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. 2017 Jul 12;139(30):10302–10311. doi: 10.1021/jacs.7b03005

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 †,‡,*, Antonio M Echavarren †,§,*
PMCID: PMC5543397  PMID: 28700226

Abstract

graphic file with name ja-2017-03005n_0018.jpg

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 ortho-substituted 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

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

Scheme 1

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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 electron-deficient12,13 or strained alkenes.14 Other transition-metal catalysts also promote the [2 + 2] cycloaddition of strained alkenes with alkynes.15,16 The reaction of propiolates 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 1,3-dienes 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 (η2-alkyne)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 1,6-enyne.27

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.

Scheme 2

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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 1,3-dienes 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 retro-Buchner reaction. This study leads to a comprehensive picture of the gold(I)-catalyzed reactions of alkynes with alkenes.

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, the reaction of o-tolylacetylene (1b) with 2a in the presence of gold(I) complex A′ led to cyclobutene 3b together with 1,3-diene 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 o-anisylacetylene (1f) and 2b, cyclobutene 3m was obtained as 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.

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

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entry 1 2 3 (yield, %)b 11 (yield, %)b
1 1a 2a 3a (95)c  
2d,e 1b 2a 3b (37) 11b (29)
3 1c 2a 3c (64) 11c (3)
4e–g 1d 2a 3d (9) 11d (48)
5f 1e 2a 3e (3, 3i) 11e (45, 43i)
6 1f 2a 3f (54, 54)  
7 1g 2a   11g (36)
8e,h 1h 2a 3h (75) 11h (5)
9 1b 2b 3i (65) 11i (27)
10 1c 2b 3j (50, 49i) 11j (25, 20i)
11 1d 2b 3k (54, 49) 11k (33, 28)
12 1e 2b 3l (44) 11l (25)
13 1f 2b 3m (50) 11m (3)
14 1i 2b 3n (40) 11n (22)
15 1j 2b 3o (48) 11o (19)
16 1b 2c 3p (61) 11p (38)
17 1c 2c 3q (51, 44) 11q (33, 17)
18 1d 2c 3r (25) 11r (43)
19 1e 2c 3s (24) 11s (42)
20 1f 2c 3t (58, 53) 11t (24, 12)
21 1e 2d 3u (40, 41j) 11u (34, 37)
22 1e 2e 3v (84) 11v (5)
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a

Alkyne:alkene in a 1:2 ratio.

b

Yields 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

d

Alkyne:alkene in a 1:4 ratio.

e

A 4 mol % concentration of A′.

f

Catalyst A instead of A′.

g

Alkyne:alkene in a 1:3 ratio.

h

A′ prepared in situ from tBuXPhosAuCl and NaBAr4F.

i

Reaction on a 1 g scale of the alkyne.

j

Mixture of 1,3,4,4- and 1,3,3,4-tetrasubstituted cyclobutenes in a 2.4:1 ratio.

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).

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

Scheme 3

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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 1,3-diene 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 1-phenyl-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

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

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entry Au catalyst 13a yieldb (%) entry Au catalyst 13a yieldb (%)
1 A 70 5 E 56
2 A′ 70 6 F 78 (72)
3 C 70 (60) 7 F′ 74
4 D 69 8 G 16c
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a

1,3-Diyne:alkene in a 1:2 ratio.

b

Yields determined by 1H NMR using 1,4-diacetylbenzene as the internal standard. Isolated yields in parentheses.

c

Conversion of 45%.

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Differently substituted 1-aryl-1,3-diynes 12a–h and 1-thienyl-1,3-diyne (12i) react with alkene 2f to give 1-ethynylcyclobutenes 13a–i in good to excellent yields (Table 3). Alkyl-substituted 1,3-diyne 12j also leads to the 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

Table 3. Gold(I)-Catalyzed [2 + 2] Cycloaddition of 1,3-Diynes 12a–j with Alkenes 2c–ja.

graphic file with name ja-2017-03005n_0017.jpg

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a

1,3-Diyne:alkene in a 1:2 ratio. Isolated yields.

b

Small amounts of 1,3-diene product were detected by 1H NMR.

c

The minor regioisomer is the 1,3,4,4-tetrasubstituted cyclobutene.

d

The minor regioisomer is the 1,4,4-trisubstituted cyclobutene. Reaction at 40 °C.

e

Reaction at 50 °C.

