Gold- and copper-catalyzed cycloisomerizations towards the synthesis of thujopsanone-like compounds

Article abstract of DOI:10.1002/chem.201002797

In the search for a new access to thujopsanone related compounds by cycloisomerization reactions of unsaturated propargylic alcohols and acetates, we found several interesting reaction types and demonstrated the complementarity of Au, Pt, and Cu catalysts

Full text of DOI:10.1002/chem.201002797

DOI: 10.1002/chem.201002797
Gold- and Copper-Catalyzed Cycloisomerizations towards the Synthesis of
Thujopsanone-Like Compounds
Charles Fehr,*[a] Magali Vuagnoux,[a, c] Andrea Buzas,[a, b] Jeremy Arpagaus,[a] and
Horst Sommer[a]
Abstract: In the search for a new
access to thujopsanone related com-
pounds by cycloisomerization reactions
of unsaturated propargylic alcohols and
acetates, we found several interesting
reaction types and demonstrated the
complementarity of Au, Pt, and Cu cat-
alysts. Thus, 6-en-1-yn-3-ol 10a under-
went clean cyclization/ether formation
to 16, in particular using Au catalysts
(76–98%) or a newly prepared CuI-
triflimidate-catalyst (94%). The corre-
sponding acetate 11a underwent either
the cycloisomerization with concomi-
tant [1,2]-acyl shift (to 12: 78% using
AuCl3) or an unprecedented rearrange-
ment-cycloaddition leading to 20 (43%
using [(tBuXPhos)AuNTf2]), a strained
fused tricyclic ring system containing a
[2.2.0] bicyclic subunit.
Keywords: copper · cycloisomeriza-
tion · fragrances · gold · rearrange-
ment
Introduction
In 2006, we reported the
copper-catalyzed cycloisomeri-
zation of 5-en-1-yn-3-ols (cyclo-
propanation/1,2-alkyl
shift;
Scheme 1)[1] and related enynol
esters, as exemplified by the
Scheme 1. Cycloisomerization with concomitant 1,2-alkyl shift.[1]
synthesis
of
(ꢀ)-cubebol
(Scheme 2).[2] These cyclopro-
panation reactions,[3] leading se-
lectively to complex polycyclic
compounds, are generally cata-
lyzed by platinum[4] or gold.[5] It
has been demonstrated that
esters of type 3 first undergo
Scheme 2. Cycloisomerization with concomitant 1,2-pivalate shift.[2]
cyclization, then [1,2]-acyl migration, as the propargylic ste-
reogenic center controls the stereochemical outcome of the
cycloisomerization (Scheme 3; A!B!C). The alternative
reaction pathway in which the [1,2]-acyl shift precedes the
[a] Dr. C. Fehr, Dr. M. Vuagnoux, Dr. A. Buzas, J. Arpagaus,
Dr. H. Sommer
Firmenich SA
Corporate R&D Division
P. O. Box 239, CH-1211 Geneva 8 (Switzerland)
Fax : (+41)22 780 33 34
E-mail: charles.fehr@firmenich.com
cgfehr@bluewin.ch
[b] Dr. A. Buzas
Postdoctoral fellow at Firmenich SA (November 2008–October 2009)
Procter & Gamble
Route de Saint Georges 47
1213 Petit Lancy (Switzerland)
[c] Dr. M. Vuagnoux
Postdoctoral fellow at Firmenich SA (July 2007–June 2008)
Syngenta Crop Protection
Route de l’Ile au Bois
1870 Monthey (Switzerland)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002797.
Scheme 3. Cycloisomerizations of enynol esters with [1,2]-acyl shift: pos-
sible reaction pathways.
6214
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6214 – 6220

FULL PAPER
cyclization (Scheme 3; A!F!G) is only operative when
the cyclization is slow enough to allow the [1,2]-acyl shift to
occur first. This is the case in intermolecular reactions[5b,i]
and medium-sized ring closures.[5c]
We recognized that these cycloisomerization reactions
could be applied to the synthesis of sesquiterpenes such as
thujopsanone 7 or the structurally related isomer 8. Whereas
(ꢀ)-7 (used as a 1:1 mixture of diastereomers), prepared
from (ꢀ)-thujopsene ((ꢀ)-9),[6] is an appreciated fragrance
compound with woody, cedar-like, camphoraceous, ambery
odor notes, 8 of undetermined configuration had only been
prepared once in low yield and without any mention of the
odor (Scheme 4).[7]
Results and Discussion
The synthesis of the key precursors 10ab and 11ab was
straightforward (Scheme 6). Ketone 14, obtained by Claisen
rearrangement of b-cyclogeraniol 13,[8] was treated with bro-
momagnesium acetylide in the presence of CeCl3 and
Scheme 6. Synthesis of 10ab and 11ab. a) CeCl3 (1.2 equiv), LiCl
(1.2 equiv), HCCMgBr (2.4 equiv), THF, RT. b) Ac2O (2.5 equiv), NEt3
(3.0 equiv), DMAP (0.3 equiv), CH2Cl2, RT.
Scheme 4. Target compounds 7 and 8.
LiCl.[9] The two diastereomers 10a and 10b, obtained in
good yield in a 73:27 ratio, could be easily separated by
chromatography. For the determination of their configura-
tions, 10a and 10b were converted into the rigid bicyclic tet-
rahydrofurans 15a and 15b (cat. BF3·Et2O, CH2Cl2, 5 min).
The shown configurations are also consistent with the results
discussed below.
The major diastereomer 10a was treated with a variety of
Au, Pt, and Cu catalysts (Scheme 7). Unfortunately, the de-
sired 7-endo-dig cyclization that should have afforded cyclo-
propane 7 was never observed.
Retrosynthetic analysis of thujopsanone 7 leads back to
enynol 10. A formal 7-endo-dig cycloisomerization reaction
of 10 (via H/I) and subsequent [1,2]-methyl shift, would gen-
erate 7. Of course, the 6-exo-dig reaction mode (via J) was
expected to be kinetically favored, but as the cyclization
step (to H or J) can be reversible, the outcome of the reac-
tion may depend on the rate of the ensuing reactions
(Scheme 5).
On the contrary, all catalysts in-
duced the 6-exo-dig cycloiso-
AHCTUNGTRENGNmUN erization, affording exclusive-
ly the bridged ether 16
(Scheme 7). The use of the
more oxophilic AuCl3 (entry 3)
did not alter the cyclization
mode.
