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Cyclobutene vs 1,3-Diene Formation in the Gold-Catalyzed Reaction
of Alkynes with Alkenes: The Complete Mechanistic Picture
M. Elena de Orbe,† Laura Amenós,† Mariia S. Kirillova,† Yahui Wang,† Verónica López-Carrillo,†
Feliu Maseras,*,†,‡ and Antonio M. Echavarren*,†,§
†

Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Av. Països Catalans 16,
43007 Tarragona, Spain
‡
Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
§
Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, C/Marcel·li Domingo s/n, 43007 Tarragona,
Spain
S
* Supporting Information

ABSTRACT: The intermolecular gold(I)-catalyzed reaction
between arylalkynes and alkenes leads to cyclobutenes by a [2 +
2] cycloaddition, which takes place stepwise, first by formation
of cyclopropyl gold(I) carbenes, followed by a ring expansion.
However, 1,3-butadienes are also formed in the case of orthosubstituted arylalkynes by a metathesis-type process. The
corresponding reaction of alkenes with aryl-1,3-butadiynes,
ethynylogous to arylalkynes, leads exclusively to cyclobutenes.
A comprehensive mechanism for the gold(I)-catalyzed reaction
of alkynes with alkenes is proposed on the basis of density
functional theory calculations, which shows that the two pathways leading to cyclobutenes or dienes are very close in energy. The
key intermediates are cyclopropyl gold(I) carbenes, which have been independently generated by retro-Buchner reaction from
stereodefined 1a,7b-dihydro-1H-cyclopropa[a]naphthalenes.

■

INTRODUCTION
Cycloisomerizations of 1,n-enynes catalyzed by gold(I) and
other electrophilic metals proceed by mechanistically complex,
multistep transformations that lead to novel architectures1 and
have been applied for the total synthesis of a variety of natural
products.2 The parent intermolecular reaction between
terminal alkynes 1 and alkenes 2 gives rise to cyclobutenes 3
as a result of a [2 + 2] intermolecular cycloaddition (Scheme
1).3 Key for the success of this reaction was the use of cationic
gold(I) complex A with a very bulky phosphine. By exchanging
the anion of catalyst A from SbF6− to softer BAr4F−,
cyclobutenes 3 were obtained in better yields presumably by
decreasing the rate of formation of σ,π-digold(I) alkyne
complexes, which were shown to be unproductive dead ends
in this transformation.4 We have extended this [2 + 2]
cycloaddition for the synthesis of up to 15-membered ring
macrocycles by performing the reaction with 1,n-enynes (n =
10−16),5 which has been applied for the enantioselective total
synthesis of rumphellaone A.6
Cyclobutenes are highly valuable synthons for the preparation of functionalized cyclobutanes and other compounds.7,8
Besides photochemical processes,9 other transition metals
different from gold(I) have been used to promote [2 + 2]
cycloaddition reactions, which are however rather limited with
respect to the range of alkenes that can be used.10,11 Thus, the
rhodium-catalyzed [2 + 2] cycloaddition only proceeds with
© 2017 American Chemical Society

Scheme 1. Gold(I)-Catalyzed [2 + 2] Cycloaddition of
Alkynes with Alkenes3,4 or Formation of 1,3-Dienes and
Lactones20

electron-deficient12,13 or strained alkenes.14 Other transitionmetal catalysts also promote the [2 + 2] cycloaddition of
strained alkenes with alkynes.15,16 The reaction of propiolates
Received: March 26, 2017
Published: July 12, 2017
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and other alkynes bearing electron-withdrawing groups with
alkenes in the presence of Lewis17 or Brønsted18 acids also
leads to cyclobutenes.19 Interestingly, in the presence of
gold(I), this type of alkyne reacts with alkenes to form 1,3dienes 5 or lactones 6 (Scheme 1).20
On the basis of studies on the mechanism of gold(I)catalyzed cyclization of 1,n-enynes21−24 and other electrophiles,25,26 we hypothesized that the reaction of alkynes with
alkenes could take place by the electrophilic addition of (η2alkyne)gold(I) complexes 7 to the alkene to form intermediate
cyclopropyl gold(I) carbenes 8, which undergo ring expansion
to give (η2-cyclobutene)gold(I) complexes 9 (Scheme 2). An
intermediate (η2-cyclobutene)gold(I) complex has been
spectroscopically detected at low temperature from a 1,6enyne.27

