Selective mono- and 1,2-difunctionalisation of cyclopentene derivatives via Mg and Cu intermediates

Article abstract of DOI:10.1002/chem.200701431

A single Br/Mg exchange of 1,2-dibromocyclopentene with iPrMgCl-LiCl provides the corresponding β-bromocyclopentenylmagnesium reagent, which can then be reacted with various electrophiles (yields: 65-82%). In the presence of a secondary alkylmagnesium halide and Li₂CuCl₄ (2 mol%), these 2-bromoalkenylmagnesium compounds undergo bromine substitution and can then further react with electrophiles to give 1,2-difunctionalised cyclopentenes (63-79%). The mechanism of this process is discussed.

Full text of DOI:10.1002/chem.200701431

FULL PAPER
DOI: 10.1002/chem.200701431
Selective Mono- and 1,2-Difunctionalisation of Cyclopentene Derivatives via
Mg and Cu Intermediates
Christina Despotopoulou,[a] Richard C. Bauer,[b] Arkady Krasovskiy,[a] Peter Mayer,[a]
Jeffrey M. Stryker,[b] and Paul Knochel*[a]
Abstract: A single Br/Mg exchange of 1,2-dibromocyclopentene with iPrMgCl·
LiCl provides the corresponding b-bromocyclopentenylmagnesium reagent, which
Keywords: alkenylmagnesium re-
can then be reacted with various electrophiles (yields: 65–82%). In the presence
agents · cross-coupling · Cu cataly-
of a secondary alkylmagnesium halide and Li2CuCl4 (2 mol%), these 2-bromoalke-
sis · functionalized cyclopentenes ·
nylmagnesium compounds undergo bromine substitution and can then further
Grignard reaction
react with electrophiles to give 1,2-difunctionalised cyclopentenes (63–79%). The
mechanism of this process is discussed.
Introduction
dency to eliminate MgClBr at 258C and can be stored for
more than a month at room temperature as a 1m solution in
THF under argon with only a minimal decrease in activity.
Organomagnesium reagents are key organometallic inter-
mediates in organic synthesis.[1,2] Recently, we have shown
that I/Mg exchange using iPrMgCl·LiCl allows the stereose-
lective preparation of alkenylmagnesium reagents starting
from polyfunctional alkenyl iodides.[3] Whereas this ex-
change proceeds at low temperatures, alkenyl bromides do
not react with iPrMgCl·LiCl even at 40–508C.[4] The prepa-
ration of magnesium derivatives of 1,2-dibromocycloalkenes
would be of special interest, since the corresponding lithium
organometallics[5] are elusive intermediates. For example,
Results and Discussion
Reactions of the magnesium reagent 2 with various electro-
philes produced the functionalised cyclopentenyl bromides
3a–g in yields of 65–82% (Table 1).Treatment of the magne-
sium reagent 2 with iodine provided the unsymmetrical 1-
bromo-2-iodocyclopentene (3a) in 82% yield (entry 1 in
Table 1). Quenching of 2 with DMF gave the unsaturated b-
bromo aldehyde 3b (82%, entry 2). Reactions with aliphatic
and aromatic aldehydes afforded the allylic alcohols 3c and
3d in yields of 80 and 77%, respectively (entries 3 and 4).
Dimerisation of 2 was best performed by means of a palladi-
um-catalysed Negishi cross-coupling reaction,[7] giving 3e in
80% yield (entry 5). Reaction with (iPrO)3B, followed by
the addition of 2,2-dimethylpropane-1,3-diol, yielded the cy-
cloalkenyl boronic ester 3 f in 72% yield (entry 6). Benzoy-
lation of 2 after transmetallation with ZnCl2 and addition of
CuCN·2LiCl (20 mol%) provided the ketone 3g in 65%
yield (entry 7).[8]
single Br/Li exchanges of 2,3-dibromobicycloACHTREU[NG 2.2.1]hept-2-
ene and 1,2-dibromocyclopentene (1) using nBuLi at À788C
lead to unstable organolithium compounds, which decom-
pose at room temperature within 18 h.[6] Herein, we wish to
report that the reaction of 1,2-dibromocyclopentene (1) with
iPrMgCl·LiCl (1.1 equiv, 258C, 24–30 h) provides the corre-
sponding magnesium reagent 2 bearing a b-bromo substitu-
ent. Remarkably, this new magnesium species shows no ten-
[a] Dipl. Chem. C. Despotopoulou, Dr. A. Krasovskiy, Dr. P. Mayer,
Prof. Dr. P. Knochel
In the presence of an excess of iPrMgCl·LiCl (2.4 equiv)
and a catalytic amount of Li2CuCl4 (2 mol%, 08C, 8–12 h),
the b-bromo substituent of the intermediate Grignard re-
agent 2 was substituted by an isopropyl group, furnishing
the Grignard reagent 4a (Scheme 1). After transmetallation
with ZnCl2, copper-catalysed acylation yielded the unsatu-
rated ketone 5a (entry 1 in Table 2). Quenching with alde-
Department Chemie und Biochemie
Ludwig-Maximilians-Universität München
Butenandtstrasse 5–13, Haus F, 81377 München (Germany)
Fax: ( +49)89-2180-77680
E-mail: paul.knochel@cup.uni-muenchen.de
[b] Ms. Sci. R. C. Bauer, Prof. Dr. J. M. Stryker
Department of Chemistry, University of Alberta
Edmonton, Alberta, T6G 2G2 (Canada)
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Table 1. Reactions of b-bromoalkenylmagnesium chloride (2) prepared
by a selective Br/Mg exchange reaction.
Entry
1
Electrophile
I2
Product
Yield [%][a]
82
Scheme 1. Reaction of alkenylmagnesium reagents 4 prepared by a Cu-
catalysed coupling starting from the Grignard reagent 2.
2
3
DMF
82
80
equivalents of the reagent being required to complete both
the exchange and coupling steps. Attempts to extend the
scope of the reaction beyond secondary alkylmagnesium re-
agents proved unsuccessful. With nBuMgCl, nBuLi,
tBuMgCl, PhMgCl, and PhLi, coupling between the alkenyl-
magnesium species (of both types 2 and 4) was a major side
reaction. Preliminary experiments also showed the same dif-
ficulties when allyl- and benzyl-organomagnesium reagents
were used.
4
5
77
Extension of this reactivity pattern to the norbornadiene
framework[5b,9] was effective, as shown in Scheme 2. Br/Mg
80[b]
6
7
72
PhCOCl
65[c]
[a] Yield of analytically pure product. [b] 2 was transmetallated with
ZnCl2 (1 equiv), and then [Pd(dba)2] (5 mol%) and tfp (7 mol%) were
AHCTREUNG
added. [c] 2 was transmetallated with ZnCl2 (1 equiv) at À208C, and then
CuCN·2LiCl (20 mol%) was added.
hydes provided the allylic and benzylic alcohols 5b–g in
yields of 63–79% over three steps in a one-pot procedure
(entries 2–7). An excess of alkylmagnesium reagent was nec-
essary to overcome undesired homocoupling reactions; this
was most prevalent when cC5H9MgCl·LiCl was used, three
Scheme 2. Preparation and reactions of norbornadienylmagnesium re-
agent 7.
exchange as in the case of 1,2-dibromocyclopentene (1) on
1,2-dibromonorbornadiene (6) proceeded at a similar rate
(258C, 7 h) and coupling with iPrMgCl was accomplished
using Li2CuCl4 (1 mol%). The reaction of 7 with DMF pro-
duced the unsaturated aldehyde 8a in 72% yield. Transme-
tallation of 7 to give the corresponding zinc reagent, fol-
lowed by copper-catalysed benzoylation, afforded the unsa-
turated ketone 8b. Negishi cross-coupling with ethyl 4-iodo-
benzoate gave the arylated norbornadiene 8c in 63% yield.