Taking
inspiration
from
Gagoszꢁ gold triflimidate cata-
lysts,[5n] we decided to test an
analogous Cu catalyst. Interest-
ingly, the highly electrophilic
CuI-triflimidate of tentative
structure [Cu
readily obtained from Cu2O
and NHTf2 in CH3CN
(Scheme 7, entry 6),[10] showed dramatically increased reac-
tivity as compared to [Cu(CH3CN)4]BF4 (Scheme 7, entry 5)
ACHTNUGTNERN(UGN CH3CN)4]NTf2,
Scheme 5. Projected synthetic scheme: 7-endo-dig versus 6-exo-dig cyclization mode.
On the other hand, acetate 11 is ideally suited for cyclo-
G
ACHTUNGTRENNUNG
and afforded 16 after 15 minutes at room temperature in
94% yield. In a control experiment, the replacement of [Cu-
AHCUTNTGERG(NNUN CH3CN)4]NTf2 (2 mol%) by the same amount of HNTf2
led to 15a in 98%. After completion of this study we tested
the reactivity of [(IPr)CuNTf2].[11] Using [(IPr)CuNTf2] (5
Chem. Eur. J. 2011, 17, 6214 – 6220
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6215

C. Fehr et al.
The desired cycloisomerization of 11a to 12 was readily
achieved with Au, Pt, or Cu catalysts (Scheme 9). Of all the
catalysts tested, AuCl3 proved to be the most efficient one
in terms of selectivity and yield (Scheme 9, entries 1 and 2).
[(Ph3P)AuNTf2], [(JohnPhos)AuNTf2] and [(XPhos)-
AHCTUNGTRENNUNG
uNTf2][5n] were less selective and many unidentified side
products were also formed (Scheme 9, entries 3–5). Much to
our surprise, the structurally closely related [(tBuXPhos)-
AHCTUNGRTENNNUG uNTf2] induced a completely different reaction to afford
enol acetate 20 (Scheme 9, entry 6). Although the reaction
appeared to be clean by GC (72% of 20 + 9% of 12), pure
20 was isolated in only 43% yield, owing to its limited sta-
bility. We also tested the reactivity of a N-heterocyclic car-
bene bound gold catalyst ([(IPr)AuNTf2]; Scheme 9,
entry 7), but in addition to 12, we observed the formation of
nonvolatile products. PtCl2 showed diminished reactivity.
Using 5 mol% of catalyst, heating in dichloroethane at
708C for 4 hours was necessary and afforded 12 in 43%
yield (Scheme 9, entry 8). [Cu
ACHTNUGTRNEN(UGN CH3CN)4]BF4 and [Cu-
AHCTNUGTER(GNNNU CH3CN)4]NTf2 promoted the reaction more efficiently and
gave 12 in acceptable yield (Scheme 9, entries 9 and 10). Fi-
nally, [(IPr)CuNTf2][11] led to 12 in good yield (Scheme 9,
entry 11).
Scheme 7. Cycloisomerization of 10a. Tf=triflyl.
Using AuCl3 (3 mol%) in dichloroethane at 08C for
10 minutes, the minor diastereomer 11b also gave 12, al-
though in slightly lower yield (66%).
mol%) in (CH2)2Cl2 at 238C for 15 minutes, 10a produced
16 in 35% yield.
The enol acetates 12 and 20 were readily transformed into
the parent carbonyl compounds 8 and 21, using K2CO3 in
MeOH (Scheme 9). Ketone 8 was formed as a single diaste-
reomer. Its configuration was determined by NOE experi-
ments, and the spectral data are different from those report-
ed earlier without defined configuration.[7] It possesses a
pleasant, but faint woody, cedar-like, ambery odor. Alde-
hyde 21 was initially formed as a mixture of two epimers
(58:42 after 5 min at 08C) which underwent epimerization
to afford 21 as the major isomer (91:9 after 20 min at RT).
The aldehyde 21 is of limited stability. After chromatograph-
ic purification, a new unidentified by-product was formed,
probably during concentration of the collected fractions. A
pure sample of 21, obtained after carefully repeated chro-
matography, showed an intense woody odor.
Whereas the formation of 12 can be rationalized by a
[1,2]-acyl shift-cyclopropanation (via K and L), the forma-
tion of 20 may be the result of a non-concerted [2+2]-cyclo-
addition of an allenic species Q
In sharp contrast to the CuI catalysts, in which the olefin
reacts as the nucleophile, [CuACHTUNRGTNEUNG(OTf)2] activates the C=C
bond for nucleophilic attack of the hydroxyl function to-
wards the incipient carbocation, thus leading to the bridged
ether 15a. The formation of ketone 17 in 6% yield may be
rationalized by an initial attack of the OH group onto the
acetylene, followed by pentannulation.
The minor diastereomer 10b was no better suited for cy-
clopropanation to give 7. In the presence of AuCl3, smooth
formation of hydrocarbons 18 and 19 was exclusively ob-
served (Scheme 8). Here, the intramolecular capture of the
carbocationic species N by the OH group seems to be im-
peded for reasons of strain and the metathesis pathway (via
N, O and P) is preferred.
We next focused on the synthesis of “regioiso-thujopsa-
none” 8 by cycloisomerization of propargylic acetate 11a
(Scheme 5 and Scheme 9).
(Scheme 10).[12] Alternatively, a
6-exo-dig cyclization-[1,3]-acyl
shift, (via R,S,(U) or via R,T,U)
is also plausible.
To support the hypothetic in-
termediacy of an allene of type
Q during formation of 20, we
tried to prepare allene 22 from
acetate 11a. However, AgBF4
(1
mol%)
in
1,2-di-
AHCTUNGERTGmNNUN ethoxyethane at RT gave no
Scheme 8. Metathesis of 10b.
reaction, and upon heating at
6216
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6214 – 6220

Gold- and Copper-Catalyzed Cycloisomerization reactions
FULL PAPER
yield together with 21 was iden-
tified as 25 of unknown config-
uration. Its formation may be
explained by rearrangement of
intermediate U (to give 24) fol-
lowed by hydrolysis. Therefore,
the formation of both 20 and
presumed enol acetate 24
would follow a common mecha-
nism via U.[15]
In conclusion, we have found
a
direct access to tricyclic
ketone 8 possessing the basic
skeleton of thujopsanone by
gold-, copper-, or platinum-cat-
alyzed cycloisomerization of
11a. In addition, we have dis-
covered new reaction types and
demonstrated that a variety of
complex, highly functionalized
compounds can be accessed se-
lectively by the proper choice
of catalyst (Scheme 12).
Scheme 9. Cycloisomerization of 11a. a) K2CO3 (1.5 equiv), MeOH, RT, 20 min. [A] Yield of 8 from 11a.
Scheme 11. Formation of 23 during attempted synthesis of allene 22.
Experimental Section
Scheme 10. Mechanistic proposals for the formation of 12 and 20.
