Axially chiral N-heterocyclic carbene gold(I) complex catalyzed asymmetric cycloisomerization of 1,6-enynes

Article abstract of DOI:10.1021/om2004404

A new class of axially chiral NHC-Au(I) complexes (1-11) has been developed from optically active BINAM and fully characterized by NMR, ESI-MS, and IR spectroscopic data, where structures of complexes 1, 2a, and 6 have been further determined by X-ray diffraction studies of their single crystals, exhibiting a nearly linear coordination geometry around the gold(I) center. Within the carried out investigations herein, the sterically less hindered gold(I) complex (aR)-6, having a pyrrolidin-1-yl group, has been realized to be the best catalyst in gold(I)-catalyzed asymmetric acetoxycyclization of 1,6-enyne 52a, giving product 53a in >99% yield with -59% ee at 0 °C, and the sterically less hindered gold(I) catalyst (aS)-2a is the best catalyst in the asymmetric oxidative rearrangement of 1,6-enynes, affording the corresponding aldehydes 56a,c-h in excellent yields (up to >99%) and modest enantioselectivities (3.1-70% ee) using PhCl as the solvent at 10 °C.

Full text of DOI:10.1021/om2004404

ARTICLE
pubs.acs.org/Organometallics
Axially Chiral N-Heterocyclic Carbene Gold(I) Complex Catalyzed
Asymmetric Cycloisomerization of 1,6-Enynes
Wenfeng Wang,† Jinming Yang,† Feijun Wang,† and Min Shi*,†,‡
†Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering,
East China University of Science and Technology, 130 Mei-Long Road, Shanghai 200237, People's Republic of China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, People's Republic of China
S Supporting Information
b
ABSTRACT: A new class of axially chiral NHC-Au(I) complexes (1ꢀ11) has been
developed from optically active BINAM and fully characterized by NMR, ESI-MS, and
IR spectroscopic data, where structures of complexes 1, 2a, and 6 have been further
determined by X-ray diffraction studies of their single crystals, exhibiting a nearly
linear coordination geometry around the gold(I) center. Within the carried out
investigations herein, the sterically less hindered gold(I) complex (aR)-6, having a
pyrrolidin-1-yl group, has been realized to be the best catalyst in gold(I)-catalyzed
asymmetric acetoxycyclization of 1,6-enyne 52a, giving product 53a in >99% yield
with ꢀ59% ee at 0 °C, and the sterically less hindered gold(I) catalyst (aS)-2a is the
best catalyst in the asymmetric oxidative rearrangement of 1,6-enynes, affording the
corresponding aldehydes 56a,cꢀh in excellent yields (up to >99%) and modest
enantioselectivities (3.1ꢀ70% ee) using PhCl as the solvent at 10 °C.
’ INTRODUCTION
features such as stability to air and moisture, low toxicity, and
strong σ-donor and poor π-acceptor properties.9 Thus far, in
almost all successful systems for asymmetric gold catalysis, chiral
phosphines were employed as ligands,2ꢀ6 but chiral NHC-Au(I)
complexes as catalysts were very scarcely reported,6g,10 although
NHCs have emerged as an effective alternative for a number of
homogeneous gold catalyses.8k,11 During our ongoing survey in
the literature, there is only one unique relevant paper, reported
by Tomioka and co-workers using C2-symmetric NHC-Au(I)
complexes in the cycloisomerization of 1,6-enynes, providing the
corresponding cyclopentane products in high yields but with
moderate enantioselectivities (up to 59% ee).6g On the basis of
our previous successful examples in the NHC-metal complex
catalyzed asymmetric transformations,12 herein we wish to
represent the first synthesis and characterization of a series of
axially chiral NHC-Au(I) complexes and the subsequent inves-
tigation on their applications as catalysts in the asymmetric
cycloisomerization of 1,6-enynes1j,6aꢀ6d,6g to achieve the best
results of stereochemical induction.
During the past decade homogeneous gold catalysis has been
achieved, with an explosive growth in CꢀC, CꢀO, or CꢀN
bond formations being mainly attributed to the soft carbophilic
Lewis acid properties of gold complexes toward CꢀC multiple
bonds.1 In comparison with other transition metal catalysts, gold
complexes could efficiently catalyze reactions under very mild
conditions tolerant of air or moisture to give excellent chemos-
electivity and wide functional group compatibility. Although the
first example of a gold-catalyzed enantioselective reaction was
reported by Hayashi and Ito in 1986 for the aldol condensation
between isocyanates and aldehydes,2 gold-catalyzed asymmetric
transformations are still challenging topics with scarce investiga-
tions even at the present stage3 despite the rapid development of
several synthetic applications.4 To the best of our knowledge,
most studies on this topic have been focused on the gold acti-
vation of allenes toward nucleophilic attack, such as asymmetric
hydrofunctionalization of allenes4bꢀf and [2+2] cycloaddition
and cycloisomerization of enallenes.5 Only a few reports ad-
dressed the asymmetric activation of substrates containing an
alkyne functional group.4a,6 The difficulty of enantioselective
gold(I)-catalyzed transformations is probably due to the linear
coordination geometry of the Au(I) center with the reaction site
far away from the chiral environment; thus special strategies or
chiral ligands were needed to provide spatial arrangements of the
opposite site of the metal cation.3,7
’ RESULTS AND DISCUSSION
Synthesis of Axially Chiral NHC-Au(I) Complexes. As
summarized in Figure 1, a series of axially chiral NHC-Au(I)
N-Heterocyclic carbenes (NHCs) represent a growing class of
Received: May 25, 2011
Published: June 23, 2011
ligands in transition metal catalysis8 and have several typical
r
2011 American Chemical Society
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Complexes 2ꢀ5 are also air and moisture stable in the solid or
solution state and even under the heating conditions, and their
structures were all confirmed by NMR, ESI-MS, and IR spectro-
scopic data. Notably, the structure of complex 2a was further
determined by an X-ray diffraction study of single crystals grown
from a solution of 2a in mixed ethyl ether/CH2Cl2 (1:1) (Figure 3).
The molecular structure and selected crystal data are shown in
Figure 3,15 which reveals that the acetyl amide moiety still does
not participate in the coordination on the gold center. While the
bond length of Au(1)ꢀC(1) (2.038(14) Å) is consistent with
the data of AuꢀCNHC bonds in the previous literature, the angle
of C(1)ꢀAu(1)ꢀI(1) = 179.1(4)o also typically indicates a
nearly linear coordination geometry around the gold(I) center
(Figure 3).11
Moreover, if nitro-group-containing compound 14 was reacted
with Br(CH2)4Br in the presence of iPr2NEt, the compound 32,
having a pyrrolidin-1-yl group, could be obtained in 66% yield,
which was followed by a sequence of palladium-catalyzed hydro-
genation of the nitro group, ring closing of the o-phenylenedia-
mine moiety in triethyl orthoformate, and N-methylation to easily
give imidazolium salt 35 in a reasonable yield (see the Supporting
Information). Then the reaction of NHC precursor 35 with
[(Me2S)AuCl] and NaOAc at 85 °C in CH3CN successfully
afforded NHC-gold(I) complex (aS)-6 as a white solid in 64%
yield (Scheme 3). According to the slightly modified procedures
similar to that of gold(I) complex 6, bearing a pyrrolidin-1-yl
group, the gold(I) complexes 7ꢀ9, with N(H)-alkyl or N,N-
dialkyl substituents on the binaphthyl scaffold, were also success-
fully synthesized from compound 14 (see the Supporting
Information). While complexes 6ꢀ9 were all fully characterized
by NMR, ESI-MS, and IR spectroscopic data, the structure of
complex 6 was further confirmed by an X-ray diffraction study of
single crystals grown from a solution of 6 in mixed petroleum
ether/CH3CN/CH2Cl2 (1:1:1) (Figure 4). The molecular
structure and selected crystal data are shown in Figure 416 and
exhibit similar features to those of complexes 1 and 2a. For
example, our determined Au(1)ꢀC(1) bond length of 1.988(6)
Å is consistent with the previously reported data, and the angle of
C(1)ꢀAu(1)ꢀI(1) = 177.1(3)o also indicates a nearly linear
coordination geometry around the gold(I) center (Figure 4).11
In addition, upon treatment of the corresponding imidazolium
salts with [(Me2S)AuCl] and NaOAc, we have also synthesized
NHC-gold(I) complexes 10 and 11, containing an imino moiety,
in 66% and 41% yield, respectively.14b The imino moiety was
perfectly preserved during the reaction and even through pur-
ification by silica gel flash column chromatography. Particularly, a
Figure 1. Axially chiral NHC-Au(I) complexes 1, 2a,b, and 3ꢀ11.
