Gold(I)-catalysed alkene cycloaddition reactions of propargyl acetals

Article abstract of DOI:10.1002/ejoc.201201328

Studies on gold(I)-catalysed reactions of propargyl acetals are scarce, unlike those of the corresponding esters. We have investigated gold(I)-catalysed cyclization reactions of both propargyl acetals and esters in order to identify the abilities of the t

Full text of DOI:10.1002/ejoc.201201328

FULL PAPER
DOI: 10.1002/ejoc.201201328
Gold(I)-Catalysed Alkene Cycloaddition Reactions of Propargyl Acetals
Naseem Iqbal,[a] Christian A. Sperger,[a] and Anne Fiksdahl*[a]
Keywords: Propargyl acetal / Gold / Cycloaddition / Cyclopentenyl / Chemoselectivity
Studies on gold(I)-catalysed reactions of propargyl acetals
are scarce, unlike those of the corresponding esters. We have
investigated gold(I)-catalysed cyclization reactions of both
propargyl acetals and esters in order to identify the abilities
of the two substrate groups to follow two different cyclization
pathways with vinylic reactants, such as vinyl amides and
vinyl ethers, in chemoselective manner. Corresponding reac-
tions with indoles allowed the construction of biologically
interesting polycyclic indole-based compounds. The relative
reactivities of propargyl acetals and esters were also studied.
The gold(I)-catalysed cyclization reactions of propargyl acet-
als were characterized by two important features: i) in con-
trast with the conventional olefin cyclopropanation that nor-
mally takes place with propargyl esters, the favoured general
reaction pathway for the corresponding acetals is an atypical
cyclopentenylation by [2+3] cycloaddition to afford trans-cy-
clopentenyl products, and ii) the propargyl acetals showed
significantly higher reactivities than the corresponding es-
ters, in line with the assumption that the alkoxy substituent
might activate the gold-propargyl acetal complex intermedi-
ate. Different factors affecting the specific pathways are dis-
cussed, with the aim of achieving better mechanistic under-
standing of the reactions.
Introduction
It is well known that gold(I) complexes are efficient cata-
lysts for promotion of a variety of organic transformations.
In particular, gold catalysts have an exceptional ability to
activate C–C multiple bonds toward nucleophilic attack.[1–4]
Propargylic esters I (Scheme 1) are versatile substrates for
gold-based catalysts. Such substrates have been shown to
undergo gold(I)-catalysed 1,2- and also 1,3-acyloxy shifts
by 5-exo-dig and 6-endo-dig attack, respectively, of the carb-
onyl O atom on the alkyne moiety.[4,5] The outcomes of the
reactions have been shown to be dependent on the ligand,
the natures of the substrates and the reaction conditions. It
has been demonstrated that the key species I, II and III
exist in rapid equilibrium, which could be expected to lead
irreversibly to different stable products.[5]
Gold species II, generated by gold-catalysed 1,2-acyloxy
migration of terminal propargyl esters I, might give rise to
vinylcyclopropyl products IV through [1+2] cycloadditions
with alkenes. Gold vinyl carbenoids II have been generated
by many methods.[5a,5e,6–8] In recent years, easily accessible
propargylic esters I have been investigated as precursors for
the formation of gold vinyl carbenoids II, which have been
proposed as reactive intermediates in a variety of reactions,
Scheme 1. Gold-promoted activation of propargylic substrates and
possible subsequent alkene cycloadditions.
[a] Department of Chemistry, Norwegian University of Science
and Technology,
in particular olefin cyclopropanations.[5e,6a,7,8] Alternatively,
gold complexes II might possibly also be potential precur-
sors to afford cyclopentenyl products V through alkene
[2+3] cycloadditions.
We have recently reported gold(I)-catalysed cyclopropan-
ation reactions between different terminal propargyl esters I
Høgskoleringen 5, 7491 Trondheim, Norway
Fax: +47-735-50877
E-mail: anne.fiksdahl@chem.ntnu.no
Homepage: http://www.nt.ntnu.no/users/annefix/english/
index.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201328.