608C nonvolatile products formed.[5e] Heating 11a in AcOH
in the presence of catalytic amounts of Ag2CO3 furnished
General comments: Bulb-to-bulb distillation: Bꢂchi GKR-51 glass-oven,
b.p. correspond to the oven temp. TLC: silica gel F-254 plates (Merck);
detection with EtOH/anisaldehyde/H2SO4 18:1:1. Column chromatogra-
phy: silica gel 60 (Merck; 0.063–0.2 mm, 70–230 mesh, ASTM). GC:
[13]
exclusively the dienol acetate 23, which formally is the
Cope-rearrangement product of the expected allene 22[14]
(Scheme 11). 23 may also arise from 20 by retro-[2+2]-cyclo-
addition. Incidentally, 20 and 23 possess the same enol ace-
tate configuration, and heating 20 in (CH2)2Cl2 at 708C for
1 hour gave cleanly 23, as shown by NMR analysis.
Varian instrument, model 3500; cap. columns: DB1 30 W (15 m
ꢃ
0.319 mm), DB-WAX 15W (15 m ꢃ 0.32 mm); carrier gas He at 0.63 bar.
1H- and 13C NMR: Bruker AVANCE III 400 (400 MHz) and AVANCE I
500 (500 MHz). MS: Agilent MSD 5973N, electron energy 70 eV.
Preparation of the catalysts:
Finally,
a pathway via U for the formation of 20
A
bis(trifluoromethanesulfonyl)imidate
(Scheme 10) is favored for the following reasons. First, it
would account for the (Z)-configuration of enol acetate 20.
Moreover, a side product obtained in approximately 10%
AHCTUNGTRENNUNG
dropwise (not exothermic) to a mixture of copper(I) oxide (150 mg,
1 mmol) in acetonitrile (5 mL) (not completely soluble; fuchsia colored
Chem. Eur. J. 2011, 17, 6214 – 6220
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6217

C. Fehr et al.
the pale solution was evaporated and the white complex dried under
vacuum (131 mg; 87%).
AHCTUNGTERG(NNUN S,R)-2-Methyl-1-[(R,S)-1,3,3-trimethyl-2-methylenecyclohexyl]but-3-yn-
2-ol (10a) and (S,R)-2-methyl-1-[(S,R)-1,3,3-trimethyl-2-methylenecyclo-
hexyl]but-3-yn-2-ol (10b): LiCl (2.64 g, 62.3 mmol) was added at RT to a
solution of CeCl3 (15.35 g, 62.3 mmol; dried under reduced pressure at
1608C in a bulb to bulb distillation apparatus for 2 h) in THF (54 mL)
under nitrogen. The suspension was stirred for 50 min at RT (pale yellow
color). Ethynylmagnesium bromide (125 mL; 0.5m in THF) was then
added in one portion (exothermic) and the resulting mixture was stirred
1 h at RT (solution became brown). 1-(1,3,3-Trimethyl-2-methylenecyclo-
hexyl)propan-2-one (10.09 g, 51.9 mmol) in THF (80 mL) was then added
dropwise. After stirring for 1 h, more ethynylmagnesium bromide
(125 mL; 0.5m in THF) was added and stirring continued for 90 min. The
mixture was poured into 5% aqueous HCl/ice and extracted with Et2O
(3ꢃ150 mL). The combined organic layers were washed with water, satu-
rated aqueous NaHCO3 solution, and a saturated aqueous solution of
NaCl, dried over Na2SO4, filtered and concentrated to afford 10.46 g of a
yellow oil. Bulb to bulb distillation at 1308C and 3 mbar, followed by
flash chromatography on SiO2 (pentane/Et2O=95:5) gave successively
10a (6.12 g, 54%) and 10b (2.5 g, 22%). 10a: 1H NMR (400 MHz,
CDCl3): d=1.15 (s, 3H), 1.21 (s, 3H), 1.27–1.40 (m, 2H), 1.48 (s, 3H),
Scheme 12. Summary of cycloisomerization reactions of 10a and 11a.
1.50 (s, 3H), 1.49–1.60 (m, 2H), 1.63–1.82 (m, 2H), 1.71 (d(AB), JAB
=
14.8 Hz, 1H), 2.34 (d(AB), JAB =14.8 Hz, 1H), 2.50 (s, 1H), 5.22 (s, 1H),
5.34 ppm (s, 1H); 13C NMR (100 MHz, CDCl3): d=18.0 (t), 30.5 (q), 31.2
(q), 32.9 (q), 33.9 (q), 36.8 (s), 40.0 (s), 40.6 (t), 42.2 (t), 51.0 (t), 66.9 (s),
72.1 (d), 89.7 (s), 110.9 (t), 164.2 ppm (s); MS (EI): m/z (%): 220 (4)
[M]+, 205 (11), 202 (9), 187 (50), 159 (51), 133 (53), 121 (51), 105 (51), 95
solution with a few crystals of Cu2O). The resulting mixture, which
turned from fuchsia to pale pink (containing trace amounts of solid
Cu2O) was stirred at RT for 15 min. The mixture was then stored in a
closed vessel in the refrigerator for 5 days (no crystals observed). The
mixture was filtered over Celite (to remove the remaining solid Cu2O),
and the resulting pale solution was evaporated under reduced pressure to
give a pale pink–brown solid which was dried at reduced pressure and
kept under nitrogen. The complex became oily after 30 min under N2.
Yield: 477 mg (94%). It was used as such, and its structure is not estab-
lished.
1
(100), 91 (57), 81 (65), 69 (76), 55 (42), 43 (65). 10b: H NMR (400 MHz,
CDCl3): d=1.15 (s, 3H), 1.19 (s. 3H), 1.29 (s, 3H), 1.35–1.44 (m, 2H),
1.47–1.76 (m, 3H), 1.55 (s, 3H), 1.94 (d(AB), JAB =15.0 Hz, 1H), 2.24
(d(AB), JAB =15.0 Hz, 1H), 2.19–2.28 (m, 1H), 2.48 (s, 1H), 5.07 (s, 1H),
5.12 ppm (s, 1H); 13C NMR (100 MHz, CDCl3): d=18.2 (t), 31.9 (q), 32.0
(q), 33.1 (q), 34.3 (q), 36.4 (s), 37.8 (t), 39.7 (s), 40.0 (t), 52.1 (t), 67.4 (s),
72.2 (d), 89.3 (s), 109.1 (t), 164.0 ppm (s); MS (EI): m/z (%): 220 (2)
[M]+, 205 (9), 202 (12), 187 (51), 95 (100), 91 (54), 81 (61), 69 (73), 43
(63).