complexes have been synthesized from optically active bi-
naphthyl-2,20-diamine (BINAM) during this whole work.
At first, we found that when benzimidazolium salt 13 derived
from (aR)-12 was treated with [(Me2S)AuCl] at 85 °C in
CH3CN for 9 h in the presence of NaOAc, the corresponding
NHC-gold complex 1 could be produced as a white solid in 52%
yield after purification by silica gel flash column chromatography
(Scheme 1).11a This complex is air and moisture stable in the
solid or solution state and even under the heating conditions. Its
characteristic structure was determined by NMR, ESI-MS, and
IR spectroscopic data. Single crystals of complex 1 suitable for an
X-ray diffraction study were grown from a solution of 1 in mixed
petroleum ether/CH3CN/CH2Cl2 (1:2:2) (Figure 2). The mol-
ecular structure and selected crystal data are shown in Figure 2,13
which reveals actually a two-metal-center structure, similar to bis-
gold(I) biarylphosphine complexes.2ꢀ6 The crystal data of Au-
(1)ꢀC(1) (2.005(7) Å) and Au(2)ꢀC(29) (2.000(7) Å) are
both typical AuꢀCNHC bond lengths, in line with those of other
reported examples.11 Furthermore, angles of C(1)ꢀAu(1)ꢀI(1)
= 178.3(2)o and C(29)ꢀAu(2)ꢀI(2) = 178.1(2)o suggested a
nearly linear coordination geometry around the gold(I) center,
which was also a typical feature for known gold(I) complexes.11
Aiming at conveniently modifying the structures of NHC-
Au(I) complexes, a type of mono-NHC ligands was next
designed by the introduction of various substituents on the 20-
amino moiety of the binaphthyl scaffold (Figure 1).
As a representative complex of NHC-amide ligands, NHC-
Au(I) complex (aS)-2a, with an acetyl amide substituent on the
binaphthyl scaffold, was synthesized according to the procedures
shown in Scheme 2. In one word, monobenzimidazole compound
(aS)-17 was initially prepared from (aS)-BINAM via a sequence
of palladium-catalyzed coupling, acetylation of primary amine,
palladium-catalyzed hydrogenation of the nitro group, and ring
closing with triethyl orthoformate.14 While imidazolium salt
(aS)-18 was obtained upon refluxing (aS)-17 and CH3IinCH3CN,
the treatment of NHC precursor 18 with [(Me2S)AuCl] and
NaOAc at 85 °C in CH3CN smoothly afforded NHC-gold(I)
complex (aS)-2a as a white solid in 54% yield (Scheme 2). The
gold(I) complexes 2b and 3ꢀ5 of NHC-amide ligands were also
successfully prepared from nitro-group-containing compound
14 according to the slightly modified procedures similar to that of
complex 2a (see the Supporting Information).
1
signal at δ 11.82 ppm in the H NMR spectra for complex 10
indicated the intramolecular hydrogen bonding between the OH
and imine nitrogen atom without cleavage even in the presence
of NaOAc as the base (see the Supporting Information).14b
NHC-Au(I) Complex Catalyzed Asymmetric Acetoxycycli-
zation of 1,6-Enyne. An initial experiment was performed to
examine the gold(I)-catalyzed asymmetric cyclization of 1,6-
enyne 52a in the presence of these NHC-Au(I) complexes
(5 mol %) and AgSbF6 (5 mol %) using anhydrous acetic acid
as the solvent at room temperature.1j,6aꢀ6d,6g After the reaction
was conducted for 50 h, the expected acetoxycyclization product
53a was obtained as a single diastereoisomer in >99% yield and
40% ee using bis[NHC-Au(I)] complex (aR)-1 as the catalyst
(Table 1, entry 1).17 The use of NHC-Au(I) complex (aS)-2a
resulted in product 53a in 73% yield and a slightly decreased
enantioselectivity of 35% ee, but its absolute configuration was
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Scheme 1. Synthesis of Bis[NHC-Au(I)] Complex (aR)-1
enantioselectivities (Table 2, entries 3ꢀ5), which may be at-
tributed to AgX being directly involved in the formation of active
cationic NHC-Au+ species.1,3,4 Notably, the control experiments
suggested that a potential Ag-catalyzed process was almost neg-
ligible during this transformation (Table 2, entry 6).18 Reducing
the reaction temperature could offer better results, with the
formation of 53a in 88% yield and 55% ee at ꢀ20 °C as an
example (Table 2, entries 7 and 8). The 80% yield and 25% ee of
product 53a obtained by using bis[NHC-Au(I)] complex (aR)-1
as the catalyst have both been decreased in DCE in comparison
with those in AcOH (Table 2, entry 9). While introducing bulky
substituents on the N-heterocycle or the binaphthyl scaffold was
detrimental to the chiral induction (Table 2, entries 10ꢀ13),
gold(I) complex (aR)-6, bearing a pyrrolidin-1-yl group, was re-
alized as the best catalyst in this reaction, giving 53a in 91% yield
and ꢀ53% ee at room temperature (Table 2, entry 14). Further-
more, properly lowering the reaction temperature gave a better
reaction outcome, where complex (aR)-6 afforded 53a in >99%
yield and ꢀ59% ee at 0 °C, although a trace of product was
formed at ꢀ20 °C (Table 2, entries 15 and 16).
Figure 2. ORTEP drawing of bis[NHC-Au(I)] complex 1 with thermal
ellipsoids at the 30% probability level. Selected bond distances (Å) and
angles (deg): Au(1)ꢀC(1) = 2.005(7), Au(1)ꢀI(1) = 2.5376(7),
Au(2)ꢀC(29) = 2.000(7), Au(2)ꢀI(2) = 2.5189(8), C(1)ꢀAu(1)ꢀI-
(1) = 178.3(2), C(29)ꢀAu(2)ꢀI(2) = 178.1(2), N(1)ꢀC(1)ꢀN(2) =
106.5(6), N(3)ꢀC(29)ꢀN(4) = 107.8(6).