The mechanism of this copper-catalysed bromine substitu-
tion reaction was investigated. Under our standard condi-
tions, the Grignard reagent 2 did not appear to eliminate
MgClBr to provide cyclopentyne. No trapping of this highly
reactive intermediate could be achieved by the addition of
furan, 2,3,4,5-tetraphenylcyclopentadienone, or dihydropyr-
Abstract in German: Durch einen Br/Mg-Austausch an 1,2-
Dibromcyclopenten mit iPrMgCl·LiCl werden die entspre-
chenden b-Bromcyclopentenyl-magnesium-Verbindungen er-
halten, die anschließend mit verschiedenen Elektrophilen um-
gesetzt werden (65–82%). Zusätzlich kçnnen diese 2-Brom-
alkenylmagnesium-Verbindungen in Anwesenheit eines
sekundären Alkylmagnesiumhalogenids und Li2CuCl4
(2 mol%) eine Bromsubstitution eingehen und danach mit
verschiedenen Elektrophilen abgefangen werden, sodass 1,2-
difunktionalisierte Cyclopentenderivate (63–79%) erhalten
werden. Zusätzlich wird der Mechanismus dieser Reaktion
diskutiert.
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Chem. Eur. J. 2008, 14, 2499 – 2506

Functionalisation of Cyclopentenes
FULL PAPER
Table 2. Products of type 5 obtained by Cu-catalysed coupling.
the copper-catalysed coupling
of 11 with iPrMgCl were ob-
tained by using a stoichiometric
amount of CuCN·2LiCl. Fol-
lowing completion of the cou-
pling, transmetallation with zinc
and copper-catalysed acylation
with benzoyl chloride yielded
the unsaturated ketone 13 in
30% overall yield from 9.[12]
Characterisation by 1D and 2D
NMR experiments, as well as
by X-ray crystallographic analy-
sis, confirmed the structure of
13, proving that the new
carbon–carbon bond to iPr had
indeed been formed at the
carbon atom that initially bore
the bromine atom (Figure 1).[13]
Therefore, we propose the
mechanism shown in Scheme 4
for the copper-catalysed cou-
Entry
RMgCl·LiCl
Electrophile
Product
Yield [%][a]
66[b]
1
iPrMgCl·LiCl (2.4 equiv)
PhCOCl (1.5 equiv)
2
3
4
iPrMgCl·LiCl (2.4 equiv)
sBuMgCl·LiCl (2.8 equiv)
sBuMgCl·LiCl (2.8 equiv)
tBuCHO (1.5 equiv)
74
68
79
PhCHO (1.6 equiv)
5
6
sBuMgCl·LiCl (2.8 equiv)
cPentMgCl·LiCl (3.0 equiv)
63
73
pling.
Transmetallation
of
iPrMgCl to iPrCu(CN)Li, fol-
lowed by oxidative addition to
the carbon–bromine bond in 11
is tentatively believed to gener-
ate intermediate 14. Reductive
elimination would then give in-
termediate 12, which would be
acylated with benzoyl chloride
7
cPentMgCl·LiCl (3.0 equiv)
65
[a] Isolated, analytically pure product. [b] 4a was transmetallated with ZnCl2 (1 equiv) at À208C, and then
CuCN·2LiCl (20 mol%) was added.
an.[10] We therefore prepared the unsymmetrical bicyclo-
ACHTREUNG[2.2.1]alkenyl 2,3-dihalide 9 in order to determine the regio-
selectivity of the cross-coupling. The synthesis of the 2-
bromo-3-iodocamphor derivative 9 was accomplished regio-
selectively in 40% overall yield over four steps starting
from d-camphor. The final step was an Sn/I exchange reac-
tion on the cycloalkenyltin derivative 10 (Scheme 3).[11]
I/Mg exchange of the dihalide 9 with iPrMgCl·LiCl
(1.1 equiv) proceeded within 1 h at 08C. The Grignard re-
agent 11 proved to be significantly less reactive than the cor-
responding norbornadiene derivative 7. The best results in
Figure 1. X-ray crystal structure of compound 13.
upon transmetallation with CuCN·2LiCl (1 equiv). Alterna-
tively, the reaction may proceed through a copperACHTREUNG(III)-cy-
clopropane intermediate,[14] from which the alkenylmagnesi-
um reagent 12 would be obtained through b-elimination as-
sisted by the polymetallic components of the organocuprate.
Scheme 3. Regioselective Cu-catalysed cross-coupling of alkenyl- and al-
kylmagnesium species.
Chem. Eur. J. 2008, 14, 2499 – 2506
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P. Knochel et al.
508CminÀ1 to 2508C, holding at 2508C for 5 min, heating at a ramp rate
of 508CminÀ1 to 3008C, holding at 3008C for 3 min.
Starting materials: The reagents iPrMgCl·LiCl and s-BuMgCl·LiCl were
obtained from Chemetall as 14% and 15% solutions, respectively, in
THF and were titrated with iodine prior to use. c-PentMgCl·LiCl was
prepared from cyclopentyl chloride and Mg in the presence of LiCl ac-
cording to the published procedure.[16]
A 1.0m CuCN·2LiCl solution was first prepared by heating 1 equiv of
CuCN (100 mmol, 8.9 g) and 2 equiv of LiCl (200 mmol, 8.4 g) under
vacuum at 1308C for 6 h; THF (100 mL) was slowly added and the result-
ing solution was stirred overnight. Li2CuCl4 was purchased as a 0.1m so-
lution in THF from Acros Organics.
Acid chlorides, DMF, and liquid aldehydes were distilled under argon
prior to use. Solid aldehydes were used without further purification.
Scheme 4. Proposed mechanism for the regioselective CuI-catalysed
cross-coupling reaction.
1,2-Dibromocyclopentene 1 was prepared according to the published pro-
cedure.[17] 2,3-Dibromo-bicyclo
ACHTRE[UNG 2.2.1]hepta-2,5-diene 6 was prepared fol-
lowing the published procedure.[5b]
Typical procedure A for the synthesis of compounds 3a–g: Dibromide 1
(1 equiv) was added to a flame-dried flask equipped with a magnetic stir-
ring bar, an argon inlet, and a septum. iPrMgCl·LiCl (1.1 equiv in THF)
was added at room temperature with stirring. Upon completion of the ex-
change (as determined by GC analysis of aliquots of the reaction mixture
quenched with saturated aqueous NH4Cl solution; 24–30 h), the reaction
mixture was cooled to 08C in an ice bath. The electrophile was slowly
added and the solution was warmed to 258C. After stirring for 2 h at
room temperature, saturated aqueous NH4Cl solution (5 mL) was added
and the aqueous layer was extracted with Et2O (3”10 mL). The com-
bined organic extracts were washed with saturated NaCl solution, dried
over MgSO4, and filtered. Removal of the solvent in vacuo and purifica-
tion of the residue by column chromatography (SiO2, initially neutralised
with 3% Et3N) afforded the desired product.
The presence of a carbon–magnesium bond in the b-posi-
tion with respect to the carbon–bromine bond, as found in
compound 11, may have an accelerating effect on such
cross-couplings.[15]
Conclusion
In conclusion, we have shown that the use of iPrMgCl·LiCl
allows a simple, high-yielding preparation of previously un-
known cyclic b-bromo-substituted alkenylmagnesium re-
agents. We have performed a copper-catalysed heterocou-
pling reaction, allowing the regioselective formation of a
new b-alkylated cycloalkenylmagnesium compound that can
be further reacted with a range of electrophiles. This se-
quence constitutes an effective one-pot cascade difunctional-
isation of cycloalkenes. Extensions of this work, which in-
clude the investigation of this reaction pattern on 1,2-dibro-
mocyclohexene, are currently underway in our laboratories.