Table 1. Cycloaddition vs Rearrangement in the Reaction of
Alkynes 1a−j with Alkenes 2a−ea,31

entry
1
2d,e
3
4e−g
5f
6
7
8e,h
9
10
11
12
13
14
15
16
17
18
19
20
21
22

Scheme 2. Mechanistic Hypothesis for the [2 + 2]
Cycloaddition of Electron-Rich Alkynes3,4 vs Formation of
1,3-Dienes or Lactones from Electron-Deficient Alkynes20

In the case of electron-rich alkynes, the alkene reacts by
attack at the internal carbon,3,4 whereas electron-deficient
alkynes react at the terminal carbon, leading to intermediates
10, which can undergo formal 1,3-migration to give 1,3-dienes
5 or experience intramolecular attack by the carboxylic acid (Z
= CO2H) to afford 6 (Scheme 2).20
The very different outcomes of the reactions of electron-rich
aryl- or cyclopropyl-substituted alkynes and alkynes bearing
electron-withdrawing groups are rather striking. Therefore, we
decided to examine in detail the reaction of a broader range of
terminal alkynes to get a clearer perspective of this fundamental
reaction in gold(I) chemistry. Surprisingly, we found that some
ortho-substituted arylalkynes react with alkenes to give 1,3dienes in a metathesis-type process. On the other hand, less
sterically demanding 1,3-butadiynes lead exclusively to cyclobutenes. Here we report these results along with a detailed
theoretical analysis of the mechanism of formation of
cyclobutenes or 1,3-dienes. To support the initial involvement
of cyclopropyl gold(I) carbenes in these transformations, we
also studied the generation of these intermediates by a retroBuchner reaction. This study leads to a comprehensive picture
of the gold(I)-catalyzed reactions of alkynes with alkenes.

1
1a
1b
1c
1d
1e
1f
1g
1h
1b
1c
1d
1e
1f
1i
1j
1b
1c
1d
1e
1f
1e
1e

2
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2b
2c
2c
2c
2c
2c
2d
2e

3 (yield, %)b

11 (yield, %)b

c

3a (95)
3b (37)
3c (64)
3d (9)
3e (3, 3i)
3f (54, 54)
3h (75)
3i (65)
3j (50, 49i)
3k (54, 49)
3l (44)
3m (50)
3n (40)
3o (48)
3p (61)
3q (51, 44)
3r (25)
3s (24)
3t (58, 53)
3u (40, 41j)
3v (84)

11b (29)
11c (3)
11d (48)
11e (45, 43i)
11g (36)
11h (5)
11i (27)
11j (25, 20i)
11k (33, 28)
11l (25)
11m (3)
11n (22)
11o (19)
11p (38)
11q (33, 17)
11r (43)
11s (42)
11t (24, 12)
11u (34, 37)
11v (5)

a
Alkyne:alkene in a 1:2 ratio. bYields determined by 1H NMR using
1,4-diacetylbenzene as the internal standard. Selected isolated yields in
italics. See the Supporting Information for the other isolated yields.
c
Reaction with A′ (3 mol %) at 23 °C.4 dAlkyne:alkene in a 1:4 ratio.
e
A 4 mol % concentration of A′. fCatalyst A instead of A′.
g
Alkyne:alkene in a 1:3 ratio. hA′ prepared in situ from tBuXPhosAuCl and NaBAr4F. iReaction on a 1 g scale of the alkyne. jMixture of
1,3,4,4- and 1,3,3,4-tetrasubstituted cyclobutenes in a 2.4:1 ratio.

