Gold-catalyzed intermolecular addition of carbonyl compounds to 1,6-enynes: Reactivity, scope, and mechanistic aspects

Article abstract of DOI:10.1002/chem.200901614

A full account of a recently discovered gold(I)-catalyzed reaction, a cycloaddition of carbonyl compounds to enynes yielding 2-oxabicyclo[3.1.0] hexanes with four stereogenic centers, is presented. The reaction proceeds with very high diastereoselectivity

Full text of DOI:10.1002/chem.200901614

DOI: 10.1002/chem.200901614
Gold-Catalyzed Intermolecular Addition of Carbonyl Compounds to
1,6-Enynes: Reactivity, Scope, and ACTHNUTRGNEUNGMechanistic Aspects
Mathias Schelwies, Ralph Moser, Adrian L. Dempwolff, Frank Rominger, and
Gꢀnter Helmchen*[a]
Abstract: A full account of a recently
discovered gold(I)-catalyzed reaction, a
cycloaddition of carbonyl compounds
to enynes yielding 2-oxabicyclo-
and DFT calculations concerning
mechanistic aspects were carried out.
The reaction course varies with the
substitution pattern of the alkene
moiety of the starting enyne. Branched
olefins led to 2-oxabicyclo[3.1.0]hex-
AHCTUNGTRENNaGUN nes; terminally substituted olefins
proceeded with the incorporation of
two carbonyl components to give
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG[3.1.0]hexanes with four stereogenic
centers, is presented. The reaction pro-
ceeds with very high diastereoselectiv-
ity. The scope of the reaction has been
investigated. In addition, experiments
hexahydrocyclopenta[d]ACHTUGNTREN[UNG 1,3]dioxACHTUNGTRENNUNGines.
Keywords: aldehydes · cyclization ·
enynes · gold · homogeneous cataly-
sis · ketones
Introduction
In recent years, gold complexes have found increasing use
as homogeneous catalysts for the activation of alkynes, and
numerous novel reaction pathways have been discovered.[1,2]
Among them are isomerization reactions of 1,6-enynes.
These can be induced by many transition-metal catalysts.[3]
Gold-catalyzed processes are distinguished by an unusually
large spectrum of new reaction modes.[4] The fundamental
Au-catalyzed isomerizations are described in Scheme 1.
Typically, Au-catalyzed isomerization reactions of 1,6-
enynes of type I yield the dienes IV and/or V. The ratio of
these reaction products depends on the connector Z and the
substituents at the enyne moiety.[5] Crucial intermediates are
the carbene complexes II and III. Evidence for their in-
volvement was provided by DFT calculations.[2d,6,7c] The car-
benoid character of II and III was illustrated by cyclopropa-
nation of alkenes.[1b,7] Fꢀrstner and others have pointed out
that the nature of these complexes may be better described
as gold-stabilized carbocations.[1b,2e,8] A 6-endo-dig pathway
has been proposed for the formation of products V;[2d] how-
Scheme 1. Isomerization reactions of 1,6-enynes.
ever, recent research suggests that both IV and V are
formed by 5-exo-dig cyclizations through carbene intermedi-
ates II and III.[9]
Furthermore, the intermediates of type II and III undergo
a variety of addition reactions with nucleophiles (arenes[10]
and alcohols or water[5]). In a communication, we have re-
cently shown that oxabicycloACTHNUTRGNEUGN[3.1.0]hexanes of type VI can
be obtained by an Au-catalyzed reaction of 1,6-enynes with
carbonyl compounds (Scheme 2).[11] Echavarren et al.[12] had
previously described a different reaction mode, an intramo-
lecular gold-catalyzed reaction of en-yn-ones, which pro-
ceeds through a Prins-type reaction and gives rise to other
types of products.
[a] Dr. M. Schelwies, R. Moser, A. L. Dempwolff, Dr. F. Rominger,
Prof. Dr. G. Helmchen
Organisch-Chemisches Institut der Universitꢁt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax : (+49)6221-544205
After publication, we extended our investigation. In par-
ticular, we have investigated the scope and mechanism of
the formation of products VI. In the course of this work a
E-mail: g.helmchen@oci.uni-heidelberg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901614.
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FULL PAPER
Table 1. Results for the reaction of 1a with benzaldehyde (2a).
Entry Catalyst
Conditions
Yield of 3a
[%]
[b]
1[a]
2[c]
A
A
1.5 h ꢀ458C
–
Scheme 2. Addition of carbonyl compounds to 1,6-enynes.
6 h ꢀ458C, then ! RT
38
(16 h)
3
A
6 h ꢀ458C, then ! RT
(16 h)
68
new reaction mode was discovered: twofold addition of the
carbonyl component to give 1,3-dioxolanes VII, which is ob-
served with terminally substituted olefins as substrates
(Scheme 2). A further reaction mode that leads to products
of type VIII was very recently reported by Echavarren
et al., who employed gold complexes with ligands L other
than PPh3 as catalysts.[13]
4
5
6
A
A
B
4 h ꢀ208C
66
42
1.5 h RT
[d]
6 h ꢀ458C, then ! RT
–
(12 h)
7
C
6 h ꢀ458C, then ! RT
(14 h)
59
8
[Au
(2 mol%)
(NTf2)
(PPh3)]
6 h ꢀ458C, then ! RT
68
(22 h)
9
G
E
6 h ꢀ458C, then ! RT
(13 h)
n.r.[e]
n.r.[e]
n.r.[e]
n.r.[e]
Results and Discussion
10
11
12
6 h ꢀ458C, then ! RT
(15 h)
6 h ꢀ458C, then ! RT
(12 h)
The reaction conditions of the conversion I!VI were opti-
mized by varying the catalyst, the temperature, and the ratio
of the carbonyl component and enyne. The reaction of the
enyne 1a with benzaldehyde (2a) was used as a probe
(Table 1). The best yields were obtained at a reaction tem-
perature of ꢀ458C with an excess of benzaldehyde (Table 1,
6 h ꢀ458C, then ! RT
(18 h)
[a] No benzaldehyde (2a) was added. [b] Yield of 4: 49%. [c] One equiv-
alent of benzaldehyde (2a) was added. [d] Conversion to 3a <50% after
18 h (GC–MS). [e] No reaction.
entries 3, 4, and 8). The cationic catalysts [AuCl
AgSbF6 (A) and [Au(NTf2)
fonyl) showed high activity,[14] whereas AuCl, AuCl3, CuOTf,
ZnOTf, PtCl2, and AgSbF6 as well as [AuCl(PPh3)], without
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
4 and 5 were formed after approximately 30 min in a ratio
4/5=11:1. Echavarren et al. reported a ratio 4/5=7:1 for the
reaction at 08C.[5]
Conversion versus time for the reaction of enyne 1a in
the presence of catalyst A and two equivalents of benzalde-
hyde is described in Figure 2. The amount of the products of
the enyne isomerization was significantly reduced, that is, at
.
added silver salt, or BF3 Et2O, were not catalytically active
(entries 9–12, and experiments that are not listed). Among
ꢀ
the weakly coordinating anions that were tested, SbF6
proved best suited (entries 1–5). Success with [Au
ACHTUNGERTN(NUNG NTf2)-
ACHTUNGTRENNUNG
soluble silver salts, formed in conjunction with most of the
catalysts, do not exert a significant effect on the reaction.
In the absence of an aldehyde, enyne 1a expectedly[5]
gave product 4 at a low temperature (Table 1, entry 1). This
compound was also detected (GC–MS) in the reaction mix-
ture containing only one equivalent of benzaldehyde
(entry 2) and in reactions run at temperatures
ꢁꢀ208C (entries 4 and 5). With the exception of a run ac-
cording to entry 1, the compound was not isolated; in the
presence of catalyst A, diene 4 was unstable at room tem-
perature and gave rise to side products, which were not
identified. The diene 4 was not formed upon use of the opti-
mal reaction conditions (entry 3).
ꢀ208C, the oxabicyclo
ACHTUNGTRNE[NUNG 3.1.0]hexane 3a was formed as the
main product and diene 4 as a side product. Diene 5 was
not detected under these conditions.
These experiments show that there are several competing
reaction pathways. An excess of benzaldehyde favors the
formation of the oxabicycloACHTNUTRGNE[UNG 3.1.0]hexane 3a at the expense
of the enyne isomerization. Furthermore, the addition of
only 0.2 equiv benzaldehyde leads to a significant decrease
in the reaction rate. Thus, it is likely that 3a is formed from
one of the species in the isomerization manifold.
Investigation of the scope of the reaction with respect to
the carbonyl component gave the following results
(Scheme 3). Isobutyraldehyde (2c) and o-nitrobenzaldehyde
(2b) reacted at about the same rate as benzaldehyde 2a.
The reactions of acetone (2d) and cyclohexanone (2e) were
comparatively slow; reaction temperatures above 08C were
To gain more insight into the competing reaction path-
ways, the reaction was monitored by NMR spectroscopy at
ꢀ208C. Results for the reaction of enyne 1a in the presence
of catalyst A are displayed in Figure 1. The isomeric dienes
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G. Helmchen et al.
Figure 1. Conversion of 1a to 4 and 5 versus reaction time; conditions:
ꢀ208C, CD2Cl2 (c(1a)=0.17m), 5 mol% of A (cf. Table 1, entry 1).
ACHTUNGTRENNUNG
Scheme 3. Products of the intermolecular addition of different aldehydes
and ketones to 1a.
entry 5), which incorporated a 1-methylvinyl group, reacted
significantly faster than compound 1a. The reaction of sub-
strate 1i with a stereogenic center led exclusively to the dia-
stereomer represented in entry 8.[18] The influence of the
backbone was assessed with the substrates 1k and 1l.
Whereas the bis-sulfonyl derivative 1k (entry 10) reacted
with a yield comparable to that of the malonic esters, a
lower yield was obtained with 1l, which contained an ortho-
phenylene moiety as backbone (entry 11).
Limits became apparent upon further varying the back-
bone of the enyne. With Z=NTs (Ts=tosylyl) or O (cf.
Scheme 2), selective formation of the oxabicyclo-
AHCTUNGTREG[NNNU 3.1.0]hexanes of type VI was not accomplished. Compounds
Figure 2. Conversion of 1a to 3a and 4 in the presence of 2 equiv benzal-
dehyde; conditions: ꢀ208C, CD2Cl2 (c(1a)=0.17m), 5 mol% of A.
AHCTUNGTRENNUNG
with Z=NTs yielded complex product mixtures, and those
with Z=O did not react. This could be due to coordination
effects of the heteroatoms or lack of a gem-disubstitution
effect.[19]
For exploration of the steric course of the reaction, deu-
terated substrates were subjected to the optimal reaction
conditions. The enyne [3’-2H1]-1a with a trans configuration
of the double bond furnished product [1-2H1]-3b as a 1:1
mixture of epimers with respect to C-1 (Scheme 4), and its
isotopomer [3’’-2H1]-1a gave [1a-2H1]-3b as product.
required. Surprisingly, the addition of ketone 2 f[16] to 1a
gave the adduct 3 f, an oil, as a single diastereoisomer. This
experiment was conducted with the idea of probing the in-
terception of an intermediate of the addition reaction.
The scope of the reaction was further explored with 1,6-
enynes and the 1,7-enyne 1j (Table 2). The products 3b, 6d,
6e, 6 f, 6i, 6j, and 6l were characterized by X-ray crystal
structure analysis (see Table 4 in the Experimental Section).
In all cases, the reaction proceeded with complete diastereo-
selectivity with respect to the stereogenic centers C-1a, C-3,
C-3a, and C-6a. Despite the formation of two quaternary
centers in vicinal positions,[17] the substrate 1 f (Table 2,
Mechanistic proposal and computational investigation: Our
initial proposal for the mechanism of the new reaction is dis-
played in Scheme 5. The mechanism is supported by DFT
calculations described below.
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Addition of Carbonyl Compounds to 1,6-Enynes
FULL PAPER
Table 2. Addition of ortho-nitrobenzaldehyde (2b) to various enynes.[a]
Entry
Enyne
t [h]
Product (Yield [%])
1
3[b]
2
3
4
1[b]
4[b]
7
Scheme 4. Addition of carbonyl compounds to deuterated enynes
[3’-2H1]-1a and [3’’-2H1]-1a.
5
6
7
4[b]
16
18
8
21
43
16
22
9
Scheme 5. Mechanistic working hypothesis concerning the formation of
the products VI.
10
11
represented by the cationic complex [AuACTHNUTRGNEUNG
(PMe3)]+. The
methods used in the computational investigation are out-
lined in the computational details part of the Experimental
Section (below). The rearrangement of the unsubstituted
1,6-enyne has previously been theoretically investigated
with respect to the formation of dienes of type V.[9] The es-
tablished reaction pathway leading to the dienes of type
IV,[2d,6,7c] which constitutes the first part of our mechanistic
proposal for the addition reaction depicted in Scheme 5, has
only been calculated with enynes substituted at the alkene
moiety. Results of our investigation of the corresponding
pathway of the rearrangement of the unsubstituted 1,6-
enyne and the subsequent reaction with benzaldehyde are
described in Figure 3.