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N. Iqbal, C. A. Sperger, A. Fiksdahl
FULL PAPER
and olefins directly connected to heteroatoms, such as vinyl responding cyclopentenyl products V in the presence of the
acetates (Scheme 2).[9] The reactions efficiently provided particular bulky gold(I) phosphane catalyst A, shown in
highly functionalized vinylcyclopropyl derivatives IV (see Scheme 1, were unsuccessful. Our investigations thus indi-
also Table 1, Entry 1) with diastereoselectivities of up to cated that, in our case, a direct [2+3] cycloaddition pathway,
99%, being controlled by the steric more demanding olefin involving intermediates II (Scheme 1) is more likely than
substituents.
subsequent ring expansion of cyclopropanes IV, as pro-
posed by others in the case of a different gold(I)-phosphite
catalyst.[10] These observations might contribute to dis-
cussions on possible reaction pathways in the ongoing de-
bate about the “true natures” of gold carbenoid intermedi-
ates.[5a,6,11]
Propargyl acetals IЈ[4,12] (Scheme 1) are also known to
undergo rearrangements to provide gold carbenoids[4] by a
modified gold-catalysed 1,4-alkoxy shift pathway, including
cleavage of a ketone or an aldehyde leaving group. This mi-
gration/fragmentation sequence of propargyl acetal sub-
strates has been used to afford alkoxyvinyl gold carbenoid
species IIЈ.[4] Such reactions might alternatively involve
Scheme 2. AuI-catalysed reactions between propargyl esters and
vinyl derivatives.[9]
Moreover, we also observed chemo- and stereoselective active gold species with more delocalized positive charges,
formation of trans-cyclopentenyl esters V through formal as represented by the gold-stabilized allyl cation IIbЈ, which
[2+3] cycloaddition reactions between propargyl pivaloates would explain their general electrophilic natures.[13] Higher
I and electron-rich vinyl compounds such as vinylmethyl- reactivity towards olefins, for example, would thus be ex-
tosylamide or silylenol ethers (Scheme 2 and Table 1, En- pected; this is discussed in more detail in the Selectivity Sec-
tries 2 and 3), corresponding to observations recently made tion below (Scheme 4, a). The chemistry of propargyl acet-
by others.[10] Other than those reports on propargyl es- als is, in general, virtually uninvestigated, and studies of
ters,[9a,10] no such formation of cyclopentenyl products V gold(I) catalysis with such substrates have been limited to
through all-carbon [2+3] cycloaddition were known. All the gold(I)-catalysed [2+3] cycloadditions between propar-
our attempts to convert cyclopropane products IV into cor- gyl acetals and aldehydes to give 2,5-dihydrofurans through
Table 1. Gold(I)-catalysed reactions between propargyl substrates and vinylic compounds.[a]
908
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Gold(I)-Catalysed Alkene Cycloaddition Reactions
Table 1. (Continued)
[a] The reactions were performed with propargyl substrates 1–8 and 3 equiv. (based on propargyl substrates) of vinyl compounds 9–17 in
dichloromethane [c = 100 mm], together with 5 mol-% of the gold catalyst at room temp. [b] 32:68 cis/trans ratio. [c] 80:20 cis/trans ratio.
[d] When the reaction was carried out in other solvents (dichloromethane, CH3NO2, THF, toluene) or with other catalysts {[Au{P(tBu)
2(o-biphenyl)CH3CN}]SbF6, [Au[P(tBu)2(o-biphenyl)]]Cl + AgSbF6 or [Au(PPh3)]Cl + AgSbF6}, lower levels of conversion, but approxi-
mately similar ratios of 18l/cis-/trans-20 products were obtained The catalyst picAuCl2(III) afforded a 60% yield of the corresponding
propargyl alcohol by acetal cleavage.
a different reaction pathway, as discussed below (Scheme 4, chemoselective cyclizations with vinylic reactants and to
b).[4]
compare the relative reactivities of such substrates as well.