It is worth noting that conjugate diene 55 was more or less
detected as a concomitant product during the reaction, particu-
larly that which was isolated in 22% yield for entry 12 of Table 2.1j,19
On the basis of previous literature on the gold(I)-catalyzed
transformations, a plausible reaction mechanism as shown in
Figure 5 was proposed to explain the generation of products 53,
54, and 55.1j,6aꢀ6d,19 An initial complexation of the carbophilic
Lewis acid cationic gold catalyst to the alkyne π-bond was
followed by a stereoselective attack of the alkene functional
group on the alkyne to then form a transient cyclopropylcarbene
species B.20,21 When nucleophiles such as AcOH were present,
the proposed gold(I)-carbenoid intermediate B could be at-
tacked on the cyclopropyl group to release vinylaurate inter-
mediate C, which underwent a protodemetalation process to
afford the corresponding acetoxycyclization product 53a
(Figure 5, path 1). If any nucleophile was absent in the reaction
system, a skeletal rearrangement of intermediate B could allow
the formation of carbocation D, which then underwent metal
elimination to give diene 55 (Figure 5, path 2).
NHC-Au(I) Complex Catalyzed Asymmetric Oxidative Re-
arrangement of 1,6-Enynes. During screening different silver
salts in Table 2, we found that using AgClO4 (30 mol %) instead
of AgSbF6 (5 mol %) exceptionally afforded another main
product, 56a, as a single diastereoisomer in 32% yield and 47%
ee, rather than acetoxycyclization product 53a (Table 3, entry 1).
Additionally, a similar result with 47% yield and 41% ee for
aldehyde 56a was also obtained in the presence of AgClO4,
without the addition of AcOH, after 12 h (Table 3, entry 2).
Aldehyde 56a was seemingly generated by an oxygenation
identical with that induced by gold(I) complex (aR)-1 (Table 1,
entry 2). Furthermore, the transformation of 1,6-enyne 52b also
proceeded smoothly to give the corresponding product 53b in
moderate yields along with 30% and 20% ee,17 respectively, using
complexes (aR)-1 and (aS)-2a as catalysts under the standard
conditions (Table 1, entries 3 and 4).
The use of 1,2-dichloroethane (DCE) as the solvent also led
to acetoxycyclization product 53a in 58% yield and 48% ee with
20 equiv of AcOH as the additive (Scheme 4, eq 1). Because of a
trace of H2O occurring in the commercially available AcOH,
hydroxycyclization product 54 was simultaneously isolated in
40% yield and 48% ee. The same 48% ee value for 53a and 54
indicated that the enantioselectivity was possibly not influenced
by nucleophiles such as AcOH and H2O, which was further
supported by the similar result of a control experiment with H2O as
the only additive (Scheme 4, eq 2). The absolute configurations of
the products 53a and 54 were assigned by comparison of the sign of
the optical rotation of 54 with that in the previous literature.6b,17
The reaction conditions were next investigated to achieve
better catalytic results by using anhydrous AcOH (20 equiv) as
the nucleophile in the solvent of DCE (Table 2). The system of
complex (aS)-2a (5 mol %) and AgSbF6 (5 mol %) exclusively
gave the acetoxycyclization product 53a in 93% yield and 43% ee
(Table 2, entry 1). Using another silver salt (AgX) instead could
significantly change the yields but slightly decrease the
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Scheme 2. Synthesis of NHC-Au(I) Complex (aS)-2a
process via the transfer of an oxygen atom from AgClO4 to the
gold(I)-carbenoid intermediate B, which was similar to the
results reported by Toste et al., where an oxygen atom could
transfer from various sulfoxides to the gold(I)-carbenoid
intermediate.20c
Thus, we next attempted to use dimethylsulfoxide (2 equiv) as
the oxidantin this reaction and foundthat the desired aldehyde56a
was successfully obtained in 27% yield and 34% ee along with most
of the unreacted starting material 52a even after 6 days (Table 3,
entry 3). Furthermore, replacing DMSO with diphenylsulfoxide
could significantly improve the yield of aldehyde 56a to >99% after
only 8 h along with 43% ee (Table 3, entry 4). These preliminary
experiments in Table 3 were in fact intercepting the proposed
gold(I)-carbenoid intermediate B in the cycloisomerization of 1,6-
enyne 52a by using relevant oxidants (Figure 5, path 3).20
Reducing the employed amount of diphenylsulfoxide to 1.5
equiv did not significantly affect the reaction outcome because
NHC-Au(I) complex (aS)-2a could still afford aldehyde 56a in
>99% yield and 43% ee after 2 h (Table 4, entry 2). Later on,
various NHC-Au(I) complexes were investigated for this gold-
(I)-catalyzed oxidative rearrangement of 1,6-enyne to seek out
better catalytic activities and chiral inductions. For example,
bis[NHC-Au(I)] complex (aR)-1 could accomplish the trans-
formation of 52a efficiently, giving aldehyde 56a in 91% yield and
29% ee within 3 h, although it had a different configuration of the
chiral binaphthyl scaffold compared with (aS)-2a (Table 4, entry
1). While complex (aS)-2b, with the N-heterocycle substituted
by a N-CH2Ph moiety afforded 56a in a similar yield (94%) but
lower ee value (25%), the bulky amide substituents on the
binaphthyl scaffold of NHC-Au(I) complexes were also detri-
mental to the enantioselectivities, and in some cases, the
corresponding products were obtained with only 3% ee values
despite being in high yields (Table 4, entries 3ꢀ7).
Figure 3. ORTEP drawing of NHC-Au(I) complex 2a with thermal
ellipsoids at the 30% probability level. Selected bond distances (Å) and
angles (deg): Au(1)ꢀC(1) = 2.038(14), Au(1)ꢀI(1) = 2.5005(14),
C(1)ꢀAu(1)ꢀI(1) = 179.1(4), N(1)ꢀC(1)ꢀN(2) = 107.6(12).
tested during this transformation of 1,6-enyne 52a. In contrast
with the acetoxycyclization of 52a (Table 2, entries 1 and 14), the
results of >99% yields along with 36% ee and ꢀ32% ee obtained
by using gold(I) complexes (aS)-6 and (aR)-6, respectively,
indicated that they were also effective catalysts in this reaction,
but slightly less effective than gold(I) complex (aS)-2a (Table 4,
entries 8 and 9). Furthermore, sterically less hindered N,N-
dimethyl gold(I) complex (aS)-7 was also effective herein, giving
aldehyde 56a in 97% yield and 44% ee, but complexes with
sterically bulky substituents such as N(H)-benzyl (8) and
On the other hand, NHC-Au(I) complexes with various
N(H)-alkyl substituents on the binaphthyl scaffold were also
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Scheme 3. Synthesis of NHC-Au(I) Complex (aS)-6
Table 1. Asymmetric Intramolecular Cyclization of 1,6-En-
ynes Catalyzed by NHC-Au(I) Complexesa
entry
substrate
catalyst time (h) yield (%)b ee (%)c
1
2
3
4
52a (R1 = Ph, R2 = H) (aR)-1
52a (R1 = Ph, R2 = H) (aS)-2a
50
66
50
50
>99 (53a)
73 (53a)
74 (53b)
66 (53b)
40
35
30
20
52b (R1 = R2 = Me)
52b (R1 = R2 = Me)
(aR)-1
(aS)-2a
a Reaction conditions: 5 mol % of catalyst based on Au center; 5 mol % of
AgSbF6; 0.1 mmol of 52; 1 mL of AcOH. b Isolated yields. c Determined
by chiral HPLC using a Chiralpak AD-H column.
harmful to the catalytic activities of NHC-gold(I) complexes,
presumably attributed to their coordination on the metal center
of the gold(I) complex against the generation of free cationic
NHC-Au+ species (Table 5, entries 4ꢀ6). On the other hand,
the reactions in EtOAc, CH3NO2, or acetone could proceed
smoothly within a short reaction time, but providing the product
56a in less than 24% ee (Table 5, entries 7ꢀ9). Notably,
changing the solvent from CH2Cl2 to CHCl3 allowed an increase
of enantioselectivity from 48% ee to 55% ee despite a lower yield
(80%) for the formation of 56a (Table 5, entries 3 and 10).