[a] Reaction conditions: 0.2m enyne in CH2Cl2, 5 equiv o-nitrobenzalde-
hyde (2b), catalyst: 5 mol% A, 6 h ꢀ458C, then !RT. [b] Complete con-
version after the time indicated at ꢀ458C; for details see the Experimen-
tal Section. [c] The reaction proceeded without racemization.
The eastern part of the catalytic cycle, leading to the in-
termediate III, is adopted from previous work of the Echa-
varren group.[6,7b] The subsequent addition of the carbonyl
compound and the following cyclization was assumed to
proceed by means of a stepwise cationic mechanism includ-
ing the six-membered ring intermediate X. Alternatively, a
1,3-dipolar cycloaddition as typical for addition reactions of
rhodium carbene complexes[20] was suggested because of the
observed high diastereoselectivity.
Consistent with the findings of the Echavarren group for
substituted enynes, the initial enyne gold complex A reacts
through two steps to give intermediate E, which contains a
ꢀ
partially opened cyclopropyl moiety with a C C distance of
about 1.8 ꢃ (drawn with a dashed line in Figure 3). This in-
termediate has previously been presented as achiral gold
carbene III (cf. Scheme 5). However, E possesses character-
For a DFT study, the unsubstituted 1,6-enyne and benzal-
dehyde were chosen as model substrates. The catalyst was
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G. Helmchen et al.
Figure 3. Formation of products VI according to DFT calculations.
istics of a homoallyl cation as well as of a cyclopropyl
methyl cation and displays a low barrier to racemization;
this is consistent with the observed lack of stereoselectivity
in the reaction of the deuterated substrate [3’-2H1]-1a
(Scheme 4). The highly cationic character of gold carbene
complexes has recently been demonstrated experimentally
by Fꢀrstner et al.[8a]
Examples of intermolecular additions of nucleophiles to
gold complexes of type II and III have been described by
Echavarren et al.[21] Furthermore, Hashmi et al.[21] proposed
an intramolecular addition of a carbonyl oxygen to a carbe-
noid gold complex. Toste et al.[22] have described oxidations
of intermediary carbenoid gold complexes with sulfoxides.
According to the DFT calculations, the reaction of E with
benzaldehyde to give F proceeds with a low activation barri-
er. No transition state was found for this step; this was
ty of possibilities for the coordination of the gold species
exist.
Overall, our proposal for the western part of the catalytic
cycle as described in Scheme 5 is strongly supported by the
DFT calculations.
Twofold addition of aldehydes to substituted enynes: Fur-
ther investigation of the scope of the addition reaction re-
vealed another reaction mode in which 1,6-enynes with a
terminal substituent at the alkene moiety led to dioxolanes
of type 8 (Table 3) rather than to products of type 3. The di-
oxolanes 8a, 8b, and 8c were obtained as single diastereo-
isomers. The relative configurations of 8a and 8b were de-
termined by X-ray crystal structure analysis.
The reaction to give dioxolanes 8 does not proceed by
means of an enyne isomerization to give a diene of type IV
followed by a Prins-type reaction of two aldehydes and a
diene, a reaction known to occur upon acid catalysis.[23] This
was established by a control experiment with the diene 9,
which did not form a product of type 8 under the stated re-
action conditions (Scheme 6). The diene 9 was prepared
from 7b by PtCl2-catalyzed rearrangement.[24]
ꢀ
sought by stepwise variation of the C O bond length. The
ꢀ
reactive conformer H was found by C C bond rotation.
Two steps rather than a concerted pathway were identi-
fied for the cyclization of H. The first step, in which the dia-
stereoselectivity with respect to C-3 is determined, leads to
the six-membered-ring intermediate K with the phenyl ring
and the catalyst in equatorial positions. The cyclization of K
furnishes the intermediate M with an opened cyclopropyl
moiety, in which the positive charge is delocalized at the
Conclusion
ꢀ
newly formed C O bond. M is finally transformed to the
gold complex O of the final product through a relatively
high reaction barrier of about 55 kJmolꢀ1. The final two
steps are possibly not traversed in solution in which a varie-
A gold(I)-catalyzed cycloaddition of carbonyl compounds to
enynes yielding 2-oxabicycloACHTUNGERTN[NUNG 3.1.0]hexanes with four stereo-
genic centers has been found and mechanistically character-
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Addition of Carbonyl Compounds to 1,6-Enynes
FULL PAPER
Table 3. Intermolecular additions of aldehydes to enynes 7 and 7b.
set on C, H, O, and P[29] and the LANL2DZ effective core potential and
basis set on Au.[27] Single-point energy calculations were performed using
the LACV3P++** basis set. For all Gibbs free energies stated, the
single-point energies were combined with the Gibbs correction data for
298.15 K and 1 atm obtained from the frequency analyses. The energies
and geometries of all calculated compounds are presented in the Sup-
porting Information.
General: Unless stated otherwise, reactions were carried out under argon
using anhydrous conditions. 1H NMR spectra were recorded at RT using
the following spectrometers: Bruker AC-300 (300 MHz), Bruker Avance
500 (500 MHz). Chemical shifts are reported in d units relative to CHCl3
(dH =7.26). 13C NMR spectra were recorded using the following spec-
trometers: Bruker AC-300 (75 MHz), Bruker Avance 500 (125 MHz).
Chemical shifts are reported in d units relative to CHCl3 (dC =77.16 {cen-
tral line of the triplet}). The following abbreviations were used through-
out: s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet. The as-
signments of signals for compounds 1–8 were confirmed by H,H COSY,
H,C COSY, HMBC, and DEPT spectra. Atom numbers are specified in
Entry
1
Enyne
t [h]
Product (Yield [%])
7a
1 h at ꢀ408
1
the formulas. H NMR spectra of all newly described compounds are pre-
sented in the Supporting Information. Optical rotations were measured
using a Perkin–Elmer 341 polarimeter in a 1 dm curvette with a thermo-
stat using a mercury lamp. Concentration c is given in g per 100 mL.
High resolution mass spectra (HRMS) were recorded using a JEOL
JMS-700 instrument. Elemental analyses were carried out at the Organ-
isch-Chemisches Institut, Universitꢁt Heidelberg. Enantiomeric excesses
were determined by chiral HPLC using an HP 1100 instrument; column:
Chiralpak AD-H (Daicel, 250ꢄ4.6 mm, 5 mm) with guard cartridge AD-
2
3
7b
7b
5 h at ꢀ408C
2 h at ꢀ408C
H
(Daicel, 10ꢄ4 mm, 5 mm). For preparative HPLC, the following
system was used: a Gilson-305 pump coupled with a Knauer UV detector
2600; column: silica gel (Latek, 5 m, 21ꢄ250 mm and/or Prontosil 120-10-
SI, 10 m, 20ꢄ250 mm). X-ray data were collected using a Bruker Smart
CCD (6d, 6j, 6l) or a Bruker APEX (3b, 6e, 6 f, 6i, 8a, 8b) diffractome-
ter equipped with a MoKa radiation source (l=0.71073 ꢃ) and a graphite
monochromator. Intensities were corrected for Lorentz and polarization
effects; an empirical absorption correction was applied using
SADABS.[30] All structures were solved by direct methods and refined
against F2 using the SHELXTL-PLUS software package.[31] The corre-
sponding crystallographic data are displayed in Table 4. CCDC-641967
(3b), 696063 (6d), 696064 (6e), 641968 (6 f), 641969 (6i), 641970 (6j),
641971 (6l), 696065 (8a), and 696066 (8b) contain 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.
Scheme 6. Control experiment concerning the formation of the products
of type 8.
Syntheses and spectroscopic data of the following compounds have been
published previously: 1a,[32a,b] 1 f,[33] 1j,[34] 1k,[35a,b] 4,[36] 5,[37] 7a,[38] 7b,[32a]
and 9.[39] Syntheses of enynes [3’-2H1]-1a, [3’’-2H1]-1a, 1b, 1c, 1d, 1e, 1g,
1h, 1i, 1l, and 2 f are described in the Supporting Information.
ized. The reaction proceeds with a very high level of diaste-
reoselectivity. The scope of the reaction has been investigat-
ed. Additionally, DFT calculations concerning mechanistic
aspects were carried out. The reaction course varies with the
substitution pattern of the alkene moiety of the enyne.
Whereas branched olefins led to 2-oxabicycloACTHUNRTGNEUNG[3.1.0]hexanes,
terminally substituted olefins proceeded with the incorpora-
tion of two carbonyl components to give hexahydrocyclo-
General procedure for the reaction of enynes with carbonyl compounds
(GP): In a flame-dried Schlenk flask under an argon atmosphere, a
stirred solution of the enyne 1 (1 equiv), the carbonyl compound 2, and
AgSbF6 (0.05 equiv) in anhydrous CH2Cl2 (5 mL) was treated with
[AuClACTHNUGRTENUNG(PPh3)] (0.05 equiv) at the temperature indicated. The mixture was
stirred for the time and at the temperature indicated, filtered through
Celite, and washed with CH2Cl2. The solvent was removed under reduced
pressure and the residue subjected to flash column chromatography.
ACHTUNGTRENNUNGpenta[d]ACHTUNGTRENNUNG[1,3]dioxines. A third reaction mode has been re-
cently described by Echavarren et al.
(ꢂ)-Dimethyl (1aR,3R,3aR,6aR)-3-phenyltetrahydro-3H-cyclopenta[c]-
cyclopropa[b]furan-5,5(6H)-dicarboxylate (3a): According to GP, a mix-
ture of benzaldehyde (530 mg, 5.0 mmol), enyne 1a (210 mg, 1.0 mmol),
and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2 (5 mL) was cooled to
ꢀ458C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg, 50 mmol). The mixture
Experimental Section
turned orange and was kept at ꢀ458C for 6 h. The cooling device was
switched off, which initiated slow warming to RT. After an overall reac-
tion time of 22 h, a black precipitate had formed and GC–MS indicated
complete consumption of the substrate. Workup according to GP and
flash column chromatography on silica (25 g, petroleum ether/ethyl ace-
Computational details: The geometries of all structures described here
were optimized using the Jaguar 6.5 quantum chemistry program package
at the BP86/LACVP* level of theory.[25,26,27] Stationary points were char-
acterized as equilibrium structures (number of imaginary frequencies
(NIMAG)=0) or transition states (NIMAG=1) using the Gaussian 03
program package[28] at the BP86 level of theory[26] with the 6-31G* basis
tate 10:1) yielded 2-oxabicycloACHTUNTRGNEU[GN 3.1.0]hexane 3a (216 mg, 68%) as a color-
less oil. Rf =0.31 (petroleum ether/ethyl acetate 3:1); 1H NMR
(300 MHz, CDCl3, 258C): d=0.98 (dd, J=6.2, 5.1 Hz, 1H; 1-Ha), 1.14
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G. Helmchen et al.
Table 4. Data of the crystal structure analysis of several products.