Typical procedure B for the synthesis of compounds 5a and 8b: The ap-
propriate dibromide 1 or 6 (1 equiv) was added to a flame-dried flask
equipped with a magnetic stirring bar, an argon inlet, and a septum.
iPrMgCl·LiCl (2.2–2.4 equiv) was added at room temperature with stir-
ring. Upon completion of the exchange (as determined by GC analysis;
6 h), the solution was cooled to À108C. Li2CuCl4 (0.1m in THF, 2 mol%)
was added dropwise and the solution was slowly warmed to 08C. Upon
completion of the coupling (as determined by GC analysis; 9 h), the solu-
tion was cooled to À308C and ZnCl2 solution (1m in THF, 1 equiv) was
added. After stirring for 30 min, the solution was warmed to À208C and
a solution of CuCN·LiCl (1.0m in THF, 20 mol%) was added. After stir-
ring for 5 min, the requisite acid chloride (1.2–1.5 equiv) was added and
the solution was warmed to room temperature. The reaction mixture was
stirred at room temperature for 2 h, then quenched with saturated aque-
ous NH4Cl solution. The aqueous layer was extracted with Et2O (3”
10 mL) and the combined organic extracts were washed with saturated
NaCl solution, dried over MgSO4, and filtered. Removal of the solvent in
vacuo and purification of the residue by column chromatography (SiO2,
initially neutralised with 3% Et3N) afforded the desired product.
Experimental Section
General: Unless otherwise indicated, all reactions were carried out with
magnetic stirring in flame-dried glassware under argon. Syringes used to
transfer reagents and solvents were purged with argon prior to use. Reac-
tions were monitored by gas chromatography (GC and GC-MS) or thin-
layer chromatography (TLC). TLC was performed on aluminium plates
coated with SiO2 (Merck 60, F-254); spots were visualised either by UV
detection or following immersion in KMnO4 solution (KMnO4 (1.5 g),
K2CO3 (10 g), and 10% NaOH solution (1.25 mL) in H2O (200 mL)).
Column chromatography was performed using Merck silica gel 60 (40–
63 mm, 230–400 mesh ASTM). Melting points were measured using a
Büchi B-540 apparatus and are uncorrected.
Typical procedure Cfor the synthesis of compounds 5b–g, 8a, and 8c :
The appropriate dibromide 1 or 6 (1 equiv) was added to a flame-dried
flask equipped with a magnetic stirring bar, an argon inlet, and a septum.
RMgCl·LiCl (2.2–3.0 equiv in THF) was added at room temperature with
stirring. Upon completion of the exchange (as determined by GC analysis
of hydrolysed aliquots of the reaction mixture; 6 h), the solution was
cooled to À108C. Li2CuCl4 (0.1m solution in THF, 2 mol%) was added
dropwise and the solution was slowly warmed to 08C. Upon completion
of the coupling (as determined by GC analysis; 9 h), the requisite electro-
phile (1.3–1.7 equiv) was slowly added and the solution was warmed to
258C. After stirring for 2 h at room temperature, the reaction mixture
was quenched by the addition of saturated aqueous NH4Cl solution and
the aqueous layer was extracted with Et2O (3”10 mL). The combined or-
ganic extracts were washed with saturated NaCl solution, dried over
MgSO4, and filtered. Removal of the solvent in vacuo and purification of
the residue by column chromatography (SiO2, initially neutralised with
3% Et3N) afforded the desired product.
NMR spectra were recorded from samples in CDCl3 or C6D6 solution;
chemical shifts (d) are reported in parts per million (ppm) relative to the
residual solvent peak: CDCl3 (d=7.25 ppm (1H) and d=77.0 ppm (13C));
C6D6 (d=7.16 ppm (1H) and d=128.0 ppm (13C)). Mass spectra and high-
resolution mass spectra (HRMS) were recorded in electrospray ionisation
(ESI) mode, except where otherwise noted. GC was performed on Hew-
lett-Packard 6890 or 5890 Series II chromatographs (column: 5% phenyl-
methylpolysiloxane, length: 10 m, diameter: 0.25 mm, film thickness:
0.25 mm). The method used to determine GC purity, referred to as
“method 70”, was as follows: 708C for 1 min, heating at a ramp rate of
2502
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Chem. Eur. J. 2008, 14, 2499 – 2506

Functionalisation of Cyclopentenes
FULL PAPER
1-Bromo-2-iodocyclopentene (3a): According to typical procedure A, di-
with ZnCl2 (1.00m solution in THF, 2.75 mL) at À208C and the solution
was stirred for 15 min. 1-Bromo-2-iodocyclopentene (3a) (5.00 mmol,
1.36 g) was then added to the reaction mixture at À208C, followed by
bromide
1 (1.00 mmol, 226 mg) was reacted with iPrMgCl·LiCl
(1.10 mmol, 1.24m in THF, 0.89 mL). After completion of the exchange,
the mixture was quenched with a solution of iodine (1.20 mmol, 305 mg)
in THF (2.00 mL) at À208C. The product was purified according to typi-
cal procedure A (column chromatography eluting with pentane) to yield
3a as a pale-yellow oil (223 mg, 82%). GC purity ꢀ99% (retention
time: 2.92 min, measured by method 70). 1H NMR (CDCl3, 300 MHz):
d=2.67–2.59 (m, 4H), 2.05 ppm (quint, 3JH,H =7.5 Hz, 2H); 13C NMR
(CDCl3, 75 MHz): d=130.2, 97.2, 43.5, 39.6, 24.1 ppm; IR (film): n˜ =2951
(m), 2848 (m), 1604 (m), 1440 (m), 1382 (w), 1306 (m), 1287 (w), 1199
(w), 1132 (w), 1091 (s), 1042 (w), 1028 (w), 903 (w), 824 (s), 747 (w),
692 cmÀ1 (w); MS (EI, 70 eV): m/z (%): 272 (100) [M+], 206 (2), 193
(17), 145 (21), 127 (13), 65 (63); HRMS (EI): m/z: calcd for C5H679BrI:
271.8698; found: 271.8686.
[PdACHTRE(UNG dba)2] (5 mol%, 144 mg) and trifurylphosphine (tfp) (7 mol%,
81 mg). After standard work-up, the resultant oil was purified by column
chromatography (pentane) to give 3e (1.16 g, 77%) as a colourless oil.
GC purity ꢀ99% (retention time: 4.11 min, measured by method 70);
1H NMR (CDCl3, 300 MHz): d=2.71–2.53 (m, 8H), 1.96 ppm (quint,
3JH,H =7.6 Hz, 4H); 13C NMR (CDCl3, 75 MHz): d=136.9, 119.0, 41.4,
35.0, 22.8 ppm; IR (film): n˜ =4329 (w), 4250 (w), 2966 (m), 2946 (m),
2893 (m), 2846 (s), 1668 (w), 1615 (w), 1435 (m), 1308 (m), 1283 (m),
1202 (w), 1134 (w), 1118 (w), 1082 (m), 1033 (s), 998 (w), 922 (m), 907
(m), 876 (w), 784 cmÀ1 (s); MS (EI, 70 eV): m/z (%): 292 (100) [M+], 290
(47), 213 (32), 211 (32), 132 (58), 131 (61), 129 (10), 117 (28), 116 (11),
115 (14), 104 (16), 103 (14), 91 (30), 77 (17), 65 (23), 64 (25), 63 (10), 51
(16); HRMS (EI): m/z: calcd for C10H1279Br2: 289.9306; found 289.9316.
