Gold- And platinum-catalyzed cycloisomerization of enynyl esters versus alleneyl esters: An experimental and theoretical study

FULL PAPER

DOI: 10.1002/chem.200801387

Gold- and Platinum-Catalyzed Cycloisomerization of Enynyl Esters versus

Allenenyl Esters: An Experimental and Theoretical Study

Nicolas Marion,^{[a, f]}Gilles Lemiꢀre,^[b]Andrea Correa,^[c]Chiara Costabile,^[c]

Rubꢁn S. Ramꢂn,^{[a, g]}Xavier Moreau,^[b]Pierre de Frꢁmont,^[d]Rim Dahmane,^[b]

Alexandra Hours,^[b]Denis Lesage,^[e]Jean-Claude Tabet,^[e]Jean-Philippe Goddard,^[b]

Vincent Gandon,^[b]Luigi Cavallo,*^[c]Louis Fensterbank,*^[b]Max Malacria,*^[b]and

Steven P. Nolan*^{[a, d, g]}

Abstract: Experimental and theoretical

studies on Au- and Pt-catalyzed cyclo-

ACHTUNGTRENNUNGisomerization of a branched dienyne

with an acetate group at the propargyl-

ic position are presented. The peculiar

architecture of the dienyne precursor,

which has both a 1,6- and a 1,5-enyne

skeleton, leads, in the presence of alky-

nophilic gold catalysts, to mixtures of

bicyclic compounds 3, 4, and 5. Forma-

cyclization of an enantioenriched dien-

yne precursor, ¹⁸O-labeling experi-

ments, and DFT calculations, allowed

an unprecedented reaction pathway to

be proposed. We show that bicyclo-

in the formation of 5. Additionally, the

possibility of OAc migration from al-

lenyl acetates was supported by a trap-

ping experiment with styrene that af-

forded the corresponding cyclopropane

derivative. This unprecedented genera-

tion of a vinyl metal carbene from an

allenyl ester supports a facile enynyl

ester/allenenyl ester equilibrium. Fur-

ther examination of the difference in

reactivity between enynyl acetates and

their corresponding [3,3]-rearranged al-

lenenyl acetates toward Au- and Pt-cat-

alyzed cycloisomerization is also pre-

sented.

AHCTUNGTRENGN[UN 3.1.0]hexene 5 is likely formed by a

1,3-OAc shift/allene–ene cyclization/

1,2-OAc shift sequence, as calculated

by DFT and supported by Au-catalyzed

cyclization of isolated allenenyl acetate

7, which leads to improved selectivity

tion

of

unprecedented

bicyclo-

ACHTUNGTRENNUNG[3.1.0]hexene 5 is the main focus of this

study. The effect of the ancillary ligand

on the gold center was examined and

found to be crucial for formation of 5.

Further mechanistic studies, involving

Keywords: alkynes · allenes · cyclo-

isomerization · density functional

calculations · gold

[a] Dr. N. Marion, R. S. Ramꢀn, Prof. Dr. S. P. Nolan

[d] Dr. P. de Frꢃmont, Prof. Dr. S. P. Nolan

Institute of Chemical Research of Catalonia (ICIQ)

Av. Paꢁsos Catalans 16, 43007 Tarragona (Spain)

Fax : (+34)977-920-224

Department of Chemistry, University of New Orleans

2000 Lakeshore Drive, New Orleans, LA 70148 (USA)

[e] D. Lesage, Prof. Dr. J.-C. Tabet

E-mail: snolan@iciq.es

Laboratoire de Chimie Structurale Organique et Biologique

UMR CNRS 7613, Universitꢃ Pierre et Marie Curie (UPMC)

B. 229, 4 place Jussieu, 75005 Paris (France)

sn17@st-andrews.ac.uk

[b] G. Lemiꢂre, Dr. X. Moreau, R. Dahmane, Dr. A. Hours,

Dr. J.-P. Goddard, Dr. V. Gandon, Prof. Dr. L. Fensterbank,

Prof. Dr. M. Malacria

[f] Dr. N. Marion

Present address: Department of Chemistry

Massachusetts Institute of Technology

77 Massachusetts Avenue, Room 18-343, Cambridge, MA 02139

(USA)

Laboratoire de Chimie Organique, UMR CNRS 7611-FR2769

UPMC—Univ. Paris 06

B. 229, 4 place Jussieu, 75005 Paris (France)

E-mail: louis.fensterbank@upmc.fr

[g] R. S. Ramꢀn, Prof. Dr. S. P. Nolan

max.malacria@upmc.fr

Present address: School of Chemistry, University of St-Andrews

St-Andrews KY16 9ST (UK)

[c] A. Correa, C. Costabile, Prof. Dr. L. Cavallo

Department of Chemistry, University of Salerno

via Ponte don Melillo, Fisciano, 84084 (Italy)

E-mail: lcavallo@unisa.it

Supporting information for this article is available on the WWW

under http://dx.doi.org/10.1002/chem.200801387.

Chem. Eur. J. 2009, 15, 3243 – 3260

ꢄ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Introduction

Results and Discussion

Atom-economic reactions, as defined by Trost,^[1]are of pri-

mary importance in modern organic chemistry. In this field,

polyunsaturated substrates have become ubiquitous and

have led to the discovery of a number of unprecedented

transformations in the presence of late transition-metal cata-

lysts.^[2]Among available atom-economic transformations,^[3]

the cycloisomerization of enynes remains unique because of

the increased molecular complexity achieved in one chemi-

cal step.^[4]After extensive studies with palladium^[5]and plati-

Access to extremely elaborate structural motifs, such as

fused polycyclic systems from acyclic substrates, is often de-

pendant on subtle modifications in the precursor architec-

ture. In this context, we have reported on the importance of

oxo substituents—and of their nature—at the propargylic

position in enyne systems.^[11]Furthermore, we recently in-

vestigated the reactivity of dienyne 2, which formally exhib-

its 1,5- and 1,6-enyne scaffolds, and observed different selec-

tivity as a function of the nature of the catalyst employed

(Scheme 2).^[12]

num,^[6]gold(I) and gold

ACTHNUTRGNEU(GN III) salts have emerged lately as

powerful catalysts for a myriad of transformations involving

enynes.^[7,8]In this context, enyne derivatives with an ester

group at the propargylic position can be regarded as a spe-

cial class of substrates due to their atypical reactivity pat-

tern.^[9,10]More specifically, an appropriately situated O-ester

group undergoes an internal 1,2- or 1,3-shift upon electro-

ꢀ

philic activation of the C C bond (Scheme 1, I) to give rear-

ranged products II and III respectively, which can then fur-

ther evolve as a function of the remaining pendant groups

(Scheme 1).

Scheme 2. Pt- and Au-catalyzed cycloisomerization of 2. [a] Reaction

conditions: PtCl₂(5 mol%), toluene (0.025m), 808C. [b] Reaction condi-

tions: [(IPr)AuCl]/AgBF₄(2 mol%), CH₂Cl₂(0.1m), RT.

Thus, formation of bicyclo

ACHTUNGTRENNUNG

A

4

used,^[11a]while various gold catalysts afforded different prod-

uct ratios. More interestingly, the use of Au^Isalts in lieu of

Pt^IIones led to the formation of unexpected bicyclo-

AHCTUNGTRENNUNG

a particular set of steric and electronic parameters favoring

formation of compound 5, and the ability of N-heterocyclic

carbenes (NHCs)^[13,14]to promote this unexpected transfor-

mation. Therefore, intrigued by this unprecedented mode of

cyclization, we thoroughly examined the reaction parame-

ters that might influence the formation of this type of carbo-

cycle. Moreover, we carried out ¹⁸O-labeling experiments

and theoretical calculations to gain further insight into the

mechanism of this cyclization. Herein we disclose the results

of these studies, which permit a new type of reactivity in the

enynyl ester series to be explained. Thus, we have shown

that the most likely pathway to 5 involves, after formation

of an allenyl ester, carbocyclization of an allenene core fol-

lowed by “retro-migration” of the ester moiety. The retro-

migration process was further studied on an extended set of

substrates.

Influence of reaction conditions: We began our study on

model substrate 2 by evaluating the influence of the ligand

using a series of [(NHC)AuCl] complexes^[15]leading to the

formation of bicyclic product 5 (Table 1).^[16]Overall, the

combined yields of cycloisomerized products range from

good to excellent with a slight decrease of activity for the

less encumbered ligands (Table 1, entries 14–16 and 21).

Scheme 1. Reactivity of propargylic acetates in the presence of gold cata-

lysts.

The wide diversity and complexity of accessible structures

from readily assembled precursors is probably the most ap-

pealing feature of enyne cycloisomerization reactions. How-

ever, it can also be seen as a disadvantage, since small

changes in the starting compound can lead to unexpected

outcomes, so that the reactivity of a specific substrate is

often rendered unpredictable. This is why insights into the

skeletal rearrangements of enynes catalyzed by gold salts

are still needed in order to understand the mechanism of

these transformations. Here we present our experimental

and theoretical findings on platinum- and gold-catalyzed cy-

cloisomerization of enynes bearing a propargylic acetate

group. Driven by theoretical findings, we focused our studies

on the reversibility of OAc migration between the propar-

gylic esters and their corresponding [3,3]-rearranged coun-

terparts, namely, the allenyl esters.