Furthermore, when PhCl was used as the solvent instead of
toluene, it was found that aldehyde 56a was obtained in 91% yield
and 60% ee within 4 h, indicating a significant improvement for
the asymmetric induction (Table 5, entries 2 and 11). However,
1,2-dichlorobenzene and PhF, which are more polar solvents
than PhCl, did not bring about further increase of ee values for
the formation of 56a (Table 5, entries 12 and 13).
Figure 4. ORTEP drawing of NHC-Au(I) complex 6 with thermal
ellipsoids at the 30% probability level. Selected bond distances (Å) and
angles (deg): Au(1)ꢀC(1) = 1.988(6), Au(1)ꢀI(1) = 2.5462(6),
C(1)ꢀAu(1)ꢀI(1) = 177.1(3), N(1)ꢀC(1)ꢀN(2) = 106.2(5).
N,N-dibenzyl (9) both led to a significant decrease of enantios-
electivities alongwith ꢀ12% ee and ꢀ4% ee, respectively (Table 4,
entries 10ꢀ12). In addition, gold(I) complexes 10 and 11, sub-
stituted with imine moieties, were successfully prepared, but
unfortunately they all exhibited poor asymmetric induction
abilities in this reaction under the standard conditions, affording
aldehyde 56a in ꢀ6% ee and ꢀ2% ee, respectively (Table 4,
entries 13 and 14).
Under the standard conditions mentioned above and using
gold(I) complex (aS)-2a as the best catalyst, the solvent effect
was next investigated at room temperature. It was found that,
besides DCE, toluene and CH2Cl2 were both suitable media in
this reaction, affording product 56a in excellent yields with 42%
ee and 48% ee, respectively (Table 5, entries 1ꢀ3). However,
coordinative solvents such as THF, DMF, and CH3CN were
All of the above-mentioned results suggested that this NHC-
Au(I) complex catalyzed transformation of 1,6-enyne was typi-
cally dependent upon the employed solvent with regard to the
catalytic activity and selectivity. Later on, the influence of
reaction temperature was also explored using PhCl as the solvent.
Lowering the temperature would bring about a dramatic decrease
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Scheme 4. Asymmetric Intramolecular Cyclization of 1,6-Enyne
of the catalytic activity but have a minor effect on the enantios-
electivity, such that product 56a was obtained in >99% yield and
63% ee at 10 °C but in 25% yield and 66% ee within 90 h at 0 °C
(Table 5, entries 14 and 15). Moreover, the addition of 4 Å MS
allowed only a slight improvement of the results, in which 56a was
isolated in >99% yield and 65% ee at 10 °C (Table 5, entry 16).
In consideration of oxidants having some influence on this
transformation (Table 3), other aryl sulfoxides were next synthe-
sized and tested here to seek out better reaction outcomes
(Figure 6).20c However, compared with the results using Ph2SO
as the oxidant at 10 °C, more sterically hindered sulfoxides 57b and
57c both slowed the reaction rate and gave the corresponding
product in moderate asymmetric induction at 10 °C (Table 6,
entries 1 and 2). However, when the reaction was carried out at
50 °C, the corresponding product 56a was afforded in yields and
enantioselectivities similar to those of 57a (Table 6, entries 1 and 2).
Therefore, the optimized conditions were identified as using
complex (aS)-2a and AgSbF6 as the best catalyst system and Ph2SO
as the oxidant in a solvent of anhydrous PhCl at 10 °C with the
addition of 4 Å MS (50 mg). Under these conditions, the substrate
scope of 1,6-enynes was next investigated for their gold(I)-cata-
lyzed oxidative rearrangements. The substrates with aryl substitu-
ents on the nonterminal alkenyl moiety were all tolerable in short
times, such that mesityl 52c was converted into 56c in >99% yield
and 58% ee, while naphthyl 52d offered 56d in >99% yield and 64%
ee (Table 6, entries 3 and 4). On the other hand, the substituent on
the nitrogen-tethered 1,6-enynes has significant influence on the
enantioselectivities of the aldehyde products. For example, a 99%
yield and the highest 70% ee were obtained for 4-bromobenzene-
sulfonyl product 56e within 10 h, and 94% yield and 66% ee for
4-nitrobenzenesulfonyl product 56f after 42 h (Table 6, entries 5
and 6). However, more sterically bulky and electron-rich substrate
2,4,6-triisopropylbenzenesulfonyl 52g afforded the corresponding
aldehyde 56g only with 10.3% ee despite its >99% yield within
12.5 h (Table 6, entry 7). Similar results were delivered by the
reaction of oxygen-tethered and sterically less hindered 1,6-enyne
52h, giving the corresponding product 56h in 86% yield with only
3.1% ee (Table 6, entry 8). All experiments mentioned above
suggested that enantioselectivities for this oxidative rearrangement
of 1,6-enynes were significantly dependent on the solvent as well as
the substrate. On the other hand, as for substrate 52b and other 1,6-
enynes having a terminal alkenyl moiety or nonterminal alkynyl
moiety, the reactions proceeded very sluggishly to afford the
corresponding products in very poor yields.
Table 2. NHC-Au(I) Complex Catalyzed Asymmetric Intra-
molecular Cyclization of 1,6-Enynea
entry catalyst
AgX
temperature (°C) time (h) yield (%)b ee (%)c
1
2
3
4
5
6
7
8
9
(aS)-2a AgSbF6
25
25
24
93
43
d
e
none AgSbF6
7 days
72
NR
16
_
(aS)-2a AgOTs
(aS)-2a AgOTf
(aS)-2a AgBF4
25
39
42
29
ꢀ20
ꢀ20
25
75
73
75
73
e
(aS)-2a AgOC(O)CF3
(aS)-2a AgSbF6
(aS)-2a AgSbF6
(aR)-1 AgSbF6
6 days
24
trace
83
_
0
50
ꢀ20
25
24
88
55
36
80
25
10 (aS)-2b AgSbF6
11 (aS)-3 AgSbF6
12 (aS)-4 AgSbF6
13 (aS,S)-5 AgSbF6
14 (aR)-6 AgSbF6
15 (aR)-6 AgSbF6
16 (aR)-6 AgSbF6
25
12
76
21
25
13
81
60g
ꢀ1f
ꢀ2f
ꢀ11f
ꢀ53f
25
36
25
9
84
25
12
91
e
ꢀ20
0
24
trace
_
24
>99
ꢀ59f
a Reaction conditions: 5 mol % of catalyst; 5 mol % of AgX; 0.1 mmol of
52a; 1.0 mL of dry AcOH. b Isolated yields. c Determined by chiral
HPLC using a Chiralpak AD-H column. d Only 20 mol % of AgSbF6
was used. e Undetermined. f The negative sign of the ee value indicates an
inversed absolute configuration compared with that of other entries.
g Product 55 was also isolated in 22% yield.
active BINAM as the starting material. These NHC-Au(I)
complexes have been conveniently isolated in satisfactory yields
and fully characterized by NMR, ESI-MS, and IR spectroscopic
data. Moreover, the structures of complexes 1, 2a, and 6 have
been further determined by X-ray diffraction studies of single
crystals, where they all exhibited a nearly linear coordination
geometry around the gold(I) center.11 The catalytic activity and
chiral induction ability of these chiral NHC-Au(I) complexes
were initially examined in the gold(I)-catalyzed asymmetric
acetoxycyclization of 1,6-enynes. Within the carried out investi-
gations herein, the sterically less hindered gold(I) complex
In conclusion, we have developed a new class of gold(I)
complexes 1ꢀ11 of axially chiral NHC ligands using optically
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Figure 5. Proposed mechanism for the intramolecular rearrangements of 1,6-enyne.