Mechanism of the Formation of Cyclobutenes or 1,3-Dienes

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. The alternative product, 11e-d1′, resulting from a double-cleavage-type rearrangement (formal cleavage of both the alkyne and the alkene; see below), was not observed.

Scheme 4. Cycloaddition of Alkyne 1e-d1 with 2a.

Scheme 4

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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 2b.

Scheme 5

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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 (η2-alkyne)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 ring-opened 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 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

Scheme 6. Ligand Substitution and Formation of Key Intermediates Int4.

Scheme 6

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Free energies in kcal/mol. L = PMe3.

Calculations using 2-methylpropene instead of α-methylstyrene.

Depicted configuration of C3 for Int3a. Opposite configuration of C3 for Int3b.

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 1,3-diene 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

Scheme 7. Formation of Cyclobutene or 1,3-Dienes from Intermediate Int4a.

Scheme 7

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Free energies in kcal/mol. L = PMe3.

The reaction of (o-bromophenyl)acetylene (1e) with α-methylstyrene (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 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 (η2-cyclobutene)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.

Scheme 8. Mechanism of the Reaction between 1e (Ar = o-Bromophenyl) and 2a.

Scheme 8

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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.

Transformations among Int4c–f via bond rotations: see the Supporting Information.

Transformation of Int5f into Int5d via C2–C3 bond rotation: ΔG⧧ = 14.0 kcal/mol, ΔG° = −0.6 kcal/mol.

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

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

Scheme 9

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Free energies in kcal/mol. L = PMe3.

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 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 (η2-cyclobutene)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.

Scheme 10. Formation of (Z,Z)-1,4-Diphenylbuta-1,3-diene by Retro-Buchner Reaction of Cycloheptatriene 14(47).

Scheme 10

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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,7b-dihydro-1H-cyclopropa[a]naphthalenes (Scheme 11).48 The 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-phenylnaphthalene (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

Scheme 11. Retro-Buchner Reactions of 19a,b.

Scheme 11

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

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 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

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

Scheme 12

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Free energies in kcal/mol. L = PMe3.

The 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.

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

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 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

Scheme 13. Photochemical58 (a), Metal-Catalyzed59 (b), and Thermal61 (c) Generation and Fate of Cyclopropyl Carbenes.

Scheme 13

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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, electron-deficient 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 1,3-dienes 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 retro-Buchner reaction, which also leads to the formation 1,3-dienes 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.

Acknowledgments

We thank the Ministerio de Economía, Industria y Competitividad (MINECO)/Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea (UE) (Grant CTQ2016-75960-P), 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.

Supporting Information Available

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

  • 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)

The authors declare no competing financial interest.

Supplementary Material

ja7b03005_si_001.pdf (17.7MB, pdf)
ja7b03005_si_002.pdf (791.7KB, pdf)
ja7b03005_si_003.cif (320.7KB, cif)
ja7b03005_si_004.cif (804.9KB, cif)
ja7b03005_si_005.cif (1.4MB, cif)
ja7b03005_si_006.cif (624.8KB, cif)
ja7b03005_si_007.cif (769.5KB, cif)

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  54. Similar results were obtained from substrate 19c, prepared from an enyne analogous to 18b but with a p-tolyl group at the alkyne.54
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Supplementary Materials

ja7b03005_si_001.pdf (17.7MB, pdf)
ja7b03005_si_002.pdf (791.7KB, pdf)
ja7b03005_si_003.cif (320.7KB, cif)
ja7b03005_si_004.cif (804.9KB, cif)
ja7b03005_si_005.cif (1.4MB, cif)
ja7b03005_si_006.cif (624.8KB, cif)
ja7b03005_si_007.cif (769.5KB, cif)

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