Simple “ligandless” gold(I) and gold

ACHTUNGERTN(NUNG III) chloride salts led

to the same selectivity,^[17]yielded 3 and 4 in similar propor-

3244

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Chem. Eur. J. 2009, 15, 3243 – 3260

Cycloisomerization of Enynyl Esters versus Allenenyl Esters

FULL PAPER

Table 1. Effect of ligands on the cycloisomerization of 2.

Entry

[M]

3:4:5^[a]

Total

Entry

[M]

3:4:5^[a]

Total

yield [%]^[a]

1^[b]

2^[c]

3

PtCl₂

PtCl₂/AgBF₄

AuCl

AuCl/AgBF₄

AuCl₃

AuCl₃/AgBF₄

1/0.1/0

1/0.7/0.2

1/0.5/0

1/0.8/0.2

1/0.3/0

1/0.8/0.1

1/0.1/0

1/0.5/1.5

1/0.4/1.7

1/0.4/1.4

98

33

86

84

88

77

80

81

78

72

84

12

N

1/0.3/0.9

1/0.5/0.4

1/0.1/0.2

1/0.2/0.1

1/0.2/0.3

1/0.6/0.4

1/0.1/0.6

1/0.1/0.7

1/0.2/0.5

1/0.1/0.2

1/0.6/0.1

90

94

62

70

63

88

73

95

76

64

54

13

14^[g]

15

4

5^[d]

6^[e]

7^[f]

8^[d]

9

16^[g]

17

T

18

19

N

20

10

11

T

21^[g]

22

A

1

[a] Yields of isolated products, average of two runs, products ratio determined by H NMR spectroscopy. [b] Reaction performed with PtCl₂(5 mol%) in

toluene at 808C for 2 h. [c] Reaction performed with PtCl₂(5 mol%)/AgBF₄(10 mol%) in toluene at 808C for 2 h. 26% of 2 was recovered along with

8% of allenyl ester 7, and significant amounts of oligomerized byproducts were also formed. [d] Reaction stirred for 2 h. [e] Reaction performed with

AuCl₃(2 mol%)/AgBF₄(6 mol%) for 1 h. [f] Reaction stirred for 2 h, 8% of allenyl ester 7 was also formed. [g] No starting material remaining; signifi-

ACHTUNGTRENNUNGcant amounts of oligomerized byproducts were formed.

tion, and only gave small amounts of 5 (Table 1, entries 3

and 5). Interestingly, when these salts were employed in

combination with a silver(I) salt, formation of 5 was not ob-

served, and the 3:4 ratio increased (Table 1, entries 4 and 6)

and approached the selectivity displayed by PtCl₂(Table 1,

entry 1). Notably, platinum(II) chloride in conjunction with

2 equiv AgBF₄displayed poorer activity than PtCl₂alone.

The last “simple” and commercially available gold salt

tested was [(Me₂S)AuCl] (Table 1, entries 7 and 8). As ex-

pected, it could be used without silver salt (Table 1, entry 7)

and, under these conditions, behaved as AuCl, supporting

decoordination of Me₂S from the gold center prior to cata-

lytic activity.

On the other hand, the addition of AgBF₄to

[(Me₂S)AuCl] led to a selectivity comparable with those of

AuCl/AgBF₄and AuCl₃/AgBF₄, whereby formation of 5 was

not observed (Table 1, entry 8). This can be interpreted in

two ways: either Me₂S as ligand has little influence on the

course of the cycloisomerization or the catalytically active

species is simply the gold cation, formed upon chloride ab-

straction and Me₂S decoordination.

If we examine the influence of the ancillary ligand on the

gold center by considering the formation of 5 as the main

parameter, the ligands employed here can be divided into

three classes. Those displaying low steric hindrance fur-

nished only minor amounts of bicycle 5 (Table 1, entries 13–

17 and 21; 3/5 1/<0.4), whereas highly hindered ligands led

to slightly higher 3/5 ratios (ca. 1/0.6; Table 1, entries 18–

20). The third class of ligands can be regarded as intermedi-

ate in terms of steric hindrance between the other two

classes.^[18]It includes the widely used IPr and IMes ligands

and their saturated analogues SIPr and SIMes. Only these li-

gands produced mixtures in which 5 was the major com-

pound (Table 1, entries 9–12). Considering the minor differ-

ences in the electronic properties of the NHCs employed

here,^[18]we believe that formation of unexpected bicyclo-

AHCTUNGTREG[NNNU 3.1.0]hexene 5 is mainly under steric control and responds

favorably to a medium/high steric demand.

Chem. Eur. J. 2009, 15, 3243 – 3260

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3245

S. P. Nolan, M. Malacria, L. Fensterbank, L. Cavallo et al.

Table 2. Au- and Pt-catalyzed cycloisomerization of enantioenriched 2.

Since prolonged reaction time, under strictly similar reac-

tion conditions, led to comparable ratios of cyclopropyl car-

bocycles, the possibility of chemical equilibrium between the

different products is excluded.

Subsequently, we attempted a trapping experiment using

methanol as solvent in order to possibly isolate relevant in-

termediates that would have allowed for a better under-

standing of the formation of product 5. Under these condi-

tions, enol ether 6, which results from addition of methanol

to the alkyne moiety, was the only observed product

[Eq. (1)].^[19]

Entry

2

Conditions

Yield [%] (%ee)

4^[a]5^[a]

3^[a]

1

2

3

4

R=Ac, PtCl₂(5 mol%) toluene,

66% ee RT!808C, 2 h

88 (38) 8 (rac)

83 (42) 7 (rac)

78 (20) 6 (rac)

–

R=Ac, PtCl₂(5 mol%) toluene,

66% ee RT, 2 h

–

R=Piv, PtCl₂(5 mol%) toluene,

76% ee 808C, 48 h

R=Ac, AuCl₃(2 mol%) CH₂Cl₂, 46 (8)

60% ee RT, 10 min

36 (rac) 5 (4)

[a] Yields of isolated 3/4/5 mixtures, ratios, and ee values determined by

chiral GC. rac=racemic.

logue of 2, led to a further decrease of the ee of 3-Piv

Sequential acetate migration/cyclopropanation: A key fea-

ture of the reactivity of propargylic acetates in the presence

of soft p Lewis acidic metals such as gold and platinum lies

in the ability of the acetate moiety to act as an internal nu-

(Table 2, entry 3 versus entry 1).

Finally, using goldACHTNUGRTENUNG(III) chloride afforded 3 and 5 with

very low ee values and 4 as a racemic mixture (Table 2,

entry 4), and this suggests that with gold catalysts both se-

quences are likely to compete in the formation of all cyclo-

propanated products, with preference given to the migration

then cyclopropanation pathway.

At this point of our study, several mechanistic scenarios

were still to be considered,^[23]including, in addition to the

aforementioned two sequential pathways, carbocyclization

ꢀ

cleophile that migrates in a 1,2 or 1,3 fashion onto the C C

bond. In the context of enyne cycloisomerization, this mi-

grating ability of the acetate group has raised questions

about the order of the migration/cyclopropanation se-

quence.^[20,21]In our preliminary study,^[12]we proposed a mi-

gration then cyclopropanation sequence, which appeared

ꢁ

more consistent with the formation of bicyclo

[3.1.0]hexene

onto the oxonium intermediate before rupture of the C O

5. Nevertheless, at the time we did not exclude the possibili-

ty that a cyclopropanation then migration sequence could be

involved in the formation of bicyclic compounds 3 and 4.

To gain insights into this crucial issue, we synthesized

enantioenriched dienyne 2 and subjected it to cycloisomeri-

zation conditions. In the case of cyclopropanation followed

by migration, some chiral information should be translated

into the product, whereas in the case of the opposite se-

quence, which involves an achiral intermediate of type II

(see Scheme 1), chirality transfer would be precluded.^[22]

Enantioenriched 2, in the presence of 5 mol% PtCl₂,

yielded rearranged products 3 and 4 in comparable yields

and ratio to those previously observed but with distinct

enantioselectivities (Table 2, entries 1 and 2). Cyclohexene

derivative 3 was formed with 40% ee, while cyclopentene 4

was found to be racemic. Starting from a 66% ee-enriched

dienyne, this could indicate that in the formation of 3, the

initial cyclopropanation would not be completely stereose-

lective^[22b]or that both sequences are at play with a prefer-

ence for the scenario of cyclopropanation then migration.

On the contrary, the formation of 4 would appear to primar-

ily result from a migration then cyclopropanation sequence,

leading to complete loss of chirality transfer. However, in

this case, we cannot also exclude a totally nonselective ini-

tial cyclopropanation step. Additionally, the nature of the

migrating ester group seems to play an important role in the

choice of the sequence, since using 2-Piv, the pivalate ana-

bond to regenerate the ester functionality. This possibility,

first proposed by Fehr and Galindo,^[22b]implies that the ste-

reochemical information, still present in the oxocarbenium

intermediate, is transferred in the cyclization step.

The additional information gathered so far on the cycliza-

tion of 2 and the formation of 3, 4, and 5 suggests competing

pathways, the balance of which can be shifted by means of

the ancillary ligand. Greater chirality transfer is observed

with platinum(II) chloride compared to gold catalysis.

Nevertheless, a rationale for the formation of the unpre-

cedented cyclopropyl derivative 5 remained elusive, notably

because of little precedent in the literature.^[12,24]We there-

fore performed DFT calculations on a full catalytic cycle for

the formation of 3–5, focusing on 5.

DFT calculations on the formation of 3–5: For the sake of

clarity, we numbered the atoms in dienyne 2 and we labeled

structures from the DFT calculations with lowercase bold

letters. The only exceptions are starting dienyne 2, allene 7,

and bicyclic products 3, 4 and 5, all of which were character-

ized experimentally. For these species we use labels such as

2Au, 4Au, and so on, to indicate that these substrates are

coordinated to Au.