ACHTUNGTRENNUNG[1,3-Bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazol-2-yl][1,1,1-tri-
fluoro-N-(trifluoromethylsulfonyl)methylsulfonamido]gold
NTf2]): AgNTf2 (62 mg, 0.16 mmol) was added to
([(IPr)Au-
solution of
G
a
[(IPr)AuCl] (100 mg, 0.16 mmol) in dry CH2Cl2 (3.2 mL). The resulting
solution was stirred for 5 min and filtered over Celite. The pad of Celite
was further washed twice with 3.2 mL of CH2Cl2 and the resulting solu-
tion was concentrated under vacuum to ca. 1.6 mL. Pentane (6.4 mL) was
then added, which resulted in the immediate precipitation of a white
solid. This solid was filtered and further washed with pentane (3ꢃ
3.2 mL), concentrated, and dried under high vacuum for 30 min. Yield:
111 mg (80%).
AHCTUNGTERG(NNUN S,R)-2-Methyl-1-[(R,S)-1,3,3-trimethyl-2-methylenecyclohexyl]but-3-yn-
2-yl acetate (11a): Basic conditions: Et3N (7.6 mL, 54.5 mmol), Ac2O
(4.3 mL, 45.4 mmol), and a catalytic amount of 4-dimethylaminopyridine
(DMAP; 665 mg, 5.45 mmol) were added to a solution of 10a (4.00 g,
18.15 mmol) in CH2Cl2 (20 mL), and the resulting mixture was stirred at
RT over night. The mixture was poured into 5% HCl solution and ex-
tracted with Et2O (2ꢃ30 mL). The combined organic layers were washed
with water, a saturated aqueous NaHCO3 solution, a saturated aqueous
solution of NaCl, dried (Na2SO4), filtered, and concentrated to furnish a
pale yellow oil (5.07 g). Flash chromatography on SiO2 (pentane/Et2O=
95:5) afforded 11a as a pale yellow oil (4.38 g, 89%). Acidic conditions:
A catalytic amount of p-TsOH (30 mg, 0.153 mmol) was added to a solu-
tion of 10a (845 mg, 3.84 mmol) in Ac2O (9 mL, 101.4 mmol), and the re-
sulting mixture was stirred at RT overnight. The mixture was washed
with water, a saturated aqueous NaHCO3 solution, water, and a saturated
aqueous solution of NaCl, dried (Na2SO4), filtered, and concentrated to
afford 11a as a yellow oil (10.06 g). Yield after chromatography: (9.22 g;
92%). 11a: 1H NMR (400 MHz, CDCl3): d=1.13 (s, 3H), 1.17 (s, 3H),
1.26–1.40 (m, 2H), 1.32 (s, 3H), 1.45–1.57 (m, 2H), 1.68–1.81 (m, 1H),
1.74 (s, 3H), 2.01 (s, 3H), 2.10 (mc, 1H), 2.19 (d(AB), JAB =15.2 Hz,
[P
N
ACHTUNGTRENNUNG[bis(trifluoromethanesulfonyl)imidate]gold(I)
([(John
ACHTUNGTRENNUNG
tion of [(JohnPhos)AuCl] (85 mg, 0.16 mmol) in dry CH2Cl2 (4 mL), and
the resulting solution was stirred for 15 min. The instantaneously formed
AgCl precipitate was removed by filtration over Celite. The pad of Celite
was further washed twice with 4 mL of CH2Cl2 and the resulting pale so-
lution was evaporated under reduced pressure and dried under high
vacuum to afford the title compound as a white solid. Yield: 101 mg
(81%).
ACHTUNGTRENNUNG[(tBuXPhos)AuCl]: [AuClACHTUGNTREN(NUGN SMe2)] (128 mg, 0.375 mmol) and the phos-
phine tBu-XPhos (163 mg, 0.375 mmol) were weighed (in air) and placed
under N2. CH2Cl2 (10 mL) was added, which resulted in the dissolution
of the starting material and the formation of a pale yellow solution.
After stirring at RT for 45 min the solution was concentrated to 2 mL
and hexane was added (10 mL). The complex was precipitated and fil-
tered, washed with hexane, and dried under vacuum. Yield: 151 mg of a
white solid (151 mg; 61%).
1H), 2.26 (d(AB),
JAB =15.2 Hz, 1H), 2.61 (s, 1H), 4.97 (s, 1H),
5.03 ppm (s, 1H); 13C NMR (100 MHz, CDCl3): d=18.5 (t), 22.2 (q), 29.3
(q), 30.3 (q), 31.3 (q), 33.2 (q), 36.4 (s), 38.8 (t), 40.0 (s), 40.7 (t), 50.2 (t),
74.5 (s), 74.6 (d), 84.8 (s), 108.8 (t), 162.9 (s), 169.2 ppm (s); MS (EI): m/
z (%): 262 (2) [M]+, 220 (34), 187 (75), 137 (64), 123 (75), 95 (100), 81
(62), 43 (86).
A
ACHTUNGTRNE(NUNG tBuXphos)gold(I) ([(tBuXPhos)-
Compounds 15a and 17: [CuACHTNUGTRNEUNG(OTf)2] (18.5 mg; 0.05 mmol) was added to
ACHTUNGTRENNUNG
10a in toluene (5 mL). The mixture was heated to 708C for 90 min and
cooled to RT. The dark grey mixture was filtered through a short pad of
SiO2 (4 g) using CH2Cl2. The solvents were removed under vacuum to
give an orange colored oil (265 mg). Flash chromatography on SiO2 (cy-
was dissolved in CH2Cl2 (6 mL), and AgNTf2 (90 mg, 0.23 mmol) was
added, thus resulting in the instantaneous precipitation of AgCl. The
mixture was stirred for an additional 15 min. After filtration over Celite
6218
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6214 – 6220

Gold- and Copper-Catalyzed Cycloisomerization reactions
FULL PAPER
clohexane/AcOEt=98:2) afforded successively 15a (130 mg, 59%) and
0.06 mbar afforded 12 (83 mg; 93% pure; 78%). Likewise, a solution of
11a (655 mg, 2.49 mmol) in CH2Cl2 (3 mL), was cooled at 08C and treat-
ed with AuCl3 (7.57 mg, 0.025 mmol; weighted in the glove box). The
color turned immediately to purple. After 9 h, the mixture was filtered
through a cartridge of SiO2 (4 g) and concentrated (640 mg). 1H NMR
(400 MHz, CDCl3): d=0.58 (s, 3H), 0.74 (dd, J=8.8/5.0 Hz, 1H), 0.83 (t,
J=5.0 Hz, 1H), 1.09 (s, 3H), 1.14 (s, 3H), 1.14–1.19 (m, 1H), 1.28–1.59
(m, 6H), 1.46 (d, J=1.3 Hz, 3H), 1.78 (mc, 1H), 1.97 (mc, 1H), 2.18 ppm
(s, 3H); 13C NMR (100 MHz, CDCl3): d=10.6 (t), 16.0 (q), 19.4 (t), 20.4
(d), 20.8 (q), 26.4 (q), 27.8 (q), 29.0 (q), 32.6 (s), 33.6 (s), 35.0 (s), 36.4
(t), 40.0 (t), 45.8 (t), 112.2 (s), 141.7 (s), 169.2 ppm (s); MS: m/z (%): 262
(9) [M]+, 220 (100), 205 (17), 149 (19), 135 (60), 123 (57), 121 (34), 109
(30), 69 (20), 43 (25).