(aR)-6, having a pyrrolidin-1-yl group, was realized to be the best
catalyst in this reaction, giving product 53a in >99% yield and
ꢀ59% ee at 0 °C. On the basis of the understanding of a possible
mechanism for gold(I)-catalyzed cycloisomerization of 1,6-en-
yne, we have in fact intercepted the proposed gold(I)-carbenoid
intermediate B during the process by using AgClO4 or sulfoxides
as oxidants.20 Furthermore, these axially chiral NHC-Au(I)
complexes were successfully applied in the asymmetric oxidative
rearrangement of 1,6-enynes, for the first time, to give the
corresponding aldehyde products in good to high yields along
with moderate ee values. Enantioselectivities for this transforma-
tion were significantly dependent on the solvent as well as
substrate, where the reactions of 1,6-enynes 52a,cꢀh all pro-
ceeded smoothly to give the corresponding aldehydes 56a,cꢀh
in excellent yields and 3.1ꢀ70% ee's using complex (aS)-2a as
catalyst and PhCl as the solvent. To the best of our knowledge,
the enantioselectivity of up to 70% ee was by far the best result for
NHC-Au(I) complex catalyzed transformations.3,6g,10 Although
there are still many deficiencies, such as a limited scope of
substrates, the work presented in this paper is beneficial to the fu-
ture development of designing much more efficient chiral NHC-
gold(I) complexes and exploring their asymmetric catalysis.7
This work as well as detailed mechanistic investigations are
currently underway in our laboratories to obtain more perspec-
tive results for gold(I)-catalyzed asymmetric cycloisomerization
of 1,6-enynes and their potential utilization.
Table 3. Asymmetric Oxidative Rearrangement of 1,6-Enyne
52aa
entry
oxidant
time (h) yield (%)b ee (%)c
1d
2d
3
AgClO4 (30 mol %)/AcOH (20 equiv) 72
32
47
47
41
34
43
AgClO4 (1 equiv)
Me2SO (2 equiv)
Ph2SO (2 equiv)
12
6 days
8
27
4
>99
a Reaction conditions: 5 mol % of (aS)-2a; 5 mol % of AgSbFe; 0.1 mmol
of 52a; oxidant; 1.0 mL of DCE. b Isoated yields. c Determined by chiral
HPLC using a Chiralpak AD-H column. d Without the addition of
AgSbFe (5 mol %).
in mixed ethyl ether/CH2Cl2 (1:1). White solid: mp 259.5ꢀ260.6 °C
(dec); [R]20D ꢀ52 (c 0.25, CHCl3); IR (direct irradiation) ν 3324, 1702,
1507, 1482, 1465, 1391, 1354, 1306, 1245, 1150, 1133, 1013, 863, 828,
808, 763, 750, 693 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS) δ 2.07 (s,
3H), 3.94 (s, 3H), 6.82 (t, J = 8.0 Hz, 1H), 6.89 (d, J = 8.4 Hz, 1H),
7.12ꢀ7.22 (m, 5H), 7.25ꢀ7.29 (m, 1H), 7.39ꢀ7.46 (m, 2H),
7.64ꢀ7.69 (m, 3H), 7.80 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.8 Hz,
1H), 8.11 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 9.2 Hz, 1H); LRMS (ESI) m/e
638.1 [M+ ꢀ I]; HRMS (ESI) calcd for [C30H23N3IAu ꢀ I] requires
638.1507, found 638.1484 [M+ ꢀ I].
’ EXPERIMENTAL SECTION
Synthesis of NHC-Au(I) Complexes 1ꢀ11. As a representative
complex, axially chiral NHC-Au(I) complex 2a was synthesized via the
following procedure from imidazolium salt 18. Under an argon atmo-
sphere, to a flame-dried Schlenk tube equipped with a septum and stir-
ring bar were added NHC precursor 18 (57 mg, 0.1 mmol), NaOAc
(17 mg, 0.2 mmol), and [(Me2S)AuCl] (30 mg, 0.1 mmol) followed by
the addition of dry CH3CN (5.0 mL) as the solvent. After refluxing at
85 °C for about 12 h, the reaction mixture was cooled to room
temperature and filtered through Celite. Then volatiles were removed
under reduced pressure, and the residue was purified by a silica gel flash
column chromatography (eluent: petroleum ether/EtOAc, 2.5:1) to
give complex 2a as a white solid in 54% yield. Single crystals of 2a
suitable for an X-ray diffraction study were grown from a solution of 2a
The NHC-Au(I) complexes 1, 2b, and 3ꢀ11 were also successfully
obtained from their corresponding imidazolium salts according to modi-
fied procedures, similar to that of complex 2a.
Complex (aR)-1: white solid; mp 300.4ꢀ301.5 °C (dec); [R]20D +24
(c 0.25, CHCl3); IR (direct irradiation) ν 3058, 2923, 2852, 1592, 1462,
1436, 1391, 1360, 1261, 1241, 1133, 1099, 1063, 1014, 862, 828, 806,
763, 738, 697 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS) δ 4.24 (s, 6H),
6.54 (t, J = 8.0 Hz, 2H), 6.60 (d, J = 8.4 Hz, 2H), 7.14 (t, J = 7.6 Hz, 2H),
7.46 (d, J = 8.4 Hz, 2H), 7.55ꢀ7.70 (m, 8H), 7.95 (d, J = 9.2 Hz, 2H),
7.99 (d, J = 8.4 Hz, 2H); LRMS (ESI) m/e 1035.1 [M+ ꢀ I]; HRMS
(ESI) calcd for [C36H26N4I2Au2 ꢀ I] requires 1035.0533, found
1035.0527 [M+ ꢀ I].