Since N-heterocyclic carbene ligands are necessary in

order to obtain satisfactory amounts of unprecedented car-

bocycle 5, we performed the calculations with IDM bound

to the gold(I) center (IDM=1,3-dimethylimidazol-2-yli-

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Cycloisomerization of Enynyl Esters versus Allenenyl Esters

FULL PAPER

in a first approach (see Figures S1–S3, Supporting Informa-

tion). Furthermore, in order to give a general and more real-

istic picture of the mechanistic processes at play, which are

interdependent, we have gathered in one single scheme

every pathway considered here.

ꢁ

The catalytic cycle starts with displacement of a BF₄

ꢁ

counterion from [(IDM)Au⁺]BF₄species a by the alkyne

group of 2 to furnish intermediate 2Au.^[25]In CH₂Cl₂dis-

ꢁ

dene); therefore, in all schemes and figures regarding DFT

calculations, the label “Au” in fact represents “[(IDM)Au]”.

placement of the BF₄counterion by the substrate is exer-

G

gonic by 26 kJmol^ꢁ1. Structure 2Au is then the branching

For the readerꢅs convenience, the different reaction path-

ways, which are interconnected, are discussed independently

and compared when relevant. Accordingly, a figure depic-

point for three different reaction paths (Scheme 3). The first

ꢁ

consists of nucleophilic attack of the C6 C7 double bond on

the C1 atom^[26](see Scheme 3 and Figure S1, Supporting In-

formation). This cyclopropanation step leads to intermediate

b, which already has the bicyclic skeleton of product 3. The

ACHTUNGTRENNUNG

Scheme 3. Possible mechanistic pathways based on calculations (energies given in kJmol^ꢁ1

)

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3247

S. P. Nolan, M. Malacria, L. Fensterbank, L. Cavallo et al.

Au carbene intermediate b is 60 kJmol^ꢁ1lower in energy

than the starting alkyne-coordinated intermediate 2Au, and

is reached through transition state 2Au-b, with a rather low

energy barrier of 32 kJmol^ꢁ1(Scheme 3 and Figure S1, Sup-

porting Information). Formation of 3 from b involves a 1,2-

shift of the ester group from C3 to C2. After a first step

leading to formation of intermediate c via transition state b-

c with a barrier of 25 kJmol^ꢁ1, the 1,2-shift is then complet-

ed via transition state c-3Au with a barrier of 13 kJmol^ꢁ1,

and finally affords the coordinated product 3Au. Both inter-

mediate c and 3Au are lower in energy than intermediate

2Au (by 82 and 147 kJmol^ꢁ1, respectively), and thus forma-

tion of 3Au is a substantially downhill path from the starting

alkyne-coordinated species 2Au to the coordinated product

species 3Au. Product release from 3Au assisted by a coordi-

26 kJmol^ꢁ1lower in energy than starting alkyne-coordinated

intermediate 2Au, and is obtained via transition state 2Au-f

with a rather low energy barrier of 36 kJmol^ꢁ1.

Transition state 2Au-f is slightly higher in energy than the

similar transition state 2Au-b because of the higher steric

strain associated with formation of a more strained five-

membered ring in 2Au-f, compared to formation of a 6-

membered ring in 2Au-b. Formation of 4 from f then in-

volves 1,2-shift of the ester group from C3 to C2. The first

step of this 1,2-shift is the formation of intermediate g

through transition state f-g with a barrier of 14 kJmol^ꢁ1.

Final formation of coordinated product 4Au occurs through

transition state g-4Au with an energy barrier of 16 kJmol^ꢁ1.

Both intermediates g and 4Au are lower in energy than in-

termediate 2Au (by 61 and 127 kJmol^ꢁ1, respectively), and

thus formation of 4Au, similar to that of 3Au, is a substan-

tially downhill path from the starting alkyne-coordinated re-

actant 2Au to the coordinated product 4Au (Figure S2, Sup-

nating BF₄counterion is endergonic by 6 kJmol^ꢁ1, leads to

ꢁ

product 3, and closes the catalytic cycle by forming the start-

ing [(IDM)Au]BF₄species a. However, product 3 can be

reached from 2Au through an alternative reaction pathway.

Indeed, as mentioned before, in addition to the cyclopropa-

nation then migration sequence that was just examined, the

migration then cyclopropanation sequence must be consid-

ered. Thus, starting from alkyne-coordinated species 2Au, a

1,2-shift of the ester group corresponding to attack of O16

on C2 leads to intermediate d through transition state 2Au-

d with an energy barrier of 18 kJmol^ꢁ1(Scheme 3). Inter-

mediate d, which is 35 kJmol^ꢁ1lower in energy than 2Au, is

another branching point in this complex reaction manifold.

porting Information). Product release from 4Au assisted by

ꢁ

a

coordinating BF₄

counterion is endergonic by

13 kJ.mol^ꢁ1, leads to product 4, and closes the catalytic cycle

by forming the starting [(IDM)Au][BF₄] species a.

AHCTUNGTRENNUNG

Like 3, 4 can be reached from 2Au through an alternative

path that involves initial 1,2-shift of the ester group. As dis-

cussed above, the branching point is intermediate d (see

ꢁ

Scheme 3). In fact, breaking of the C3 O13 bond can alter-

natively lead to intermediate (Z)e, with

a

ꢁ

barrier of

ꢁ1

33 kJmol , which, upon attack of the C11 C12 double

bond on C1, leads to coordinated product species 4Au via

transition state (Z)e-4Au with an energy barrier of

ꢁ

The branch that leads to 3 involves breaking of the C3 O13

bond to furnish intermediate (E)e, with

a

barrier of

34 kJmol^ꢁ1, and a subsequent cyclopropanation step, corre-

22 kJmol^ꢁ1. Bicyclo

ACTHNGUTERN[UNG 3.1.0]hexene 4 is then released from

ꢁ

sponding to attack of the C6 C7 double bond on C1

4Au by coordination of a BF₄anion, and the catalytic cycle

closed. Intermediate (Z)e is 13 kJmol^ꢁ1lower in energy

than 2Au, and it is less stable than the (E)e isomer by

9 kJmol^ꢁ1. Considering that transition state 2Au-d is

18 kJmol^ꢁ1lower in energy than transition state 2Au-f, we

believe that formation of 4 proceeds to a great extent

through a 1,2-shift followed by a cyclopropanation, confirm-

ing the results obtained with enantioenriched dienyne 2 (see

Table 2).

through transition state (E)e-3Au. A last step with an

almost negligible energy barrier of only 1 kJmol^ꢁ1leads to

coordinated product species 3Au, from which 3 is released,

closing the catalytic cycle. Intermediate (E)e is 22 kJmol^ꢁ1

lower in energy than 2Au.

The actual pathway that is followed to reach 3 is deter-

mined by the energy difference between the transition states

of highest energy along the two alternative pathways, that is,

transition states 2Au-d and 2Au-b. According to our calcula-

tions, transition state 2Au-d is lower in energy than 2Au-b

by 14 kJmol^ꢁ1, which suggests that the main reaction chan-

nel leading to 3 involves 1,2-shift of the ester group first and

then a cyclopropanation step, although the alternative path

corresponding to the cyclopropanation then 1,2-shift se-

quence is competitive.

While the possible mechanistic pathways explaining for-

mation of 3 and 4 from 2Au were already proposed in the

literature,^{[11a,12,21,22]}the formation of 5 from 2Au had only

little mechanistic explanation prior to this study.^[12,24,27]We

anticipated that 5 could be formed by at least three different

reaction paths. In all cases allene-coordinated intermediate

7Au is the key intermediate for rationalizing formation of 5

(see Scheme 3). The simplest pathway involves a 1,3-shift of

the ester group from 2Au to give intermediate h through

transition state 2Au-h with an energy barrier of 41 kJmol^ꢁ1

(see Scheme 3 and Figure S3, Supporting Information). In-

termediate h, which is 14 kJmol^ꢁ1lower in energy than 2Au,

then evolves, via transition state h-7Au with an almost negli-

gible energy barrier of 3 kJmol^ꢁ1, to allene-coordinated spe-

cies 7Au, which is 36 kJmol^ꢁ1lower in energy than 2Au.

Several geometries, each rather similar in energy, can be

adopted by 7Au. For the sake of simplicity, in all reaction

Next we focused on the formation of 4, which can also be

reached through two alternative pathways (cyclopropanation

then 1,2-shift or the reverse sequence) that are very similar

to those described above to rationalize the formation of 3.

ꢁ

The first path again involves nucleophilic attack of a C C

ꢁ

double bond on C1, but in this case it is the C11 C12

double bond that we have to consider (see Scheme 3 and

Figure S2, Supporting Information). This cyclopropanation

step leads to intermediate f, which already has the bicyclic

skeleton of product 4. Gold carbene intermediate f is

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Cycloisomerization of Enynyl Esters versus Allenenyl Esters

FULL PAPER

pathways presented, the most stable isomer of 7Au is dis-

cussed. Allene-coordinated species 7Au can evolve towards

coordinated product species 5Au through simultaneous

to intermediate (Z)k via transition state (Z)e-(Z)k with an

energy barrier of 20 kJmol^ꢁ1, and then to Au allene species

7Au through transition state (Z)k-7Au with an energy barri-

er of 50 kJmol^ꢁ1. Once intermediate 7Au has been reached,

the reaction can evolve to 5, as described before. In this

case, 1,2-shift transition state (Z)e-(Z)k must compete with

cyclopropanation transition state (Z)e-4Au, which is only

2 kJmol^ꢁ1higher in energy. This implies that branching from

(Z)e along both reaction pathways is a very likely event.