3b
6d
6e
6 f
6i
formula
Mr
C18H19NO7
361.34
0.47ꢄ0.39ꢄ0.20
orthorhombic
P212121
9.3604(15)
9.9285(16)
17.935(3)
90
C17H19NO5
317.33
0.47ꢄ0.24ꢄ0.10
orthorhombic
Pbca
9.1698(2)
15.1226(3)
21.0707(4)
90
C17H17NO6
331.32
0.20ꢄ0.13ꢄ0.11
monoclinic
P21/c
24.968(5)
5.8198(12)
21.670(4)
90
110.040(6)
90
C19H21NO7
375.37
0.39ꢄ0.24ꢄ0.13
monoclinic
P21
8.1973(6)
14.1531(10)
15.6051(11)
90
98.515(2)
90
C24H23NO7
437.43
1.10ꢄ0.14ꢄ0.12
triclinic
crystal size [mm3]
crystal system
space group
a [ꢃ]
P1
8.5155(12)
9.7995(13)
13.5216(19)
87.912(3)
79.187(3)
87.987(3)
1107.1(3)
2
b [ꢃ]
c [ꢃ]
a [8]
b [8]
90
90
90
90
g [8]
V [ꢃ3]
Z
1666.8(5)
4
1.440
2921.90(10)
8
1.44
2958.2(10)
8
1.49
1790.5(2)
4
1.392
1calcd [Mgmꢀ3
]
1.312
0.097
m [mmꢀ1
Tmax, Tmin
]
0.11
0.11
0.11
0.107
0.98, 0.95
ꢀ12 to 12,
ꢀ13 to 13,
ꢀ23 to 23
2.27 to 28.33
200(2)
0.99, 0.95
ꢀ11 to 11,
ꢀ19 to 19,
ꢀ27 to 27
1.9 to 27.5
200(2)
0.99, 0.98
ꢀ32 to 32,
ꢀ7 to 7,
ꢀ27 to 27
1.7 to 27.1
200(2)
0.99, 0.96
ꢀ10 to 10,
ꢀ18 to 18,
ꢀ20 to 20
2.51 to 28.39
200(2)
0.99, 0.90
ꢀ11 to 11,
ꢀ13 to 13,
ꢀ18 to 18
2.08 to 28.37
200(2)
index ranges hkl
q [8]
T [K]
reflns collected
independent reflns (Rint
observed reflns (I>2s(I))
data/restraints/params
GOF on F2
16742
4145 (0.0320)
3813
4145/0/273
1.09
28198
3345 (0.0911)
2506
3345/0/208
1.03
27167
6518 (0.0625)
5016
6518/0/433
1.21
18982
8797 (0.0255)
8239
8797/1/541
1.08
11221
9876 (0.0273)
8659
9876/3/645
1.03
)
final R indices (I>2s(I)) R1, wR2
absolute structural params
0.047, 0.117
0.3(9)
0.40 and ꢀ0.28
0.041, 0.098
–
0.24 and ꢀ0.22
0.083, 0.144
–
0.31 and ꢀ0.25
0.045, 0.112
0.0(6)
0.27 and ꢀ0.21
0.047, 0.119
ꢀ0.2(6)
residual electron density [eꢃꢀ3
]
0.31 and ꢀ0.21
6j
6l
8a
8b
formula
Mr
C19H21NO7
375.37
0.26ꢄ0.14ꢄ0.12
C18H15NO3
293.31
0.55ꢄ0.27ꢄ0.04
monoclinic
P21/n
8.1289(1)
20.4867(4)
8.4067(2)
90
94.858(1)
90
C27H28N2O10
540.51
C31H30O6
498.55
0.60ꢄ0.20ꢄ0.17
monoclinic
P21/c
9.5686(16)
12.954(2)
20.972(3)
90
97.172(3)
90
crystal size [mm3]
crystal system
space group
a [ꢃ]
0.42ꢄ0.12ꢄ0.05
triclinic
triclinic
¯
¯
P1
P1
9.0680(1)
9.8733(2)
10.5679(2)
81.437(1)
73.921(1)
77.761(1)
884.82(3)
2
7.7398(9)
9.7750(11)
18.297(2)
100.934(2)
100.087(2)
103.236(2)
1288.0(3)
2
b [ꢃ]
c [ꢃ]
a [8]
b [8]
g [8]
V [ꢃ3]
Z
1394.97(5)
4
1.397
2579.2(7)
4
1.28
1calcd [Mgmꢀ3
]
1.409
0.108
1.39
0.11
m [mmꢀ1
Tmax, Tmin
]
0.096
0.09
0.99, 0.97
ꢀ11 to 11,
ꢀ12 to 12,
ꢀ13 to 13
2.01 to 27.45
200(2)
1.00, 0.95
ꢀ10 to 10,
ꢀ26 to 26,
ꢀ10 to 10
1.99 to 27.52
200(2)
0.99, 0.96
ꢀ10 to 10,
ꢀ12 to 13,
ꢀ24 to 24
2.2 to 28.4
200(2)
0.99, 0.95
ꢀ12 to 12,
ꢀ17 to 17,
ꢀ27 to 27
1.9 to 28.3
200(2)
index ranges hkl
q [8]
T [K]
reflns collected
independent reflns (Rint
obsd reflns (I>2s(I))
data/restraints/params
GOF on F2
8993
4017 (0.0721)
2599
4017/0/246
1.01
13739
3202 (0.0581)
2323
3202/0/200
1.04
13392
6334 (0.0278)
4858
6334/0/356
1.10
26573
6418 (0.0297)
5495
6418/0/336
1.03
)
final R indices (I>2s(I)) R1, wR2
0.059, 0.136
0.27 and ꢀ0.25
0.049, 0.109
0.26 and ꢀ0.17
0.063, 0.135
0.43 and ꢀ0.29
0.046, 0.118
0.35 and ꢀ0.22
residual electron density [eꢃꢀ3
]
(dd, J=6.3, 1.8 Hz, 1H; 1-Hb), 2.38 (s, 2H; 6-H), 2.47–2.62 (m, 3H; 3a-
H, 4-H), 3.75 (s, 3H; OCH3), 3.84 (s, 3H; OCH3), 3.87 (dd, J=5.1,
1.7 Hz, 1H; 1a-H), 5.09 (dt, J=7.5, 3.7 Hz, 1H; 3-H), 7.22–7.35 ppm (m,
5H; Ph); 13C NMR (75 MHz, CDCl3, 258C, DEPT, HMBC): d=23.08 (t;
C-1), 36.50 (s; C-6a), 37.98, 38.33 (2 t; C-4, C-6), 53.05 (q; 2OCH3), 55.13
(d; C-3a), 61.56 (s; C-5), 65.57 (d; C-1a), 95.70 (d; C-3), 125.74 (d; Ph),
127.68 (d; Ph), 128.54 (d; Ph), 141.63 (s; Ph), 171.94 (s; CO2CH3),
172.27 ppm (s; CO2CH3); HRMS (EI): m/z: calcd for C18H20O5: 316.1311;
found: 316.1324 [M+]; elemental analysis calcd (%) for C18H20O5 (316.4):
C 68.34, H 6.37; found: C 68.32, H 6.33.
10894
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10888 – 10900

Addition of Carbonyl Compounds to 1,6-Enynes
FULL PAPER
(ꢂ)-Dimethyl (1aR,3R,3aR,6aR)-3-(2-nitrophenyl)tetrahydro-3H-cyclo-
penta[c]cyclopropa[b]furan-5,5(6H)-dicarboxylate (3b): According to
GP, a solution of enyne 1a (210 mg, 1.0 mmol), 2-nitrobenzaldehyde (2b)
(756 mg, 5.0 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2
carried out according to GP. Flash column chromatography on silica
(80 g, petroleum ether/ethyl acetate 10:1) furnished [1a-2H1]-3b (80%
[2H1], 200 mg, 55%) as
a
slightly yellow crystalline solid. 1H NMR
(300 MHz, CDCl3, 258C): d=0.82 (d, J=6.9 Hz, 1H; 1-Ha), 1.00 (d, J=
6.9 Hz, 1H; 1-Hb), 2.30 (d, J=13.6 Hz, 1H; 6-Ha), 2.43 (d, J=13.6 Hz,
1H; 6-Hb), 2.50 (ddd, J=8.1, 6.2, 5.3 Hz, 1H; 3a-H), 2.70 (dd, J=14.2,
8.4 Hz, 1H; 4-Ha), 2.77 (dd, J=14.2, 6.6 Hz, 1H; 4-Hb), 3.72 (s, 3H;
OCH3), 3.80 (s, 3H; OCH3), 5.81 (d, J=4.8 Hz, 1H; 3-H), 7.35–7.41 (m,
1H; Ar), 7.58 (td, J=7.6, 1.0 Hz, 1H; Ar), 7.72 (d, J=7.8 Hz, 1H; Ar),
7.94 ppm (dd, J=8.1, 1.1 Hz, 1H; Ar); 13C NMR (125 MHz, CDCl3,
258C, DEPT, HMBC): d=19.08 (t; C-1), 35.29 (s; C-6a), 38.11 (t; C-6),
(5 mL) was cooled to ꢀ508C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg,
50 mmol). The temperature was allowed to rise to ꢀ258C over a period
of 5 h when GC monitoring indicated complete conversion. Workup and
flash column chromatography on silica (35 g, petroleum ether/ethyl ace-
tate 10:1) afforded 3b (168 mg, 47%) as a yellow solid. Crystallization
from methanol at RT gave colorless crystals, suitable for X-ray crystal
structure analysis; for data, see Table 4. Rf =0.37 (petroleum ether/ethyl
acetate 3:1); m.p. 98–1008C; 1H NMR (300 MHz, CDCl3, 258C): d=0.83
(dd, J=6.1, 6.1 Hz, 1H; 1-H), 1.01 (dd, J=6.8, 1.1 Hz, 1H; 1-H), 2.30 (d,
J=13.6 Hz, 1H; 6-H), 2.43 (d, J=13.6 Hz, 1H; 6-H), 2.50 (dt, J=7.8,
5.9 Hz, 1H; 3a-H), 2.65–2.81 (m, 2H; 4-H), 3.73 (d, J=0.9 Hz, 3H;
OCH3), 3.81 (d, J=0.9 Hz, 3H; OCH3), 3.88 (dd, J=5.1, 1.3 Hz, 1H; 1a-
H), 5.80 (d, J=4.9 Hz, 1H; 3-H), 7.38 (dd, J=7.6, 7.6 Hz, 1H; Ar), 7.58
(dd, J=7.4, 7.4 Hz, 1H; Ar), 7.71 (d, J=7.7 Hz, 1H; Ar), 7.94 ppm (d,
J=8.1 Hz, 1H; Ar); 13C NMR (75 MHz, CDCl3, 258C, DEPT, HMBC):
d=19.26 (t; C-1), 35.43 (s; C-6a), 38.15 (t; C-6), 40.26 (t; C-4), 53.00 (q;
OCH3), 54.80 (d; C-3a), 61.01 (s; C-5), 66.32 (d; C-1a), 88.70 (d; C-3),
124.79 (d; Ar), 128.06 (d; Ar), 128.17 (d; Ar), 133.45 (d; Ar), 139.42 (s;
Ar), 147.32 (s; Ar), 172.09 (s; C=O), 172.15 ppm (s; C=O); IR (KBr): n˜ =
729, 791, 1077, 1120, 1165, 1202, 1242, 1277, 1349, 1433, 1528, 1735 (C=
O), 2953, 3436 cmꢀ1; HRMS (FAB): m/z: calcd for C18H20NO7: 362.1240;
found: 362.1267 [M+H+]; elemental analysis calcd (%) for C18H19NO7
(361.3): C 59.83, H 5.30, N 3.88; found: C 59.73, H 5.28, N 3.85.
40.29 (t; C-4), 53.00 (q; OCH3), 54.80 (d; C-3a), 61.00 (s; C
ACHTUGNERTN(NUNG CO2Me)2),
65.96 (t, J
AHCTUNGTRENNUNG
88.67 (d; C-3), 124.80 (d; Ar), 128.05 (d; Ar), 128.17 (d; Ar), 133.45 (d;
Ar), 139.46 (s; Ar), 147.31 (s; Ar), 172.10 (s; C=O), 172.16 ppm (s; C=
O); HRMS (FAB): m/z: calcd for C18H19DNO7: 363.1303; found:
363.1327 [M+H+].
(ꢂ)-Dimethyl (1aR,3S,3aR,6aR)-3-isopropyltetrahydro-3H-cyclopenta[c]-
cyclopropa[b]furan-5,5(6H)-dicarboxylate (3c): According to GP, a solu-
tion of enyne 1a (210 mg, 1.0 mmol), 2-methylpropanal (2c) (1.44 g,
20 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2 (5 mL)
was cooled to ꢀ458C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg, 50 mmol).