2-Bromocyclopent-1-ene-1-carbaldehyde (3b): According to typical pro-
cedure A, iPrMgCl·LiCl (1.75 mmol, 1.06m, 1.65 mL) was added to 1
(1.59 mmol, 359 mg). The alkenylmagnesium species 2 was quenched
with DMF (1.91 mmol, 0.15 mL). Following work-up, the resultant oil
was purified by column chromatography (pentane/CH2Cl2 1:1) to give 3b
(228 mg, 82%) as a pale-yellow oil. GC purity ꢀ99% (retention time:
2-(2-Bromocyclopent-1-en-1-yl)-5,5-dimethyl-1,3,2-dioxaborinane
(3 f):
According to typical procedure A, iPrMgCl·LiCl (1.10 mmol, 1.22m,
0.90 mL) was added to 1 (1.00 mmol, 226 mg) at room temperature. The
alkenylmagnesium species
2 was reacted with (iPrO)3B (1.20 mmol,
0.28 mL) at À208C and the reaction mixture was slowly warmed to 258C.
Neat 2,2-dimethylpropane-1,3-diol (1.50 mmol, 156 mg) was then added
to the solution. After standard work-up, the resultant oil was purified by
column chromatography (pentane/diethyl ether 7:3) to give 3 f (185 mg,
72%) as a brown oil. GC purity ꢀ99% (retention time: 4.08 min, mea-
sured by method 70). 1H NMR (C6D6, 300 MHz): d=3.34 (s, 4H), 2.61–
2.53 (m, 4H), 1.58 (quint, 3JH,H =7.6 Hz, 2H), 0.57 ppm (s, 6H);
13C NMR (C6D6, 75 MHz): d=132.2, 71.9, 44.0, 36.3, 31.3, 23.4, 21.5 ppm
(olefinic C attached to B not observed due to quadropolar coupling); IR
(film): n˜ =2958 (m), 2926 (m), 1731 (m), 1616 (m), 1476 (m), 1418 (w),
1318 (s), 1253 (s), 1118 (s), 1073 (w), 840 (w), 696 (m), 672 cmÀ1 (w); MS
(EI, 70 eV): m/z (%): 258 (100) [M+], 180 (40), 179 (63), 135 (46), 93
(62), 79 (28); HRMS (EI): m/z: calcd for C10H1611B79BrO2: 258.0427;
found 258.0433.
2.53 min, measured by method 70). 1H NMR (CDCl3, 300 MHz): d=9.89
3
(s, 1H), 2.92–2.87 (m, 2H), 2.55–2.50 (m, 2H), 2.01 ppm (quint, JH,H
=
7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz): d=189.5, 141.6, 140.3, 42.8,
29.5, 21.6 ppm; IR (film): n˜ =2925 (w), 1662 (s), 1599 (s), 1329 (w), 1240
(w), 1195 (w), 1074 (m), 909 (m), 720 cmÀ1 (s); MS (EI, 70 eV): m/z (%):
174 (100) [M+], 145 (10), 95 (45), 94 (12), 67 (90), 66 (41), 65 (73), 41
(20); HRMS (EI): m/z: calcd for C6H779BrO: 173.9680; found: 173.9681.
(2-Bromocyclopent-1-en-1-yl)(cyclohexyl)methanol (3c): According to
typical procedure A, iPrMgCl·LiCl (1.01 mmol, 1.22m, 0.83 mL) was
added to 1 (0.92 mmol, 208 mg) and the newly formed alkenylmagnesium
species
2 was quenched with cyclohexylcarbaldehyde (1.10 mmol,
0.13 mL). After standard work-up, the resultant oil was purified by
column chromatography (pentane/CH2Cl2 4:1) to give 3c (192 mg, 80%)
as a colourless oil. GC purity ꢀ99% (retention time: 4.50 min, measured
by method 70). 1H NMR (CDCl3, 300 MHz): d=4.22 (d, 3JH,H =9.0 Hz,
1H), 2.66–2.61 (m, 2H), 2.53–2.42 (m, 1H), 2.31–2.20 (m, 1H), 2.07–2.03
(2-Bromocyclopent-1-en-1-yl)phenylmethanone (3g): According to typi-
cal procedure A, iPrMgCl·LiCl (1.10 mmol, 1.30m, 0.85 mL) was added
to 1 (1.00 mmol, 226 mg). After the exchange was complete, the solution
was cooled to À308C and ZnCl2 solution (1.00m in THF, 1.00 mmol,
1.00 mL) was added. After stirring for 30 min, the solution was warmed
to À208C and a solution of CuCN·2LiCl (1.00m in THF, 1.00 mmol,
1.00 mL) was added. After stirring for 5 min, benzoyl chloride
(1.20 mmol, 0.14 mL) was added and the solution was warmed to 258C.
After stirring for 2 h at 258C, saturated aqueous NH4Cl solution (5 mL)
was added and the aqueous layer was extracted with Et2O (3”10 mL).
The combined organic extracts were washed with saturated NaCl solu-
tion, dried over MgSO4, and filtered. Removal of the solvent in vacuo
and purification of the residue by column chromatography (pentane/di-
ethyl ether 9:1) afforded 3g (162 mg, 65%) as a pale-yellow oil. GC
purity ꢀ99% (retention time: 4.58 min, measured by method 70).
1H NMR (C6D6, 400 MHz): d=7.92 (d, 3JH,H =7.0 Hz, 2H), 7.20–7.12 (m,
3H), 2.49–2.40 (m, 4H), 1.50 ppm (quint, 3JH,H =7.6 Hz, 2H); 13C NMR
(C6D6, 75 MHz): d=194.0, 140.7, 136.7, 133.0, 129.6, 128.6, 123.4, 41.9,
35.5, 22.1 ppm; IR (film): n˜ =1653 (s), 1616 (m), 1595 (m), 1451 (m),
1321 (s), 1283 (s), 1072 (m), 955 (m), 840 (m), 792 (m), 713 (s), 687 (s),
675 cmÀ1 (s); MS (EI, 70 eV): m/z (%): 252 (64), 251 (17), 250 (66) [M+],
175 (23), 173 (23), 172 (13), 171 (100), 170 (11), 143 (32), 128 (15), 105
(47), 77 (22); HRMS (EI): m/z: calcd for C12H1179BrO: 249.9993; found
249.9992.
3
(m, 1H), 1.94 (quint, JH,H =7.5 Hz, 2H), 1.78–1.62 (m, 3H), 1.56 (s, 1H),
1.48–1.38 (m, 2H), 1.26–1.15 (m, 3H), 1.08–0.87 ppm (m, 2H); 13C NMR
(CDCl3, 75 MHz): d=141.8, 118.7, 74.4, 42.0, 40.4, 30.0, 29.7, 28.9, 26.6,
26.2, 26.0, 22.0 ppm; IR (film): n˜ =3360 (s), 2929 (s), 2851 (s), 2668 (w),
2246 (w), 1712 (w), 1651 (m), 1448 (m), 1385 (w), 1317 (m), 1263 (m),
1205 (m), 1971 (m), 1013 (m), 961 (w), 893 (m), 844 (w), 734 cmÀ1 (m);
MS (EI, 70 eV): m/z (%): 258 (2) [M+], 179 (40), 177 (96), 175 (100), 97
(23), 96 (19), 95 (10), 83 (10), 67 (37), 55 (15), 41 (15); HRMS (EI): m/z:
calcd for C12H1979BrO: 258.0619; found: 258.0608.