We also explored whether the C1 and C3 atoms of the

ꢁ

attack of the C11 C12 double bond on C1 and C3 to form

the bicyclo[3.1.0]hexene skeleton of 5 in a single step lead-

G

ing to intermediate i through transition state 7Au-i with an

energy barrier of 24 kJmol^ꢁ1.

Finally, a 1,2-shift of the ester group of i, through inter-

mediate j and transition states i-j and j-5Au with energy bar-

riers of 16 kJmol^ꢁ1and 21 kJmol^ꢁ1, respectively, leads to the

Au-coordinated product 5Au. Product release from 5Au as-

ꢁ

7Au allene species can be attacked by the C6 C7 double

ꢁ

sisted by a coordinating BF₄counterion is endergonic by

bond of the substrate (see Scheme 4). In this case, the

14 kJmol^ꢁ1, leads to product 5, and closes the catalytic cycle

bicycloACTHNGUTERNN[UG 3.2.0]heptene skeleton of m is formed through tran-

ꢁ

by forming the starting [(IDM)Au]BF₄species a. The BF₄

sition state 7Au-m with a barrier of 55 kJmol^ꢁ1. Transition

state 7Au-m is 31 kJmol^ꢁ1higher in energy than transition

state 7Au-i, which is in agreement with the experimental

counterion can also displace allene 7 from 7Au, yielding

starting [(IDM)Au]ACHTUNGTRENNUNG[BF₄] species a and releasing the allene 7

into the reaction medium.

finding that no product having a bicyclo

framework was observed.

ACHTUNGTREN[NGNU 3.2.0]heptene

Formation of 5 can be also explained by two other path-

ways that branch from intermediates (E)e and (Z)e, which

we already introduced to rationalize formation of 3 and 4,

respectively (Scheme 3). We first discuss branching from in-

termediate (E)e. Instead of the cyclopropanation step corre-

For the sake of completeness, we calculated the full cata-

lytic cycle. Thus, intermediate m is 52 kJmol^ꢁ1lower in

energy than 2Au, and is connected to the product o through

intermediate n at ꢁ80 kJmol^ꢁ1, and transition states m-n

and n-o at ꢁ48 kJmol^ꢁ1and ꢁ69 kJmol^ꢁ1, respectively. The

coordinated product o is 144 kJmol^ꢁ1lower in energy than

2Au.

ꢁ

sponding to nucleophilic attack of the C6 C7 double bond

on C1, (E)e can undergo a 1,2-shift of the ester group, lead-

ing initially to intermediate (E)k via transition state (E)e-

(E)k with an energy barrier of 33 kJmol^ꢁ1, and then to Au

allene species 7Au through transition state (E)k-7Au with

an energy barrier of 48 kJmol^ꢁ1. Once intermediate 7Au has

been reached, the reaction can

Finally, we also explored formation of 5 according to the

pathway shown in Scheme 5, which starts with displacement

ꢁ

of the BF₄counterion from [(IDM)Au]BF₄species a by the

evolve to 5, as described before

(Scheme 3 and Figure S3, Sup-

porting Information). However,

this branching is quite unlikely

considering that 1,2-shift transi-

tion state (E)e-(E)k must com-

pete with cyclopropanation

transition

state

(E)e-3Au,

which is 32 kJmol^ꢁ1lower in

energy (Scheme 3).

We now discuss branching

from intermediate (Z)e. Instead

of the cyclopropanation step

corresponding to nucleophilic

ꢁ

attack of the C11 C12 double

bond on C1, (Z)e, similarly to

(E)e, can undergo a 1,2-shift of

the ester group, leading initially

Scheme 4. Alternative cyclization pathway from 7Au.

Scheme 5. Alternative pathway to form 5.

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3249

S. P. Nolan, M. Malacria, L. Fensterbank, L. Cavallo et al.

ꢁ

C11 C12 double bond of 2, rather than by the C1 C2 triple

formed with NHC ligands of low steric bulk such as ITM

(see Table 1).

bond.^[28]Intermediate p, in which the C11 C12 double bond

ꢁ

is coordinated to the Au atom,^[29]is only 2 kJmol^ꢁ1higher in

energy than 2Au, which indicates that coordination of the

alkyne or of the alkene group of the substrate is scarcely se-

lective. Nucleophilic attack of the C1 C2 triple bond on the

coordinated C11 C12 double bond proceeds through transi-

Finally, 7Au is another excellent way off the carousel,

since the transition state 7Au-i that connects intermediate

7Au and product 5 is considerably lower in energy (by 33

and 37 kJmol^ꢁ1, respectively) than transition states 7Au-

(Z)k and 7Au-(E)k, which must be reached by 7Au to move

on the carousel. Thus, the relatively small amount of 5 pro-

duced with 2Au as entry point into the carousel is explained

by the relatively high-energy transition state (Z)k-7Au,

which does not allow easy formation of 7Au from (Z)e. On

the other hand, the direct 1,3-shift pathway from 2Au to

7Au is blocked by relatively high energy transition state

2Au-h. Finally, the golden carousel clearly explains the large

amount of 5 that is formed when allene species 7Au is used

as entry point.

Overall, the theoretical results presented allow us to ra-

tionalize the formation of unprecedented bicyclo-

AHCTUNGTREG[NNUN 3.1.0]hexene 5. According to our calculations, cyclization

would occur after formation of the allenyl ester, between

the allene and the ene part of the 1,4-allenene core.^[30]To

verify this hypothesis, we prepared allenyl ester 7 by a

simple silver-catalyzed procedure^[31]and subjected it to cycli-

zation conditions. In the presence of 2 mol% of

[(IPr)AuCl]/AgBF₄, cycloisomerization of 7 led to the for-

mation of 5 as major product (Table 3, entry 1). The reaction

ꢁ

tion state p-q, which is 62 kJmol^ꢁ1higher in energy than

2Au, so that this reaction path is excluded. In this case too,

for the sake of completeness, we calculated the full catalytic

cycle. Thus, intermediate q is 49 kJmol^ꢁ1lower in energy

than p, and is connected to 5Au through transition state q-

5Au with an energy barrier of only 4 kJmol^ꢁ1.

Our calculations clearly indicate that this catalytic reac-

tion is characterized by numerous highly competitive reac-

tion pathways. We cannot exclude that there are other reac-

tion pathways which we were not able to envisage, and that

bulkier NHC ligands could result in somewhat different en-

ergetics. However, exploring this complex manifold of reac-

tions with a larger NHC is almost prohibitive. Nevertheless,

calculations clearly demonstrate that the high reactivity of

the starting structure 2Au is at the origin of this diversity.

As we already indicated, the alkyne-coordinated species can

undergo both 1,2 and 1,3-shift of the ester group, leading re-

spectively to Au carbene species (E)e and (Z)e, and to Au

allene species 7Au. All these species are connected in a cat-

alytic cycle we dubbed “Golden Carousel”. To better illus-

trate this, the most relevant sections of the numerous reac-

tion pathways are shown in Scheme 6.

Table 3. Cyclization of allenyl ester 7.

Clearly, alkyne-coordinated species 2Au is the intermedi-

ate of highest energy in the cycle, while the reservoir of

active species are intermediate d (which is not a way off the

cycle) and allene species 7Au. Intermediate d is easily

formed from 2Au. The Au carbene species (E)e and (Z)e

are ways off the carousel to products 3 and 4, respectively,

while Au-allene species 7Au is the way off to product 5.

Evolution of (E)e, (Z)e, and 7Au depends on the relative

energy of the three transition states (two of them corre-

spond to clockwise and counterclockwise movements on the

Golden Carousel, and the third is a way off the carousel)

that can be reached from each of these intermediates.

Entry

[M]

3:4:5^[a]

Total

yield [%]^[a]

1

A

1/1.4/9.3

1/0.5/0.7

1/0.8/4.5

1/1.4/1.9

93

51

63

50

2^[b]

3^[b]

4^[b]

ACHTUNGTRENNUNG

AuCl

AuCl₃

[a] Yields of isolated products, average of two runs, products ratio deter-

mined by ¹H NMR spectroscopy. [b] No starting material remained; sig-

nificant amounts of oligomerized by-products were formed.

Intermediate (E)e is an excellent way off the carousel,

since the transition state that connects intermediate (E)e

and product 3, (E)e-3Au, is quite lower in energy (by

20 kJmol^ꢁ1and 32 kJmol^ꢁ1, respectively) than transition

states d-(E)e and (E)e-(E)k, which are the transition states

to be reached by (E)e in order to move on the carousel.

This explains the easy formation of 3. In contrast, (Z)e is

not a good way off the carousel, since the most likely event

is a counterclockwise move on the carousel, to yield the

highly stable intermediate d. The two other transition states

of highest energy accessible from intermediate (Z)e, namely,

(Z)e-4Au and (Z)k-7Au, correspond respectively to the way

off the carousel leading to 4Au and to a clockwise move to-

wards allene intermediate 7Au (Scheme 6). They are 11 and

23 kJmol^ꢁ1higher in energy than transition state d-(Z)e,

which explains the small amount of products 4 and 5

was more selective in favor of 5 than the cyclization of 2 (3/

4/5, 1/1.4/9.3 vs. 1/0.4/1.4), which strongly supports allenyl

ester 7 as intermediate in the transformation 2!5. Impor-

tantly, this is the first reaction producing 3 as the minor

product.

