyzed reaction of E- or Z-dienynes 1a–g.[a]
Understanding the mechanisms and stereochemistry by which
enynes react with metal catalysts is central for the application
of these transformations in synthesis. Recently, the similar-
ities of metal-catalyzed additions of nucleophiles to 1,6-
enynes with polyene cyclizations,[1] which proceed with an
anti stereochemistry,[2-5] have been emphasized. However,
substrates with strongly electron-donating groups on the
alkene react nonstereospecifically via open carbocations.[6]
We have now found that propargyl alcohols, ethers, and silyl
Entry
1a–g
R
t [min]
Products (yield [%]; ratio)
ethers 1 react with gold(I) catalysts by a new type of
intramolecular 1,5-migration of OR groups (Scheme 1). This
reaction leads to the tricyclic compounds 2, which are related
1
2
3
(E)-1a
(E)-1b
(E)-1c
(E)-1d
(E)-1e
(E)-1 f
(E)-1g
(Z)-1a
(Z)-1b
(Z)-1c
(Z)-1d
(Z)-1 f
H
TMS
Me
MOM
Bn
PNBn
Ac
H
TMS
Me
MOM
PNBn
5
10
5
10
10
15
10
5
10
5
10
40
2a + 6a (14; 7:1)
2b (33) + 6b (5)[b,c]
2c (84)
2d + 6d (57; 50:1)
2e (64)
2 f + 6 f (74; 16:1)
2g + 11 (96; 1.4:1)
7a + 8a (52; 11:1)
7b + 8b (46; 6:1)
7c + 8c (81; 9:1)
7d + 8d (72; 7:1)
7 f + 8 f (87; 7:1)
4[d]
5
6
7
8
9[d]
10
11[d]
12[d]
[a] 2 mol% 5. [b] 9 (20% yield) and 10 (14% yield) were obtained.
1
[c] Yield determined by H NMR methods. [d] 1 mol% 5. TMS=trime-
thylsilyl, MOM=methoxymethyl, Bn=benzyl, PNBn=p-nitrobenzyl.
Scheme 1. Gold(I)-catalyzed 1,5-migration of OR groups in dienynes 1.
to the sesquiterpenes globulol (3a), epiglobulol (3b),[7] and
halichonadin F (3c).[8] Significantly, the migration proceeds
via allylgold cations 4 by a syn addition of the alkyne and the
OR group to the alkene. A related 1,6-migration was also
found in 1,7-enynes.
Propargyl alcohol (E)-1a reacted with the gold(I) catalyst
5 to give a 7:1 mixture of 2a and 6a in low yield (Table 1,
entry 1). Whereas the TMS-ether (E)-1b also gave products
of skeletal rearrangement,[2,3,9] 9 and 10 (Table 1, entry 2), the
reaction of ethers (E)-1c–f gave products 2c–f in 56–84%
yield (Table 1, entries 2–6). Interestingly, although acetate
(E)-1g had been shown to react exclusively by 1,2-acyl
migration to give 11 with AuCl3 or PtCl2,[10] the 1,5-migration
derivative 2g was obtained as the major product using the
gold(I) catalyst 5 (Table 1, entry 7). Reactions of dienynes
(Z)-1a–f led to 7a–f in 39–76% yield (Table 1, entries 8–
12).[11] The configurations of 2 f and 7 f were confirmed by
X-ray diffraction.[12] As minor compounds, products 6a–f and
8a–f having a trans-bicyclo[5.1.0]octane skeleton were also
obtained.[12] Similar results were obtained with other cationic
gold(I) complexes, whereas AuCl or platinum(II) complexes
gave poor results.[13]
[*] E. Jimꢀnez-Nfflæez, M. Raducan, Dr. T. Lauterbach, K. Molawi,
C. R. Solorio, Prof. A. M. Echavarren
Institute of Chemical Research of Catalonia (ICIQ)
Av. Països Catalans 16, 43007 Tarragona (Spain)
E-mail: aechavarren@iciq.es
[**] This work was supported by the MEC (projects CTQ2004-02869,
Consolider Ingenio 2010 Grant CSD2006-0003, predoctoral fellow-
ships to E.J.-N, M.R., C.R.S., Juan de la Cierva Contract to T.L.), and
the ICIQ Foundation. We also thank Dr. J. Benet-Buchholz and E.
Escudero-Adµn (X-ray diffraction unit, ICIQ) for the structures of 2 f,
7 f, and 22a.
Reaction of dienyne (Z)-1c in a 30:1 mixture of CH2Cl2
and MeOH gave the ether 2c in addition to 7c and 8c. The
ether 2c was the product of the reaction of dienyne (E)-1c
(Table 1, entry 3). When this reaction was performed with
CD3OD, 7c and 8c showed no deuterium incorporation,
whereas the methoxy group of 2c was deuterated (Scheme 2).
This experiment confirms that the 1,5-migration is an intra-
Supporting information for this article is available on the WWW
6152
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 6152 –6155