Arylation of alkenylidenecyclopropanes via Heck reaction. A simple access to arylallylidenecyclopropanes

Article abstract of DOI:10.1016/j.tet.2010.01.052

Five alkenylidenecyclopropanes have been arylated using a catalytic amount of [Pd(C₃H₅)Cl]₂ (0.004%) associated to the tetradentate ligand cis, cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane or Tedicyp as t

Full text of DOI:10.1016/j.tet.2010.01.052

Tetrahedron 66 (2010) 2181–2188
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Arylation of alkenylidenecyclopropanes via Heck reaction. A simple access
to arylallylidenecyclopropanes
,
a,
*
Yacoub Fall a, Henri Doucet b , Maurice Santelli
*
a Laboratoire Chimie Provence, UMR 6264, Faculte´ des Sciences de St-Je´roˆme, Universite´ d’Aix-Marseille, Avenue Escadrille Normandie-Niemen 13397 Marseille Cedex 20, France
b Institut Sciences Chimiques de Rennes, UMR 6226, Universite´ de Rennes 1 ‘‘Catalyse et Organome´talliques’’, Campus de Beaulieu 35042 Rennes, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Five alkenylidenecyclopropanes have been arylated using a catalytic amount of [Pd(C3H5)Cl]2 (0.004%)
associated to the tetradentate ligand cis, cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane
or Tedicyp as the catalyst. The carbo-palladation step occurs on the terminal double bond of the vinyl-
idenecyclopropanes, without interaction with the internal one. The addition of the complex PdArL2
corresponds to an electrophilic attack on the face of the double bond, syn to the best electron-donor
cyclopropyl substituent.
Received 16 December 2009
Accepted 11 January 2010
Available online 25 January 2010
Keywords:
Alkenylidenecyclopropanes
Arylallylidenecyclopropanes
Heck reaction
Ó 2010 Elsevier Ltd. All rights reserved.
Tetradentate ligand
Allenes
1. Introduction
Here, we wish to describe the Heck type coupling reaction of
aryl bromides with alkenylidenecyclopropanes to give arylallyli-
In the modern chemistry of the palladium-catalyzed reactions,
the Heck–Mizoroki vinylation reaction is one of the most important
carbon–carbon bonds forming process. From the seminal reports of
Heck, which described the fascinating reactivity of organo-
palladium compounds prepared in situ by exchange reactions with
corresponding organomercury derivatives,1 and Mizoroki,2 con-
cerning the phenylation of ethylene, propene and styrene using
a catalytic amount of palladium catalyst; an impressive number of
applications have been described both at the laboratory and in-
dustrial scale.
denecyclopropanes in good yields.3 To the best of our knowledge,
alkenylidenecyclopropanes have not been employed in the Heck
reactions.4
Vinylidenecyclopropanes are some of the most remarkable hy-
drocarbon compounds known. They have an allene moietyconnected
by a cyclopropane ring, and yet they are thermally stable and reactive
substances. Alkenylidenecyclopropanes are readily available by the
addition of Hatzler’s carbene (alkenylidene carbene)5 to alkenes
(Scheme 1).6 The synthetic availability of vinylidenecyclopropanes
enhances their attractiveness as reactive building blocks.
or
or
3
2
Me
Me
R
R
t-BuOK
pentane
1
1
2
3
+
R
H
H
Cl
Me
or
3
R
= Me or H
5
4
Scheme 1. Preparation of alkenylidenecyclopropanes 1–5.
These highly unsaturated small-ring compounds undergo ther-
mal interconversions,7 and present an unusual behavior in the
course of electrophilic additions (acidic medium,8 acetoxymercura-
tion,9 ozonolysis,10 radical additions,11 cycloadditions,12 homoallenyl
* Corresponding authors. Fax: þ33 4 91289112.
E-mail addresses: henri.doucet@univ-rennes1.fr (H. Doucet), m.santelli@
univ-cezanne.fr (M. Santelli).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.052