Further examination of the reactivity of 7 in the presence

of [(PPh₃)AuCl] revealed the importance of the ligand on

the gold center (Table 3, entry 2). The phosphine-containing

catalyst notably produced significant amounts of oligomer-

ized products, as previously observed in the cyclization of di-

enyne 2, and afforded a more contrasting ratio of cyclopro-

panated bicycles. Keeping in mind that products 3 and 4 are

likely produced via direct cyclopropanation of enyne 2 and/

or intermediate I, both arising from “retro-migration” of the

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Cycloisomerization of Enynyl Esters versus Allenenyl Esters

FULL PAPER

Scheme 6. Golden Carousel linking 2, 3, 4, 5, and 7.

OAc group in 7, it appears that the competition between

acetate and alkene as internal nucleophiles in 7 is strongly

influenced by the ligand on gold. More precisely, allenyl

acetate 7 seems to be less prone to isomerization back to I

and 2 when activated by the cationic [(NHC)Au]⁺species

than with the phosphine gold catalyst.^[32]Finally, the absence

of rearranged product from the 1,5-allenene framework

seems to indicate a strong pref-

We also carried out the cycloisomerization of allenene 8,

which afforded a quantitative yield of novel cyclopropyl

compound 9 [Eq. (2)]. In this case, excellent selectivity was

already obtained when starting from the corresponding

propargylic acetate 10, but the yield of 9 was clearly im-

proved. While this total selectivity in favor of the new type

of product was unexpected at the time of our preliminary

erence for the 1,4-allenene scaf-

fold in the present catalytic

system, as was predicted in our

theoretical

studies

(see

Scheme 4).^[33,34]

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3251

S. P. Nolan, M. Malacria, L. Fensterbank, L. Cavallo et al.

communication,^[12]it can now be easily rationalized. Forma-

tion of allenyl acetate 8 from 10 is favored by the alkyl sub-

stituents of the alkyne, and therefore leads straightforwardly

to cyclized product 9.

1,2- versus 1,3-OAc migration: ¹⁸O-labeling experiments:

Upon p activation, propargylic esters can lead to allenyl

esters that are further activated by the metal center, giving

rise to a wide variety of products.^[9]Even though it is also

observed in the presence of platinum,^[35]this reactivity is

mostly triggered by gold catalysts.^[36]We have established

Scheme 7. ¹⁸O-labeling experiments in the cycloisomerization of 2.

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Cycloisomerization of Enynyl Esters versus Allenenyl Esters

FULL PAPER

that allenyl ester 7 is very likely a key intermediate in the

pathway leading to carbocycle 5. This crucial insight was

provided by our theoretical calculations. Additionally, the

computed values for the double 1,2-OAc migration were

found to be slightly higher than those for the direct 1,3-OAc

migration (i.e., 50 vs. 41 kJmol^ꢁ1), which, taking into consid-

eration the possible experimental error, renders both path-

ways competitive. Therefore, in an effort to try to under-

stand every aspect of the cyclization studied here, and will-

ing to consider thoroughly any possibility, we carried out la-

beling experiments with 2-¹⁸O, our model substrate with a

carbonyl oxygen atom 47% enriched in ¹⁸O, to address this

issue.^[37]

We then analyzed, by high-resolution mass spectrometry,

the isotopic distribution of different mixtures of products

from reactions performed in the presence of PtCl₂,

AuCl₃,and [(IPr)AuCl]/AgBF₄(Scheme 7). Both products of

the Pt-catalyzed cycloisomerization showed nearly quantita-

tive transfer of the ¹⁸O content at the vinylic position

(Scheme 7, top bracket), consistent with a net 1,2-migration

of the acetate group. On the contrary, the reactions conduct-

ed in the presence of gold revealed a more complex behav-

ior (middle and bottom brackets). The three produced car-

bocycles 3-¹⁸O, 4-¹⁸O, and 5-¹⁸O displayed scrambled isotopic

contents carbonyl/enol ranging from 75/25 to 40/60. These

results indicate that gold catalysts, both AuCl₃and the cat-

ionic [(IPr)Au]⁺fragment, isomerize propargylic acetates to

allenyl acetates by both double 1,2-migration (Scheme 1,

I!II!III) and direct 1,3-migration (I!III) randomly. No-

tably, under the present conditions, isomerization between

the alkyne and the allene presumably occurs several times

before the cyclization step is achieved.^[38,39]

Scheme 8. 1,2-OAc migration via an oxirenium intermediate.

7-¹⁸O to 5-¹⁸O. The absence of scrambling in this case could

appear surprising and points to the faster rate of nucleophil-

ic attack by the alkene than by the carbonyl group. We be-

lieve that the improved selectivity observed in the formation

of 5 when allene 7 was used as cyclization precursor in place

of 2 and the absence of ¹⁸O scrambling from 7-¹⁸O both sup-

port this reactivity pattern.^[43,44]

Interestingly, these findings correlate well with the results

of the cycloisomerization of the enantioenriched precursor

2. Better chirality transfer was observed with platinum(II)

catalysis, while gold catalysis, which shows significant ¹⁸O

scrambling, also furnished nearly racemic products.

Reversibility of acetate migration: One of the main findings

of the experimental and theoretical studies described above

on the model dienyne 2 is that an apparent 1,2-OAc migra-

tion in the final cyclized product can in fact result from a

1,3-shift followed by a “retro” 1,2-migration of the acetate

group. This “retro-migration” process has only been ob-

served adventitiously previously^[45]and has not been the sub-

ject of further investigations. We now provide additional

data supporting this reactivity.

We also envisaged, as a possible alternative, that migra-

tion of the acetate group could occur via an oxirenium inter-

mediate, as proposed by Gevorgyan et al. for the isomeriza-

tion of propargylic acetates and phosphates,^[40]and by

Hotha and Kashyap for the activation of propargyl glyco-

sides.^[41,42]This possibility was ruled out by DFT calculations,

since the oxirenium-like transition state, connecting in a

single step the alkyne-coordinated species 2Au and the Au

carbene intermediate (E)e, lies 121 kJmol^ꢁ1above 2Au (see

Scheme 8), which is much higher in energy than other tran-

sition states that can be reached from 2Au.

Intermolecular cyclopropanation: Intermolecular cyclopro-

panation of propargylic esters with alkene was first reported

by Ohe and Uemura using ruthenium(II) catalysts^[46]and

subsequently studied by Toste et al. with gold catalysts.^[21]

Our goal was to use allenyl acetates in this reaction and

prove “retro-migration” of the ester by intermolecular trap-

ping of the gold carbenoid by an olefin.

We carried out the reaction of allenyl acetate 11 with

3 equivalents of styrene in the presence of platinum(II),

gold(I), and goldACTHNUTRGNEU(GN III) catalysts (Table 4). Thus, under typical

“platinum conditions” (toluene, 808C), we observed forma-

tion of cyclopropane derivative 12 in moderate yield

(Table 4, entry 1). GoldACTHNUGRTENUNG(III) chloride led to decomposition

(Table 4, entry 2), while gold(I) catalysts showed compara-

ble activity to PtCl₂and had the advantage of being active

Next, we prepared allene 7-¹⁸O from 2-¹⁸O and subjected

it to cyclization conditions. Interestingly, we observed com-

plete loss of ¹⁸O [Eq. (3)], in strong support of 1,2-migration

of the acetate group through its carbonyl oxygen atom, from

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S. P. Nolan, M. Malacria, L. Fensterbank, L. Cavallo et al.

Table 4. Intermolecular cyclopropanation of allenyl ester 11.

Table 5. Cycloisomerization of allenyl acetate 15.

Entry [M] (mol%)

Reaction conditions Yield of

16 [%]^[a]

1

2

3

PtCl₂(5 mol%)

AuCl₃(2 mol%)

toluene, 808C, 4 h

neat, 808C, 2 h

CH₂Cl₂, reflux, 2 h

49

61

24

51

20

Entry [M]

Reaction conditions

Yield of

12 [%]^[a]

4

ACHTNUGTERN[NUNG (PPh₃)AuCl]/AgSbF₆(2 mol%) CH₂Cl₂, reflux, 2 h

5^[b]

A

CH₂Cl₂, reflux, 8 h

1

PtCl₂(5 mol%)

AuCl₃(2 mol%)

toluene, 808C, 15 min 55

2^[b]

3

CH₂Cl₂, RT, 2 h

–

[a] Yields of isolated products. [b] [Au^I]=

A

46

51

62

4

5

N

CH₂Cl₂, RT, 4 h

CH₂Cl₂, RT, 2 h

T

1

[a] Yields of isolated products, d.r. determined by H NMR spectroscopy.

[b] Decomposition

of

11

was

mainly

observed.

[c] [Au^I]=

transformation than its triphenylphosphine counterpart

(Table 5, entry 5 versus entry 4). The results presented here

show the viability of ester migration onto the allene moiety

in the context of intramolecular cyclization. As observed

previously in the cyclization of the corresponding propargyl-

ic acetate,^[49]the reaction produced only one diastereomer.