(2-Bromocyclopent-1-en-1-yl)(3,5-dimethoxyphenyl)methanol (3d): Ac-
cording to typical procedure A, iPrMgCl·LiCl (1.04 mmol, 1.22m,
0.85 mL) was added to 1 (0.94 mmol, 213 mg) and the newly formed alke-
nylmagnesium species 2 was quenched with 3,5-dimethoxybenzaldehyde
(1.13 mmol, 188 mg). After standard work-up, the resultant oil was puri-
fied by column chromatography (pentane/CH2Cl2 4:1) to give 3d
(236 mg, 77%) as a colourless oil. GC purity ꢀ99% (retention time:
6.08 min, measured by method 70). 1H NMR (CDCl3, 300 MHz): d=6.57
(d, 4JH,H =2.2 Hz, 2H), 6.36 (t, 4JH,H =2.2 Hz, 1H), 5.69 (s, 1H), 3.78 (s,
6H), 2.68–2.59 (m, 2H), 2.53–2.44 (m, 1H), 2.18–2.00 (m, 2H), 1.96–
1.80 ppm (m, 2H); 13C NMR (CDCl3, 75 MHz): d=161.1, 144.4, 142.0,
118.4, 103.7, 99.6, 71.5, 55.6, 40.5, 29.6, 21.7 ppm; IR (film): n˜ =3428 (s),
2956 (s), 2840 (m), 1651 (w), 1608 (s), 1464 (s), 1428 (m), 1319 (m), 1293
(m), 1204 (s), 1153 (s), 1088 (w), 1067 (m), 1038 (m), 925 (w), 895 (w),
848 (s), 743 (m), 704 cmÀ1 (m); MS (EI, 70 eV): m/z (%): 314 (42), 312
(43) [M+], 241 (60), 240 (15), 220 (12), 219 (67), 208 (30), 165 (74), 151
(26), 139 (100), 122 (11), 115 (12), 107 (12), 95 (67), 77 (17), 67 (36), 64
(25); HRMS (EI): m/z: calcd for C14H1779BrO3: 312.0361; found:
312.0360.
(2-Isopropylcyclopent-1-en-1-yl)phenylmethanone (5a): According to
typical procedure B, iPrMgCl·LiCl (2.30 mmol, 1.22m, 1.90 mL) was
added to 1 (0.96 mmol, 218 mg). After the exchange was complete,
Li2CuCl4 (0.02 mmol, 0.10m in THF, 0.19 mL) was added. The newly
formed alkenylmagnesium species 4a was transmetallated with a solution
of ZnCl2 (0.96 mmol, 1.00m in THF, 0.96 mL) and then CuCN·2LiCl
(0.19 mmol, 1.00m in THF, 0.19 mL) was added; the resultant copper–
zinc reagent was then quenched with benzoyl chloride (1.40 mmol,
0.17 mL). Following work-up, the resultant oil was purified by column
chromatography (pentane) to give 5a (137 mg, 66%) as a colourless oil.
2,2’-Dibromo-1,1’-bi(cyclopent-1-en-1-yl) (3e): According to typical pro-
cedure A, iPrMgCl·LiCl (5.50 mmol, 1.22m, 4.50 mL) was added to 1
(5.00 mmol, 1.13 g). The alkenylmagnesium species 2 was transmetallated
Chem. Eur. J. 2008, 14, 2499 – 2506
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2503

P. Knochel et al.
GC purity ꢀ99% (retention time: 4.34 min, measured by method 70).
(18), 173 (46), 145 (12); HRMS (EI): m/z: calcd for C17H21F3O: 298.1544;
found: 298.1553.
1H NMR (CDCl3, 300 MHz): d=7.79 (d, 3JH,H =7.0 Hz, 2H), 7.55–7.41
3
(m, 3H), 2.71–2.62 (m, 3H), 2.54–2.49 (m, 2H), 1.91 (quint, JH,H
=
(2-sec-Butylcyclopent-1-en-1-yl)(3,5-dimethoxyphenyl)methanol
(5e):
7.4 Hz, 2H), 0.95 ppm (d, 3JH,H =6.9 Hz, 6H); 13C NMR (CDCl3,
75 MHz): d=198.3, 157.4, 139.0, 134.7, 132.8, 129.0, 128.6, 36.2, 32.3, 28.6,
22.7, 21.3 ppm; IR (film): n˜ =3392 (s), 3063 (w), 2961 (s), 2932 (m), 2871
(m), 1649 (s), 1598 (m), 1578 (m), 1464 (w), 1448 (m), 1384 (w), 1340
(m), 1263 (s), 1175 (w), 1099 (m), 1072 (m), 1024 (m), 891 (w), 796 (m),
715 (m), 697 cmÀ1 (m); MS (EI, 70 eV): m/z (%): 214 (26) [M+], 199
(100), 184 (10), 171 (10), 105 (28), 77 (25); HRMS (EI): m/z: calcd for
C15H18O: 214.1358; found: 214.1352.
According to typical procedure C, sBuMgCl·LiCl (3.50 mmol, 1.08m,
3.25 mL) was added to 1 (1.25 mmol, 283 mg). After the exchange was
complete, Li2CuCl4 (0.02 mmol, ꢁ0.10m in THF, 0.25 mL) was added.
The newly formed alkenylmagnesium species 4b was quenched with 3,5-
dimethoxybenzaldehyde (2.00 mmol, 333 mg). After standard work-up,
the resultant oil was purified by column chromatography (pentane/
CH2Cl2 4:1) to give 5e (229 mg, 63%) as a pale-yellow oil. GC purity
ꢀ99% (retention time: 6.06 min, measured by method 70); 1H NMR
(C6D6, 400 MHz): d=6.80 (d, 4JH,H =2.0 Hz, 2H), 6.51 (t, 4JH,H =2.3 Hz,
1H), 5.58 (s, 1H), 3.40 (s, 6H), 2.58–2.51 (m, 2H), 2.25–2.14 (m, 3H),
1.67–1.56 (m, 2H), 1.36–1.24 (m, 3H), 0.97 (d, 3JH,H =6.7 Hz, 3H),
0.82 ppm (t, 3JH,H =7.2 Hz, 3H); 13C NMR (C6D6, 100 MHz): d=161.4,
146.5, 143.0, 137.6, 104.1, 99.1, 69.7, 54.7, 34.3, 31.2, 31.0, 28.3, 21.9, 19.6,
12.6 ppm; IR (film): n˜ =3431 (w), 2957 (m), 1595 (s), 1458 (m), 1427 (m),
1293 (w), 1203 (m), 1154 (s), 1035 (m), 830 (w), 689 cmÀ1 (w); MS (EI,
70 eV): m/z (%): 290 (50) [M+], 272 (98), 257 (11), 243 (53), 233 (100),
215 (44), 165 (30), 152 (24), 151 (32), 139 (25), 121 (12), 95 (24); HRMS
(EI): m/z: calcd for C18H26O3: 290.1882; found: 290.1889.
1-(2-Isopropylcyclopent-1-en-1-yl)-2,2-dimethylpropan-1-ol (5b): Accord-
ing to typical procedure C, iPrMgCl·LiCl (2.40 mmol, 1.06m, 2.27 mL)
was added to 1 (1.00 mmol, 226 mg). After the exchange was complete,
Li2CuCl4 (0.02 mmol, 0.10m in THF, 0.20 mL) was added. The newly
formed alkenylmagnesium species 4a was quenched with pivaldehyde
(1.20 mmol, 0.13 mL). After standard work-up, the resultant oil was puri-
fied by column chromatography (pentane/CH2Cl2 4:1) to give 5b
(146 mg, 74%) as a colourless oil. GC purity ꢀ99% (retention time:
3.32 min, measured by method 70); 1H NMR (C6D6, 400 MHz): d=4.14
(s, 1H), 2.72 (sept, 3JH,H =6.7 Hz, 1H), 2.53–2.15 (m, 5H), 1.73–1.56 (m,
3
3
2H), 0.98 (s, 9H), 0.95 (d, JH,H =7.0 Hz, 3H), 0.92 ppm (d, JH,H =6.7 Hz,
3H); 13C NMR (C6D6, 100 MHz): d=145.4, 135.0, 75.8, 35.9, 33.6, 30.6,
27.1, 26.9, 22.9, 21.5, 20.9 ppm; IR (film): n˜ =3628 (w), 3460 (s), 2956 (s),
2868 (s), 1649 (w), 1480 (s), 1464 (s), 1392 (m), 1381 (m), 1362 (s), 1329
(w), 1292 (w), 1240 (m), 1190 (m), 1167 (w), 1100 (w), 1047 (s), 998 (s),
956 (m), 935 (w), 898 (m), 861 (w), 769 (w), 753 cmÀ1 (w); MS (EI,
70 eV): m/z (%): 196 (2) [M+], 163 (16), 139 (100), 121 (15), 95 (15), 93
(12), 81 (82), 69 (12), 67 (11), 43 (24), 41 (14); HRMS (EI): m/z: calcd
for C13H24O: 196.1827; found: 196.1823.