17 (14 mg, 6%). Likewise, BF3ACTHNUTRGNEUNG
(OEt)2 also afforded 15a. 15a: 1H NMR
(400 MHz, CDCl3): d=0.94 (s, 3H), 1.01 (s, 3H), 1.09 (s. 3H), 1.10–1.14
(m, 1H), 1.28–1.38 (m, 2H), 1.31 (s, 3H), 1.40–1.57 (m, 1H), 1.61 (s, 3H),
1.58–1.73 (m, 2H), 1.81 (d(AB),
JAB =12.9 Hz, 1H), 2.36 (s, 1H),
2.42 ppm (d(AB), JAB =12.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
17.5 (q), 18.9 (t), 22.9 (q), 25.0 (q), 27.4 (q), 31.1 (q), 36.5 (s), 37.5 (t),
38.0 (t), 44.5 (s), 56.0 (t), 68.9 (d), 70.4 (s), 89.1 (s), 92.2 ppm (s); MS
(EI): m/z (%): 220 (0.2) [M]+, 205 (19), 136 (100), 96 (14), 85 (38), 69
(16), 55 (16), 43 (28).
Compound 15b: BF3ACHTUNGTRENNUNG(OEt)2 (29 mg; 0.20 mmol) was added to a stirred
solution of 10b (100 mg; 0.45 mmol) in toluene (3 mL). After 2 min the
red solution was quenched with ice and a solution of saturated aqueous
NaHCO3. Extraction (Et2O) in the usual manner, concentration, and
bulb-to-bulb distillation at 1008C and 0.1 mbar afforded 15b (86 mg;
86%). 15b: 1H NMR (400 MHz, CDCl3): d=0.94 (s, 3H), 0.99 (s, 3H),
1.07 (s, 3H), 1.09 (s, 3H), 1.11 (mc, 1H), 1.30 (mc, 1H), 1.35–1.44 (m,
1H), 1.51 (mc, 1H), 1.56 (s, 3H), 1.74 (ddd, J=13.1/13.1/3.1 Hz, 1H),
2.04 (d(AB), JAB =12.7 Hz, 1H), 2.09 (d(AB), JAB =12.7 Hz, 1H), 2.39
(ddd, J=13.6/13.6/4.06 Hz, 1H), 2.45 ppm (s, 1H); 13C NMR (100 MHz,
CDCl3): d=18.6 (t), 19.5 (q), 22.8 (q), 24.9 (q), 27.3 (q), 32.5 (q), 36.2 (t),
36.6 (s), 37.5 (t), 45.1 (s), 55.8 (t), 70.4 (d), 71.3 (s), 88.5 (s), 90.2 ppm (s);
MS (EI): m/z (%): 205 (17), 136 (100), 121 (16), 91 (18), 85 (40), 55 (16),
Compound 8: The above crude product 12 (640 mg, max.2.44 mmol) was
dissolved in methanol (7 mL), treated with K2CO3 (506 mg, 3.66 mmol)
at RT, and stirred for 20 min. The mixture was poured into water and ex-
tracted with Et2O (3ꢃ20 mL). The combined organic phases were
washed with a solution of saturated aqueous NaCl, dried over Na2SO4,
filtered, and concentrated to afford 8 (447 mg ; 87% pure; 71% from
11a). Pure 8 (>97%) was obtained by flash chromatography on SiO2 (cy-
clohexane/AcOEt=95:5). M.p. 64–668C. 1H NMR (400 MHz, CDCl3):
d=0.60 (s, 3H), 0.95 (ddd, J=10.8/5.1/0.9 Hz, 1H), 1.04 (d, J=6.9 Hz,
3H), 1.11 (s, 3H), 1.14 (ddd, J=5.1/5.1/0.5 Hz, 1H), 1.20 (d, J=0.6 Hz,
3H), 1.26 (dd, J=14.7/6.3 Hz, 1H), 1.27–1.31 (m, 1H), 1.31–1.37 (m,
1H), 1.40 (dd, J=14.7/13.1 Hz, 1H), 1.50 (mc, 1H), 1.56 (mc, 1H), 1.67
(td, J=13.1/3.9 Hz, 1H), 1.85 (mc, 1H), 1.95 (dd, J=10.8/5.1 Hz, 1H),
2.25 ppm (ddq, J=13.1/6.9/6.3 Hz, 1H); 13C NMR (125 MHz, CDCl3):
d=13.0 (t), 15.8 (q), 18.8 (t), 27.2 (q), 28.4 (q), 28.6 (q), 32.0 (d), 33.3 (s),
33.6 (s), 36.0 (t), 37.1 (d), 38.5 (s), 40.2 (t), 44.0 (t), 212.2 ppm (s); MS
(EI): m/z (%): 220 (15) [M]+, 205 (9), 178 (14), 137 (100), 123 (17), 107
(17), 93 (18), 79 (13), 55 (12).
1
43 (32), 41 (24). 17: H NMR (500 MHz, CDCl3): d=1.11 (s, 3H), 1.12 (s,
3H), 1.15–1.23 (m, 2H), 1.25 (s, 3H), 1.29 (s, 3H), 1.44–1.53 (m, 2H),
1.61 (d(AB), JAB =13.3 Hz, 1H), 1.68–1.82 (m, 2H), 2.12 (s, 3H), 2.13
(d(AB),
J
AB =13.3 Hz, 1H), 5.26 ppm (s, 1H); 13C NMR (125 MHz,
CDCl3): d=19.5 (t), 24.5 (q), 25.6 (q), 27.2 (q), 28.7 (q), 31.4 (q), 34.3 (s),
41.5 (t), 42.8 (t), 46.8 (s), 52.8 (t), 58.9 (s), 124.3 (d), 158.6 (s), 212.9 ppm
(s); MS (EI): m/z (%): 177 (100), 121 (30), 107 (23), 105 (10), 95 (16), 91
(15), 69 (17), 43 (13).
Compound 16 by Cu-catalysis: [CuACTHNUTRGNE(UNG CH3CN)4]NTf2 (2 mol%, 5.1 mg,
Compound 20: [(tBuXPhos)AuNTf2] (25 mg, 0.0285 mmol) was added to
a solution of 11a (1.50 g, 5.72 mmol) in CH2Cl2 (5.7 mL) under nitrogen
at 08C, and the resulting mixture was stirred at 08C for 45 min. As GC
showed incomplete conversion, more [(tBuXPhos)AuNTf2] (13 mg,
0.014 mmol) was added and the mixture (which turned from yellow to
dark orange) was stirred for 2 h at 08C. Filtration over a SiO2 pad im-
pregnated with CH2Cl2 and concentration afforded a pale yellow oil.