After 6 h, the cooling device was switched off, which initiated slow warm-
ing to RT. GC monitoring indicated complete conversion after an overall
reaction time of 14.5 h. Workup according to GP and flash column chro-
matography on silica (20 g, petroleum ether/ethyl acetate 10:1) afforded
3c (189 mg, 67%) as a colorless oil. Rf =0.50 (petroleum ether/ethyl ace-
(ꢂ)-[1-2H1]-Dimethyl (1aR,3R,3aR,6aR)-3-phenyltetrahydro-3H-cyclo-
penta[c]cyclopropa[b]furan-5,5(6H)-dicarboxylate ([1-2H1]-3b): Accord-
ing to GP, a mixture of 2-nitrobenzaldehyde (755 mg, 5.0 mmol), enyne
[3’-2H1]-1a (84% [2H1], 211 mg, 1.0 mmol), and AgSbF6 (17 mg, 50 mmol)
in anhydrous CH2Cl2 (5 mL) was cooled to ꢀ458C and treated with
1
tate 3:1); H NMR (300 MHz, CDCl3, 258C): d=0.78–0.89 (m, 2H; 1-H),
0.80 (d, J=6.8 Hz, 3H; CH3), 0.86 (d, J=6.4 Hz, 3H; CH3), 1.45–1.62 (m,
1H; CHACHTNUGTRNEUGN(CH3)2), 2.24 (dd, J=8.8, 3.4 Hz, 1H; 3a-H), 2.27–2.30 (m, 2H;
6-H), 2.36 (dd, J=13.8, 3.1 Hz, 1H; 4-H), 2.48 (dd, J=13.8, 9.1 Hz, 1H;
4-H), 3.66 (dd, J=4.4, 2.4 Hz, 1H; 1a-H), 3.72 (s, 3H; OCH3), 3.77 (s,
3H; OCH3), 3.80 ppm, (dd, J=7.8, 7.8 Hz, 1H; 3-H); 13C NMR (75 MHz,
CDCl3, 258C, DEPT, HMBC): d=18.49 (q; CH3), 19.36 (q; CH3), 23.27
[AuClACHTUNGTRENNUNG(PPh3)] (24.7 mg, 50 mmol). The mixture turned orange and was
kept at ꢀ458C for 6 h. The cooling device was switched off, which initiat-
ed slow warming to RT. After an overall reaction time of 18 h, TLC con-
trol indicated complete consumption of the substrate. Workup according
to GP and flash column chromatography on silica (40 g, petroleum ether/
ethyl acetate 10:1) yielded [1-2H1]-3b (84% [2H1], 185 mg, 51%) as a
slightly yellow crystalline solid. The product was a 55:45 mixture of the
(t; C-1), 33.47 (d; CHACHTNUGRTNEUNG(CH3)2), 36.47 (s; C-6a), 38.40 (t; C-6), 38.97 (t; C-
4), 49.69 (d; C-3a), 52.91 (q; OCH3), 52.97 (q; OCH3), 61.81 (s; C-5),
64.90 (d; C-1a), 100.94 (d; C-3), 172.06 (s; C=O), 172.15 ppm (s; C=O);
IR (film): n˜ =795, 815, 840, 879, 939, 978, 1014, 1043, 1074, 1111, 1205,
1223, 1270, 1324, 1366, 1388, 1436, 1736 (C=O), 2876, 2957 cmꢀ1; HRMS
(EI): m/z: calcd for C15H22O5: 282.1467; found: 282.1464 [M+]; elemental
analysis calcd (%) for C15H22O5 (282.3): C 63.81, H 7.85; found: C 63.65,
H 7.83.
1
epimers with respect to C-1 according to H NMR spectroscopy. Rf =0.36
(petroleum ether/ethyl acetate 3:1); 1H NMR (300 MHz, CDCl3, 258C;
the epimers are designated by A and B, A/B=55:45): d=0.79 (d, J=
5.5 Hz, 1H; epimer A, 1-H), 0.98 (d, J=2.1 Hz, 1H; epimer B, 1-H), 2.27
(d, J=13.6 Hz, 1H, A and B; 6-Ha), 2.40 (d, J=13.6 Hz, 1H, A and B; 6-
Hb), 2.47 (ddd, J=8.2, 5.9, 5.3 Hz, 1H; A and B, 3a-H), 2.67 (dd, J=14.0,
8.4 Hz, 1H; A and B, 4-Ha), 2.75 (dd, J=14.1, 6.2 Hz, 1H; A and B, 4-
Hb), 3.70 (s, 3H; A and B, OCH3), 3.78 (s, 3H; A and B, OCH3), 3.83–
3.87 (m, 1H; A and B, 1a-H), 5.80 (d, J=4.9 Hz, 1H; A and B, 3-H),
7.33–7.39 (m, 1H; A and B, Ar), 7.56 (td, J=7.6, 1.2 Hz, 1H; A and B,
Ar), 7.69 (d, J=7.7 Hz, 1H; A and B, Ar), 7.91 ppm (dd, J=8.2, 1.2 Hz,
1H; A and B, Ar); 13C NMR (125 MHz, CDCl3, 258C, DEPT, HMBC):
(ꢂ)-Dimethyl (1aR,3aR,6aR)-3,3-dimethyltetrahydro-3H-cyclopenta[c]-
cyclopropa[b]furan-5,5(6H)-dicarboxylate (3d): According to GP, a solu-
tion of enyne 1a (210 mg, 1.0 mmol), acetone (2d) (1.16 g, 20 mmol), and
AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2 (5 mL) was cooled to
ꢀ58C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg, 50 mmol). The solution
was kept at ꢀ58C for 8.5 h until GC monitoring indicated complete con-
version. Workup according to GP and flash column chromatography on
silica (20 g, petroleum ether/ethyl acetate 10:1) afforded 3d (148 mg,
55%) as a colorless oil. Rf =0.41 (petroleum ether/ethyl acetate 3:1);
1H NMR (300 MHz, CDCl3, 258C): d=0.78 (dd, J=6.0, 5.7 Hz, 1H; 1-
H), 0.96 (dd, J=6.4, 1.8 Hz, 1H; 1-H), 1.15 (s, 3H; CH3), 1.18 (s, 3H;
CH3), 2.19 (dd, J=11.6, 7.6 Hz, 1H; 4-H), 2.29–2.48 (m, 4H; 3a-H, 4-H,
6-H), 3.59 (dd, J=5.3, 1.8 Hz, 1H; 1a-H), 3.73 (s, 3H; OCH3), 3.75 ppm
(s, 3H; OCH3); 13C NMR (75 MHz, CDCl3, 258C, DEPT, HMBC): d=
23.26 (t; C-1), 25.63 (q; CH3), 31.28 (q; CH3), 36.24 (s; C-6a), 36.38 (t; C-
4), 38.54 (t; C-6), 52.85 (q; OCH3), 52.99 (q; OCH3), 55.76 (d; C-3a),
62.64 (s; C-5), 62.98 (d; C-1a), 89.18 (s; C-3), 171.90 (s; C=O),
172.45 ppm (s, C=O); IR (film): n˜ =889, 1077, 1124, 1175, 1202, 1228,
1252, 1277, 1367, 1384, 1436, 1736 (C=O), 2972 cmꢀ1; HRMS (EI): m/z:
calcd for C14H20O5: 268.1311; found: 268.1290 [M+]; elemental analysis
calcd (%) for C14H20O5 (268.3): C 62.67, H 7.51; found: C 62.54, H 7.42.
d=18.81 (dt, JACHTUNGTRENNUNG ACHUTNGTRENNGUN
(13C-D)=24.5 Hz; A or B, C-1), 18.90 (dt, J(13C-D)=
24.0 Hz; A or B, C-1), [19.18 (t; C-1, nondeuterated)], 35.23, 35.25 (s; A
and B, C-6a), 38.04 (t; A and B, C-6), 40.16 (t; A and B, C-4), 52.91 (q;
A and B, OCH3), 54.68, 54.69 (d; A and B, C-3a), 61.91 (s; A and B, C-
ACHTUNGTRENNUNG(CO2Me)2), 66.15, 66.17 (d; A and B, C-1a), 88.60, 88.63 (d; A and B, C-
3), 124.69 (d; A and B, Ar), 127.96, 127.98 (d; A and B, Ar), 128.12 (d; A
and B, Ar), 133.38 (d; A and B, Ar), 139.30 (s; A and B, Ar), 147.24 (s;
A and B, Ar), 172.00 (s; A and B, C=O), 172.06 ppm (s; A and B, C=O);
HRMS (FAB): m/z: calcd for C18H19DNO7: 363.1303; found: 363.1328
[M+H+].
(ꢂ)-[1a-2H1]-Dimethyl
(1aR,3R,3aR,6aR)-phenyltetrahydro-3H-cyclo-
penta[c]cyclopropa[b]furan-5,5(6H)-dicarboxylate ([1a-2H1]-3b): Accord-
ing to GP, a mixture of 2-nitrobenzaldehyde (770 mg, 5.0 mmol), enyne
[3’’-2H1]-1a (82% [2H1], 211 mg, 1.0 mmol), and AgSbF6 (17 mg, 50 mmol)
in anhydrous CH2Cl2 (5 mL) was cooled to ꢀ458C and treated with
(ꢂ)-Dimethyl (1a’R,3a’R,6a’R)-tetrahydrospiro(cyclohexane-1,3’-cyclo-
penta[c]cyclopropa[b]furan)-5’,5’ACTHNUTRGENUGN(6’H)-dicarboxylate (3e): According to
GP, a solution of enyne 1a (210 mg, 1.0 mmol), cyclohexanone (2e)
(1.96 g, 20 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2
(5 mL) was cooled to 58C and treated with [AuClACTHGNUTRENNU(G PPh3)] (24.7 mg,
[AuClACHTUNGTRENNUNG(PPh3)] (25 mg, 50 mmol). The mixture turned orange and was kept
at ꢀ458C for 6 h. The cooling device was switched off, which initiated
slow warming to RT. After an overall reaction time of 18 h, workup was
Chem. Eur. J. 2009, 15, 10888 – 10900
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10895

G. Helmchen et al.
50 mmol). After 16 h, the cooling device was switched off, which initiated
slow warming to RT. GC monitoring indicated complete conversion after
an overall reaction time of 17 h. Workup according to GP and flash
column chromatography on silica (20 g, petroleum ether/ethyl acetate
10:1) afforded 3e (139 mg, 45%) as a slightly yellow oil. Rf =0.64 (petro-
leum ether/ethyl acetate 3:1); 1H NMR (300 MHz, CDCl3, 258C): d=
0.74 (dd, J=5.9, 5.8 Hz, 1H; 1’-H), 0.92 (dd, J=6.4, 1.7 Hz, 1H; 1’-H),
1.15–1.68 (m, 10H; 5 CH2), 2.24–2.47 (m, 5H; 3a’-H, 4’-H, 6’-H), 3.58
(dd, J=5.3, 1.7 Hz, 1H; 1a’-H), 3.73 (s, 3H; OCH3), 3.76 ppm (s, 3H;
OCH3); 13C NMR (75 MHz, CDCl3, 258C, DEPT, HMBC): d=22.48 (t;
C-1’), 23.33 (t; CH2), 23.36 (t; CH2), 25.50 (t; CH2), 34.42 (t; CH2), 35.48
(s; C-6a’), 35.67, 38.42 (2t; C-4’, C-6’), 41.05 (t; CH2), 52.85 (q; OCH3),
52.98 (q; OCH3), 54.57 (d; C-3a’), 62.28 (s; C-5’), 62.90 (d; C-1a’), 90.33
(s; C-3’), 171.99 (s; C=O), 172.54 ppm (s; C=O); IR (film): n˜ =703, 819,
882, 921, 992, 1071, 1125, 1169, 1201, 1271, 1373, 1437, 1735 (C=O), 2858,
PhCH2), 5.80 (d, J=4.0 Hz, 1H; 3-H), 7.20–7.43 (m, 11H; Ph, Ar), 7.58
(td, J=7.6, 0.9 Hz, 1H; Ar), 7.76 (d, J=7.9 Hz, 1H; Ar), 7.97 ppm (dd,
J=8.1, 1.1 Hz, 1H; Ar); 13C NMR (75 MHz, CDCl3, 258C, DEPT, H,C-
COSY): d=18.31 (t; C-1), 35.40 (s; C-6a), 36.71 (t; C-6), 40.05 (t; C-4),
49.93 (s; C-5), 55.02 (d; C-3a), 66.74 (d; C-1a), 73.33 (t; PhCH2), 73.33 (t;
PhCH2), 74.03 (t; BnOCH2), 74.30 (t; BnOCH2), 88.48 (d; C-3), 124.81,
127.45, 127.52, 127.53, 127.62, 127.83, 127.95, 128.38, 128.41, 133.26 (10d;
Ar, Ph), 138.89, 138.90 (2s; Ph), 140.48, 147.16 ppm (2s; Ar); HRMS
(FAB): m/z: calcd for C30H32NO5: 486.2280; found: 486.2336 [M+H+];
elemental analysis calcd (%) for C30H31NO5 (485.6): C 74.21, H 6.43, N
2.88; found: C 74.03, H 6.58, N 2.74.
(ꢂ)-(1aR,3R,3aR,6aR)-2’,2’-Di-tert-butyl-3-(2-nitrophenyl)tetrahydro-
3H-spiro(cyclopenta[c]cyclopropa[b]furan-5,5’-[1,3,2]dioxasilinane) (6c):
According to GP, a solution of enyne 1c (295 mg, 1.0 mmol), 2-nitroben-
zaldehyde (2b) (756 mg, 5.0 mmol), and AgSbF6 (17 mg, 50 mmol) in an-
hydrous CH2Cl2 (5 mL) was cooled to ꢀ408C and treated with [AuCl-
2934 cmꢀ1
; HRMS (EI): m/z: calcd for C17H24O5: 308.1624; found:
308.1628 [M+]; elemental analysis calcd (%) for C17H24O5 (308.4): C
66.21, H 7.84; found: C 66.37, H 7.81.