1,1’-Bi(cyclopentan)-1-en-2-yl[4-(trifluoromethyl)phenyl]methanol (5 f):
According to typical procedure C, c-PentMgCl·LiCl (3.08 mmol, 0.81m,
3.80 mL) was added to 1 (1.03 mmol, 232 mg). After the exchange was
complete, Li2CuCl4 (0.02 mmol, 0.10m in THF, 0.20 mL) was added. The
newly formed alkenylmagnesium species 4c was quenched with 4-(tri-
fluoromethyl)benzaldehyde (1.75 mmol, 304 mg). After standard work-
up, the resultant oil was purified by column chromatography (pentane/
CH2Cl2 4:1) to give 5 f (234 mg, 73%) as a pale-yellow oil. GC purity
ꢀ99% (retention time: 5.18 min, measured by method 70); 1H NMR
3
3
(CDCl3, 600 MHz): d=7.56 (d, JH,H =8.2 Hz, 2H), 7.45 (d, JH,H =7.9 Hz,
2H), 5.76 (s, 1H), 3.05 (quint, 3JH,H =9.0 Hz, 1H), 2.45–2.30 (m, 3H),
1.97–1.91 (m, 1H), 1.84 (brs, 1H), 1.76–1.66 (m, 6H), 1.66–1.58 (m, 2H),
1.53–1.43 ppm (m, 2H); 13C NMR (CDCl3, 150 MHz): d=147.2, 144.6,
135.7, 129.2 (q, 2JC,F =32.3 Hz), 126.1, 125.5 (q, 1JC,F =272.0 Hz), 125.3 (q,
3JC,F =3.9 Hz), 69.6, 38.9, 32.4, 31.9, 31.7, 30.9, 26.1, 26.0, 21.9 ppm; IR
(film): n˜ =3348 (w), 2952 (m), 1326 (s), 1161 (m), 1121 (s), 1066 (s), 1016
(m), 852 cmÀ1 (w); MS (EI, 70 eV): m/z (%): 310 (12) [M+], 292 (80),
252 (10), 251 (13), 250 (10), 249 (16), 241 (100), 223 (27), 173 (25), 159
(10), 133 (19), 91 (11); HRMS (EI): m/z: calcd for C18H21F3O: 310.1544;
found: 310.1546.
(2-sec-Butylcyclopent-1-en-1-yl)phenylmethanol (5c): According to typi-
cal procedure C, sBuMgCl·LiCl (2.93 mmol, 1.08m, 2.71 mL) was added
to 1 (1.04 mmol, 236 mg). After the exchange was complete, Li2CuCl4
(0.02 mmol, 0.10m in THF, 0.21 mL) was added. The newly formed alke-
nylmagnesium species 4b was quenched with benzaldehyde (1.66 mmol,
0.17 mL). After standard work-up, the resultant oil was purified by
column chromatography (pentane/CH2Cl2 4:1) to give 5c (164 mg, 68%)
as a colourless oil. GC purity ꢀ99% (retention time: 4.58 min, measured
by method 70). 1H NMR (CDCl3, 300 MHz): d=7.34–7.21 (m, 5H), 5.70
3
(s, 1H), 2.70 (sext, 3JH,H =7.1 Hz, 1H), 2.51–2.41 (m, 1H), 2.29 (t, JH,H
=
7.4 Hz, 2H), 2.09–1.98 (m, 1H), 1.77–1.69 (m, 3H), 1.45–1.35 (m, 2H),
1.03 (d, 3JH,H =6.8 Hz, 3H), 0.87 ppm (t, 3JH,H =7.4 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): d=144.5, 143.3, 136.7, 128.4, 127.1, 125.9, 70.1, 34.6,
31.4, 31.0, 28.4, 21.9, 19.8, 12.8 ppm; IR (film): n˜ =3392 (s), 3066 (w),
2954 (s), 2868 (s), 1661 (w), 1596 (w), 1473 (m), 1451 (m), 1384 (m), 1336
(w), 1261 (w), 1187 (m), 1095 (w), 1077 (w), 1035 (m), 973 (m), 895 (w),
854 (w), 791 (w), 723 (w), 698 cmÀ1 (m); MS (EI, 70 eV): m/z (%): 230
(10) [M+], 212 (32), 183 (17), 173 (100), 155 (19), 105 (14); HRMS (EI):
m/z: calcd for C16H22O: 230.1671; found: 230.1661.
1,1’-Bi(cyclopentan)-1-en-2-yl(3-chlorophenyl)methanol (5g): According
to typical procedure C, c-PentMgCl·LiCl (3.07 mmol, 0.81m, 3.79 mL)
was added to 1 (1.02 mmol, 231 mg). After the exchange was complete,
Li2CuCl4 (0.02 mmol, 0.10m in THF, 0.20 mL) was added. The newly
formed alkenylmagnesium species 4c was quenched with 3-chlorobenzal-
dehyde (1.74 mmol, 245 mg). After standard work-up, the resultant oil
was purified by column chromatography (pentane/CH2Cl2 4:1) to give 5g
(184 mg, 65%) as a pale-yellow oil. Note: this compound decomposed
after two days. GC purity ꢀ99% (retention time: 6.04 min, measured by
method 70); 1H NMR (C6D6, 400 MHz): d=7.43 (s, 1H), 7.11–7.04 (m,
3H), 6.93 (t, 3JH,H =7.5 Hz, 1H), 5.41 (s, 1H), 2.84 (quint, 3JH,H =9.0 Hz,
1H), 2.40–2.29 (m, 2H), 2.26–2.11 (m, 2H), 1.97–1.89 (m, 1H), 1.68–1.48
(m, 7H), 1.43–1.29 ppm (m, 2H); 13C NMR (C6D6, 100 MHz): d=143.0,
136.3, 134.4, 129.4, 126.9, 126.1, 123.9, 69.0, 38.7, 32.2, 31.7, 31.5, 30.8,
26.0, 25.9, 21.7 ppm; IR (film): n˜ =3392 (s), 2946 (s), 1661 (w), 1596 (m),
1575 (m), 1472 (w), 1426 (w), 1187 (m), 1035 (m), 790 (w), 699 cmÀ1 (w);
MS (EI, 70 eV): m/z (%): 276 (1) [M+], 260 (30), 258 (100), 223 (10), 217
(26), 215 (10), 191 (11), 189 (33), 165 (16), 154 (15), 153 (16), 152 (12),
133 (37), 125 (13), 115 (10), 91 (20); HRMS (EI): m/z: calcd for
C17H21ClO: 276.1281; found: 276.1284.
(2-sec-Butylcyclopent-1-en-1-yl)[4-(trifluoromethyl)phenyl]methanol
(5d): According to typical procedure C, s-BuMgCl·LiCl (3.02 mmol,
1.08m, 2.80 mL) was added to 1 (1.08 mmol, 244 mg). After the exchange
was complete, Li2CuCl4 (0.02 mmol, 0.10m in THF, 0.22 mL) was added.