Because our preliminary observations had shown that Here we report our comparative studies on gold-catalysed
the cyclopentannulation reaction pathway can in some cycloaddition reactions of propargyl esters and acetals with
cases supplant cyclopropanation, we wanted to study the vinyl amides and ethers (Table 1), as well as with indoles
different abilities of propargyl acetals and esters to undergo (Table 3, below). To allow direct comparison of selectivity
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N. Iqbal, C. A. Sperger, A. Fiksdahl
1
FULL PAPER
and reactivity, all reactions were performed under a com- less active (31–42% yields by H NMR). The importance
mon set of reaction conditions.
of generating the active gold species by chloride counterion
–
–
exchange (e.g., with SbF6 or NTf2 ) was also demon-
strated, because no reaction took place with only
[Au{P(tBu)2(o-biphenyl)}]Cl (Entry 8) or only [Au(PPh3)Cl]
(Entry 9). The reaction is not catalysed by silver salts (En-
tries 11, 12), whereas gold(III) salts were able to promote
the reaction in low to moderate yields (17–45%, Entries 13,
14).
Results and Discussion
Propargyl Esters
To supplement our previous results[9a] and to confirm
that gold(I)-catalysed olefin cyclopropanation is the fav-
oured reaction pathway for propargyl esters (Table 1, En-
Table 2. Optimization studies of gold(I)-catalysed cyclopentannul-
try 1), additional reactions between pivaloyl propargyl ester ation.
3 and ethyl and silyl vinyl ethers (compounds 12 and 13)
were carried out (Entries 4 and 5). Cyclopropane products
18j and 18k were formed (54%, 46%); this supported the
previously observed general trend, indicating that the elec-
tron-withdrawing ester group might disfavour the formation
of the delocalized allyl cationic resonance form IIb
Entry Gold catalyst
Solvent Yield [%][a]
CH2Cl2 61[b]
(Scheme 1). The cyclopropanation reaction via the vinyl es-
ter gold carbenoid resonance form IIa might thus be gen-
erally favoured. In contrast with the two reaction pathways
observed for propargyl esters with electron-deficient vinyl
acetates and electron-rich amides or ethers (Entries 1–5), no
cyclization took place between propargyl ester 3 and the
electron-deficient vinylpyrrolidinone 15 (Entry 6).
1
2
3
4
5
[Au{P(tBu)2(o-biphenyl)CH3CN}]SbF6
[Au{P(tBu)2(o-biphenyl)CH3CN}]SbF6
[Au{P(tBu)2(o-biphenyl)CH3CN}]SbF6
[Au{P(tBu)2(o-biphenyl)CH3CN}]SbF6
[Au{P(tBu)2(o-biphenyl)CH3CN}]SbF6
THF
32
CH3CN 21
CH3NO2 49
toluene
20
6
7
8
[Au{P(tBu)2(o-biphenyl)}]Cl + AgSbF6
[Au{P(tBu)2(o-biphenyl)}]Cl + AgNTf2
[Au{P(tBu)2(o-biphenyl)}]Cl
[Au(PPh3)]Cl
[Au(PPh3)]Cl+ AgSbF6
AgSbF6
AgNTf2
AuCl3(III)
PicAuCl2(III)
CH2Cl2 42
CH2Cl2 35
CH2Cl2 n.c.[c]
CH2Cl2 n.c.
CH2Cl2 31
CH2Cl2 n.c.
CH2Cl2 n.c.
CH2Cl2 17
CH2Cl2 45
9
10
11
12
13
14
Propargyl Acetals
The corresponding gold(I)-catalysed cyclization reactions
of propargyl acetals were readily characterizable by two im-
portant features. Firstly, unlike the cyclopropanation that
mainly took place with propargyl esters[9a] (Entries 1, 4, and
5), gold-catalysed cyclization of propargyl acetals in general
followed the unusual and atypical [2+3] cycloaddition cy-
1
[a] Calculated by H NMR. [b] Isolated yield. [c] No conversion.