Flash chromatography on SiO2 (cyclohexane/Et2O=95:5) gave 20
(660 mg, 43%) of limited stability. In another experiment, the reaction of
11a (200 mg) went to completion with only 0.5 mol% of [(tBuXPho-
s)AuNTf2] (1 h; 08C). Yield of 20 after filtration (SiO2/CH2Cl2): 168 mg
(67% by GC). 1H NMR (400 MHz, CDCl3): d=0.70 (s, 3H), 0.93 (s,
3H), 1.02 (s, 3H), 1.33–1.49 (m, 4H), 1.53 (s, 3H), 1.54–1.65 (m, 1H),
0.01 mmol) was added to a solution of 10a (110 mg, 1.00 mmol) in
CH2Cl2 (1 mL), and the resulting mixture was stirred at RT for 15 min,
filtered on a pad of SiO2 using CH2Cl2 and concentrated to afford 16
(103 mg; 94%) as a pale yellow oil.
Compound 16 by Au-catalysis: [(XPhos)AuNTf2] (1 mol%, 9.5 mg,
0.01 mmol) was added to a solution of 10a (220 mg, 1.00 mmol) in
CH2Cl2 (1 mL), and the resulting mixture was stirred at RT for 5 min, fil-
tered on a pad of SiO2 using CH2Cl2, and concentrated to afford 16
1
(216 mg; 98%) as a pale yellow oil. 16: H NMR (400 MHz, CDCl3): d=
0.97 (s, 3H), 1.01 (s, 3H), 1.17 (s, J=0.5 Hz, 3H), 1.23–1.31 (m, 1H),
1.34–1.45 (m, 3H), 1.43 (s, 3H), 1.49–1.72 (m, 4H), 2.41–2.58 (m, 2H),
4.62 (t, J=2.0 Hz, 1H), 4.69 ppm (t, J=2.5 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=18.5 (q), 19.2 (t), 23.9 (q), 24.8 (q), 27.0 (q), 34.2
(s), 35.2 (t), 38.3 (t), 40.9 (t), 43.7 (s), 56.4 (t), 84.5 (s), 90.2 (s), 98.4 (t),
155.9 ppm (s); MS (EI): m/z (%):220 (81) [M]+, 205 (54), 177 (47), 147
(83), 137 (100), 123 (61), 107 (50), 95 (47), 69 (37), 43 (70).
1.66 (d(AB), JAB =11.6 Hz, 1H), 1.77–1.84 (m, 1H), 2.04 (d(AB), JAB
=
11.6 Hz, 1H), 2.08 (s, 3H), 2.54 (dd, J=16.2/2.0 Hz, 1H), 2.78 (dd, J=
16.2/2.0 Hz, 1H), 6.66 ppm (t, J=2.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=18.3 (t), 20.8 (q), 21.0 (q), 22.1 (q), 24.1 (q), 25.7 (q), 27.6 (t),
33.7 (s), 37.5 (s), 39.9 (t), 41.1 (t), 47.7 (t), 48.5 (s), 55.0 (s), 123.9 (d),
132.7 (s), 168.3 ppm(s); MS (EI): m/z (%): 262 (6) [M]+, 220 (100), 205
(22), 149 (36), 135 (48), 123 (65), 109 (86), 91 (28), 43 (62).
Compounds 18/19: A solution of 10b (440 mg, 2.00 mmol) in (CH2)2Cl2
(20 mL) was treated with AuCl3 (35.0 mg, 0.115 mmol). After 20 min, the
mixture was quenched with a solution of saturated aqueous NaHCO3.
Extraction (Et2O) in the usual manner, concentration (413 mg), and
bulb-to-bulb distillation at 1008C and 0.1 mbar afforded a mixture of 18
and 19 (290 mg; 63+18% by GC; 58%). 18/19 of higher purity (70+
18%) was obtained by flash chromatography on SiO2 (cyclohexane/
AcOEt=95:5). 18: (characteristic signals): 1H NMR (400 MHz, CDCl3):
d of Me-signals: d=1.13 (s), 1.19 (s), 1.28 (s), 1.86 ppm (s), olefinic CH:
5.11 (d,d, J=18.0/2.1 Hz, 1H), 5.21 (d,d, J=11.0/2.1 Hz, 1H), 5.79 (brs,
1H), 6.67 ppm (d,d, J=18.0/11.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d=15.4 (q), 19.3 (t), 22.3 (q), 26.4 (q), 33.8 (q), 35.5 (t), 36.7 (s), 43.8 (t),
52.2 (s), 117.0 (t), 134.2 (d), 134.4 (s), 137.5 (s), 141.0 (d), 155.8 ppm (s);
MS (EI): m/z (%): 202 (29) [M]+, 187 (100), 159 (14), 145 (19), 133 (28),
115 (13), 105 (16), 91 (13), 77 (7).
Compound 21: Repetition of the above conditions starting from 11a
(262 mg; 1.00 mmol) afforded crude 20 (210 mg), which was dissolved in
methanol (2 mL), treated with K2CO3 (166 mg, 1.20 mmol) at RT, and
stirred for 20 min. The mixture was poured into aqueous 5% HCl and ex-
tracted with Et2O (3ꢃ10 mL). The combined organic phases were
washed with a solution of saturated aqueous NaCl, dried over Na2SO4,
filtered, and concentrated to afford the title compound as a pale yellow
oil. Flash chromatography on SiO2 (cyclohexane/Et2O=90:10) furnished
21 (85 mg; 3 isomers (by MS)): 4%; 59%; 9% by increasing retention
times on a DB-1 column; 28% from 11a). 1H NMR (400 MHz, CDCl3):
d=0.68 (s, 3H), 0.98 (d, J=0.8 Hz, 3H), 1.01 (s, 3H), 1.34 (dd, J=12.0/
1.0 Hz, 1H), 1.36–1.46 (m, 4H), 1.54 (s, 3H), 1.56–1.65 (m, 1H), 1.70–
1.82 (m, 1H), 1.92 (dd, J=13.0/9.9 Hz, 1H), 1.99 (d, 12 Hz, 1H), 2.56
(dd, J=13.0/9.0 Hz, 1H), 2.86 (ddt, J=9.9/9.0/1.0 Hz, 1H), 9.74 ppm (d,
J=1.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): d=18.2 (t), 21.2 (q), 22.2
(t), 23.4 (q), 24.7 (q), 26.1 (q), 33.5 (s), 39.2 (s), 39.6 (t), 40.4 (t), 42.3 (t),
45.8 (s), 53.8 (d), 54.5 (s), 204.0 ppm (d) ; MS (EI): m/z (%): 220 (2)
Compound 12:
A solution of 11a (100 mg, 0.377 mmol) in CH2Cl2
(2 mL), was cooled at 08C and treated with AuCl3 (3.43 mg, 0.011 mmol;
weighted in the glove box). The color turned immediately to purple.