In an attempt to extend the scope of this reaction, forma-

tion of tricyclic derivative 18 was envisioned. Unexpectedly,

we only recovered the unchanged allene 17, even after pro-

longed reaction in the presence of Au^Iand Au^IIIcatalysts

[Eq. (4)].

at room temperature (Table 4, entries 3 and 4). This set of

experiments validates the aforementioned possibility of

forming transition metal vinyl carbenoid intermediates on

activation of an allenyl ester moiety, which, to the best of

our knowledge, is unprecedented.^[47]In the present case, 12

is likely formed through the intermediacy of carbene species

14, resulting from a 1,2-OAc

shift in 13.^[48]Encouraged by

these results, we decided to fur-

ther examine the behavior of

allenyl esters in the presence of

soft p-acid catalysts and espe-

cially the possible dichotomy

between allenenyl esters and

their corresponding enynyl

esters.

Cyclization of propargylic ace-

tates versus allenyl acetates:

scope and limitations: Acetate

15 having a 1,6-allenene core

was subjected to typical cycliza-

tion conditions in the presence

of gold and platinum catalysts

(Table 5).

Formation of tricyclic com-

pound 16 was observed in all

cases, whereby PtCl₂and

[(PPh₃)AuCl]/AgSbF₆were the

most efficient catalytic systems

(Table 5, entries 1, 2, and 4).

The gold(I) catalyst bearing a

bulky ortho-biphenylphosphine

ligand was less effective in this

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Cycloisomerization of Enynyl Esters versus Allenenyl Esters

FULL PAPER

Even though a thorough explanation of this observation is

lacking at the moment, it appears that, as in the case of

enyne, minute changes in the architecture of the allenene

precursor can be detrimental to the cycloisomerization pro-

cess.

various enynyl acetates with their corresponding allenenyl

acetates showed that the latter substrates could lead to for-

mation of alternative products.

This combined experimental and theoretical study permit-

ted the details of a novel cycloisomerization mode to be un-

covered and more generally to gain insight into mechanistic

aspects of the intricate cyclization mode of enynes bearing a

propargylic ester group. Further studies taking advantage of

this experimental/theoretical approach to complex synthetic

issues are ongoing.

Turning our attention to other substrates, we examined

the reactivity of different unsaturated cyclization precursors.

Interestingly, 1,5-allenene 19 and its 1,6-enyne counterpart

20 afforded similar yields and product ratio of 21 and 22

[Eq. (5)], whereby the cyclization from the allene was slight-

ly more efficient than from the alkyne.^[50]The formation of

cyclized product 22, which is formally an enyne ring-closing

metathesis product,^[51]from allene 19 implies in situ forma-

tion of alkyne 20 via 1,3-shift of the acetate moiety.

In light of the difference in reactivity observed between

15 and 17, we decided to examine close analogues of 19 and

20, namely, 23 and 26. In the presence of gold(I) catalyst,

alkyne 23 afforded a mixture of cyclopropane and diene de-

rivatives 24 and 25 [Eq. (6)].^[52]In contrast to the cyclobutyl

derivatives, in this series the cyclopropanated product 24 is

favored and formed in a 3/1 ratio over the metathesis prod-

uct, diquinane 25.

Starting from the corresponding allenyl acetate 26 re-

vealed a different behavior of the gold(I) catalyst employed

here. In this case, tricyclic acetate 24 was only formed as the

minor product along with triene 27 as major compound

[Eq. (7)]. Additionally, no formal metathesis product 25

could be observed. The formation of 27 results presumably

from a [3,3] rearrangement catalyzed by the cationic gold(I)

center. A thermal [3,3] sigmatropic rearrangement is pre-

sumably ruled out since the reaction occurs at room temper-

ature.^[53]

Experimental Section

General information: All reagents were used as purchased. Dry THF and

dry dichloromethane were purified by passing through a purification

column from Innovative Technology Inc. (SPS-400-6). Silver salts were

stored in a desiccator wrapped in aluminum foil. TLC analysis of reaction

mixtures was performed on EMD Chemicals silica gel 60 F₂₅₄plates and

visualized by UV. Flash chromatography was performed on silica gel 60

(230–400 mesh, Silicycle). ¹H and ¹³C NMR spectra were recorded on a

Varian 300, Varian 400, or Bruker 300 MHz spectrometer at ambient

temperature in CDCl₃containing TMS. Chemical shifts were referenced

to the peak of TMS (0.0 ppm). Assignments of some ¹H and ¹³C NMR

signals rely on COSY and/or HMBC experiments. Chiral GC analyses

were performed under isothermal conditions (1108C) on a chiral column

CP-Chirasil-DEX CB (25 m). [(NHC)AuCl]^[15]complexes and [Au^I]^[54]

were synthesized according to literature procedures. Compounds 2,^[11a]

7,^[12]10,^[12]15,^[49]17,^[49]19,^[49]20,^[49]and 23^[49]were synthesized according

to literature procedures, and their spectroscopic data found to be in good

agreement with previously reported characteristic data. Characterization

of cyclized compounds 3,^[11a]4,^[12]5,^[12]9,^[12]16,^[49]21,^[49]and 24^[49]was

based on previous reports, and their spectroscopic data were in good

agreement with previously reported characteristic data.

Synthesis of [(IDD)AuCl]: [(IDD)AgCl]^[55](200 mg, 0.37 mmol, 1 equiv)

and dimethyl sulfide gold(I) chloride (130 mg, 0.44 mmol, 1.1 equiv) were

dissolved in a minimal amount of CH₂Cl₂and stirred overnight at room

temperature. Charcoal was added and the reaction mixture stirred for a

further 3 h. After filtration over Celite, a clear greenish solution was ob-

tained. The volume of CH₂Cl₂was reduced, and the desired complex pre-

cipitated and was washed with pentane to yield 180 mg (77% yield) of a

white powder. ¹H NMR (400 MHz, CDCl₃): d=6.94 (s, 2H, CH^Im), 4.91

(pent, J=6.6 Hz, 2H, CH^Cyclododecyl), 2.06–1.96 (m, 4H), 1.69–1.60 (m,

8H), 1.56–1.5 (m, 2H), 1.46–1.28 ppm (m, 30H); ¹³C NMR (100 MHz,

CDCl₃): d=169.8 (C, CAu), 117.6 (CH, CH^Im), 58.0 (CH, CH^Cyclododecyl),

31.2 (CH₂), 23.7 (CH₂), 23.5 (CH₂), 23.4 (CH₂), 23.2 (CH₂), 21.6 ppm

(CH₂); HRMS calcd for C₂₉H₅₂AuN₃[MꢁCl+MeCN]⁺: 639.3821; found:

639.3825. CCDC 679915 contains the supplementary crystallographic

data for this paper. These data can be obtained free of charge from The

Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_-

request/cif..

Conclusion

A thorough study of the reactivity pattern of a peculiar

branched dienyne in the presence of gold and platinum cata-

lysts has been presented. We examined the effect of the an-

cillary ligand bound to the gold center and found that bulky

N-heterocyclic carbenes are a key parameter for obtaining

significant ratios of bicycloACTHNUTRGENUGN[3.1.0]hexene 5 over compounds

3 and 4. Further experimental and theoretical mechanistic

studies allowed the formation of all cyclized products to be

accounted for. Notably, a reaction pathway leading to cy-

clized compound 5 has been proposed. The cycloisomeriza-

tion reaction leading from 2 to 5 would occur by a 1,3-OAc

shift/allene–ene cyclization/1,2-OAc shift sequence. Support-

ing this hypothesis, which translates the apparent 1,2-OAc

shift from 2 to 5 in a 1,3-OAc migration followed by a 1,2-

OAc “retro-migration”, cyclization of allenenyl acetate 7 af-

forded a greater proportion of 5 over 3 and 4. Additionally,

theoretical calculations suggested that the selectivity to-

wards the three cyclopropyl derivatives 3, 4, and 5 is dictat-

ed by the following equilibrium: [gold propargyl acetates

IQgold carbenoid vinyl acetates IIQgold allenyl acetates

III]. Finally, examination of the differences in reactivity of

Typical procedure for cycloisomerization of (2): To a solution of gold

[platinum] catalyst (2 mol% [5 mol%]) in CH₂Cl₂[toluene] (5 mL) in a

scintillation vial equipped with a stir bar, AgBF₄(if required) was added.

The solution instantly became cloudy. A solution of dienyne 2 (44 mg,

0.2 mmol) in CH₂Cl₂[toluene] (3 mL) was then added. After consump-

tion of the starting material, the solvent was removed. The resulting mix-

ture was dissolved in pentane, filtered through Celite, and the filtrate

concentrated in vacuo. Yields refer to mixtures of isolated products;

1

ratios are based on H NMR integration.