The results from the reactions between propargyl acetals
clopentenylation pathway, similarly to the case of the prod- 5–8 and the vinylic compounds 12–17 in the presence of
ucts obtained from propargyl esters[9a] and electron-rich [Au{P(tBu)2(o-biphenyl)CH3CN}]SbF6 in dichloromethane
vinylic compounds (11, 14, Table 1, Entries 2 and 3). The are presented in Table 1 and demonstrate that the electron-
cyclopentannulations took place in a trans diastereoselec- releasing alkoxy groups are essential to favour the [2+3] cy-
tive way. Secondly, the propargyl acetals showed signifi- cloaddition reaction pathway. The immediate conversion of
cantly higher reactivities than the corresponding esters, the acetals afforded products 18–21. No by-products, except
consistently with the assumption that the alkoxy substitu- decomposition products, were observed. Because of their
ents can activate the gold–propargyl acetal complex systems high reactivities, the acetals 5–8 had to be stored in a freezer
to give highly reactive cationic forms (IIbЈ, Scheme 1). Im- and used within 10–15 min at room temperature to avoid
mediate conversion of the acetal substrates, indicated by a decomposition.
spontaneous colour change to yellow-brownish, thus took
place.
The cyclizations between phenylpropargyl ethyl acetal (6)
and vinylpyrrolidinone 15 (Entry 7) and between methyl or
The cyclopentannulation of phenylpropargyl methyl ethyl acetals (5 and 6) and vinyltosylamide 14 (Entry 8) pro-
acetal (5, Table 2) with vinylpyrrolidinone 15 hence pro- vided the cyclopentenyl ethers 19e (53%), 19f (58%) and
vided the cyclopentenyl product 19d. An optimization study 19g (37%), respectively. These results emphasize the impor-
showed that use of the [Au{P(tBu)2(o-biphenyl)CH3CN}]- tant effect of the activating acetal group, in contrast with
SbF6 gold(I) catalyst in dichloromethane afforded the high- the ester group, as shown by the unsuccessful reaction be-
est activity, as shown by the isolation of the cyclization tween vinylpyrrolidinone 15 and the corresponding ester 3
product 19d in 61% yield (Table 2, Entry 1). Reduced yields (Entry 6). It was noticed that isomerization of the cyclo-
(20–49% by 1H NMR) were obtained in other solvents, pentenyl double bonds in products 19d and 19e, relative to
such as THF, acetonitrile, nitromethane and toluene (En- products 19f, 19g and V (Scheme 2), had taken place, prob-
tries 2–5). Two similar gold(I) catalytic systems (Entries 6 ably due to a combination of the benzylic moiety and the
and 7) lacking the acetonitrile ligand, as well as the tri- more electron-withdrawing pyrrolidinone amide group.
phenylphosphane-based gold(I) catalyst of Entry 10, were Mixtures of cyclopentenyl products 19h and 19i (51/22%)
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Gold(I)-Catalysed Alkene Cycloaddition Reactions
Scheme 3. Proposed mechanism for gold(I)-catalysed formation of C2-extended allenic products.
and 19j and 19k (35/14%) were isolated from the corre- ment to give 6-endo-dig alkoxy attack and internal SN2Ј
sponding reactions between propargyl acetal 5 and vinylpi- substitution. This 1,5-alkoxy shift could be followed by
peridinone 16 or vinyloxazolidinone 17, respectively (En- gold-catalysed intermolecular [2+2] cycloaddition with the
tries 9 and10). The fact that the reaction between the analo- vinylic compounds to cause the formation of cyclobutyl-
gous methylpropargyl acetal 7 and vinyltosylamide 14 also idene products VIЈ. Gold-catalysed intramolecular [2+2] cy-
provided cyclopentenyl ether 19l (73%, Entry 11) demon- cloadditions of allene-alkene substrates are known,[14–18]
strates that benzylic stabilization is not a requirement for and one study of corresponding cyclizations of propargyl
[2+3] cycloaddition, In contrast, however, the correspond- ester/alkene systems to afford bicyclic cyclobutylidene cy-
ing dimethylated propargyl acetal 8 mainly followed the ole- cloadducts through in situ alkynyl/allenyl transformation
fin cyclopropanation pathway and afforded cyclopropyl has been reported.[19]
products (18l/22% and 18m/49%; Entries 12 and 13). The
Lastly, gold-catalysed cyclizations between vinyl ethers
different reaction pathway observed for the dimethyl- and phenyl- or dimethylpropargyl acetals (compounds 5
propargyl acetal 8 (Entries 12 and 13) in relation to the and 8) were studied. Both ethyl vinyl ether (12) and
monomethyl substrate 7 (Entry 11) can be explained by TBDMS vinyl ether (13) afforded cyclopentenyl products
steric effects. The bulky Me2C centre in propargyl substrate (19m/43% and 19n/37%; Entries 14 and 15). However,
8 would be less available for cyclopentenylation, thus phenyl- and dimethylpropargyl ethyl acetals (compounds 6
favouring cyclopropanation (Scheme 1, R2 = R3 = Me).