After 10 min, the mixture was filtered through a cartridge of SiO2 (4 g)
and concentrated (90 mg). Bulb-to-bulb distillation at 1308C and
Chem. Eur. J. 2011, 17, 6214 – 6220
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6219

C. Fehr et al.
[M]+, 163 (13), 137 (100), 121 (27), 109 (30), 95 (83), 91 (29), 81 (55), 69
(27), 41 (29).
no, J. Marco-Contelles, J. Org. Chem. 2007, 72, 2651; J. Barluenga,
L. Riesgo, R. Vicente, L. A. Lopez, M. Tomas, J. Am. Chem. Soc.
2007, 129, 7772 (Pt and Cu); S. Anjum, J. Marco-Contelles, Tetrahe-
dron 2005, 61, 4793; E. Soriano, P. Ballesteros, J. Marco-Contelles,
Organometallics 2005, 24, 3182; E. Soriano, J. Marco-Contelles, J.
Org. Chem. 2005, 70, 9345; C. Blaszykowski, Y. Harrak, M.-H. Gon-
Åalves, J.- M. Cloarec, A.- L. Dhimane, L. Fensterbank, M. Malacria,
Org. Lett. 2004, 6, 3771; Y. Harrak, C. Blaszykowski, M. Bernard, K.
Cariou, E. Mainetti, V. Mouriꢅs, A.- L. Dhimane, L. Fensterbank,
M. Malacria, J. Am. Chem. Soc. 2004, 126, 8656; V. Mamane, T.
Gress, H. Krause, A. Fꢂrstner, J. Am. Chem. Soc. 2004, 126, 8654.
[5] a) N. Marion, G. Lemiꢅre, A. Correa, C. Costabile, R. S. Ramon, X.
Moreau, P. de Frꢄmont, R. Dahmane, A. Hours, D. Lesage, J.-C.
Tabet, J.-P. Goddard, V. Gandon, L. Cavallo, L. Fensterbank, M.
Malacria, S. P. Nolan, Chem. Eur. J. 2009, 15, 3243; b) I. D. G.
Watson, S. Ritter, F. D. Toste, J. Am. Chem. Soc. 2009, 131, 2056;
c) X. Moreau, J.-P. Goddard, M. Bernard, G. Lemiꢅre, J. M. Lꢆpez-
Romero, E. Mainetti, N. Marion, V. Mouriꢅs, S. Thorimbert, L. Fen-
sterbank, M. Malacria, Adv. Synth. Catal. 2008, 350, 43 (Au and Pt);
d) A. Fꢂrstner, A. Schlecker, Chem. Eur. J. 2008, 14, 9181; e) A.
Fꢂrstner, P. Hannen, Chem. Eur. J. 2006, 12, 3006; f) G. Lemiꢅre, V.
Gandon, K. Cariou, T. Fukuyama, A.- L. Dhimane, L. Fensterbank,
M. Malacria, Org. Lett. 2007, 9, 2207; g) A. Buzas, F. Gagosz, J. Am.
Chem. Soc. 2006, 128, 12614; h) E. J. Cho, M. Kim, D. Lee, Org.
Lett. 2006, 8, 5413; i) M. J. Johansson, D. J. Gorin, S. T. Staben, F. D.
Toste, J. Am. Chem. Soc. 2005, 127, 18002; j) M. R. Luzung, J. P.
Markham, F. D. Toste, J. Am. Chem. Soc. 2004, 126, 10858; k) F.
Gagosz, Org. Lett. 2005, 7, 4129; l) A. Correa, N. Marion, L. Fen-
sterbank, M. Malacria, S. P. Nolan, L. Cavallo, Angew. Chem. 2008,
120, 730; Angew. Chem. Int. Ed. 2008, 47, 718; see also: m) C. M.
Grisꢄ, E. M. Rodrigue, L. Barriault, Tetrahedron 2008, 64, 797;
n) For the seminal work on the development of [(PR3)AuNTf2] cata-
lysts, see: N. Mꢄzailles, L. Richard, F. Gagosz, Org. Lett. 2005, 7,
4133; o) D. Garayalde, K. Krꢂger, C. Nevado, Angew. Chem. 2011,
123, 941; Angew. Chem. Int. Ed. 2011, 50, 911; p) Y. Harrak, M.
Makhlouf, S. Azzaro, E. Mainetti, J. M. L. Romero; K. Cariou, V.
Gandon, J.-P. Goddard, M. Malacria, L. Fensterbank, J. Organomet.
Chem. 2011, 696, 388; K. Cariou, V. Gandon, J.-P. Goddard, M. Mal-
acria, L. Fensterbank, J. Organomet. Chem. 2011, 696, 388.
Compound 23:
A mixture of Ag2CO3 (14 mg; 0.05 mmol), AcOH
(0.58 mL; 0.59 g; 9.90 mmol), and 11a (500 mg; 1.87 mmol) was heated at
908C for 8 h. The cooled mixture was quenched with ice and a solution
of saturated aqueous NaHCO3. Extraction (Et2O) in the usual manner,
concentration (430 mg), and flash chromatography on SiO2 (cyclohexane/
AcOEt=98:2) gave 23 (149 mg, 30%). 1H NMR (400 MHz, CDCl3): d=
0.98 (s, 6H), 1.45–1.51 (m, 2H), 1.55 (s, 3H), 1.57–1.66 (m, 2H), 1.97 (dd,
J=1.6/0.8 Hz, 3H), 1.99 (brt, J=6.6 Hz, 2H), 2.10 (s, 3H), 2.81 (brs,
2H), 4.92 (mc, 1H), 5.00 (mc, 1H), 6.70 ppm (t, J=2.0 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=19.4 (t), 20.3 (q), 20.9 (q), 22.7 (q), 28.4
(q), 31.4 (t), 32.4 (t), 34.9 (s), 39.6 (t), 113.7 (t), 124.3 (s), 130.7 (s), 132.3
(d), 132.6 (s), 142.6 (s), 168.0 ppm (s); MS (EI): m/z (%): 262 (5) [M]+,
220 (86), 205 (19), 149 (37), 135 (50), 123 (71), 109 (95), 91 (34), 81 (29),
69 (29), 55 (27), 43 (100).