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Table 4. NHC-Au(I) Complex Catalyzed Asymmetric
Oxidative Rearrangement of 1,6-Enyne 52aa
Table 5. Optimization for Asymmetric Oxidative
Rearrangement of 1,6-Enyne 52a Catalyzed by (aS)-2aa
temperature time (h) yield (%)b ee (%)c
entry
catalyst
time (h)
yield (%)b
ee (%)c
entry
solvent
DCE
1
rt
2
>99
94
43
42
48
20
1
(aR)-1
(aS)-2a
(aS)-2b
(aS)-3
3
2
3
3
5
4
6
3
3
4
7
4
7
6
91
>99
94
29
2
toluene
CH2Cl2
THF
rt
5
2
43
3
rt
6
97
3
25
30d
NRd
64d
89
4
>99
>99
99
ꢀ3d
7
ꢀ3d
9
4
rt
12 days
e
5
DMF
rt
7 days
_
5
(aS)-4
6
CH3CN
EtOAc
CH3NO2
acetone
CHCl3
PhCI
rt
7 days
5
6
(aS,S)-5
(aS,R)-5
(aS)-6
7
rt
5.5
3
24
11
6
7
99
8
rt
91
8
>99
>99
97
36
9
(aR)-6
(aS)-7
ꢀ32d
44
ꢀ12d
ꢀ4d
ꢀ6d
ꢀ2d
9
rt
4
41
10
11
12
13
14
15
16f
rt
4
80
55
60
57
56
66
63
65
10
11
12
13
14
rt
4
91
(aS)-8
91
1,2-Cl,Cl-Ph
PhF
rt
3
>99
94
25d
>99
>99
(aS)-9
94
rt
3
(aS)-10
94
PhCl
0 °C
10 °C
10 °C
90
12
12
(aS)-11
>99
a Reaction conditions: 5 mol % of catalyst; 5 mol % of AgSbF6; 0.1 mmol
of 52a; 1.5 equiv of Ph2SO; 1 mL of DCE. b Isolated yields. c Determined
by chiral HPLC using a Chiralpak AD-H column. d The negative sign of
ee indicates an inversed absolute configuration compared with that of
other entries.
PhCl
PhCl
a Reaction conditions: 5 mol % of (aS)-2a; 5 mol % of AgSbF6; 0.1 mmol
of 52a; 1.5 equiv of Ph2SO; 1 mL of solvent. b Isolated yields.
c Determined by chiral HPLC using a Chiralpak AD-H column.
d
1
e
Determined by H NMR integration of the crude product. Undeter-
mined. f 50 mg of 4 Å MS was used as additive.
Complex (aS)-2b: white solid; mp 291.9ꢀ293.0 °C (dec); [R]20
D
ꢀ31 (c 0.25, CHCl3); IR (direct irradiation) ν 3428, 2923, 2853, 1701,
1618, 1595, 1568, 1495, 1423, 1402, 1346, 1306, 1278, 1252, 1223, 1192,
1013, 839, 823, 755, 731, 697 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS)
δ 1.99 (s, 3H), 5.37 (d, J = 15.6 Hz, 1H), 5.84 (d, J = 15.6 Hz, 1H),
6.82ꢀ6.84 (m, 2H), 6.89 (t, J = 7.2 Hz, 1H), 6.95ꢀ7.09 (m, 5H), 7.19 (t,
J = 7.2 Hz, 1H), 7.28ꢀ7.29 (m, 4H), 7.48ꢀ7.49 (m, 2H), 7.66 (d, J =
8.4 Hz, 1H), 7.68ꢀ7.72 (m, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.85 (d, J =
8.8 Hz, 1H), 8.10 (d, J = 8.8 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.29 (d, J =
8.4 Hz, 1H); LRMS (ESI) m/e 714.2 [M+ ꢀ I]; HRMS (ESI) calcd for
[C36H27N3IOAu ꢀ I] requires 714.1820, found 714.1821 [M+ ꢀ I].
Figure 6. Aryl sulfoxides as the oxidants.
Complex (aS)-3: white solid; mp 141.5ꢀ142.9 °C (dec); [R]20
Complex (aS,S)-5: white solid; mp 224.9ꢀ225.8 °C (dec); [R]20
D
D
ꢀ149 (c 0.25, CHCl3); IR (direct irradiation) ν 3419, 3057, 2924, 2852,
1682, 1596, 1501, 1487, 1466, 1427, 1391, 1346, 1277, 1238, 1099, 1024,
860, 820, 744, 706 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS) δ 3.77 (s,
3H), 6.79 (d, J = 8.4 Hz, 1H), 7.02 (t, J = 7.2 Hz, 1H), 7.14 (d, J = 8.0 Hz,
1H), 7.20ꢀ7.30 (m, 5H), 7.36 (t, J = 7.2 Hz, 1H), 7.43ꢀ7.47 (m, 2H),
7.56ꢀ7.66 (m, 3H), 7.72 (d, J = 9.2 Hz, 2H), 7.76ꢀ7.81 (m, 3H), 8.21
(d, J = 8.4 Hz, 1H), 8.28 (d, J = 8.8 Hz, 1H), 8.40 (d, J = 9.2 Hz,
1H); LRMS (ESI) m/e 700.2 [M+ ꢀ I]; HRMS (ESI) calcd for
[C35H25N3IOAu ꢀ I] requires 700.1663, found 700.1661 [M+ ꢀ I].
ꢀ102 (c 0.25, CHCl3); IR (direct irradiation) ν 3360, 2924, 2853, 1691,
1596, 1501, 1467, 1451, 1425, 1391, 1362, 1305, 1274, 1254, 1156, 1114,
1089, 873, 831, 817, 745 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS) δ
1.20 (s, 9H), 1.62ꢀ2.10 (m, 6H), 2.86 (s, 1H), 3.77 (s, 3H), 4.31 (br,
1H), 7.10ꢀ7.13 (m, 1H), 7.21ꢀ7.32 (m, 3H), 7.38 (t, J = 7.6 Hz, 1H),
7.45 (d, J = 8.0 Hz, 1H), 7.50ꢀ7.54 (m, 1H), 7.59 (t, J = 7.2 Hz, 2H),
7.63 (d, J = 9.2 Hz, 1H), 7.73 (t, J = 7.6 Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H),
8.08 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.31 (d, J = 9.2 Hz, 1H), 8.53 (s,
1H); LRMS (ESI) m/e 793.2 [M+ ꢀ I]; HRMS (ESI) calcd for
[C38H36N4IO3Au ꢀ I] requires 793.2453, found 793.2471 [M+ ꢀ I].
Complex (aS)-4: white solid; mp 153.4ꢀ154.5 °C (dec); [R]20
D
ꢀ9.0 (c 0.25, CHCl3); IR (direct irradiation) ν 3420, 2973, 2925, 1715,
1599, 1502, 1455, 1427, 1391, 1367, 1346, 1270, 1232, 1153, 1083, 1059,
871, 820, 804, 743 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS) δ 1.53 (s,
9H), 3.99 (s, 3H), 6.27 (s, 1H), 6.56ꢀ6.61 (m, 2H), 7.04ꢀ7.10 (m, 2H),
7.19ꢀ7.23 (m, 2H), 7.29ꢀ7.32 (m, 1H), 7.37ꢀ7.45 (m, 2H), 7.59 (d, J
= 8.8 Hz, 1H), 7.65ꢀ7.69 (m, 2H), 7.92 (d, J = 8.8 Hz, 1H), 7.95 (d, J =
8.4 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H); LRMS
(ESI) m/e 696.2 [M+ ꢀ I]; HRMS (ESI) calcd for [C33H29N3IO2Auꢀ I]
requires 696.1925, found 696.1937 [M+ ꢀ I].