AHCTUNGRTEG(NNNU PPh3)] (24.7 mg, 50 mmol). After stirring for 1 h at this temperature,
TLC monitoring showed no further conversion. Workup and flash
column chromatography on silica (50 g, petroleum ether/ethyl acetate
10:1) afforded 6c (178mg; 40%, corr. 67%) as adhesive needles. Rf =
0.24 (petroleum ether/ethyl acetate 10:1); m.p. 1008C; 1H NMR
(300 MHz, CDCl3, 258C): d=0.69 (dd, J=5.9, 5.9 Hz, 1H; 1-H), 0.84–
0.90 (m, 1H; 1-H), 1.03 (s, 9H; SiC(CH)3), 1.10 (s, 9H; SiC(CH)3), 1.78
(dd, J=14.0, 8.6 Hz, 1H; 4-H), 1.80 (d, J=13.6 Hz, 1H; 6-H), 1.92 (d,
J=13.8 Hz, 1H; 6-H), 2.12 (dd, J=13.9, 8.7 Hz, 1H; 4-H), 2.41 (td, J=
8.3, 3.7 Hz, 1H; 3a-H), 3.82–4.16 (m, 5H; SiOCH2, 1a-H), 5.80 (d, J=
3.6 Hz, 1H; 3-H), 7.39 (t, J=7.4 Hz, 1H; Ar), 7.60 (t, J=7.6 Hz, 1H;
Ar), 7.77 (d, J=7.9 Hz, 1H; Ar), 8.00 ppm (d, J=7.9 Hz, 1H; Ar);
13C NMR (75 MHz, CDCl3, 258C, DEPT, H,C-COSY): d=17.65 (t; C-1),
(ꢂ)-Dimethyl (1aR,3aR,6aR)-3-but-3-en-1-yl-3-(phenylethynyl)tetrahy-
dro-3H-cyclopenta[c]cyclopropa[b]furan-5,5(6H)-dicarboxylate (3 f): Ac-
cording to GP, a mixture of AgSbF6 (17 mg, 50 mmol), enyne 1a (210 mg,
1.0 mmol), and enyne 2 f (921 mg, 5.0 mmol) in anhydrous CH2Cl2
(5 mL) was cooled to ꢀ458C and treated with [AuCl
ACHTUNGRTENUN(NG PPh3)] (25 mg,
50 mmol). The mixture turned orange and was kept at ꢀ458C for 2 h. The
cooling device was switched off, which initiated slow warming to ꢀ58C.
After an overall reaction time of 6 h, the solution had turned brown and
GC monitoring indicated complete conversion. Workup according to GP
and flash column chromatography on silica (25 g, petroleum ether/ethyl
acetate 15:1) afforded 3 f (271 mg, 69%) as a pale yellow oil. Rf =0.12
(petroleum ether/ethyl acetate 10:1); 1H NMR (300 MHz, CDCl3, 258C):
d=0.95 (dd, J=5.8, 5.6 Hz, 1H; 1-Ha), 1.06 (dd, J=6.2, 1.7 Hz, 1H; 1-
Hb), 1.70 (ddd, J=13.1, 11.6, 5.3 Hz, 1H; CHaHbCH2CH=CH2), 1.83
(ddd, J=13.1, 11.2, 5.4 Hz, 1H; CHaHbCH2CH=CH2), 2.12–2.35 (m, 2H;
CHaHbCH2CH=CH2), 2.20 (d, J=13.2 Hz, 1H; 6-Ha), 2.55 (dd, J=8.1,
8.1 Hz, 1H; 3a-H), 2.63 (d, J=13.2 Hz, 1H; 6-Hb), 2.67–2.75 (m, 2H; 4-
H), 3.64 (s, 3H; OCH3), 3.77 (s, 3H; OCH3), 3.88 (dd, J=5.0, 1.8 Hz,
1H; 1a-H), 4.95 (ddd, J=10.2, 2.5, 0.9 Hz, 1H;=CH2), 5.02 (ddd, J=
17.1, 3.4, 1.7 Hz, 1H;=CH2), 5.82 (dddd, J=17.0, 10.3, 6.8, 5.2 Hz, 1H;
CH=CH2), 7.29–7.34 (m, 3H; Ph), 7.45–7.50 ppm (m, 2H; Ph); 13C NMR
(75 MHz, CDCl3, 258C, DEPT, HMBC): d=22.47 (t; C-1), 29.51 (t;
CH2CH2CH=CH2), 37.40 (t; C-4), 37.51 (s; C-6a), 38.42 (t; C-6), 41.60 (t;
CH2CH2CH=CH2), 52.85 (q; OCH3), 53.01 (q; OCH3), 57.96 (d; C-3a),
63.56 (d; C-1a), 64.01 (s; C-5), 88.61, 89.37 (2s; CꢃC), 93.26 (s; C-3),
114.79 (t; CH=CH2), 122.73 (s; Ph), 128.38 (d; Ph), 128.56 (d; Ph),
131.90, (d; Ph), 138.00 (d; CH=CH2), 171.48 (s; C=O), 172.49 ppm (s; C=
O); IR (film): n˜ =693, 733, 759, 913, 1008, 1072, 1227, 1273, 1436, 1491,
1641, 1735, 2225, 2251, 2341, 2358, 2846, 2952, 2988, 3067 cmꢀ1; HRMS
(FAB): m/z: calcd for C24H27O5: 395.1859; found 395.1848 [M+H]+; ele-
mental analysis calcd (%) for C24H26O5 (394.5): C 73.08, H 6.64; found: C
72.91, H 6.56.
21.49 (s; SiC
ACHTGNUERTN(NUGN CH3)3), 22.82 (s; SiCACHTNURGTENNG(UN CH3)3), 27.87 (q; SiCCAHTNUGTREN(NUGN CH3)3), 28.34 (q;
SiC(CH3)3), 35.12 (s; C-6a), 38.71 (t; C-6), 41.18 (t; C-4), 48.67 (s; C-5),
AHCTUNGTRENNUNG
54.23 (d; C-3a), 66.80 (d; C-1a), 73.50 (t; SiOCH2), 73.66 (t; SiOCH2),
88.30 (d; C-3), 125.08, 127.95, 128.03, 133.55 (4d; Ar), 140.59, 146.91 ppm
(s; Ar); HRMS (FAB): m/z: calcd for C24H35NO5Si: 446.2363; found:
446.2325 [M+H+]; elemental analysis calcd (%) for C24H35NO5Si (445.6):
C 64.69, H 7.92, N 3.14; found: C 64.46, H 7.95, N 3.03.
(ꢂ)-(1aR,3R,3aR,6aR)-3-(2-Nitrophenyl)tetrahydro-3H-spiro(cyclopen-
ta[c]cyclopropa[b]furan-5,5’-[1,3]dioxane) (6d): According to GP, a solu-
tion of enyne 1d (166 mg, 1.0 mmol), 2-nitrobenzaldehyde (2b) (756 mg,
5.0 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2 (5 mL)
was cooled to ꢀ408C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg, 50 mmol).
Stirring was continued at this temperature for 4 h until TLC monitoring
showed complete conversion. Workup according to GP and flash column
chromatography on silica (120 g, petroleum ether/ethyl acetate 3:1) af-
forded 6d (82 mg, 26%) as a white solid. Crystallization from methanol
at 08C gave colorless polyhedral crystals, suitable for X-ray crystal struc-
ture analysis; for data, see Table 4. Rf =0.14 (petroleum ether/ethyl ace-
tate 5:1); m.p. 1478C; 1H NMR (300 MHz, CDCl3, 258C): d=0.74 (dd,
J=6.7, 5.7 Hz, 1H; 1-H), 0.91 (dd, J=6.8, 2.1 Hz, 1H; 1-H), 1.81 (dd, J=
14.0, 7.4 Hz, 1H; 6-H), 1.83 (d, J=13.8 Hz, 1H; 4-H), 1.89 (d, J=
13.8 Hz, 1H; 4-H), 2.07 (dd, J=14.0, 8.8 Hz, 1H; 6-H), 2.41 (ddd, J=8.3,
7.6, 4.4 Hz, 1H; 3a-H), 3.59–3.76 (m, 2H; OCH2OCH2), 3.88–3.97 (m,
3H; OCH2OCH2, 1a-H), 4.76 (d, J=6.0 Hz, 1H; OCH2O), 4.91 (d, J=
6.0 Hz, 1H; OCH2O), 5.79 (d, J=4.1 Hz, 1H; 3-H), 7.39 (td, J=7.7,
1.1 Hz, 1H; Ar), 7.60 (td, J=7.6, 1.1 Hz, 1H; Ar), 7.76 (d, J=7.9 Hz,
1H; Ar), 7.98 ppm (dd, J=8.2, 1.1 Hz, 1H; Ar); 13C NMR (75 MHz,
CDCl3, 258C, DEPT, H,C-COSY): d=18.45 (t; C-1), 35.02 (s; C-6a),
38.39 (t; C-6), 40.11 (t; C-4), 44.67 (s; C-5), 54.54 (d; C-3a), 66.67 (d; C-
1a), 75.66 (t; OCH2OCH2), 75.75 (t; OCH2OCH2), 88.72 (d; C-3), 94.19
(t; OCH2O), 124.94, 127.95, 128.07, 133.53 (4d; Ar), 140.12, 147.03 ppm
(2s; Ar); HRMS (FAB): m/z: calcd for C17H20NO5: 318.1341; found:
318.1392 [M+H+]; elemental analysis calcd (%) for C17H19NO5 (317.3):
C 64.34, H 6.03, N 4.41; found: C 64.33, H 6.05, N 4.30.
(ꢂ)-(1aR,3R,3aR,6aR)-5,5-Bis[(benzyloxy)methyl]-3-(2-nitrophenyl)hexa-
hydro-3H-cyclopenta[c]cyclopropa[b]furan (6b): According to GP, a so-
lution of enyne 1b (335 mg, 1.0 mmol), 2-nitrobenzaldehyde (2b)
(756mg, 5.0mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2
(5 mL) was cooled to ꢀ408C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg,
50 mmol). After stirring for 3 h at this temperature, GC monitoring indi-
cated complete conversion, and the cooling device was switched off,
which initiated slow warming to RT. The reaction mixture was then fil-
tered through Celite and concentrated in vacuo. The residual oil was sub-
jected to flash column chromatography on silica (100 g, petroleum ether/
ethyl acetate 3:1). Fractions not containing 2-nitrobenzaldehyde were
collected and subjected to preparative HPLC on silica gel (column:
Latek, 5 m, 21ꢄ250 mm; petroleum ether/ethyl acetate 10:1; 22 mLminꢀ1
,
50 bar) to yield 6b (52 mg, 11%) as a colorless oil. 1H NMR (300 MHz,
CDCl3, 258C): d=0.65 (dd, J=6.1, 5.8 Hz, 1H; 1-H), 0.85 (dd, J=6.7,
1.8 Hz, 1H; 1-H), 1.67 (d, J=13.6 Hz, 1H; 6-H), 1.79 (d, J=13.4 Hz, 1H;
6-H), 1.92 (dd, J=13.6, 7.7 Hz, 1H; 4-H), 2.29 (dd, J=13.6, 8.7 Hz, 1H;
4-H), 2.43 (td, J=8.1, 4.1 Hz, 1H; 3a-H), 3.44 (s, 2H; BnOCH2), 3.57 (s,
2H; BnOCH2), 3.80 (dd, J=5.3, 1.7 Hz, 1H; 1a-H), 4.51–4.63 (m, 4H;
(ꢂ)-(1aR,3R,3aR,6aR)-3-(2-Nitrophenyl)tetrahydro-3H-spiro(cyclopen-
ta[c]cyclopropa[b]furan-5,5’-[1,3]dioxan)-2’-one (6e): According to GP, a
solution of enyne 1e (180 mg, 1.0 mmol), 2-nitrobenzaldehyde (2b)
(756 mg, 5.0 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2
(5 mL) was cooled to ꢀ408C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg,
10896
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10888 – 10900

Addition of Carbonyl Compounds to 1,6-Enynes
FULL PAPER
50 mmol). After stirring for 7 h at this temperature, TLC monitoring
showed complete conversion. The reaction mixture was filtered through
Celite and the filtrate concentrated in vacuo. The residual oil was sub-
jected to flash column chromatography on silica (100 g, petroleum ether/
ethyl acetate 3:1). Fractions not containing 2-nitrobenzaldehyde were
collected and subjected to preparative HPLC on silica gel (columns:
Latek, 5 m, 21ꢄ250 mm and Prontosil 120-10-SI, 10 m, 20ꢄ250 mm; petro-
leum ether/ethyl acetate 10:1, 22 mLminꢀ1, 50 bar) to yield 6e (173 mg,
52%) as colorless needles, suitable for X-ray crystal structure analysis;
for data, see Table 4. Rf =0.36 (petroleum ether/ethyl acetate 1:1);
1H NMR (300 MHz, CDCl3, 258C): d=0.81 (dd, J=7.0, 5.6 Hz, 1H; 1-
H), 1.00 (dd, J=7.0, 2.0 Hz, 1H; 1-H), 1.85 (d, J=13.7 Hz, 1H; 6-H),
1.99 (d, J=13.7 Hz, 1H; 6-H), 2.03 (dd, J=14.1, 7.1 Hz, 1H; 4-H), 2.25
(dd, J=14.1, 8.8 Hz, 1H; 4-H), 2.51 (ddd, J=8.7, 7.3, 4.2 Hz, 1H; 3a-H),
4.00 (dd, J=5.5, 2.0 Hz, 1H; 1a-H), 4.15–4.47 (m, 4H, O=C-OCH2),
5.82 (d, J=4.1 Hz, 1H; 3-H), 7.42 (td, J=7.7, 0.9 Hz, 1H; Ar), 7.63 (td,
J=7.6, 1.1 Hz, 1H; Ar), 7.73–7.80 (m, 1H; Ar), 8.02 ppm (dd, J=8.1,
1.3 Hz, 1H; Ar); 13C NMR (75 MHz, CDCl3, 258C, DEPT, H,C-COSY):
d=18.15 (t; C-1), 34.60 (s; C-6a), 36.94 (t; C-6), 38.89 (t; C-4), 41.44 (s;
C-5), 54.15 (d; C-3a), 66.50 (d; C-1a), 75.93 (t; O=C-OCH2), 76.12 (t;
O=C-OCH2), 88.65 (d; C-3), 125.19 (d; Ar), 127.90 (d; Ar), 128.42 (d;
Ar), 133.85 (d; Ar), 146.83 (s; Ar), 148.10 (s; Ar), 148.32 ppm (s; C=O);
HRMS (FAB): m/z: calcd for C17H18NO6: 332.1134; found: 332.1102
[M+H+].