Compound 25: 1H NMR (400 MHz, CDCl3): d=0.91 (s, 3H), 1.05 (s,
3H), 1.10–1.18 (m, 2H), 1.18 (s, 3H), 1.21 (s, 3H), 1.32–1.40 (m, 3H),
1.41–1.52 (m, 2H), 1.53–1.63 (m, 1H), 1.64–1.80 (m, 1H), 2.03 (dd, J=
11.6/2.0 Hz, 1H), 2.09–2.11 (m, 1H), 9.95 ppm (d, J=2.2 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=18.8 (q), 19.7 (t), 23.7 (q), 26.6 (q), 31.7
(q), 33.6 (s), 36.9 (t), 37.5 (t), 40.1 (t), 41.2 (s), 43.1 (s), 48.4 (t), 64.0 (d),
70.7 (s), 204.4 ppm (d) ; MS (EI): m/z (%): 220 (7) [M]+, 205 (100),
177(15), 165 (23), 149 (23), 135 (28), 121 (34), 109 (47), 107 (37), 95 (40),
91 (26), 81 (21), 69 (25), 55 (18), 41 (24).
Acknowledgement
We thank Dr. Fabien Gagosz (Ecole Polytechnique, Palaiseau, France)
and Dr. Fabrice Robvieux (Firmenich SA, Geneva, Switzerland) for help-
ful mechanistic discussions and Professor Steven P. Nolan (University of
St. Andrews, St. Andrews, UK) for a sample of [(IPr)CuNTf2].
[1] C. Fehr, I. Farris, H. Sommer, Org. Lett. 2006, 8, 1839; C. Fehr, I.
Magpantay, J. Arpagaus, X. Marquet, M. Vuagnoux, Angew. Chem.
2009, 121, 7357; Angew. Chem. Int. Ed. 2009, 48, 7221.
[2] a) C. Fehr, J. Galindo, Angew. Chem. 2006, 118, 2967; Angew. Chem.
Int. Ed. 2006, 45, 2901; b) C. Fehr, B. Winter, I. Magpantay, Chem.
Eur. J. 2009, 15, 9773; c) For a closely related synthesis, see: A.
Fꢂrstner, P. Hannen, Chem. Eur. J. 2006, 12, 3006.
[6] G. Ohloff, H. Strickler, B. Willhalm, C. Borer, M. Hinder, Helv.
Chim. Acta 1970, 53, 623.
[7] T. Hatsui, N. Suzuki, H. Takeshita, Chem. Lett. 1985, 639.
[8] A. Srikrishna, K. Krishnan, J. Org. Chem. 1993, 58, 7751.
[9] A. Krasovskiy, F. Kopp, P. Knochel, Angew. Chem. 2006, 118, 511;
Angew. Chem. Int. Ed. 2006, 45, 497.
[10] This synthesis is analogous to the one described for [Cu-
[3] Recent reviews on enyne cycloisomerizations: a) S. P. Nolan, Acc.
Chem. Res. 2011, 44, 91; b) A. M. Echavarren, E. Jimꢄnez-Nunez,
Top. Catal. 2010, 53, 924; c) A. Fꢂrstner, Chem. Soc. Rev. 2009, 38,
3208; d) H. C. Shen, Tetrahedron 2008, 64, 7847; e) E. Jimꢄnez-
Nunez, A. M. Echavarren, Chem. Rev. 2008, 108, 3326; f) V. Michel-
et, P. Y. Toullec, J.-P. GenÞt, Angew. Chem. 2008, 120, 4338; Angew.
Chem. Int. Ed. 2008, 47, 4268; g) B. Crone, S. F. Kirsch, Chem. Eur.
J. 2008, 14, 3514; h) A. Fꢂrstner, P. W. Davies, Angew. Chem. 2007,
119, 3478; Angew. Chem. Int. Ed. 2007, 46, 3410; i) E. Jimꢄnez-
Nunez, A. M. Echavarren, Chem. Commun. 2007, 333; j) D. J.
Gorin, D. Toste, Nature 2007, 446, 395; k) N. Marion, S. P. Nolan,
Angew. Chem. 2007, 119, 2806; Angew. Chem. Int. Ed. 2007, 46,
2750; l) J. Marco-Contelles, E. Soriano, Chem. Eur. J. 2007, 13, 1350;
m) L. Zhang, J. Sun, S. A. Kozmin, Adv. Synth. Catal. 2006, 348,
2271; n) C. Nieto-Oberhuber, S. Lopez, E. Jimꢄnez-Nunez, A. M.
Echavarren, Chem. Eur. J. 2006, 12, 5916; o) S. Ma, S. Yu, Z. Gu,
Angew. Chem. 2006, 118, 206; Angew. Chem. Int. Ed. 2006, 45, 200;
p) C. Bruneau, Angew. Chem. 2005, 117, 2380; Angew. Chem. Int.
Ed. 2005, 44, 2328; q) A. M. Echavarren, C. Nevado, Chem. Soc.
Rev. 2004, 33, 431; r) C. Aubert, O. Buisine, M. Malacria, Chem.
Rev. 2002, 102, 813.
AHCTNUGTREN(GUNN CH3CN)4]PF6: G. J. Kubas, Inorg. Synth. 1979, 19, 90; For the syn-
thesis of CuNTf2 from mesityl copper and NHTf2: S. H. Strauss,
O. G. Polyakov, J. W. Hammel, S. M. Ivanova, S. V. Ivanov, M. D.
Havighurst, US 6114266, 2000.
[11] A sample of [(IPr)CuNTf2] was kindly obtained by Professor Ste-
ven P. Nolan (University of St.Andrews, St.Andrews, UK). For the
preparation of [(IPr)CuNTf2]: G. C. Fortman, A. M. Z. Slawin, S. P.
Nolan, Organometallics 2010, 29, 3966.
[12] M. R. Luzung, P. Mauleon, F. D. Toste, J. Am. Chem. Soc. 2007, 129,
12402; N. D. Shapiro, F. D. Toste, Synlett 2010, 675; B. Alcaide, P.
Almendros, C. Aragoncillo, Chem. Soc. Rev. 2010, 39, 783.
[13] G. Saucy, R. Marbet, H. Lindlar, O. Isler, Helv. Chim. Acta 1959, 42,
1945.
[14] E. Vedejs, A. Cammers-Goodwin, J. Org. Chem. 1994, 59, 7541.
[15] We cannot exclude that 25 is formed by a stepwise formal [2+2]-cy-
cloaddition of Q, followed by hydrolysis of the intermediate enol
acetate 24.
[4] C. Blaszykowski, Y. Harrak, C. Brancour, K. Nakama, A.- L. Dhi-
mane, L. Fensterbank, M. Malacria, Synthesis 2007, 2037; E. Soria-
Received: September 29, 2010
Published online: April 18, 2011
6220
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6214 – 6220