and 8) failed to undergo cyclization with vinyl ethyl ether
An interesting intermolecular [2+2] cycloaddition took (12, Entry 16). Instead, a competing nucleophilic attack of
place in the gold-catalysed reaction between propargyl the vinyl ether at the gold-activated alkyne took place. Sub-
acetal 8 and the electron-rich vinyltosylamide 14 (Entry 12), sequent deauration and aldehyde cleavage and nucleophilic
mainly affording cyclobutylidene product 20 (41%), as a alkoxy attack at the oxonium ion would complete the pro-
mixture (80:20) of cis/trans isomers. The new cyclobutyl- pargyl/allene transformation (Scheme 3). Hence, C2-ex-
idene cycloaddition product is believed to be formed via tended allenic products (21a/39% and 21b/68%) were ob-
allenic gold intermediate IIIЈ (Scheme 1). The gold-cata- tained. Somewhat similar gold(I)-catalysed Claisen-type re-
lysed in situ propargyl/allene transformation would take arrangements of propargyl vinyl ethers have been used with
place similarly to the 1,3-acyloxy shift, by a 3,3-rearrange- the goal of formation of allenic aldehydes.[20] However, in
Table 3. Gold(I)-catalysed reactions between propargyl substrates and indole derivatives.[a]
[a] See Table 1, footnote [a]. [b] 88:12% cis/trans ratio.
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N. Iqbal, C. A. Sperger, A. Fiksdahl
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situ reduction of the aldehyde products was required, due the result of vinylalkoxy activation of the specific C1-posi-
to aldehyde instability, affording homoallenic alcohols. In tions in adducts VII (R = alkyl) to effect ring closure to give
contrast, our method, based on propargyl acetals, allows cyclopentenyl products V. In contrast, the cyclopropanation
the formation of the stable protected aldehyde products 21a reaction pathway of propargyl esters, to afford vinylpropane
and 21b.
products IV, can be explained in terms of the opposite deac-
tivating effect of the C2-Oacyl groups in adducts VII (R =
acyl). Dimethylpropargyl acetal 8, being an exception,
would undergo cyclopropanation due to the C1 bulkiness.
The regioselectivities of [2+3] cycloadditions might be
controlled by the electronic natures of the substrates. We
observed that our regioselective “C3–C1” reaction sequence
reported here is different with the “C1–C3” reaction order
previously reported for [2+3] cycloadditions between alde-
hydes and nonterminal propargyl acetals bearing EWGs
(Scheme 4, b).[4] As a result of initial nucleophilic attack at
the electrophilic allylic C1 position, activated by the ethoxy-
carbonyl group, the opposite “C1–C3” regioselective reac-
tion sequence took place and the formation of 2,5-dihy-
drofuran cycloaddition products VIII via intermediates
VIIЈ (R = alkyl) was proposed.