the reaction of o-tolylacetylene (1b) with 2a in the presence of
gold(I) complex A′ led to cyclobutene 3b together with 1,3diene 11b in a 1.3:1 ratio in moderate yields (Table 1, entry 2).
The reaction of (o-fluorophenyl)acetylene (1c) with 2a gave
cyclobutene 3c in good yield together with traces of 1,3-diene
11c (Table 1, entry 3). In contrast, dienes 11d,e were obtained
as the major products in the reactions of (o-chlorophenyl)- and
(o-bromophenyl)acetylenes (1d,e) with 2a (Table 1, entries 4
and 5).29 Interestingly, o-anisylacetylene (1f) gave exclusively
cyclobutene 3f (Table 1, entry 6),30 whereas arylalkyne 1g with
an o-CF3 group only afforded 1,3-diene 11g (Table 1, entry 7).
However, moving the CF3 to the para position in 1h restored
the usual reactivity, resulting in the formation of cyclobutene
3h as the major product (Table 1, entry 8). Reactions with
methylenecyclohexane (2b) or methylenecyclopentane (2c) led
to mixtures of cyclobutenes 3 and 1,3-dienes 11 (Table 1,
entries 9−20), although, in the reaction between oanisylacetylene (1f) and 2b, cyclobutene 3m was obtained as

■

RESULTS AND DISCUSSION
Formation of Cyclobutenes vs 1,3-Dienes. The gold(I)catalyzed intermolecular reaction of substituted arylalkynes
with alkenes affords cyclobutenes 3 in moderate to excellent
yields.3,4 Thus, under the optimized conditions, reaction of
phenylacetylene with α-methylstyrene (2a) gives rise to
cyclobutene 3a in 95% yield (Table 1, entry 1).28 However,
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the major product (Table 1, entry 13). 1-Naphthylacetylene
(1i) and 9-phenanthrylacetylene (1j) also react with 2b to give
cyclobutenes 3n,o and 1,3-dienes 11n,o (Table 1, entries 14
and 15). Reaction of 1e with 2-methyl-2-pentene (2d)
rendered a mixture of cyclobutene 3u and 1,3-diene 11u
products (Table 1, entry 21), whereas, in the reaction of 1e
with (Z)-cyclooctene (2e), cyclobutene 3v was obtained as the
major product in good yield (Table 1, entry 22). The structure
of bicyclo[6.2.0]dec-9-ene 3v was confirmed by X-ray
diffraction.
1,3-Dienes 11b−h were obtained as single E-stereoisomers,
which was determined by NOE experiments. This assignment
was confirmed in the case of 11e (Table 1, entry 5) by X-ray
diffraction of crystalline derivative 11w, obtained from 11e by
Suzuki coupling with p-nitrophenylboronic acid (Scheme 3).

Differently substituted 1-aryl-1,3-diynes 12a−h and 1thienyl-1,3-diyne (12i) react with alkene 2f to give 1ethynylcyclobutenes 13a−i in good to excellent yields (Table
3). Alkyl-substituted 1,3-diyne 12j also leads to the
Table 3. Gold(I)-Catalyzed [2 + 2] Cycloaddition of 1,3Diynes 12a−j with Alkenes 2c−ja

Scheme 3. Derivatization of 11e To Form 1,3-Diene 11w

a

CYLview depiction of the X-ray crystal structure of 11w.

Other metal catalysts known to promote cycloisomerization
of 1,n-enynes, such as PtCl2, GaCl3, and InCl3, fail to catalyze
the reaction between alkyne 1a or 1e with α-methylstyrene
(2a) at 23 or 50 °C. Similarly, neither cyclobutene nor 1,3diene was observed in the presence of CuCl, AgCl, AgOTf,
AgNTf2, AgSbF6, or [tBuXPhosAg(NCMe)]SbF6 under these
conditions.
Cyclobutenes from 1,3-Butadiynes. To delineate the
importance of electronic and steric effects, we examined the
gold(I)-catalyzed reaction of alkenes with aryl-1,3-butadiynes
12,32 ethynylogous to arylalkynes 1. Reaction of the parent 1phenyl-1,3-butadiyne (12a) with 2,3-dimethylbut-2-ene (2f)
led selectively to cyclobutene 13a by addition to the terminal
triple bond with all the gold(I) catalysts tested (Table 2),
although slightly better yields were obtained using NHC−
gold(I) complex F (Table 2, entry 6).33

a

1,3-Diyne:alkene in a 1:2 ratio. Isolated yields. bSmall amounts of 1,3diene product were detected by 1H NMR. cThe minor regioisomer is
the 1,3,4,4-tetrasubstituted cyclobutene. dThe minor regioisomer is the
1,4,4-trisubstituted cyclobutene. Reaction at 40 °C. eReaction at 50 °C.