Trapping experiment in methanol: formation of 4-acetyl-6,6-dimethyloc-

ta-1,7-dien-4-yl acetate (6): Following the typical procedure for the cyclo-

isomerization of 2 (1 mmol) in methanol, the crude product was purified

by flash chromatography (pentane/tert-butyl methyl ether 8/2), which af-

forded 149 mg (59% yield) of 6. ¹H NMR (CDCl₃, 400 MHz): d=5.83

Chem. Eur. J. 2009, 15, 3243 – 3260

ꢄ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

3255

S. P. Nolan, M. Malacria, L. Fensterbank, L. Cavallo et al.

(dd, J=17.6, 10.8 Hz, 1H, H²), 5.62–

5.51 (m, 1H, H⁷), 5.01–4.96 (m, 2H,

7-Allyl-9,9-dimethylundeca-5,6,10-

trien-5-yl acetate (8): The general pro-

cedure using propargylic acetate 10^[12]

H⁸), 4.84–4.77 (m, 2H, H¹), 4.38 (d,

J=2.0 Hz, 1H, 1H¹⁰), 4.04 (d, J=

(442 mg, 1.6 mmol) yielded 420 mg

(95%) of 8. ¹H NMR (400 MHz,

2.0 Hz, 1H, 1H¹⁰), 3.50 (s, 3H, OMe),

3.07 (dd, J=14.4, 8.8 Hz, 1H, 1H⁶),

CDCl₃): d=5.83 (dd, J=17.4, 10.7 Hz,

1H, H²), 5.86–5.75 (m, 1H, H⁷), 5.05–

2.54–2.47 (m, 2H, 1H⁶+ 1H⁴), 1.97 (s,

5.00 (m, 2H, 2H⁸), 4.91 (dd, J=17.5, 1.4 Hz, 1H, 1H¹), 4.89 (dd, J=11.4,

1.4 Hz, 1H, 1H¹), 2.87–2.73 (m, 2H, 2H⁶), 2.25–2.13 (m, 2H, 2H¹¹), 2.08

(s, 3H, OAc), 1.43–1.32 (m, 4H, 2H¹²+ 2H¹³), 1.04 (s, 3H, Me), 1.03 (s,

3H, Me), 0.89 ppm (t, J=7.1 Hz, 3H, 3H¹⁴); ¹³C NMR (100 MHz,

CDCl₃): d=193.9 (C, C⁹), 168.6 (C, C=O), 148.0 (CH, C⁷), 135.6 (CH,

C²), 123.6 (C, C¹⁰), 116.0 (CH₂, C⁸), 111.7 (CH₂, C¹), 110.3 (C, C⁵), 46.1

(CH₂, C⁶), 40.3 (CH₂, C⁴), 37.4 (C, C³), 31.5 (CH₂, C¹¹), 28.5 (CH₂), 27.0

(CH₃), 26.8 (CH₃), 22.1 (CH₂), 21.0 (CH₃, OAc), 13.8 ppm (CH₃, C¹⁴);

HRMS (ES+): m/z calcd for C₁₈H₂₈O₂Na [M+Na]⁺: 299.1982; found:

299.1990.

3H, OAc), 1.87 (d, J=15.2 Hz, 1H,

1H⁴), 1.01 ppm (s, 6H, 2ꢆCH₃); ¹³C NMR (CDCl₃, 100 MHz): d=169.6

(C, OC(O)Me), 161.3 (C, COMe), 148.4 (CH, C²), 132.8 (CH, C⁷), 117.9

(CH₂, C⁸), 109.1 (CH₂, C¹), 85.3 (C, C⁵), 82.2 (CH₂, C¹⁰), 54.4 (CH₃,

OMe), 44.8 (CH₂, C⁴), 40.8 (CH₂, C⁶), 37.0 (C, C³), 27.8 (CH₃, Me), 27.4

(CH₃, Me), 22.7 ppm (CH₃, OAc); elemental analysis (%) calcd for

C₁₅H₂₄O₃(M=252.35): C 71.39, H 9.09, found: C 71.18, H 9.15.

Preparation of enantioenriched dienyne acetate (2):^[56]A 2.2m solution of

nBuLi in hexanes was added to a solution of bis-oxazoline (322 mg,

1.05 mmol, 1.05 equiv) and 2,2’-bipyridine (0.2 mg) in THF (1.8 mL) at

08C till the solution turned red. After completion of addition, the reac-

tion mixture became a red-brown suspension. The reaction mixture was

warmed to room temperature and stirred for 15 min. A solution of allyl-

zinc bromide (1.5m, 0.7 mL, 1 mmol, 1 equiv) was added to the solution

of lithiated bis-oxazoline. After 30 min, ketone A^[11a](187 mg, 0.9 mmol,

0.9 equiv) in THF (1.3 mL) was added at ꢁ1008C. When the reaction

was complete, the mixture was quenched with MeOH/H₂O (0.04 mL,

1/1). The solvent was removed under vacuum and the crude product puri-

2-(2-Allylcyclopentylidene)vinyl acetate (26): The general procedure

using propargylic acetate 23 (44 mg, 0.2 mmol) yielded 23 mg (51%) of

the title compound as a mixture of two diastereomers (1/1). ¹H NMR

(CDCl₃, 400 MHz): d=7.44 (m, 1H, one dia), 7.35 (m, 1H, one dia),

5.87–5.73 (m, 1H), 5.07–4.98 (m, 2H), 2.67–2.61 (m, 1H), 2.59–2.43 (m,

2H), 2.41–2.32 (m, 1H), 2.14 (s, 3H, one dia), 2.13 (s, 3H, one dia), 2.11–

1.99 (m, 1H), 1.97–1.89 (m, 1H), 1.84–1.75 (m, 1H), 1.70–1.59 (m, 1H),

1.45–1.31 ppm (m, 1H); ¹³C NMR (CDCl₃, 100 MHz): d=190.4 (2C),

169.1 (2C), 137.3, 137.2, 124.9 (2C),

116.4, 116.3, 112.6, 112.1, 45.0, 44.2,

38.8, 38.4, 32.9, 32.8, 32.7, 32.6, 25.4,

25.3, 21.4, 21.3 ppm; IR (neat): n˜ =

3066, 2957, 1976, 1753, 1640,

1434 cm^ꢁ1; HRMS (ES+): m/z calcd

for C₁₂H₁₆O₂Na [M+Na]⁺: 215.1042;

found: 215.1042.

Procedure for isotopic labeling: ¹⁸O-la-

beled water (95% ¹⁸O, 0.84 mL,

41.6 mmol) was added to a solution of

acetyl chloride (2.96 mL, 41.6 mmol)

in dry dichloromethane (20 mL) at room temperature with vigorous stir-

ring. After 2 h, 5.5 mL of this solution (corresponding to 9.85 mmol of

acetic acid) was added to a solution of thionyl chloride (0.790 mL,

10.83 mmol) in dry dichloromethane (2 mL), and the solution was stirred

at room temperature for 12 h. The resulting reaction mixture was trans-

ferred to a solution of dienyne 2 (350 mg, 1.97 mmol) in dry dichlorome-

thane (2 mL) with triethylamine (4.15 mL, 30 mmol) and 4-dimethylami-

nopyridine (120 mg, 0.98 mmol). The reaction was stirred at room tem-

perature for 50 h, and the resulting brown solution was diluted with di-

ethyl ether (100 mL) and washed successively with a saturated aqueous

solution of NH₄Cl (2ꢆ50 mL), a saturated aqueous solution of NaHCO₃

(2ꢆ30 mL), and brine (50 mL). The organic phase was dried over anhy-

drous magnesium sulfate and the solvent was removed by evaporation

under vacuum. The crude mixture was purified by flash chromatography

on silica gel with pentane/diethyl ether (98/2). The ¹⁸O-labeled acetate

was obtained as a colorless oil (312 mg, 71%). The spectroscopic data

were in agreement with those of the corresponding ¹⁶O acetate except for

the carbonyl signal, which appeared as two peaks in the ¹³C spectrum:

169.2 ppm for C=¹⁶O and 169.3 ppm for C=¹⁸O. The HRMS spectrum

confirmed the labeling of the acetate group: ¹⁶O-2: HRMS (ES+): m/z

calcd for C₁₄H₂₀O₂Li [M+Li]⁺: 227.1618; found: 227.1620; ¹⁸O-2: HRMS

(ES+): m/z calcd for C₁₄H₂₀O¹⁸OLi [M+Li]⁺: 229.1660; found: 229.1661.

Integration of mass peaks gave an isotopic abundance of 47%. All the

isotopic labeling was localized on the oxygen atom of the carbonyl group,

which is in agreement with the preparation procedure.

fied by flash chromatography on silica gel (pentane/dichloromethane 7/3)

to afford B (105 mg, 47%). All spectroscopic data were in agreement

with a racemic sample. The enantiomeric excess was determined by

chiral gas chromatography (isotherm 1108C): enantiomer

1 (rt1=

32.4 min) and enantiomer 2 (rt2=33.2 min), 66% ee. [a]²_D⁰=+7.58 (c=

0.3, CHCl₃). Desilylation and acylation of enantioenriched alcohol B ac-

cording to reported procedures^[11a]led to formation of enantioenriched 2;

[a]²_D⁰=+3.28 (c=0.99, CHCl₃).

Computational details: All DFT calculations were performed with the

Gaussian 03 package.^[57]The BP86 GGA functional of Becke and Perdew

was used.^[58]The TZVP triple-z basis set with one polarization function

was used for main group atoms,^[59]while the relativistic SDD effective

core potential in combination with a triple-z basis set was used for the

Au atom.^[60]All geometries were verified by frequency calculations that

resulted in 0 and 1 imaginary frequency for intermediates and transition

states, respectively. The reported energies include the vibrational gas-

phase zero-point energy term, and a solvation term that was obtained

through single-point calculations on the gas-phase optimized geometries.

The polarizable continuous solvation model IEF-PCM as implemented in

the Gaussian 03 package was used.^[59]CH₂Cl₂was chosen as model sol-

vent, with a dielectric constant of e=8.93. Standard nonelectrostatic

terms were also included.

Typical procedure for synthesis of allenyl acetates: A solution of propar-

gylic acetate (1 mmol) in CH₂Cl₂(5 mL) was added to a suspension of

AgBF₄(5 mg, 0.05 mmol, 5 mol%) in CH₂Cl₂(10 mL) in a scintillation

vial equipped with a stir bar in the absence of light. When TLC analysis

showed total consumption of the starting material, the solvent was re-

moved. The resulting mixture was dissolved in pentane, filtered through

Celite, and evaporated. The crude oil was purified, when necessary, by

flash chromatography on silica gel.