1H; 6-Hb), 1.94 (d, J=14.7 Hz, 1H; 4-Ha), 2.31 (d, J=14.7 Hz, 1H; 4-
Hb), 3.46 (s, 2H; OCH2), 3.60 (d, J=8.7 Hz, 1H; OCH2), 3.68 (d, J=
8.9 Hz, 1H; OCH2), 3.71–3.74 (m, 1H; 1a-H), 4.52 (s, 2H; OCH2), 4.53
(d, J=12.1 Hz, 1H; OCH2), 4.61 (d, J=12.1 Hz, 1H; OCH2), 5.91 (s, 1H;
3-H), 7.24–7.41 (m, 11H; Ar), 7.57 (td, J=7.6, 1.2 Hz, 1H; Ar), 7.70 (dd,
J=8.0, 1.2 Hz, 1H; Ar), 7.92 ppm (d, J=8.1, 1.3 Hz, 1H; Ar); 13C NMR
(75 MHz, CDCl3, 258C, DEPT, H,C-COSY): d=16.79 (t; C-1), 22.31 (q;
CH3), 36.14 (t; C-6), 41.13 (s; C-6a), 48.64 (s; C-3a), 49.02 (t; C-4), 54.34
(s; C-5), 66.05 (d; C-1a), 73.33, 73.36, 73.70, 75.05 (4t; PhCH2OCH2),
94.53 (d; C-3), 124.46, 127.46, 127.50, 127.62, 127.81, 127.99, 128.39,
128.44, 128.69, 133.07 (10d; Ar), 137.69, 138.86, 139.00, 147.88 ppm (4s;
Ar); IR (film): n˜ =699, 731, 857, 1028, 1111, 1204, 1357, 1452, 1527, 1608,
2855, 2931, 3030, 3063 cmꢀ1; HRMS (FAB): m/z: calcd for C31H34NO5:
500.2437; found: 500.2434 [M+H+]; elemental analysis calcd (%) for
C31H33NO5 (499.6): C 74.63, H 6.66, N 2.80; found: C 74.26, H 6.88, N
2.47.
(ꢂ)-(1aR,3R,3aR,6aR)-2’,2’-Di-tert-butyl-3a-methyl-3-(2-nitrophenyl)te-
trahydro-3H-spiro(cyclopenta[c]cyclopropa[b]furan-5,5’-[1,3,2]dioxasili-
nane) (6h): According to GP, a mixture of 2-nitrobenzaldehyde (761 mg,
5.0 mmol), enyne 1h (310 mg, 1.0 mmol), and AgSbF6 (17 mg, 50 mmol)
in anhydrous CH2Cl2 (5 mL) was cooled to ꢀ458C and treated with
[AuCl
G
for 6 h. The cooling device was switched off, which initiated slow warm-
ing to RT. After an overall reaction time of 18 h, the mixture turned
(ꢂ)-Dimethyl (1aR,3R,3aR,6aR)-3a-methyl-3-(2-nitrophenyl)tetrahydro-
3H-cyclopenta[c]cyclopropa[b]furan-5,5(6H)-dicarboxylate (6 f): Accord-
ing to GP, a mixture of 2-nitrobenzaldehyde (756 mg, 5.0 mmol), enyne
1 f (224 mg, 1.0 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous
brown and TLC control (RfACTHNGUTERN(UNG 1h)=0.75, petroleum ether/ethyl acetate
4:1) indicated complete consumption of the substrate. Workup according
to GP and flash column chromatography on silica (30 g, petroleum ether/
ethyl acetate 9:1) yielded 2-oxabicycloACTHUNRGTNE[NUG 3.1.0]hexane 6h (267 mg, 58%) as
CH2Cl2 (5 mL) was cooled to ꢀ458C and treated with [AuCl
(24.7 mg, 50 mmol). The mixture turned yellow and was kept at ꢀ458C
for 4 h until TLC control (RfA(1 f)=0.43, petroleum ether/ethyl acetate
(PPh3)]
a slightly yellow oil. Rf =0.33 (petroleum ether/ethyl acetate 4:1);
1H NMR (300 MHz, CDCl3, 258C): d=0.65 (s, 3H; CH3), 0.67 (dd, J=
6.6, 5.0 Hz, 1H; 1-Ha), 0.97 (dd, J=6.7, 1.6 Hz, 1H; 1-Hb), 1.04, 1.11 (2 s,
CTHUNGTRENNUNG
3:1) indicated complete consumption of the substrate. Workup according
to GP and flash column chromatography on silica (40 g, petroleum ether/
ethyl acetate 10:1 to 5:1) yielded 6 f (342 mg, 91%) as a colorless oil.
This was dissolved in n-hexane/ethyl acetate 6:1 and the solution kept at
58C to give colorless plates. The relative configuration of 2-oxabicyclo-
18H; CACTHGNUTER(NNUG CH3)3), 1.72 (d, J=14.7 Hz, 1H; 4-Ha), 1.91 (s, 2H; 6-H), 2.22
(d, J=14.7 Hz, 1H; 4-Hb), 3.87 (dd, J=10.9, 1.3 Hz, 1H; CH2O), 3.96–
3.99 (m, 1H; 1a-H), 4.06 (d, J=11.1 Hz, 1H; CH2O), 4.13–4.23 (m, 2H;
CH2O), 5.93 (s, 1H; 3-H), 7.36–7.42 (m, 1H; Ar), 7.59 (td, J=7.6, 1.0 Hz,
1H; Ar), 7.70–7.73 (m, 1H; Ar), 7.96 ppm (dd, J=8.2, 1.2 Hz, 1H; Ar);
13C NMR (75 MHz, CDCl3, 258C, DEPT, H,C-COSY): d=16.54 (t; C-1),
ACHTUNGTRENNUNG[3.1.0]hexane 6 f was verified by X-ray crystal structure analysis; for data,
see Table 4. Rf =0.22 (petroleum ether/ethyl acetate 3:1); m.p. 81–838C;
1H NMR (300 MHz, CDCl3, 258C): d=0.67 (s, 3H; CH3), 0.81 (dd, J=
6.8, 5.0 Hz, 1H; 1-Ha), 1.07 (dd, J=6.8, 1.8 Hz, 1H; 1-Hb), 2.20 (dd, J=
13.5, 1.2 Hz, 1H; 4-Ha), 2.29 (d, J=14.6 Hz, 1H; 6-Ha), 2.51 (d, J=
13.5 Hz, 1H; 6-Hb), 3.24 (dd, J=14.6, 1.2 Hz, 1H; 4-Hb), 3.74, 3.84 (2s,
6H; OCH3), 3.82–3.87 (m, 1H; 1a-H), 5.96 (s, 1H; 3-H), 7.39 (td, J=7.7,
1.3 Hz, 1H; Ar), 7.57 (td, J=7.6, 1.0 Hz, 1H; Ar), 7.69 (dd, J=8.1,
1.3 Hz, 1H; Ar), 7.88 ppm (dd, J=8.1, 1.2 Hz, 1H; Ar); 13C NMR
(75 MHz, CDCl3, 258C, DEPT, H,C-COSY): d=18.26 (t; C-1), 21.99 (q;
CH3), 38.00 (t; C-6), 41.07 (s; C-6a), 48.49 (t; C-4), 53.03, 53.08 (2 q;
OCH3), 53.80 (s; C-3a), 60.00 (s; C-5), 65.03 (d; C-1a), 93.42 (d; C-3),
124.38, 128.27, 128.94, 132.99 (4d; Ar), 136.27, 147.95 (2s; Ar), 172.05,
172.46 ppm (2s; CO2CH3); IR (KBr): n˜ =726, 856, 970, 1014, 1067, 1083,
1113, 1142, 1175, 1199, 1235, 1261, 1278, 1357, 1434, 1529, 1734 (C=O),
2958, 3447 cmꢀ1); HRMS (FAB): m/z: calcd for C19H22NO7: 376.1396;
found: 376.1360 [M+H+]; elemental analysis calcd (%) for C19H21NO7
(375.4): C 60.79, H 5.64, N 3.73; found: C 60.82, H 5.64, N 3.68.
21.34 (s; C
ACHUTTGNRENUN(G CH3)3), 22.11 (q; CH3), 22.90 (s; CAHCTUNGTRENN(UGN CH3)3), 27.86, 28.38 (2 q;
CACHTUNGTREN(NNUG CH3)3), 38.42 (t; C-6), 41.06 (s; C-6a), 47.62 (s; C-3a), 50.41 (t; C-4),
53.99 (s; C-5), 65.92 (d; C-1a), 73.17, 75.00 (2t; OCH2), 94.25 (d; C-3),
124.65, 128.14, 128.63, 133.35 (4d; Ar), 137.72, 147.73 ppm (2s; Ar); IR
(film): n˜ =651, 726, 769, 785, 827, 1010, 1052, 1118, 1183, 1354, 1443,
1472, 1528, 2859, 2934, 2969 cmꢀ1
; HRMS (FAB): m/z: calcd for
C25H38NO5Si: 460.2519; found: 460.2529 [M+H+]; elemental analysis
calcd (%) for C25H37NO5Si (459.7): C 65.33, H 8.11, N 3.05; found: C
65.66, H 8.40, N 2.86.
(ꢀ)-Dimethyl (1aR,3R,3aR,4S,6aR)-3-(2-nitrophenyl)-4-phenyltetrahy-
dro-3H-cyclopenta[c]cyclopropa[b]furan-5,5(6H)-dicarboxylate (6i): Ac-
cording to GP, a mixture of 2-nitrobenzaldehyde (756mg, 5.0mmol),
enyne (+)-(S)-1i (98.5% ee, 286 mg, 1.0 mmol), and AgSbF6 (17 mg,
50 mmol) in anhydrous CH2Cl2 (5 mL) was cooled to ꢀ458C and treated
with [AuClACHTNUTRGENNG(U PPh3)] (24.7 mg, 50 mmol). The mixture turned orange and
was kept at ꢀ458C for 6 h. The cooling device was switched off, which in-
itiated slow warming to RT. After an overall reaction time of 15 h, TLC
(ꢂ)-(1aR,3R,3aR,6aR)-5,5-Bis[(benzyloxy)methyl]-3a-methyl-3-(2-nitro-
phenyl)hexahydro-3H-cyclopenta[c]cyclopropa[b]furan (6g): According
to GP, a mixture of 2-nitrobenzaldehyde (756 mg, 5.0 mmol), enyne 1g
(349 mg, 1.0 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2
control (RfACTHNGUTERNNU(G 1i)=0.38, petroleum ether/ethyl acetate 3:1) indicated com-
plete consumption of the substrate. Workup according to GP and flash
column chromatography on silica (30 g, petroleum ether/ethyl acetate
5:1) yielded the product as slightly yellow oil. The compound was crystal-
lized from hot ethanol to yield (ꢀ)-6i (307 mg, 70%) as colorless rod-
shaped crystals. The relative configuration of (ꢀ)-6i was verified by X-
ray crystal structure analysis; for data, see Table 4. Rf =0.21 (petroleum
ether/ethyl acetate 3:1); m.p. 127–1288C; optical rotation: [a]2D0 =ꢀ109
(c=0.42 in MeOH, >99% ee according to HPLC); 1H NMR (300 MHz,
CDCl3, 258C): d=1.03 (dd, J=6.6, 5.4 Hz, 1H; 1-Ha), 1.24 (dd, J=6.7,
1.9 Hz, 1H; 1-Hb), 2.10 (d, J=14.1 Hz, 1H; 6-Ha), 2.78 (dd, J=5.6,
3.0 Hz, 1H; 3a-H), 3.09 (d, J=14.0 Hz, 1H; 6-Hb), 3.29, 3.87 (2s, 6H;
OCH3), 3.84 (dd, J=5.2, 1.8 Hz, 1H; 1a-H), 4.65 (d, J=2.7 Hz, 1H; 4-
H), 6.28 (d, J=5.6 Hz, 1H; 3-H), 7.17–7.28 (m, 5H; Ph), 7.30–7.36 (m,
1H; Ar), 7.55 (td, J=7.7, 1.1 Hz, 1H; Ar), 7.69 (d, J=7.8 Hz, 1H; Ar),
(5 mL) was cooled to ꢀ458C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg,
50 mmol). The mixture turned yellow and was kept at ꢀ458C for 6 h. The
cooling device was switched off, which initiated slow warming to RT.