Table 2. Gold(I)-Catalyzed Reaction of 1,3-Diyne 12a with
Alkene 2fa

entry

Au catalyst

13a yieldb (%)

entry

Au catalyst

13a yieldb (%)

1
2
3
4

A
A′
C
D

70
70
70 (60)
69

5
6
7
8

E
F
F′
G

corresponding cyclobutene 13j, which is remarkable, as alkynes
with alkyl substituents are very poorly reactive with alkenes in
the presence of gold(I) catalysts.3 Other di-, tri-, and
tetrasubstituted alkenes 2c−j also reacted with 1,3-diynes
12a, 12c, and 2i to give 1-alkynylcyclobutenes 13k−p.34
Mechanism of the Formation of Cyclobutenes or 1,3Dienes. To confirm the formal alkene fragmentation (metathesis-type) in the formation of 1,3-dienes in the intermolecular
gold(I)-catalyzed reaction, a simple experiment between
terminally deuterated alkyne 1e-d1 and alkene 2a with catalyst
A was carried out (Scheme 4). In this reaction, we obtained
exclusively 1,3-diene 11e-d1, revealing that a formal insertion of
the alkyne into the alkene carbons takes place in this process.

56
78 (72)
74
16c

a

1,3-Diyne:alkene in a 1:2 ratio. bYields determined by 1H NMR using
1,4-diacetylbenzene as the internal standard. Isolated yields in
parentheses. cConversion of 45%.
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Scheme 4. Cycloaddition of Alkyne 1e-d1 with 2a

Scheme 6. Ligand Substitution and Formation of Key
Intermediates Int4a

The alternative product, 11e-d1′, resulting from a doublecleavage-type rearrangement (formal cleavage of both the
alkyne and the alkene; see below), was not observed.
Monitoring the reaction of alkyne 1d with alkene 2b (Table
1, entry 11) by 1H NMR shows that the [2 + 2] cycloaddition
leading to cyclobutene 3k is ca. 1.4 times faster than the
formation of 1,3-diene 11k (Scheme 5).
Scheme 5. Reaction of Alkyne 1d with Alkene 2ba

a
Free energies in kcal/mol. L = PMe3. bCalculations using 2methylpropene instead of α-methylstyrene. cDepicted configuration of
C3 for Int3a. Opposite configuration of C3 for Int3b.

a

formation of Int4b requires 0.9 kcal/mol lower energy than
Int4a, further evolution of Int4a to other intermediates
proceeds through lower energy barriers.39
The possibility of an oxidative cyclometalation was also
considered.40 However, neither the intermediate with the
alkyne and the alkene coordinated simultaneously to gold(I)
nor the gold(III) metalacyclopentene was found as a stable
species.
Intermediate Int4a is also in equilibrium via C4 migration
with the cyclopropyl-type intermediate Int5a, whose ring
opening leads directly to (1,3-diene)gold(I) complex Int8a
through TS5−8a (ΔG⧧ = 9.9 kcal/mol) (Scheme 7). The
alternative C3 migration would lead to a less stable cyclopropyl
methyl intermediate to ultimately form a different type of 1,3diene that was not observed experimentally. The opening of the
cyclopropane of Int5a via TS5−6a (ΔG⧧ = 10.7 kcal/mol) to
form the less stable intermediate Int6a, followed by a highly
exothermic 1,2-H shift, would give 1,3-diene−gold(I) complex
Int9a. However, formation of either Int8a or Int9a from Int5a
requires higher activation energies than the conversion of Int5a
to Int4a (ΔG⧧ = 5.7 kcal/mol). Comparing all the activation
energies, the most favored reaction pathway is the ring
expansion of Int4a to give (η2-cyclobutene)gold(I) complex
Int7a (ΔG⧧ = 8.9 kcal/mol). Conrotatory ring opening of
Int7a to form Int10a is unlikely as it would have to overcome a
prohibitively high energy barrier of 32.1 kcal/mol.41 Thus, our
calculations predict that cyclobutene 3a would be the product
of the reaction, which is consistent with the formation of 3a in a
95% yield from 1a and 2a (Table 1, entry 1).3,4,42
The reaction of (o-bromophenyl)acetylene (1e) with αmethylstyrene (2a) is more complex as four different
approaches of the alkene toward the Int4c−f could be
conceived (Scheme 8) depending on the relative orientation

