Communications
808C, 24 h) we observed an oxidation of species 1a to give the
ring-expansions worked well with phenylalkynylcyclopro-
panes 1h–1m bearing altered meta-substituents comprising
methoxy, fluoro, chloro, 2,4-dimethoxy, 2,3-methylenedioxy,
and 2-naphthyl groups; their resulting products 2h–2m were
obtained in 72–95% yields (Table 2, entries 7–12). This gold
catalysis is particularly suitable for aminoalkynylcyclopro-
panes 1n–1q; the reactions were completed within 2–5 hours,
and gave desired cyclobutenyl amides in 91–95% yields
(Table 2, entries 13–16).
desired cyclobutenyl ketone 2a (40%), diketone 3a (20%),
and starting material 1a (35%; Table 1, entry 1). Poor activity
and chemoselectivity were also observed for [IPrAuCl]/
AgSbF6 under the same reaction conditions (Table 1,
entry 2).
Although
[P(tBu)2(o-biphenyl)AuCl]/AgSbF6
showed an improved selectivity toward the desired 2a
(48%) with negligible formation of diketone 3a, the extent
of conversion was moderate (52%; Table 1, entry 3). We
selected AgNTf2 to generate [P(tBu)2(o-biphenyl)Au]NTf2
which improved the yield (52%) of desired 2a (Table 1,
entry 4). Enhanced yields were obtained with three- and
fivefold excess of Ph2SO and afforded 2a in 70% and 83%
yields, respectively (Table 1, entries 5 and 6). We speculate
that Ph2SO tends to stabilize the AuI complex from decom-
position to Au0. AgNTf2 alone failed to catalyze the reaction
at all (Table 1, entry 7). When we examined the solvent
effects (Table 1, entries 8–10), we found that nitromethane
gave the best yield of 2a (90%) over a moderate period (12 h)
at 808C. Brønsted acid TfOH was inactive as a catalysis in this
reaction (Table 1, entry 11).
Table 3 shows the applicability of this catalysis to sub-
stituted cyclopropylalkynes 4a and 4b, which delivered
cyclobutenyl ketones 6a and 6b in 71 and 76% yields,
Table 3: Gold catalyzed ring-expansion of substituted cyclopropylal-
kynes.
Entry Cyclopropane
Conditions[a]
Product (yield [%])[b]
1
2
Ar=4-MeOC6H4 (4a)
Ar=3,4-(MeO)2C6H3 (4b) MeNO2, 8 h
MeNO2, 8 h
6a (71)
6b (76)
Table 2 includes various alkynylcyclopropane derivatives
1b–1q bearing either an aryl or an amino group to ensure that
attack of Ph2SO occurs only at the Cb carbon atom. Under
optimized conditions, the gold-catalyzed ring-expansions
occurred smoothly, without formation of diketone by-prod-
ucts. Entries 1–6 of Table 2 show the effects of para-sub-
stituted phenyl substituents; we obtained excellent yields (92–
95%) of resulting cyclobutenyl ketones 2b–2c bearing
electron-donating groups such as methyl and methoxy.
Notably, the catalytic reactions maintained satisfactory effi-
ciency with substrates 1d–1g containing electron-withdraw-
ing groups including fluoro, chloro, bromo, and ethoxycar-
bonyl; the corresponding products 2d–2g were obtained in
61–86% yields after longer reaction times. Such oxidative
3
Ar=4-MeOC6H4 (4c)
MeNO2, 5 h
6c (84)[c]
4
5
R=C6H4CH2 (4d)[d]
R=n-C6H13 (4e)[d]
MeNO2/DCE[e] 6d (56)
MeNO2, 7 h 6e (61)
[a] Reaction conditions: [LAuCl]/AgNTf2 (5 mol%; L=P(tBu)2(o-
biphenyl)), [substrate]=0.1m, Ph2SO (5 equiv), 1008C, MeNO2.
[b] Yield of isolated product after separation by column chromatography
on silica gel. [c] PhArSO (1.0 equiv, Ar=2-MeC6H4) was used. [d] 1:1
mixture of diastereomers. [e] Solvent ratio of 1:1, 24 hours.
Table 2: Scope of gold-catalyzed oxidative ring-expansions.[a]
respectively. Substrate 4c underwent smooth reaction with
PhArSO (1.0 equiv, Ar= 2-MeC6H4) and gave the desired
ketone 6c in 84% yield. In the case of substituted cyclo-
propylalkynes 4d and 4e, the desired products 6d and 6e
were obtained in 56 and 61% yields, respectively. These
reaction outcomes resulted from a selective migration of the
Entry
Substrate
t [h]
Product (yield [%])[b]
1
2
3
4
5
6
7
8
R=4-MeC6H4 (1b)
R=4-MeOC6H4 (1c)
R=4-FC6H4 (1d)
R=4-ClC6H4 (1e)
R=4-BrC6H4 (1 f)
R=4-MeO2CC6H4 (1g)
R=3-MeOC6H4 (1h)
R=3-FC6H4 (1i)
10
8
2b (92)
2c (95)
2d (86)
2e (77)
2 f (69)
2g (61)
2h (85)
2i (72)
2j (72)
2k (72)
2l (95)
2m (92)
2n (94)
2o (91)
2p (95)
2q (93)
15
24
20
24
8
12
15
12
8
12
5
2
5
5
À
more substituted C C cyclopropyl bond.
For curiosity, we extended the use of this catalysis to other
arylalkyne derivatives 5a,b; these oxidation reactions pro-
ceeded smoothly using Ph2SO (1.2 equiv), but gave com-
pounds 7a,b arising from addition of Ph2S to the alkynyl
carbon atom adjacent to the aryl group. Similar results were
reported by Ujaque, Asensio, and co-workers,[10e] who pro-
posed a [3,3]-sigmatropic rearrangement rather than carbe-
noid intermediates to give these addition products. Accord-
ingly, we performed crossover experiments (Scheme 3), which
clearly indicate that external sulfides are not the reaction
sources for compounds 7c and 7c’, thus excluding the
intermediacy of a-carbonylcarbeniods C that were hypothe-
sized in Scheme 2.
9
R=3-ClC6H4 (1j)
10
11
12
13
14
15
16
R=3,5-(MeO)2C6H3 (1k)
R=3,4-(OCH2O)C6H3 (1l)
R=2-naphthyl (1m)
R=TsNMe (1n)
R=TsN(nPr) (1o)
R=MsNMe (1p)
R=MsNBn (1q)
[a] Reaction conditions: [substrate]=0.1m, 1008C, MeNO2. [b] Yield of
isolated product after separation by column chromatography on silica
gel. Bn=benzyl, L=P(tBu)2(o-biphenyl).
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 9891 –9894