Determination of isotopic distribution: Due to experimental constraints,

the isotopic distribution was not determined directly on the enol acetates

obtained after the cycloisomerization reaction. The three products were

separated and immediately subjected to methanolysis conditions

(MeONa/MeOH solution). Neutralization was done by addition of solid

NH₄Cl to avoid addition of water and hydration of the corresponding car-

3256

www.chemeurj.org

ꢄ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2009, 15, 3243 – 3260

Cycloisomerization of Enynyl Esters versus Allenenyl Esters

FULL PAPER

bonyl derivatives. MS analysis allowed for the ¹⁸O isotopic abundance

(the ratio between C₁₂H₁₈OLi and C₁₂H₁₈O¹⁸Li peaks) to be determined

on the carbonyl derivatives, and comparison with the starting material af-

forded the structural isotopic distribution (MS spectra for each experi-

ment are provided in the Supporting Information).

Acknowledgements

S.P.N. acknowledges the Petroleum Research Fund administered by the

ACS, the Ministerio de Educaciꢀn y Ciencia, the ICIQ Foundation, and

ICREA for financial support. SPN is an ICREA Research Professor.

N.M. (2007FI_A 01466) and R.S.R. (2008FI 01047) thank the AGAUR

for pre-doctoral fellowships. L.C. thanks the Regione Campania progetto

Legge5/2005 for financial support, and the INTSM (Cineca Grant) for

computer time. J.C.T. and D.L. thank the CNRS, the UPMC, and the MS

platform SM³P. L.F. and M.M. thank the MRES, the CNRS, the IUF, and

the ANR Blan 0302 “Allꢂnes” for financial support. N.M. thanks Umi-

core for a Ph.D award.

Carbene trapping experiment: formation of cyclopropyl derivative 12:

AgSbF₆(16.5 mg, 0.048 mmol) was added to a solution of [(PPh₃)AuCl]

(24 mg, 0.048 mmol) in dry dichloromethane (10 mL). The solution

became cloudy. A solution of allenyl ester 11 (400 mg, 2.41 mmol) and

styrene (1.38 mL, 12.05 mmol) in dry dichloromethane (2 mL) was added

after 5 min and the mixture stirred under the conditions (time and tem-

perature) indicated in Table 4. When TLC analysis indicated total con-

sumption of the starting material, the crude product was immediately pu-

rified by flash chromatography (pentane/diethyl ether 95/5) to afford cy-

clopropane derivatives 12^[45](300 mg, 46%) as a 3/1 mixture of cis/trans

diastereomers. Application of the same procedure to AuCl₃catalysis

without silver salt and to [(IPr)AuCl]/AgBF₄afforded respectively less

than 10 and 51% of cyclopropane derivatives 12 with similar diastereo-

meric ratio. Platinum (PtCl₂, 5 mol%) catalysis was carried out in tolu-

ene at 808C and the same products were isolated in 55% yield. All the

spectroscopic data were in agreement with those already reported.^[45]The

cis diastereomer was isolated as an analytical sample: ¹H NMR (CDCl₃,

400 MHz): d=7.26–7.19 (m, 2H), 7.18–7.14 (m, 1H), 7.06 (d, J=8.4 Hz,

2H), 2.38–2.25 (m, 2H), 2.23–2.10 (m, 4H), 2.08–1.92 (m, 2H), 1.84–1.75

(m, 1H), 1.50–1.38 (m, 1H), 1.37–1.23 (m, 4H), 1.13–1.01 (m, 2H), 0.51–

0.39 ppm (m, 1H); ¹³C NMR (CDCl₃, 100 MHz): d=169.5 (C), 139.4 (C),

135.2 (C), 130.6 (C), 127.6 (CH), 127.4 (CH), 125.6 (CH), 28.7 (CH₂),

27.6 (CH₂), 26.6 (CH₂), 26.5 (CH₂), 26.2 (C), 24.6 (CH), 21.6 (CH), 20.7

(CH₃), 11.6 ppm (CH₂).

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Cycloisomerization of propargylic acetates versus allenyl acetates: Apply-

ing the general cycloisomerization procedure to 19 or 20 with [Au^I] cata-

lyst gave 21 and 22 in 1/3 ratio and in 88% yield from 19 and 82% from

20. Dienyl derivative 22: ¹H NMR (CDCl₃, 400 MHz): d=6.33 (dd, J=

11.1, 18.0 Hz, 1H), 5.99 (brs, 1H), 5.29 (d, J=18.0 Hz, 1H), 5.03 (d, J=

11.1 Hz, 1H), 3.12–3.06 (m, 1H), 2.90–2.84 (m, 1H), 2.56–2.45 (m, 1H),

2.43–2.33 (m, 1H), 2.19–2.07 (m, 2H), 1.98 (s, 3H), 1.36–1.28 ppm (m,

1H); ¹³C NMR (CDCl₃, 100 MHz): d=169.4, 140.9, 136.0, 129.7, 115.0,

90.0, 43.5, 38.8, 31.9, 22.8, 21.6 ppm: IR (neat): n˜ =2934, 2855, 1741, 1636,

1586, 1432 cm^ꢁ1; HRMS (ES+): m/z calcd for C₁₁H₁₄O₂Na [M+Na]⁺,

201.0886; found, 201.0887.

Applying the general cycloisomerization procedure to 23 with [Au^I] cata-

lyst gave 24 and formal metathesis product 25 in 70% yield as a 3/1 mix-

ture. Diquinane derivative 25: ¹H NMR (CDCl₃, 400 MHz): d=6.32 (dd,

J=11.1, 18.0 Hz, 1H), 5.81 (m, 1H), 5.34 (dd, J=1.0, 18.0 Hz, 1H), 5.05

(dd, J=1.0, 11.1 Hz, 1H), 2.97–2.90 (m, 1H), 2.88–2.82 (m, 1H), 2.13–

1.93 (m, 3H), 1.97 (s, 3H), 1.76–1.66 (m, 1H), 1.56–1.44 (m, 1H), 1.27–

1.25 ppm (m, 1H); ¹³C NMR (CDCl₃, 100 MHz): d=170.1, 141.6, 134.6,

130.5, 114.4, 102.1, 47.3, 38.8, 38.3, 34.9, 25.0, 21.9 ppm: IR (neat): n˜ =

2999, 2951, 2856, 1752, 1711, 1643, 1451 cm^ꢁ1; HRMS (ES+): m/z calcd

for C₁₂H₁₆O₂Na [M+Na]⁺: 215.1042; found: 215.1043.

Applying the general cycloisomerization procedure to 26 with [Au^I] cata-

lyst gave 24 and triene 27 in 85% yield as a 35/65 mixture. Triene 27 was

isolated as a 2/1 (E/Z) isomer mixture: ¹H NMR (CDCl₃, 400 MHz): d=

7.23 (s, 1H^M), 6.99 (s, 1H^m), 5.87–5.77 (m, 2H), 5.10–4.97 (m, 2H), 3.12

(d, J=6.3 Hz, 2 H^M), 2.92 (dd, J=6.6, 1.6 Hz, 2H^m), 2.72–2.67 (m, 2H^m),

2.46–2.35 (m, 4H^M+ 2H^m), 2.17 (s, 3 H^M), 2.14 (s, 3H^m), 1.95–1.86 ppm

(m, 2 H^M+ 2H^m); ¹³C NMR (CDCl₃, 100 MHz): major diastereomer:

d=168.0, 139.9, 136.2, 133.3, 128.2, 121.1, 115.2, 33.0, 32.2, 31.1, 23.2,

21.0 ppm; minor diastereomer: d=168.0, 139.4, 136.8, 131.6, 130.4, 119.2,

116.2, 36.3, 34.9, 32.3, 23.6, 21.0 ppm; IR (neat): n˜ =3320, 3080, 2960,

2860, 1750, 1640, 1610 cm^ꢁ1; HRMS (ES+): m/z calcd for C₁₂H₁₆O₂Na

[M+Na]⁺, 215.1042; found, 215.1043.

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[16] A portion of the results presented here has been communicated pre-

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previously for related systems, but no migration of the ester group

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3258

www.chemeurj.org

ꢄ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2009, 15, 3243 – 3260

Cycloisomerization of Enynyl Esters versus Allenenyl Esters

FULL PAPER

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On the other hand, with a preformed allene, coordination of the

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[48] Alternatively, and in agreement to our proposal of fast interconver-

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[52] Cyclization of 23 with the same catalyst but under neat conditions

afforded 51% of a mixture of 24/25 (3/1) along with 13% of starting

material 23 and 13% of the [3,3]-rearranged allenyl acetate.

[53] We previously reported a PtCl₂-catalyzed 1,3-OAc shift followed by

[3,3]-sigmatropic rearrangement of 1,5-allenenes. In this case, [3,3]-

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mal.^[35]

[33] We previously reported the preference of gold catalysts for the cycli-

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[38] We recently reported on this phenomenon of back-and-forth isomer-

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[39] A referee evoked the possibility of ionization of the propargylic car-

boxylate leading to scrambling. We cannot, at the present time, un-

equivocally exclude such a possibility. However, the following points

are indicative of the absence of ionization of the propargylic ace-

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Received: July 8, 2008

Revised: October 22, 2008

Published online: February 6, 2009

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Gold- And platinum-catalyzed cycloisomerization of enynyl esters versus alleneyl esters: An experimental and theoretical study

DOI: 10.1002/chem.200801387

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