Reaction progress followed by 1H NMR (Ph2CH2 internal standard).

For a deeper insight into the mechanism of the formation of
cyclobutenes 3 and/or 1,3-dienes 11 as well as the influence of
the substituents on the substrates in the reaction outcome, we
performed density functional theory (DFT) calculations35 using
PMe3 as the ligand for gold(I).36 We examined the reaction
between phenylacetylene (1a) and α-methylstyrene (2a) to
give cyclobutene 3a as well as the reaction of (o-bromophenyl)acetylene (1e) with 2a leading to 1,3-diene 11e as the major
product.
Electron-rich alkenes coordinate preferentially with gold(I),4
leading to (η2-alkene)gold(I) complexes that can be isolated
and structurally characterized.37 Accordingly, the reaction
begins with the associative ligand exchange of (η2-alkene)gold(I) complex Int1a to generate the slightly less stable (η2alkyne)gold(I) complex Int2a (Scheme 6). The attack of the
alkene to the gold(I) alkyne complex Int2a can take place in an
anti or a syn fashion to form intermediates Int4a and Int4b,
which are in equilibrium due to C3−C4 bond rotation via ringopened intermediate Int4ab.38 In both cases, formation of
intermediates Int4a,b with the gold(I) carbene at the terminal
carbon is kinetically more favored than the formation of
regioisomeric Int3a,b by at least 3.8 kcal/mol. Although
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of the phenyl groups of the substrates (anti or syn) and the
position of the ortho-substituent in the alkyne with respect to
the olefin carbons (ortho-substituent closer to either the
terminal or internal alkene carbon). Thus, four distinct reaction
pathways were computed for this system (c−f, Scheme 8). As
in the case of the reaction of phenylacetylene (1a) with alkene
2a, formation of the cyclopropyl gold(I) carbene at the internal
alkyne carbon (Int4c−f, ΔG⧧ = 16.7−17.5 kcal/mol) is more
favorable than at the terminal alkyne carbon (Int3c−f, ΔG⧧ =
18.8−20.1 kcal/mol).39 Comparison of the activation energies
of the transformations of Int4c−f into Int5c−f or Int7c−f
suggests that the o-bromo substituent hampers the rearrangement of the near alkene carbon and favors the rearrangement of
the further alkene carbon. In fact, cyclopropyl gold(I) carbenes
Int4d and Int4f bearing the bromo atom closer to C3 prefer to
form intermediates Int5d and Int5f via rearrangement of C4,
which then lead to 1,3-diene−gold(I) complexes Int8d and
Int8f, respectively. In contrast, cyclopropyl gold(I) carbene
Int4e bearing the o-bromo substituent closer to C4 prefers to
undergo ring expansion through C3 to give the (η2cyclobutene)gold(I) complex Int7e. Analyzing all the energy
barriers (including bond rotations), the most favored pathway
is that to 1,3-diene−gold(I) complex Int8d. This is in
agreement with the experimental result, as 1,3-diene 11e is
obtained in a 45% yield and only traces of cyclobutene 3e are
detected (Table 1, entry 5). Nevertheless, the difference in the
activation energies of the rearrangements of cyclopropyl
gold(I) carbenes Int4 are not large, so subtle changes in the
substitution pattern of the substrates modify the steric
interactions and, consequently, the reaction outcome. Then,
reasonably, different ratios of cyclobutene and 1,3-diene
products were experimentally obtained depending on the
differently substituted substrates.
For the sake of completeness, the mechanism of the gold(I)catalyzed reaction between 1-phenyl-1,3-butadiyne (12a) and
alkenes was also studied computationally (Scheme 9). Gold(I)
complex Int2h, in which gold(I) is coordinated to the terminal
alkyne, is 2.8 kcal/mol more stable than the complex Int2g with
gold(I) coordinated to the internal alkyne. The preferential
binding of gold(I) to the less substituted multiple bond has
been experimentally observed in the case of allenes.43
(Alkyne)gold(I) complex Int2g shows an almost symmetrical
η2-coordination with a significant bending back of the phenyl
group, which is consistent with reported structures of related
(alkyne)gold(I) complexes.44 In contrast, in complex Int2h, the
terminal alkyne binds very unsymmetrically with gold(I),
resulting in longer bonds with the substituted carbon atom,
as also observed in terminal (alkene)gold(I) complexes.37,45
The free energy of activation for the attack of the alkene on
the terminal alkyne is 3.4 kcal/mol lower than the barrier
corresponding to the attack at the internal alkyne (Scheme 9).
Consequently, on both thermodynamic and kinetic grounds,
the alkene selectively attacks complex Int2h at the terminal
alkyne as a π-nucleophile, forming distorted cyclopropyl
gold(I) carbene Int4h. The ring expansion of Int4h through
C3 (ΔG⧧ = 7.0 kcal/mol) gives the (η2-cyclobutene)gold(I)
complex Int7h.39 The alternative ring expansion of cyclopropyl
gold(I) carbene Int4h through the terminal alkene carbon C4
generates a distorted (cyclobutene)gold(I) complex Int12h
through a low barrier of 5.2 kcal/mol. Interestingly, an
intermediate similar to Int12h was not found in the reaction
of phenylacetylene derivatives 1a and 1e with alkene 2a
discussed above. Intermediate Int12h undergoes formal