The newly formed alkenylmagnesium species 4b was quenched with 4-
(trifluoromethyl)benzaldehyde (1.73 mmol, 301 mg). After standard
work-up, the resultant oil was purified by column chromatography (pen-
tane/CH2Cl2 4:1) to give 5d (254 mg, 79%) as a white solid. GC purity
ꢀ99% (retention time: 4.55 min, measured by method 70); m.p. 96.9–
100.48C; 1H NMR (C6D6, 400 MHz): d=7.41 (d, 3JH,H =8.4 Hz, 2H), 7.32
(d, 3JH,H =8.4 Hz, 2H), 5.40 (s, 1H), 2.45 (sext, 3JH,H =7.1 Hz, 1H), 2.38–
2.28 (m, 1H), 2.23–2.05 (m, 2H), 1.93–1.83 (m, 1H), 1.63–1.48 (m, 2H),
3
3
1.31–1.22 (m, 3H), 0.94 (d, JH,H =6.8 Hz, 3H), 0.76 ppm (t, JH,H =7.4 Hz,
3-IsopropylbicycloCAHTRE[UNG 2.2.1]hepta-2,5-diene-2-carbaldehyde (8a): According
3H); 13C NMR (C6D6, 100 MHz): d=147.7, 144.9, 136.4, 129.0 (q, JC,F
=
2
to typical procedure C, iPrMgCl·LiCl (2.20 mmol, 1.22m, 1.80 mL) was
added to 6 (1.00 mmol, 250 mg). After the exchange was complete,
Li2CuCl4 (0.01 mmol, 0.10m in THF, 0.1 mL) was added. The newly
32.2 Hz), 126.3, 125.1 (q, 3JC,F =3.7 Hz), 124.9 (q, 1JC,F =277.0 Hz), 68.8,
34.2, 31.3, 30.9, 28.4, 21.7, 19.7, 12.7 ppm; 19F NMR (C6D6, 282 MHz): d=
À62.2 ppm (s); IR (film): n˜ =3369 (s), 2961 (s), 1620 (m), 1461 (w), 1413
(m), 1321 (s), 1164 (s), 1126 (s), 1068 (s), 1017 (m), 854 cmÀ1 (m); MS
(EI, 70 eV): m/z (%): 298 (9) [M+], 280 (30), 251 (26), 241 (100), 223
formed alkenylmagnesium species
7
was quenched with DMF
(1.50 mmol, 0.12 mL). After standard work-up, the resultant oil was puri-
fied by column chromatography (pentane/ethyl acetate 9:1) to give 8a
2504
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 2499 – 2506

Functionalisation of Cyclopentenes
FULL PAPER
(116 mg, 72%) as
a
yellow oil. GC purity ꢀ99% (retention time:
method 70); 1H NMR (C6D6, 400 MHz): d=2.34 (d, 3JH,H =3.5 Hz, 1H),
1.42–1.36 (m, 1H), 1.23–1.18 (m, 1H), 1.04–0.97 (m, 2H), 0.94 (s, 3H),
0.76 (s, 3H), 0.47 ppm (s, 3H); 13C NMR (C6D6, 75 MHz): d=139.2, 99.2,
63.8, 59.5, 56.8, 31.8, 25.0, 19.6, 18.9, 13.4 ppm; IR (film): n˜ =2958 (s),
2871 (m), 1574 (m), 1472 (w), 1441 (w), 1388 (w), 1300 (w), 1152 (w),
1111 (w), 1013 (s), 969 (m), 815 (m), 773 (m), 730 cmÀ1 (s); MS (EI,
70 eV): m/z (%): 342 (36), 340 (41) [M+], 314 (12), 216 (12), 215 (98),
214 (12), 213 (96); HRMS (EI): m/z: calcd for C10H1479BrI: 339.9324;
found 339.9335.
3.07 min, measured by method 70); 1H NMR (CDCl3, 300 MHz): d=9.87
(s, 1H), 6.65–6.63 (m, 1H), 6.38–6.36 (m, 1H), 4.09 (s, 1H), 3.22 (s, 1H),
3
3
3
2.93 (sept, JH,H =6.8 Hz, 1H), 1.77 (d, JH,H =6.7 Hz, 1H), 1.63 (d, JH,H
=
3
3
6.7 Hz, 1H), 0.81 (d, JH,H =6.8 Hz, 3H), 0.63 ppm (d, JH,H =6.8 Hz, 3H);
13C NMR (C6D6, 75 MHz): d=183.5, 182.5, 147.0, 143.7, 141.0, 70.0, 51.8,
47.7, 27.0, 19.0 ppm; IR (film): n˜ =3437 (w), 2966 (s), 1659 (s), 1465 (m),
1332 (w), 1291 (m), 701 (w), 664 cmÀ1 (w); MS (EI, 70 eV): m/z (%): 162
(45) [M+], 147 (16), 133 (10), 129 (12), 119 (21), 105 (17), 96 (10), 92
(12), 91 (52), 77 (14), 67 (10), 66 (100), 65 (13), 41 (13); HRMS (EI):
m/z: calcd for C11H14O: 162.1045; found: 162.1035.
(R)-(3-Isopropyl-4,7,7-trimethylbicycloCAHTRE[UNG 2.2.1]hept-2-en-2-yl)phenylmetha-
none (13): According to typical procedure C, iPrMgCl·LiCl (2.20 mmol,
1.22m, 1.80 mL) was added to 9 (1.00 mmol, 340 mg). After the exchange
was complete (1 h, 08C), a solution of CuCN·2LiCl (1.00 mmol, 1m in
THF, 1.00 mL) was added at À608C. The newly formed alkenylmagnesi-
um species 12 was first transmetallated with ZnCl2 (1.00 mmol, 1.00m in
(3-IsopropylbicycloACHTREUNG[2.2.1]hepta-2,5-dien-2-yl)phenylmethanone (8b): Ac-
cording to typical procedure B, iPrMgCl·LiCl (2.20 mmol, 1.22m,
1.80 mL) was added to 6 (1.00 mmol, 250 mg). After the exchange was
complete, Li2CuCl4 (0.01 mmol, 0.10m in THF, 0.10 mL) was added. The
newly formed alkenylmagnesium species
7 was transmetallated with
THF, 1.00 mL) and then, after 10 min,
a solution of CuCN·2LiCl
ZnCl2 (1.0 mmol, 1.00m in THF, 1.00 mL) and then CuCN·2LiCl
(0.20 mmol, 1.00m, 0.20 mL), and the resultant copper–zinc reagent was
quenched with benzoyl chloride (1.50 mmol, 0.17 mL). After standard
work-up, the resultant oil was purified by column chromatography (pen-
tane/ethyl acetate 9:1) to give 8b (138 mg, 58%) as a pale-yellow solid.
GC purity ꢀ99% (retention time: 4.73 min, measured by method 70);
m.p. 47.8–50.48C; 1H NMR (C6D6, 400 MHz): d=7.76 (d, 3JH,H =6.7 Hz,
2H), 7.14–7.07 (m, 3H), 6.90–6.88 (m, 1H), 6.52–6.50 (m, 1H), 3.86 (s,
1H), 3.38 (s, 1H), 2.87 (sept, 3JH,H =6.7 Hz, 1H), 1.89 (d, 3JH,H =6.5 Hz,
1H), 1.85 (d, 3JH,H =6.5 Hz, 1H), 0.91 (d, 3JH,H =3.3 Hz, 3H), 0.62 ppm
(d, 3JH,H =3.3 Hz, 3H); 13C NMR (C6D6, 75 MHz): d=193.0, 172.3, 145.4,
143.4, 141.0, 140.4, 131.8, 128.7, 128.2, 69.6, 53.0, 51.7, 28.2, 20.4,
18.7 ppm; IR (film): n˜ =2966 (m), 2868 (w), 1628 (s), 1334 (m), 1288 (m),
1250 (m), 999 (w), 884 (w), 808 (w), 725 (s), 696 (m), 662 cmÀ1 (s); MS
(EI, 70 eV): m/z (%): 238 (39) [M+], 223 (11), 195 (11), 173 (17), 172
(34), 115 (10), 105 (100), 91 (22), 78 (11), 77 (80), 66 (41), 65 (14), 51
(31), 43 (11), 41 (37); HRMS (EI): m/z: calcd for C17H18O: 238.1358;
found 238.1344.