The electronic natures of the vinylic reactants, connected
to heteroatoms, might also affect the reactivities and the
reaction pathways, because vinylic compounds attached to
electron-releasing N or O heteroatoms would enable stabili-
zation of ammonium or oxonium cation intermediates VII
after initial vinyl attack at the allylic C3-centres, activating
for the final cyclopentenylation steps (Scheme 4a). Further-
more, electron-rich vinyl compounds could compensate for
the electron-withdrawing effects of propargyl esters[10] and
thus enable [2+3] cyclizations (Table 1, Entries 2 and 3).
The opposite deactivating effect was seen in the unsuccess-
ful reaction between propargyl ester 3 and vinylpyrrolidin-
one 15 (Table 1, Entry 6).
Indoles
One important feature of indoles is the ability of their
C=C–N moieties to act as isolated enamine units, due to
the low aromaticities and the high degrees of electron local-
ization in the pyrrole heterocyclic components of such het-
eroaromatics. The development of selective methods for the
construction of polycyclic indole skeletons is important,
due to the fact that many complex biologically active natu-
ral products and pharmaceutically important substances
contain indole moieties. Of the various synthetic ap-
proaches to indole derivatives, gold-catalysed annulations
of indole have proved versatile.[21] We wanted to use N-acet-
yl- and N-tosylindoles (22a and 22b, Table 3), as well as
indole (22c) itself, as nonterminal vinyl amides in gold(I)-
catalysed cyclization studies with propargyl substrates. The
outcome of the study was in accordance with the observed
trends for the two reaction categories discussed above. The
propargyl ester 3 afforded the cyclopropanation products
23a (45%) and 23b (66%) with N-Ac-indole (22a) and N-
Ts-indole (22b), respectively (Entry 1), whereas the prop-
argyl acetals 5, 6 and 8 gave the corresponding cyclopent-
enyl products 24a–e (53–73%) on cyclization with indole
and derivatives 22a–c (Entries 2,3).
Selectivity
The atypical outcomes of the reactions caused by 1,5-
Both the cyclopropanations and the formal [2+3] cyclo- ethoxy shifts or direct vinylic attack at C3 of propargyl
additions of propargyl substrates might proceed through ethyl ethers 6 and 8 (Entries 12 and 16) might be due to
the intermediate adducts VII (Scheme 4, a), formed by ini- the bulkier ethoxy groups, disfavouring the 1,4-alkoxy shifts
tial nucleophilic vinyl attack at the allylic C3-positions of normally observed with methoxy groups. We have pre-
gold complexes II(Ј). The selective [2+3] cyclization pathway viously experienced dramatic variation in the outcomes of
favoured for acetal substrates (see Tables 1 and 2) might be gold(I)-catalysed cyclizations of highly reactive methyl and
Scheme 4. AuI-catalysed cycloadditions of propargyl substrates.
912
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Gold(I)-Catalysed Alkene Cycloaddition Reactions
unreactive ethyl derivatives of alkynes.[9b] The natures of the lysed cyclization reactions of propargyl acetals were charac-
vinylic compounds also play a role, because the atypical re- terized by two important features: i) the favoured general
actions only take place with electron-rich vinylic reactants reaction pathway is the atypical cyclopentenylation [2+3]
12 and 14, and not with the bulky vinyl TBDMS ether 13 cycloaddition, stereoselectively affording trans-cyclopentenyl
(Entry 15). However, a full understanding of how the com- products, and also ii) the gold(I)-propargyl acetal com-
bination of steric and electronic factors favour or trigger plexes showed significantly higher reactivities than the anal-
the few unpredicted reaction pathways (e.g., cyclobutyl- ogous ester complexes, as seen experimentally in spontane-
idene, Entry 12; Claisen rearrangement, Entry 16) might be ous cyclizations and by NMR studies. Similar chemoselec-
complex.
tivity trends were observed on replacement of the vinyl
compounds with indoles, with propargyl esters and acetals
selectively following the cyclopropanation and cyclopent-
enylation pathways, respectively, allowing the construction
of biologically interesting polycyclic indole-based skeletons.
The natures of the vinylic reactants might affect the reac-
tion pathways.