After an overall reaction time of 16 h, TLC control (RfACTHNUTRGNE(NUG 1g)=0.62, petro-
leum ether/ethyl acetate 3:1) indicated complete consumption of the sub-
strate. Workup according to GP and flash column chromatography on
silica (30g, petroleum ether/ethyl acetate 15:1) yielded 2-oxabicyclo-
ACHTUNGTRENNUNG[3.1.0]hexane 6g (135 mg, 27%) as a slightly yellow oil. Rf =0.46 (petro-
leum ether/ethyl acetate 3:1); 1H NMR (300 MHz, CDCl3, 258C): d=
0.60 (dd, J=6.6, 5.1 Hz, 1H; 1-Ha), 0.64 (s, 3H; CH3), 0.92 (dd, J=6.6,
1.7 Hz, 1H; 1-Hb), 1.56 (d, J=13.4 Hz, 1H; 6-Ha), 1.93 (d, J=13.6 Hz,
Chem. Eur. J. 2009, 15, 10888 – 10900
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10897

G. Helmchen et al.
7.77 ppm (dd, J=8.1, 1.2 Hz, 1H; Ar); 13C NMR (75 MHz, CDCl3, 258C,
DEPT, H,C-COSY): d=19.26 (t; C-1), 34.88 (s; C-6a), 37.31 (t; C-6),
52.17, 53.20 (2 q; OCH3), 56.03 (d; C-4), 63.03 (d; C-3a), 66.55 (s; C-5),
66.76 (d; C-1a), 90.72 (d; C-3), 124.53, 127.26, 127.97, 128.10, 128.14,
128.99, 133.21 (7d; Ar), 139.17, 141.14, 147.83 (3s; Ar), 169.09,
172.25 ppm (2s; CO2CH3); IR (KBr): n˜ =704, 746, 1156, 1219, 1274, 1352,
1435, 1455, 1528, 1736, 2954, 3445 cmꢀ1; HRMS (EI): m/z: calcd for
C24H23NO7: 437.1475; found: 437.1487 [M+]; elemental analysis calcd
(%) for C24H23NO7 (459.7): C 65.90, H 5.30, N 3.20; found: C 65.73, H
5.37, N 3.18; HPLC (Daicel Chiralpak AD-H, n-hexane/isopropanol
95:5, 208C, 210 nm): tR((ꢀ)-6i)=62.4 min, tR((+)-6i)=73.9 min,
>99% ee.
526.0994; found: 526.0989 [M+H+]; elemental analysis calcd (%) for
C26H23NO7S2 (525.6): C 59.41, H 4.41, N 2.66, S 12.20; found: C 59.15, H
4.39, N 2.61, S 12.11.
(ꢂ)-(1aR,3R,3aR,8bR)-3-(2-Nitrophenyl)-1,1a,3a,4-tetrahydro-3H-cyclo-
ACHUTNGRENUpNG ropa[b]indenoACHTUTGNREN[NUGN 1,2-c]furan (6l): According to GP, a solution of enyne 1l
(142 mg, 1.0 mmol), 2-nitrobenzaldehyde (2b) (756 mg, 5 mmol), and
AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2 (5 mL) was cooled to
ꢀ458C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg, 50 mmol). After 6 h the
cooling device was switched off, which initiated slow warming to RT. GC
monitoring indicated complete conversion after an overall reaction time
of 22 h. Workup according to GP and flash column chromatography on
silica (40 g, petroleum ether/ethyl acetate 20:1) afforded 6l (79 mg, 27%)
as a yellow solid. Crystallization from diethyl ether at ꢀ58C gave color-
less polyhedral crystals, suitable for X-ray crystal structure analysis; for
data, see Table 4. Rf =0.72 (petroleum ether/ethyl acetate 3:1); m.p. 97–
988C; 1H NMR (500 MHz, CDCl3, 258C): d=1.42 (dd, J=6.9, 2.4 Hz,
1H; 1-H), 1.51 (dd, J=6.8, 5.3 Hz, 1H; 1-H), 3.03 (ddd, J=9.2, 6.7,
6.3 Hz, 1H; 3a-H), 3.36–3.47 (m, 2H; 4-H), 4.07 (dd, J=5.3, 2.4 Hz, 1H;
1a-H), 5.94 (d, J=6.1 Hz, 1H; 3-H), 6.75 (d, J=7.1 Hz, 1H; Ph), 7.14–
7.25 (m, 3H; Ph), 7.44 (dd, J=8.1, 7.3 Hz, 1H; Ar), 7.65 (dd, J=7.9,
7.3 Hz, 1H; Ar), 7.84 (d, J=7.9 Hz, 1H; Ar), 7.96 ppm (d, J=8.1 Hz,
1H; Ar); 13C NMR (125 MHz, CDCl3, 258C, DEPT, HMBC): d=22.66
(t; C-1), 37.38 (t; C-4), 42.99 (s; C-8b), 57.30 (d; C-3a), 67.34 (d; C-1a),
90.64 (d; C-3), 118.98, 124.73, 124.84, 126.86, 126.89, 128.27, 128.35,
133.47 (8d; Ph, Ar), 138.64, 142.06, 143.34, 147.76 ppm (4s; Ph, Ar); IR
(KBr): n˜ =712, 740, 753, 788, 810, 859, 948, 1007, 1090, 1103, 1125, 1301,
1318, 1350, 1439, 1461, 1484, 1524, 1579, 1609, 3852, 2934, 3023, 3046,
3067, 3438 cmꢀ1; HRMS (FAB): m/z: calcd for C18H16NO3: 294.1130;
found: 294.1134 [M+H+].
(ꢂ)-Dimethyl (1aR,3R,3aR,7aR)-3-(2-nitrophenyl)hexahydrobenzo[c]cy-
clopropa[b]furan-6,6(7H)-dicarboxylate (6j): According to GP, a solution
of enyne 1j (224 mg, 1.0 mmol), 2-nitrobenzaldehyde (756 mg, 5.0 mmol),
and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2 (5 mL) was cooled to
ꢀ458C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg, 50 mmol). After 6 h the
cooling device was switched off, which initiated slow warming to RT.
TLC monitoring indicated complete conversion after an overall reaction
time of 43 h. Workup according to GP, flash column chromatography on
silica (30 g, petroleum ether/ethyl acetate 10:1), and further purification
by HPLC on silica (columns: Latek, 5 m, 21ꢄ250 mm and Prontosil 120-
10-SI, 10 m, 20ꢄ250 mm; petroleum ether/ethyl acetate 10:1,
13 mLminꢀ1, 46 bar) afforded 6j (108 mg, 29%) as a slightly yellow solid.
Crystallization from methanol at ꢀ58C gave colorless polyhedral crystals,
suitable for X-ray crystal structure analysis; for data, see Table 4. Rf =
0.47 (petroleum ether/ethyl acetate 3:1); m.p. 93–958C; 1H NMR
(500 MHz, CDCl3, 258C): d=0.08 (dd, J=6.2, 5.9 Hz, 1H; 1-H), 0.61
(dd, J=7.0, 1.7 Hz, 1H; 1-H), 1.49–1.59 (m, 1H; 4-H), 1.76–1.83 (m, 1H;
5-H), 1.89 (dd, J=14.3, 2.2 Hz, 1H; 7-H), 1.96–1.01 (m, 1H; 3a-H), 2.16
(d, J=14.4 Hz, 1H; 7-H), 2.22–2.28 (m, 1H; 4-H), 2.41–2.46 (m, 1H; 5-
H), 3.69 (s, 3H; OCH3), 3.81 (s, 3H; OCH3), 4.06 (dd, J=5.3, 1.3 Hz,
1H; 1a-H), 5.47 (s, 1H; 3-H), 7.37 (dd, J=7.8, 7.6 Hz, 1H; Ar), 7.58 (dd,
J=7.9, 7.4 Hz, 1H; Ar), 7.81 (d, J=8.0 Hz, 1H; Ar), 7.92 ppm (d, J=
8.1 Hz, 1H; Ar); 13C NMR (125 MHz, CDCl3, 258C, DEPT, H,C-COSY):
d=15.89 (t; C-1), 25.05 (s; C-7a), 29.10 (t; C-4), 29.78 (t; C-5), 34.57 (t;
C-7), 47.39 (d; C-3a), 52.76, 52.89 (2q; OCH3), 54.67 (s; C-6), 64.99 (d;
C-1a), 83.36 (d; C-3), 125.08, 127.90, 128.48, 133.20 (4d; Ar), 141.02,
146.87 (2s; Ar), 171.28, 172.34 ppm (2s; C=O); IR (KBr): n˜ =728, 790,
826, 959, 1006, 1080, 1104, 1122, 1171, 1260, 1352, 1436, 1451, 1526, 1610,
(ꢂ)-Dimethyl
nitrophenyl)tetrahydrocyclopenta[d]
(8a): According to GP, mixture of 2-nitrobenzaldehyde (756 mg,
(2R,4S,4aS,7aR)-7a-(2-methylprop-1-en-1-yl)-2,4-bis(2-
AHCTUNGTRENNUNG
a
5.0 mmol), enyne 7a (238 mg, 1.0 mmol), and AgSbF6 (17mg, 50 mmol) in
anhydrous CH2Cl2 (5 mL) was cooled to ꢀ458C and treated with [AuCl-
AHCTUNRTGEG(NUNN PPh3)] (24.7 mg, 50 mmol). After 1 h of stirring at this temperature, TLC
control (RfACTHNUTRGNE(UNG 7a)=0.36, petroleum ether/ethyl acetate 5:1) indicated com-
plete consumption of the substrate. Workup according to GP of the reac-
tion mixture according to the general procedure and flash column chro-
matography on silica (100 g, petroleum ether/ethyl acetate 5:1) yielded
dioxane 8a (192 mg, 36%) as a colorless solid. The product was dissolved
in warm methanol/CH2Cl2 1:1 (2 mL). Evaporation of the solvent gave
colorless needles. The relative configuration of 8a was verified by X-ray
crystal structure analysis; for data, see Table 4. Rf =0.09 (petroleum
ether/ethyl acetate 5:1); m.p. 195–1978C; 1H NMR (300 MHz, CDCl3,
258C): d=1.64 (dd, J=13.6, 8.3 Hz, 1H; 5-Ha), 1.79 (d, J=0.9 Hz, 3H;
3’E-H), 1.88 (d, J=1.1 Hz, 3H; 3’Z-H), 2.46 (d, J=14.7, 1H; 7-Ha), 2.57
(ddd, J=11.1, 8.5, 2.3 Hz, 1H; 4a-H), 2.87 (dd, J=13.7, 11.4 Hz, 1H; 5-
Hb), 3.08 (d, J=14.7 Hz, 1H; 7-Hb), 3.63, 3.68 (2s, 6H; OCH3), 5.61 (s,
1H; 1’-H), 5.84 (d, J=1.9 Hz, 1H; 4-H), 6.40 (s, 1H; 2-H), 7.39–7.46 (m,
1H; Ar), 7.50 (td, J=7.8, 1.4 Hz, 1H; Ar), 7.61 (td, J=7.6, 1.2 Hz, 1H;
Ar), 7.67 (td, J=7.7, 1.2 Hz, 1H; Ar), 7.75 (dd, J=7.9, 0.9 Hz, 1H; Ar),
7.80 (dd, J=8.1, 1.3 Hz, 1H; Ar), 7.94 (dd, J=7.9, 1.1 Hz, 1H; Ar),
8.07 ppm (dd, J=8.3, 1.3 Hz, 1H; Ar); 13C NMR (75 MHz, CDCl3, 258C,
DEPT, H,C-COSY, HMBC): d=19.64 (q; C-3’Z), 27.03 (q; C-3’E), 31.36
(t; C-5), 46.82 (d; C-4a), 46.87 (t; C-7), 52.92, 53.09 (2q; OCH3), 58.00 (s;
C-6), 72.15 (d; C-4), 85.17 (s; C-7a), 92.44 (d; C-2), 121.90 (d; C-1’),
123.98, 125.13, 128.33, 128.42, 128.43, 129.63, 132.86, 134.09 (8d; Ar),
132.51, 135.80 (2s; Ar), 142.14 (s; C-2’), 146.42, 148.60 (2s; Ar), 172.28,
1631, 1734 (C=O), 2954, 3438 cmꢀ1
; HRMS (FAB): m/z: calcd for
C19H22NO7: 376.1396; found: 376.1370 [M+H+]; elemental analysis calcd
(%) for C19H21NO7 (375.4): C 60.79, H 5.64, N 3.73; found: C 60.83, H
5.73, N 3.68.