Scheme 7. Formation of Cyclobutene or 1,3-Dienes from
Intermediate Int4aa

a

Free energies in kcal/mol. L = PMe3.

Scheme 8. Mechanism of the Reaction between 1e (Ar = oBromophenyl) and 2aa

a

Free energies in kcal/mol. L = PMe3. Depicted configuration of C3
for pathways c and d. Opposite configuration of C3 for pathways e and
f. bTransformations among Int4c−f via bond rotations: see the
Supporting Information. cTransformation of Int5f into Int5d via C2−
C3 bond rotation: ΔG⧧ = 14.0 kcal/mol, ΔG° = −0.6 kcal/mol.

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Scheme 9. Mechanism for the Reaction of the (1-Phenyl-1,3butadiyne)gold(I) Complex with 2-Methylpropenea

Scheme 10. Formation of (Z,Z)-1,4-Diphenylbuta-1,3-diene
by Retro-Buchner Reaction of Cycloheptatriene 1447

Since the generation of intermediates such as 16a by a totally
different process could be relevant to the better understanding
of the mechanism of the gold(I)-catalyzed reaction of alkynes
with alkenes, we recurred to our initial system for the
generation of gold(I) carbenes by decarbenation of 1a,7bdihydro-1H-cyclopropa[a]naphthalenes (Scheme 11).48 The
Scheme 11. Retro-Buchner Reactions of 19a,ba

a

Free energies in kcal/mol. L = PMe3.