(1.00 mmol, 1.00m in THF, 1.00 mL) was added and the mixture was
quenched with benzoyl chloride (1.50 mmol, 0.17 mL) at À308C. After
standard work-up, the resultant oil was purified by column chromatogra-
phy (pentane/ethyl acetate 19:1) to give 13 (85 mg, 30%), which was re-
crystallised from heptane to give colourless crystals. GC purity ꢀ99%
(retention time: 5.28 min, measured by method 70); m.p. 61.7–64.58C;
1H NMR (C6D6, 400 MHz): d=7.97–7.95 (m, 2H), 7.13–7.10 (m, 3H),
2.76 (sept, 3JH,H =7.0 Hz, 1H), 2.64 (d, 3JH,H =3.5 Hz, 1H), 1.86–1.79 (m,
1H), 1.59–1.43 (m, 2H), 1.29–1.22 (m, 1H), 1.03–0.95 (m, 12H), 0.62 ppm
(s, 3H); 13C NMR (C6D6, 75 MHz): d=195.7, 159.9, 140.6, 140.1, 132.1,
129.1, 128.4, 58.2, 56.1, 55.6, 33.1, 29.1, 26.3, 20.8, 20.5, 20.0, 19.3,
13.2 ppm; IR (film): n˜ =2962 (s), 2872 (w), 1629 (s), 1595 (m), 1446 (m),
1331 (m), 1272 (m), 1249 (m), 809 (m), 778 (w), 720 (s), 692 (s), 660 cmÀ1
(s); MS (EI, 70 eV): m/z (%): 283 (23), 282 (100) [M+], 280 (28), 279
(18), 267 (22), 265 (20), 254 (10), 239 (25), 237 (11), 105 (35); HRMS
(EI): m/z: calcd for C20H26O: 282.1984; found 282.1992.
Kinetic measurements: A mixture of 1-bromocyclopentene[19] (1.0 equiv)
and 1-(trimethylstannyl)-2-bromocyclopentene[20] (1.0 equiv) was cooled
to À658C. iPrMgCl·LiCl (2.0 equiv) and CuCN·2LiCl (4 mol%) were
added, and the reaction mixture was slowly allowed to warm to 58C over
5 h. The progress of the reaction was monitored by GC analysis of hydro-
lysed aliquots of the reaction mixture, taken at intervals of 30 min. It was
observed that the reaction of 1-(trimethylstannyl)-2-bromocyclopentene
(t1/2 =60 min) with iPrMgCl·LiCl and catalytic CuCN·2LiCl was much
faster than that of 1-bromocyclopentene (t1/2 =135 min); 1-(trimethylstan-
nyl)-2-bromocyclopentene was fully consumed within 150 min. The re-
sults are summarized in Figure 2.
Ethyl 4-(3-isopropylbicycloACTHRE[UNG 2.2.1]hepta-2,5-diene-2-yl)benzoate (8c): Ac-
cording to typical procedure C, iPrMgCl·LiCl (2.20 mmol, 1.22m,
1.80 mL) was added to 6 (1.00 mmol, 250 mg). After the exchange was
complete, Li2CuCl4 (0.01 mmol, 0.10m in THF, 0.10 mL) was added. The
newly formed alkenylmagnesium species 7 was coupled with 4-iodoethyl
benzoate (1.50 mmol, 414 mg) in the presence of 5% [PdACHTRE(UNG dba)2]
(0.05 mmol, 29 mg) and 7% tfp (0.07 mmol, 16 mg). After standard
work-up, the resultant oil was purified by column chromatography (pen-
tane/ethyl acetate 19:1) to give 8c (177 mg, 63%) as a white solid. GC
purity ꢀ99% (retention time: 5.45 min, measured by method 70); m.p.
42.3–43.78C; 1H NMR (C6D6, 400 MHz): d=8.24 (d, 3JH,H =8.4 Hz, 2H),
3
7.21–7.19 (m, 2H), 6.79–6.77 (m, 1H), 6.66–6.64 (m, 1H), 4.15 (q, JH,H
=
7.0 Hz, 2H), 3.52 (s, 1H), 3.44 (s, 1H), 2.93 (sept, 3JH,H =6.7 Hz, 1H),
1.93 (s, 2H), 1.08–1.03 (m, 6H), 0.72 ppm (d, 3JH,H =6.7 Hz, 3H);
13C NMR (C6D6, 75 MHz): d=166.1, 158.4, 144.6, 142.5, 142.1, 129.9,
128.6, 126.2, 69.9, 60.5, 55.0, 51.1, 27.3, 21.4, 19.0, 14.2 ppm; IR (film): n˜ =
2960 (m), 1712 (s), 1604 (m), 1463 (w), 1365 (w), 1268 (s), 1176 (m), 1103
(s), 1022 (m), 857 (w), 808 (w), 772 (s), 724 (s), 708 cmÀ1 (s); MS (EI,
70 eV): m/z (%): 283 (20), 282 (100) [M+], 259 (12), 235 (17), 215 (35),
214 (55), 171 (10), 167 (11), 165 (10), 143 (52), 128 (12); HRMS (EI):
m/z: calcd for C19H22O2: 282.1620; found: 282.1635.
(R)-2-Bromo-3-iodo-1,7,7-trimethylbicyclo
ACHTRE[UGN 2.2.1]hept-2-ene (9): (R)-2-
Bromo-1,7,7-trimethylbicyclo[2.2.1]hept-2-ene (10 mmol, 2.15 g), ob-
AHCTREUNG
tained by a Shapiro reaction from the camphor hydrazone according to
the published procedure,[18] was deprotonated at the vinylic position with
LDA (25 mmol, 1m in THF) and the anion was trapped in situ with tri-
methyltin chloride (10 mmol, 2 g) as described by De Lucchi.[11] The
product 10 was not isolated, but was quenched in situ with a solution of
iodine (11.0 mmol, 2.79 g) in THF (20 mL) to yield 9. The reaction mix-
ture was concentrated under high vacuum to remove Me3SnI, the product
was extracted with pentane, and the combined extracts were washed with
saturated Na2S2O3 solution and water. The resultant oil was purified by
column chromatography (pentane) to give 9 (1.68 g, 60%) as a pale-
yellow oil. GC purity ꢀ99% (retention time: 3.71 min, measured by
Figure 2. Rates of copper-catalysed alkylation of two bromocyclopentene
~
derivatives: ^: 1-bromocyclopenten, : 1-(trimethylstannyl)-2-bromocy-
clopentene.
Chem. Eur. J. 2008, 14, 2499 – 2506
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2505

P. Knochel et al.
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Acknowledgements
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[13] CCDC 650282 contains the supplementary crystallographic data for
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We thank the Fonds der Chemischen Industrie and the Deutsche For-
schungsgemeinschaft (DFG) for financial support. R.C.B. thanks the Nat-
ural Sciences and Engineering Research Council of Canada and the
Ludwig-Maximilians Universität for scholarships. We also thank BASF
AG (Ludwigshafen), Degussa AG (Hanau), and Chemetall GmbH
(Frankfurt) for generous gifts of chemicals.
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Received: September 11, 2007
Published online: January 29, 2008
2506
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Chem. Eur. J. 2008, 14, 2499 – 2506