Complex (aS)-6: white solid; mp 286.0ꢀ287.5 °C (dec); [R]20
D
+172 (c 0.25, CHCl3); IR (direct irradiation) ν 3061, 3035, 2957, 2922,
2899, 2853, 2831, 1614, 1595, 1504, 1468, 1440, 1426, 1393, 1377, 1345,
1244, 1150, 1133, 1010, 856, 822, 810, 746 cmꢀ1; 1H NMR (400 MHz,
CDCl3, TMS) δ 1.80ꢀ1.83 (m, 2H), 1.95ꢀ2.01 (m, 2H), 2.61 (t, J = 8.0
Hz, 2H), 2.99ꢀ3.05 (m, 2H), 4.06 (s, 3H), 6.19 (d, J = 8.4 Hz, 1H), 6.36
(t, J = 8.0 Hz, 1H), 6.71 (d, J = 8.8 Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H),
7.12ꢀ7.17 (m, 3H), 7.19ꢀ7.23 (m, 1H), 7.27 (d, J = 9.2 Hz, 1H),
7.47ꢀ7.53 (m, 2H), 7.63ꢀ7.67 (m, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.92
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Table 6. Asymmetric Oxidative Rearrangement of 1,6-Enynes Catalyzed by (aS)-2aa,bcde
a Reaction conditions: 5 mol % of (aS)-2a; 5 mol % of AgSbF6; 0.1 mmol of 52; 1.5 equiv of oxidant; 50 mg of 4 Å molecular sieves; 1 mL of dry PhCI at
10 °C. b Isolated yields. c Determined by chiral HPLC using a Chiralpak AD-H column. d The value in parentheses was that at 50 °C instead.
e Determined by a chiral HPLC analysis of the alcohol derivative of product 56f.
(d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.8 Hz,
1H); LRMS (ESI) m/e 650.2 [M+ ꢀ I]; HRMS (ESI) calcd for
[C32H27N3IAu ꢀ I] requires 650.1870, found 650.1880 [M+ ꢀ I].
Anal. Calcd for C32H27AuIN3: C 49.44, H 3.50, N 5.40. Found: C 49.24,
H 3.69, N 5.25.
(s, 3H), 4.38 (dd, J = 6.0, 16.0 Hz, 1H), 4.56 (t, J = 5.6 Hz, 1H), 4.62 (dd, J
= 5.6, 16.0 Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 6.85 (t, J = 7.6 Hz, 1H), 6.99
(d, J = 8.4 Hz, 1H), 7.02ꢀ7.05 (m, 4H), 7.08ꢀ7.17 (m, 5H), 7.23 (d, J =
8.4 Hz, 1H), 7.42ꢀ7.45 (m, 3H), 7.49 (d, J = 8.0 Hz, 1H), 7.67 (ddd, J =
2.8, 5.6, 8.0 Hz, 1H), 7.71 (d, J = 8.4Hz, 1H), 8.10 (d, J= 8.4 Hz, 1H), 8.20
(d, J = 8.4 Hz, 1H); LRMS (ESI) m/e 686.2 [M+ ꢀ I]; HRMS (ESI) calcd
for [C35H27N3IAu ꢀ I] requires 686.1870, found 686.1844 [M+ ꢀ I].
Complex (aS)-9: white solid; mp 240.8ꢀ241.8 °C (dec); [R]20D +51
(c 0.25, CHCl3); IR (direct irradiation) ν 3059, 3023, 2923, 2852, 2814,
1618, 1596, 1505, 1450, 1392, 1353, 1216, 1150, 1124, 1098, 1070, 971,
942, 824, 807, 738, 699, 684 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS)
δ 3.75 (s, 3H), 4.32 (s, 4H), 6.58 (d, J = 7.2 Hz, 4H), 6.67 (t, J = 8.4 Hz,
1H), 6.73 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 9.2 Hz, 1H), 6.89 (t, J = 7.2 Hz,
4H), 7.00 (t, J = 7.2 Hz, 2H), 7.15ꢀ7.20 (m, 2H), 7.25ꢀ7.34 (m, 5H),
7.42 (d, J = 9.2 Hz, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.65ꢀ7.67 (m, 1H),
7.74 (d, J = 8.8 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H);
LRMS (ESI) m/e 776.2 [M+ ꢀ I]; HRMS (ESI) calcd for
[C42H33N3IAu ꢀ I] requires 776.2340, found 776.2352 [M+ ꢀ I].
Complex (aS)-7: white solid; mp 259.0ꢀ260.7 °C (dec); [R]20D +48 (c
0.25, CHCl3);IR(directirradiation) ν3061, 2923, 2899, 2852, 2776, 1712,
1593, 1505, 1464, 1397, 1360, 1245, 1126, 1097, 1081, 977, 859, 819, 804,
743, 702 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS) δ 2.46 (s, 6H), 4.07
(s, 3H), 6.33 (d, J = 8.0 Hz, 1H), 6.41 (t, J = 7.2 Hz, 1H), 6.89 (d, J = 8.8
Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H), 7.16ꢀ7.27 (m, 4H), 7.42ꢀ7.45 (m, 2H),
7.58ꢀ7.65 (m, 3H), 7.85 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 7.6 Hz, 1H), 8.16
(d, J = 8.4 Hz, 1H); LRMS (ESI) m/e 624.2 [M+ ꢀ I]; HRMS (ESI) calcd
for [C30H25N3IAu ꢀ I] requires 624.1714, found 624.1696 [M+ ꢀ I].
Complex (aS)-8: pale yellow solid; mp 198.3ꢀ199.8 °C (dec);
[R]20 +20 (c 0.25, CHCl3); IR (direct irradiation) ν 3399, 2955,
D
2922, 2852, 1710, 1617, 1598, 1494, 1454, 1392, 1343, 1295, 1240, 1081,
1
827, 808, 740, 696 cmꢀ1; H NMR (400 MHz, CDCl3, TMS) δ 3.95
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Complex (aS)-10: yellow solid; mp 150.0ꢀ151.2 °C(dec); [R]20D ꢀ49
(c 0.25, CHCl3); IR (direct irradiation) ν 3055, 2921, 2851, 2814, 1710,
1606, 1571, 1493, 1461, 1390, 1279, 1239, 1203, 1188, 1151, 1081, 964,
903, 859, 818, 744, 692 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS) δ 3.76
(s, 3H), 6.68 (ddd, J = 2.8, 6.0, 8.4 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.90
(dt, J = 1.2, 8.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 7.16ꢀ7.17 (m, 2H),
7.25ꢀ7.40 (m, 5H), 7.43ꢀ7.47 (m, 1H), 7.55 (dt, J = 1.2, 8.0 Hz, 1H),
7.59ꢀ7.65 (m, 2H), 7.72 (d, J = 7.6 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.86
(d, J= 8.0 Hz, 1H), 8.10 (d, J= 8.0 Hz, 1H), 8.21 (d, J= 8.4 Hz, 1H), 8.48 (s,
1H), 11.82 (s, 1H); LRMS (ESI) m/e 700.2 [M+ ꢀ I]; HRMS (ESI) calcd
for [C35H25N3IOAu ꢀ I] requires 700.1663, found 700.1666 [M+ ꢀ I].
of China ((973)-2009CB825300), the Fundamental Research
Funds for the Central Universities, and the National Natural
Science Foundation of China for financial support (21072206,
20472096, 20872162, 20672127, 20821002, and 20732008).