insertion of the terminal alkene carbon C4 into the alkyne
carbons to form a more stable cyclopropyl-like intermediate,
Int5h. Although intermediates Int4h, Int12h, and Int5h are in
equilibrium through low barrier transformations, ring opening
of Int5h to form (1,3-diene−gold(I) complex) Int8h is more
energetically costly than the expansion of Int4h to (η2cyclobutene)gold(I) complex Int7h (10.0 vs 7.0 kcal/mol),
which is fully consistent with the experimental results.
Further Experimental Support for the Involvement of
Cyclopropyl Gold(I) Carbenes. We have discovered a
method to generate gold(I) carbenes by the retro-Buchner
reaction of 7-substituted 1,3,5-cycloheptatrienes with electrophilic gold(I) catalysts, in a process in which a molecule of
benzene is also formed in a formal decarbenation reaction.46,47
The retro-Buchner reaction proceeds by stepwise cleavage of
the norcaradienes, which are in tautomeric equilibrium with the
cycloheptatriene.46 Other related decarbenations have been
observed in the presence of gold(I).48,49
When 7-cyclopropylcycloheptatriene 14 was heated in the
presence of catalyst A, (Z,Z)-1,4-diphenyl-1,3-diene [(Z,Z)-15]
was formed selectively (Scheme 10).46 This transformation
presumably proceeds via cyclopropyl gold(I) carbene 16a,
which undergoes a formal 1,3-shift of a CHPh fragment.
Interestingly, 16a would correspond to the intermediate
generated in the gold(I)-catalyzed reaction between acetylene
and trans-stilbene. The ring expansion of 16a to form
cyclobutene 17, which would have given diene (E,E)-15 by
conrotatory opening,50 was not observed.46 This result predicts
that a cis-isomer of 7-cyclopropylcycloheptatriene 14 would
give rise to the diene (E,Z)-15. Unfortunately, this isomer could
not be prepared by the same method used for the synthesis of
14.

a

CYLview depiction of the X-ray crystal structures of 19a,b.

required starting 1,6-enynes 18a,b were prepared as a ca. 1:1
mixture of epimers at the benzylic position by olefination of the
corresponding cyclopropyl carbaldehydes.51,52 The gold(I)catalyzed cycloisomerization of 18a,b takes place under mild
conditions using catalyst A to furnish enol ethers 19a,b in 48%
and 61% yields, respectively, whose relative configurations were
determined by X-ray diffraction. When enol ether 19a was
heated with catalyst A in 1,2-dichloroethane at 60 °C, the
decarbenation reaction provided 1-methoxy-3-phenylnaphtha10307

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lene (20) and (Z,Z)-15.53 Similarly, substrate 19b reacted at 60
°C for 1 h with catalyst A to give naphthalene 20 together with
a 1:2 mixture of (E,Z)- and (E,E)-15.54
The retro-Buchner (decarbenation) reaction of 19a should
lead to the same cyclopropyl gold(I) carbene 16a (=Int4i)
generated from trans-14, whose opening by C3 migration via
Int5i leads to Int8i and ultimately to (Z,Z)-1546,55a (Scheme
12). On the other hand, 19b would give rise to intermediate

Finally, it is interesting to compare these results with known
examples of formation of cyclobutenes via cyclopropyl
carbenes. Thus, the photolysis of cis- and trans-21 has been
shown to give cis- and trans-22 cyclobutenes, respectively, as a
result of a stereospecific ring expansion (Scheme 13a).57 In
Scheme 13. Photochemical58 (a), Metal-Catalyzed59 (b), and
Thermal61 (c) Generation and Fate of Cyclopropyl Carbenes

Scheme 12. Mechanism for the Formation of 1,3-Dienes 15
via Retro-Buchner Reaction from 19a,ba

these reactions, methyl propiolate and cis- or trans-2-butene
were also obtained as a result of a competitive fragmentation.
Likewise, in the presence of AgOTf, cis- and trans-23 undergo
stereospecific ring expansion to cyclobutenes cis- and trans-24,
respectively (Scheme 13b).58,59 The thermal decomposition of
the potassium salt of tosyl hydrazone 25 also led to a product of
ring expansion (26), together with acenaphthylene (27), the
product of fragmentation (Scheme 13c).60 Ring expansion to
cyclobutenes and fragmentation to form alkenes and alkynes
have also been observed in reactions of simple cyclopropyl
carbenes.57

a

Free energies in kcal/mol. L = PMe3. bThe energy of TS4−7j was
calculated by freezing the following distances: d(C3−C1), d(C3−C2),
and d(C3−C4). The values of these distances were taken from the
previously optimized geometry of TS4−7i.