(ꢂ)-(1aR,3R,3aR,6aS)-3-(2-Nitrophenyl)-5,5-bis(phenylsulfonyl)hexahy-
dro-3H-cyclopenta[c]cyclopropa[b]furan (6k): According to GP, a solu-
tion of 2-nitrobenzaldehyde (756 mg, 5.0 mmol), enyne 1k (375 mg,
1.0 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2 (5 mL)
was cooled to ꢀ458C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg, 50 mmol).
The mixture turned orange and was kept at ꢀ458C for 6 h. The cooling
device was switched off, which initiated slow warming to RT. After an
overall reaction time of 16 h, TLC control (Rf(1k)=0.24, petroleum
ether/ethyl acetate 3:1) indicated complete consumption of the substrate.
Workup according to GP, washing with CH2Cl2 (100 mL), and flash
column chromatography on silica (15 g, petroleum ether/ethyl acetate 5:1
to 2:1) yielded 2-oxabicycloACTHNUGRTENUNG[3.1.0]hexane 6k (345 mg, 66%) as a slightly
gray solid. The melting point could not be determined because of decom-
position beginning at 2208C. Rf =0.06 (petroleum ether/ethyl acetate
3:1); 1H NMR (300 MHz, D6-DMSO, 258C): d=0.68 (dd, J=6.9, 2.0 Hz,
1H; 1-Ha), 0.77 (dd, J=6.7, 5.8 Hz, 1H; 1-Hb), 2.23 (ddd, J=8.5, 8.5,
2.4 Hz, 1H; 3a-H), 2.64 (d, J=16.4 Hz, 1H; 6-Ha), 2.75 (d, J=16.4 Hz,
1H; 6-Hb), 2.88 (d, J=8.7 Hz, 2H; 4-H), 3.64 (dd, J=5.1, 1.7 Hz, 1H; 1a-
H), 5.76 (d, J=2.1 Hz, 1H; 3-H), 7.52–8.15 ppm (m, 14H; Ar); 13C NMR
(75 MHz, D6-DMSO, 258C, DEPT, H,C-COSY): d=15.75 (t; C-1), 33.98
(t; C-6), 34.30 (s; C-6a), 38.91 (t; C-4), 53.46 (d; C-3a), 65.00 (d; C-1a),
85.06 (d; C-3), 92.72 (s; C-5), 125.24, 127.27, 128.73, 129.24, 121.00,
131.11, 134.03, 135.10, 135.14 (9d; Ar), 135.42, 136.09, 138.93, 146.04 ppm
(4s; Ar); IR (KBr): n˜ =664, 689, 727, 756, 1079, 1124, 1148, 1312, 1331,
173.07 ppm (2s; C=O); HRMS (FAB): m/z: calcd for C27H29N2O10
:
541.1822; found: 541.1827 [M+H+]; elemental analysis calcd (%) for
C27H28N2O10 (540.5): C 60.00, H 5.22, N 5.18; found: C 59.98, H 5.22, N
5.14.
(ꢂ)-Dimethyl
(2R,4S,4aS,7aR)-2,4-diphenyl-7a-[(E)-2-phenylethenyl]-
[1,3]dioxine-6,6(4H)-dicarboxylate (8b): Accord-
tetrahydrocyclopenta[d]AHCTNUGTRENNNUG
ing to GP, a solution of enyne 7b (286 mg, 1 mmol), benzaldehyde
(531 mg, 5.0 mmol), and AgSbF6 (17 mg, 50 mmol) in anhydrous CH2Cl2
(5 mL) was cooled to ꢀ408C and treated with [AuCl
ACHTUNGRTEN(NUNG PPh3)] (24.7 mg,
1447, 1522, 3432 cmꢀ1
;
HRMS (FAB): m/z: calcd for C26H24NO7S2:
50 mmol). After stirring for 5 h at this temperature, GC monitoring indi-
10898
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Chem. Eur. J. 2009, 15, 10888 – 10900

Addition of Carbonyl Compounds to 1,6-Enynes
FULL PAPER
cated complete conversion. Workup according to GP and flash column
chromatography on silica (25 g, petroleum ether/ethyl acetate 10:1) af-
forded 8b (375 mg, 75%) as a white solid. Crystallization from methanol
at 08C gave colorless polyhedral crystals, suitable for X-ray crystal struc-
ture analysis; for data, see Table 4. Rf =0.35 (petroleum ether/ethyl ace-
tate 3:1); m.p. 1188C; 1H NMR (300 MHz, CDCl3, 258C): d=1.89 (dd,
J=14.1, 8.6 Hz, 1H; CH2CH), 2.62 (d, J=14.7 Hz, 1H; CH2qCO), 2.64
(dt, J=10.6, 2.2 Hz, 1H; CH2CH), 2.87 (d, J=14.5 Hz, 1H; CH2qCO),
3.17 (dd, J=14.0, 10.8 Hz, 1H; CH2CH), 3.68 (s, 3H; OCH3), 3.69 (s,
3H; OCH3), 5.19 (d, J=2.2 Hz, 1H; CHCHO), 5.84 (s, 1H; OCHO),
6.42 (d, J=16.4 Hz, 1H; CH=CHPh), 6.84 (d, J=16.5 Hz, 1H; CH=
CHPh), 7.23–7.64 ppm (m, 15H; Ph); 13C NMR (75 MHz, CDCl3, 258C,
DEPT, H,C-COSY, HMBC): d=32.49 (t; CH2CH), 47.18 (d; CH2CH),
49.28 (t; CH2qCO), 52.92 (q; OCH3), 53.11 (q; OCH3), 57.70 (s; C-
[2] a) J. H. Teles, S. Brode, M. Chabanas, Angew. Chem. 1998, 110,
1475–1478; Angew. Chem. Int. Ed. 1998, 37, 1415–1418; b) A. S. K.
Hashmi, T. M. Frost, J. W. Bats, J. Am. Chem. Soc. 2000, 122,
11553–11554; c) M. T. Reetz, K. Sommer, Eur. J. Org. Chem. 2003,
3485–3496; d) C. Nieto-Oberhuber, M. P. MuÇoz, E. BuÇuel, C.
Nevado, D. J. Cµrdenas, A. M. Echavarren, Angew. Chem. 2004, 116,
2456–2460; Angew. Chem. Int. Ed. 2004, 43, 2402–2406; e) V.
Mamane, T. Gress, H. Krause, A. Fꢀrstner, J. Am. Chem. Soc. 2004,
126, 8654–8655; f) J. J. Kennedy-Smith, S. T. Staben, F. D. Toste, J.
Am. Chem. Soc. 2004, 126, 4526–4527; g) R. L. LaLonde, B. D.
Sherry, E. J. Kang, F. D. Toste, J. Am. Chem. Soc. 2007, 129, 2452–
2453; h) S. F. Kirsch, J. T. Binder, B. Crone, A. Duschek, T. T. Haug,
C. Liꢅbert, H. Menz, Angew. Chem. 2007, 119, 2360–2363; Angew.
Chem. Int. Ed. 2007, 46, 2310–2313.
ACHTUNGTRENNUNG(CO2Me)2), 75.15 (d; CHCHO), 85.15 (s; CH2qCO), 97.51 (d; OCHO),
[3] Reviews: a) V. Michelet, P. Y. Toullec, J.-P. GenÞt, Angew. Chem.
2008, 120, 4338–4386; Angew. Chem. Int. Ed. 2008, 47, 4268–4315;
b) C. Bruneau, Angew. Chem. 2005, 117, 2380–2386; Angew. Chem.
Int. Ed. 2005, 44, 2328–2334; c) G. C. Lloyd-Jones, Org. Biomol.
Chem. 2003, 1, 215–236; d) B. M. Trost, M. J. Krische, Synlett 1998,
1–16; e) C. Aubert, O. Buisine, M. Malacria, Chem. Rev. 2002, 102,
813–834; f) M. Mori in Handbook of Metathesis, Vol. 2 (Ed.: R. H.
Grubbs), Wiley, New York, 2004, pp. 176–204.
[4] A review: a) E. Jimꢅnez-NfflÇez, A. M. Echavarren, Chem. Rev.
2008, 108, 3326–3350.
[5] C. Nieto-Oberhuber, M. P. MuÇoz, S. López, E. Jimꢅnez-NfflÇez, C.
Nevado, E. Herrero-Gómez, M. Raducan, A. M. Echavarren, Chem.
Eur. J. 2006, 12, 1677–1693.
125.25, 126.65, 126.83, 127.39, 128.25, 128.39, 128.48, 128.61, 128.88,
129.12, 133.84 (11 d; Ph), 130.31 (d; CH=CHPh), 132.37 (d; CH=CHPh),
136.34, 138.68, 140.29 (3s; Ph), 172.04, 173.57 ppm (2s; C=O); HRMS
(FAB): m/z: calcd for C31H30O6: 498.2042; found: 498.2031 [M+]; ele-
mental analysis calcd (%) for C31H30O6 (498.6): C 74.68, H 6.07; found: C
74.26, H 5.99.
(ꢂ)-Dimethyl (2R,4S,4aS,7aR)-2,4-bis(4-methylphenyl)-7a-[(E)-2-phenyl-
ACHTUNGTRENNUNGethenyl]tetrahydrocyclopenta[d]ACHUTNGTREN[NUGN 1,3]dioxine-6,6(4H)-dicarboxylate (8c):
According to GP, a solution of enyne 7b (286 mg, 1 mmol), 4-methylben-
zaldehyde (601 mg, 5.0 mmol), and AgSbF6 (17 mg, 50 mmol) in anhy-
drous CH2Cl2 (5 mL) was cooled to ꢀ408C and treated with [AuCl-
ACHTUNGTRENNUNG(PPh3)] (24.7 mg, 50 mmol). After stirring for 2 h at this temperature, GC
monitoring indicated complete conversion. Workup according to GP and
flash column chromatography on silica (70 g, petroleum ether/ethyl ace-
tate 10:1) afforded 8c (327 mg, 62%) as a colorless oil. Rf =0.11 (petro-
leum ether/ethyl acetate 10:1); 1H NMR (300 MHz, CDCl3, 258C): d=
1.86 (dd, J=14.1, 8.7 Hz, 1H; CH2CH), 2.38 (s, 6H; PhCH3), 2.59 (d, J=
14.5 Hz, 1H; CH2qCO), 2.60 (dt, J=10.7, 2.3 Hz, 1H; CH2CH), 2.84 (d,
J=14.5 Hz, 1H; CH2qCO), 3.15 (dd, J=14.0, 10.8 Hz, 1H; CH2CH), 3.67
(s, 3H; OCH3), 3.70 (s, 3H; OCH3), 5.17 (d, J=2.2 Hz, 1H; CHCHO),
5.86 (s, 1H; OCHO), 6.34 (d, J=16.4 Hz, 1H; CH=CHPh), 6.78 (d, J=
16.4 Hz, 1H; CH=CHPh), 7.15–7.52 ppm (m, 13H; Ar, Ph); 13C NMR
(75 MHz, CDCl3, 258C, DEPT, H,C-COSY, HMBC): d=21.37 (q;
ArCH3), 21.45 (q; ArCH3), 32.50 (t; CH2CH), 47.15 (d; CH2CH), 49.33
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(t; CH2qCO), 52.93 (q; OCH3), 53.09 (q; OCH3), 57.69 (s; CACTHNUTRGNEUNG(CO2Me)2),
75.08 (d; CHCHO), 85.12 (s; CH2qCO), 97.48 (d; OCHO), 125.28,
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Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft (SFB
623), the Studienstiftung des deutschen Volkes (scholarship to M.S.), and
the Fonds der Chemischen Industrie. We thank Prof. B. F. Straub for
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Received: June 13, 2009
Published online: September 11, 2009
10900
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Chem. Eur. J. 2009, 15, 10888 – 10900