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Complex (aS)-11: pale yellow solid; mp 133.0ꢀ134.5 °C (dec); [R]20
D
ꢀ42 (c 0.25, CHCl3); IR (direct irradiation) ν 3055, 2923, 2853, 1700,
1611, 1576, 1505, 1458, 1390, 1308, 1241, 1202, 1098, 964, 870, 815,
742, 692 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS) δ 3.80 (s, 3H), 6.86
(ddd, J = 1.6, 6.0, 7.6 Hz, 1H), 7.15ꢀ7.26 (m, 4H), 7.29ꢀ7.34 (m, 3H),
7.36ꢀ7.41 (m, 2H), 7.46ꢀ7.55 (m, 4H), 7.58 (d, J = 8.4 Hz, 1H), 7.62
(d, J = 8.8 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.82
(d, J = 8.8 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.39
(s, 1H); LRMS (ESI) m/e 684.2 [M+ ꢀ I]; HRMS (ESI) calcd for
[C35H25N3IAu ꢀ I] requires 684.1714, found 684.1713 [M+ ꢀ I].
General Procedure for NHC-Au(I) Complex Catalyzed
Asymmetric Acetoxycyclization of 1,6-Enynes. A typical pro-
cedure is given below for the reactions shown in Table 2. To a solution of
NHC-Au(I) complex (5 mol %), 1,6-enyne 52a (33 mg, 0.1 mmol), and
AgX (0.005 mmol) in dry DCE (1.0 mL) was added dry acetic acid (115
μL, 2.0 mmol) as the nucleophile under an argon atmosphere. The
mixture was stirred at the proper temperature until 52a was completely
consumed by TLC monitoring. Then the reaction was quenched by
filtering through Celite with a thin pad of silica gel, and volatiles were
removed under reduced pressure. The residue was purified by silica gel
flash column chromatography to give 53a (eluent: petroleum ether/
EtOAc, 8:1) as a white solid.
General Procedure for NHC-Au(I) Complex Catalyzed En-
antioselective Oxidative Rearrangement of 1,6-Enynes. Un-
der an argon atmosphere, to a flame-dried Schlenk tube equipped with a
septum and stirring bar were added activated 4 Å MS (50 mg), NHC-
Au(I) complex (5 mol %), 1,6-enyne 52 (0.1 mmol), Ph2SO (30 mg, 0.15
mmol), and AgSbF6 (2 mg, 0.005 mmol) followed by the injection of the
corresponding drysolvent (1.0 mL). The mixture was stirredatthe proper
temperature until complete consumption of 52 by TLC monitoring
before quenching by filtering with a thin pad of silica gel. Then volatiles
were removed under reduced pressure, and the residue was purified by
silica gel flash column chromatography to give the oxidative product 56.
’ ASSOCIATED CONTENT
S
Supporting Information. Detailed descriptions of exper-
b
(7) A recent alternative approach of employing chiral counteranions
is very attractive for conducting asymmetric gold catalysis; see ref 4c and
Hashmi, A. S. K. Nature 2007, 449, 292–293.
imental procedures, spectral and analytical data for all new com-
pounds shown in schemes, figures, and tables, CIF files and X-ray
crystal data for 1, 2a, and 6, and chiral HPLC traces of
compounds 53, 54, and 56. This material is available free of
charge from the authors or via the Internet at http://pubs.acs.
org.
(8) For selected books and reviews on NHC ligands, see: (a) Nolan,
S. P., Ed. N-Heterocyclic Carbenes in Synthesis; Wiley-VCH: Weinheim,
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Angew. Chem., Int. Ed. 2004, 43, 1767–1769. (g) Cesar, V.; Bellemin-
Laponnaz, S.; Gade, L. H. Chem. Soc. Rev. 2004, 33, 619–636. (h)
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’ AUTHOR INFORMATION
Corresponding Author
*E-mail: Mshi@mail.sioc.ac.cn. Fax: 86-21-64166128.
’ ACKNOWLEDGMENT
We thank the Shanghai Municipal Committee of Science and
Technology (08dj1400100-2), National Basic Research Program
3868
dx.doi.org/10.1021/om2004404 |Organometallics 2011, 30, 3859–3869

Organometallics
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(13) The crystal data of 1 have been deposited with the CCDC with
number 759948. Empirical formula: C40H32Au2I2N6; formula weight:
1244.45; crystal color, habit: colorless, prismatic; crystal dimensions:
0.301 ꢁ 0.217 ꢁ 0.24 mm; crystal system: triclinic; lattice type:
primitive; lattice parameters: a = 9.3794(9) Å, b = 10.4523(10) Å, c =
20.784(2) Å, R = 85.843(2)o, β = 77.783(2)o, γ = 80.838(2)o, V =
1964.5(3) Å3; space group: P1; Z = 2; Dcalc = 2.104 g/cm3; F000 = 1156;
diffractometer: Bruker Smart CCD; residuals: R; Rw: 0.0448, 0.1129.
(14) (a) Zhang, T.; Liu, S. J.; Shi, M.; Zhao, M. X. Synthesis 2008,
17, 2819–2824. (b) Wang, W. F.; Zhang, T.; Wang, F. J.; Shi, M.
Tetrahedron 2011, 67, 1523–1529.
(15) The crystal data of 2a have been deposited with the CCDC with
number 757529. Empirical formula: C32H27AuCl4IN3O; formula
weight: 935.23; crystal color, habit: colorless, prismatic; crystal dimen-
sions: 0.303 ꢁ 0.122 ꢁ 0.105 mm; crystal system: orthorhombic; lattice
type: primitive; lattice parameters: a = 7.6150(13) Å, b = 14.252(2) Å, c
= 30.775(5) Å, R = 90°, β = 90°, γ = 90°, V = 3340.1(10) Å3; space
group: P2(1)2(1)2(1); Z = 4; Dcalc = 1.860 g/cm3; F000 = 1792;
diffractometer: Bruker Smart CCD; residuals: R; Rw: 0.0635, 0.1464.
(16) The crystal data of 6 have been deposited with the CCDC with
number 790740. Empirical formula: C32H27AuIN3; formula weight:
777.43; crystal color, habit: colorless; crystal dimensions: 0.350 ꢁ 0.280
ꢁ 0.221 mm; crystal system: monoclinic; lattice parameters: a =
12.8532(14) Å, b = 7.4498(8) Å, c = 14.7707(17) Å, R = 90°, β =
90.459(2)o, γ = 90°, V = 1414.3(3) Å3; space group: P2(1); Z = 2; Dcalc
= 1.826 g/cm3; F000 = 744; diffractometer: Bruker Smart CCD;
residuals: R; Rw: 0.0406, 0.0790.
(17) The absolute stereochemistries of 53a and 53b were assigned
by analogy to compound 54 followed by comparison of the sign of
optical rotation of 54 with that in the literature: Charruault, L.; Michelet,
V.; Taras, R.; Gladiali, S.; Genet, J. P. Chem. Commun. 2004, 850–851.
(18) Porcel, S.; Echavarren, A. M. Angew. Chem., Int. Ed. 2007,
46, 2672–2676.
(19) Nieto-Oberhuber, C.; Munoz, M. P.; Lopez, S.; Jimenez-
Nunez, E.; Nevado, C.; Herrero-Gomez, E.; Raducan, M.; Echavarren,
A. M. Chem.—Eur. J. 2006, 12, 1677–1693.
(20) For references on trapping of cyclypropylcarbenes, see: (a)
Nieto-Oberhuber, C.; Lopez, S.; Munoz, M. P.; Jimenez-Nunez, E.;
Bunuel, E.; Cardenas, D. J.; Echavarren, A. M. Chem.—Eur. J. 2006,
3869
dx.doi.org/10.1021/om2004404 |Organometallics 2011, 30, 3859–3869