■

CONCLUSIONS
Electron-rich alkynes have been shown to react with alkenes in
the presence of gold(I) catalysts by [2 + 2] cycloaddition to
give rise to cyclobutenes, whereas, in contrast, electrondeficient alkynes lead to 1,3-dienes in a metathesis-type
process. Now we have found that 1,3-dienes can also be
obtained in the reaction of alkenes with electron-rich alkynes
bearing ortho-substituted aryls.
The two reaction channels leading to cyclobutenes or 1,3dienes are close in energy. According to all our calculations, the
first intermediates in the gold(I)-catalyzed intermolecular
reaction of alkynes with alkenes are cyclopropyl gold(I)
carbenes, which despite all the experimental efforts27,61 are
still elusive species. To substantiate their involvement in these
transformations, we have generated these intermediates by a
totally different method based on the gold(I)-promoted retroBuchner reaction, which also leads to the formation 1,3-dienes

Int4j, which undergoes opening via Int5j to furnish (E,Z)-15,
although this 1,3-diene was obtained together with the more
stable isomer (E,E)-15.55b Control experiments showed that
(E,Z)-15 undergoes isomerization to give (E,E)-15 in the
presence of gold(I) under the reaction conditions.52 In full
agreement with the experiments, DFT calculations show that
the alternative expansion of cyclopropyl gold(I) carbenes
Int4i,j to cyclobutenes Int7i,j is a higher energy process.39
Although both reaction pathways from 19a,b could in
principle be connected by the trans- to cis-isomerization of
Int4i to Int4j via open carbocation Int4ij (Scheme 12), in
contrast to that found in the equilibrium between Int4a and
Int4b (Scheme 6), here the corresponding barriers are much
higher in energy than those leading to C3 migration.56
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by a metathesis-type mechanism. The formation of 1,3-dienes
involves a two- or three-step mechanism in which the carbon−
carbon double bond of the alkene is cleaved, similar to that
proposed in the gold(I)-catalyzed intramolecular skeletal
rearrangements of 1,6-enynes. Products of conrotatory opening
of cyclobutenes are not observed in the gold(I)-catalyzed
reaction of alkynes with alkenes, which is consistent with the
high activation energy required for this process.
The common mechanistic scenario for gold(I)-catalyzed
reactions of alkynes with alkenes involves the initial formation
of cyclopropyl gold(I) carbene intermediates, followed by fast
ring expansion or rearrangement. Formation of 1,3-dienes can
take place from both electron-rich and electron-deficient
alkynes, although cyclobutenes have only been obtained in
gold(I)-catalyzed reactions involving electron-rich alkynes.
There is another important difference between the reactions
of electron-rich and electron-deficient alkynes since in the
former case the alkene reacts with the internal carbon of the
alkyne, whereas in the second case the alkene attacks the
terminal carbon, leading to regioisomeric cyclopropyl gold(I)
carbenes.

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ASSOCIATED CONTENT

S
* Supporting Information

The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.7b03005.

■

Article

All procedures and characterization data for new
compounds (PDF)
Full details of the theoretical calculations (PDF)
X-ray crystallographic data for 3v (CIF)
X-ray crystallographic data for 11w (CIF)
X-ray crystallographic data for 19a (CIF)
X-ray crystallographic data for 19b (CIF)
X-ray crystallographic data for 19c (CIF)

AUTHOR INFORMATION

Corresponding Authors

*fmaseras@iciq.es
*aechavarren@iciq.es
ORCID

Yahui Wang: 0000-0003-4109-8318
Feliu Maseras: 0000-0001-8806-2019
Antonio M. Echavarren: 0000-0001-6808-3007
Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS
́
We thank the Ministerio de Economia, Industria y Competitividad (MINECO)/Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea (UE) (Grant CTQ2016-75960P), MINECO-Severo Ochoa Excellence Accreditation 2014−
2018, Grant SEV-2013-03 and a Severo Ochoa predoctoral
fellowship to M.E.d.O., the European Research Council
(Advanced Grant No. 321066), the Agència de Gestió d’Ajuts
Universitaris i de Recerca (AGAUR) (Grant 2014 SGR 818),
and the Centres de Recerca de Catalunya (CERCA) Program/
Generalitat de Catalunya for financial support. We also thank
the ICIQ X-ray diffraction unit for the X-ray structures.
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(54) Similar results were obtained from substrate 19c, prepared from
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mol.42
(56) Similarly, rotational barriers around the C2−C4 bond in Int5i,j
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