Rather than possible ring expansions of cyclopropyl in-
termediates, we propose formal [2+3] cycloaddition path-
ways for the formation of the cyclopentenyl products. These
rapid chemoselective [2+3] reactions might proceed through
highly reactive cationic gold intermediates, formed by 1,4-
alkoxy shifts. Allylic adducts might be formed by subse-
quent nucleophilic vinyl attack at the allylic C3-positions in
the cationic gold complexes. Unlike the deactivating C2-
acyl groups generated from propargyl esters, C2-vinylalk-
oxy groups would specifically activate the C1 positions to
favour cyclopentenylation, explaining the [2+3] cyclization
pathway. The observed regioselective “C3–C1” reaction se-
quence of our terminal propargyl acetals is in contrast with
the “C1–C3” reaction order reported for C3-EWG propar-
gyl substrates.[4]
Reactivity
NMR studies (NMR tube with a 1:1 mixture of phenyl-
propargyl ester 3 and the applied AuI biphenylphosphane
complex) allowed for monitoring of the formation of a
gold(I)propargyl ester complex of type II (see Schemes 1
and 4). Consistently with other studies[22] on alkyne com-
plexes of this gold catalyst, 31P NMR spectra showed the
instant formation of a gold-propargyl complex, observable
by the immediate disappearance of the original 31P NMR
signal of the AuI catalyst A at δ = 57.5 ppm and the appear-
ance of a new single peak at δ = 60.6 ppm. Similarly, the
1
instant disappearance of the propargyl H NMR singlets
and of the liganded acetonitrile 1H NMR singlet (δ =
1.50 ppm) indicated rapid conversion into a gold complex.
The recorded new H1 and H3 split signals, showing charac-
teristic H–P coupling, and the new “free” acetonitrile sing-
let (δ = 2.32 ppm), immediately confirmed the propargyl-
gold(I) complex as the only detectable gold species. All of
these observations were consistent with NMR spectroscopic
data obtained from a corresponding crystalline pure sample
of the gold-propargyl ester complex.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details and spectroscopic data (1H and 13C
NMR).
In contrast, the corresponding gold(I) complex with
propargyl acetal 5 was significantly more reactive and no
formation of the related acetal-gold(I) complex IIЈ could be
recorded by 1H NMR spectroscopy. In the absence of a
trapping agent such as a vinylic compound, such mixtures
instantly turned black and seemed to undergo spontaneous
polymerization even at 5 °C, as shown by the immediate
disappearance of any phenyl or CH propargyl protons in
Acknowledgments
We thank the Research Council of Norway for financial support.
[1] N. D. Shapiro, F. D. Toste, J. Am. Chem. Soc. 2008, 130, 9244.
[2] N. D. Shapiro, Y. Shi, F. D. Toste, J. Am. Chem. Soc. 2009, 131,
11654.
1
the H NMR spectrum. In the presence of vinylamide 15,
[2+3] cycloaddition took place, affording product 19d. As [3] N. Kim, Y. Kim, W. Park, D. Sung, A. K. Gupta, C. H. Oh,
Org. Lett. 2005, 7, 5289.
expected, attempts to crystallize a pure sample of the
gold(I) complex with propargyl acetal 5 failed.
[4] G. Zhang, L. Zhang, J. Am. Chem. Soc. 2008, 130, 12598.
[5] a) A. Correa, N. Marion, L. Fensterbank, M. Malacria, S. P.
Nolan, L. Cavallo, Angew. Chem. 2008, 120, 730; Angew. Chem.
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Conclusions
To contribute to better understanding of the chemistry
of the scarcely studied propargyl acetals in the presence of
gold(I), we have performed a comparative study on chemo-
selective gold(I)-catalysed cycloaddition reactions between
alkenes and propargyl acetals or esters. It was found that
such substrate types in general follow two different cycliza-
tion pathways. Our previous results[9a] and those presented
here demonstrate that the electron-deficient propargyl esters
in general afford regular cyclopropanation products with
alkenes such as vinyl ethers and esters. The gold(I)-cata-
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Received: October 8, 2012
Published Online: January 2, 2013
914
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