2182
Y. Fall et al. / Tetrahedron 66 (2010) 2181–2188
participation,13). Carbolithiation reactions led to allenols or vinyl-
cyclopropenes,14 and BuLi-mediated carboxylation to corresponding
carboxylic adducts.15 The cycloaddition of vinylidenecyclopropanes
with aldehydes gave rise to tetrahydrofuranes.16 The reaction of
Fischer chromiumcarbene complexes with alkenylidene-cyclopro-
panes afforded allylidenecyclopropanes in good yields.17 Recently,
palladium-catalyzed synthesis of 1,3-dienes from intramolecular18
or intermolecular19 Heck reactions of allenes with aryl halides have
been described. Quite often, 1,3-dienes have been trapped in situ by
Br
1
+
+
S
S
6m
7m
Br
1
N
N
a Diels–Alder reaction.20 Recently, many
p-allylpalladium com-
6n
7n
plexes resulting from the addition of [PdI(Ph)(PPh3)]2 to allenes
Scheme 3. Heck reaction of 1 with 3-bromothiophene 6m or 4-bromoisoquinoline 6n.
have been described.21
2. Results
We prepared the alkenylidenecyclopropanes 1–5 via the re-
action of propargyl chlorides with alkenes in the presence of po-
tassium tert-butoxide (Scheme 1).
Then, these compounds have been arylated using a catalytic
amount (0.004%) of [Pd(C3H5)Cl]2 associated to the tetradentate
ligand, cis, cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cy-
clopentane or Tedicyp as the catalyst.22
We have already reported several results concerning the effi-
ciency of this tetraphosphine ligand for palladium-catalyzed cross-
coupling reactions23 and particularly for Heck vinylation.24 The
presence of the four diphenylphosphino groups on the same face of
the cyclopentane ring seems to increase the stability and longevity
of the catalyst.
Figure 1. ORTEP diagram of compound 7f.
We observed that using our catalyst [Pd(C3H5)Cl]2/2 Tedicyp
with N,N-dimethylacetamide as the solvent and potassium car-
bonate as the base, the aryl bromides 6a–l cleanly react with 1 to
give the 3-aryl-2-methyl-3-(2,2,3,3-tetramethylcyclopropylide-
ne)propenes 7a–l in 46–65% yields (Scheme 2). In the course of
this reaction no formation of by-product was detected. Moreover,
the reaction allows the use of a relatively high substrate/catalyst
ratio of 250.
Table 1
Selected bond lengths and angles of 7f
Compound
Bond length (Å)
Angle (ꢀ)
C1–C2:1.328
C2–C3:1.483
C3–C4:1.338
C4–C5:1.475
C4–C6:1.473
C5–C6:1.549
C2–C7:1.494
C3–C8:1.494
C5–C9:1.512
C2–C3–C8:119.1
C5–C4–C6:63.4
C4–C5–C6:58.2
C4–C6–C5:58.4
C9–C5–C90:112.3
C10–C6–C10’:112
1
2
O
7
3
8
5
4
9
10
6
9'
10'
7f
[Pd(C H )Cl] /
2
3
5
1
0.5 Tedicyp
+
DMAc, K CO , 150 °C
2
3
Br
R
R
Ph P
2
7a−l 46-65%
PPh
2
Ph P
2
6a−l
PPh
2
Br
+
2
O
Tedicyp
R: a, H; b, 3-Me; c, 4-tert-Bu; d, 4-HCO; e, 4-MeCO;
6e
O
8 62%
f, 4-PhCO; g, 4-CO Me; h, 4-CN; i, 2-CN; j, 4-NO ;
2
2
Scheme 4. Heck reaction of 2 with 4-bromoacetophenone 6e.
k, 3-NO ; l, 4-CF .
2
3
Scheme 2. Heck reaction of 1-(2-methylpropenylidene)-2,2,3,3-tetramethylcyclopro-
pane 1 with aryl bromides 6a–l.
Heck coupling reaction of vinylidenecyclopropane 3 with 4-
bromobenzaldehyde or 4-bromoanisole led to a mixture of prod-
ucts 9d/10d and 9o/10o. With this vinylidenecyclopropane, the
elimination of PdHBrLn at the end of the catalytic cycle can occur on
both alkyl substituents (Scheme 5). The major products 9d or 9o
arises from the elimination of the most acidic proton.
The Heck coupling reaction involving vinylidenecyclopropane 4
is also very interesting, as the choice of the face for the addition of
ArPdBrLn to the allenic double bond will determine the geometry
cis-trans of the products. The NOESY of the inseparable mixture of
11e and 12e is shown in the Scheme 6. It clearly indicates that the
major isomer 11e has a Z-configuration. Therefore, the addition of
palladium seems to occur on the face containing the dimethyl
group of the cyclopropane.
The reactions using the heteroaryl bromides, 3-bromothiophene
6m or 4-bromoisoquinoline 6n also led to the corresponding aryl-
allylidenecyclopropanes 7m and 7n in good yields (Scheme 3).
The structure of products 7a–n was determined using 1H and 13
C
NMR spectroscopic data and the structure of 7f has been confirmed
by crystal X-ray analysis (Fig. 1 and Table 1).
Then, we explored the scope of this reaction using other alke-
nylidenecyclopropanes. A similar result was observed for the re-
action of 1-cyclohexenylylidene-2,2,3,3-tetramethyl-cyclopropane
2 with 4-bromoacetophenone 6e, which gave 8 in 62% yield
(Scheme 4).

Y. Fall et al. / Tetrahedron 66 (2010) 2181–2188
2183
[Pd(C3H5)Cl]2
0.5 Tedicyp
/
PdL2
3
+
+
HPdBrL2
+
DMAc, K2CO3, 150 °C
R
Br
R
R
R
6d
)
6o
)
R = CHO (
R = MeO (
9d
9o
66:34
63:37
10d
10o
Scheme 5. Heck reaction of 3 with 4-bromobenzaldehyde (6d) or 4-bromoanisol (6o).
H
R
NOE
[Pd(C3H5)Cl]2
0.5 Tedicyp
/
H
H
H
4
+
+
DMAc, K2CO3, 150 °C
R
Br
R
O
R = CHO (6d)
6e
11d
11e
11h
12d
12e
12h
72:28
76:24
80:20
11e
R = MeCO (
6h
)
R = CN (
)
Scheme 6. Heck reaction of 4 with 4-bromobenzaldehyde (6d), 4-bromoacetophenone (6e) or 4-bromobenzonitrile (6h). NOE experiments for 11e.
Similarly, the Heck reaction of the 1-cyclohexenylylidene-2,2,3-
trimethylcyclopropane 5 with three aryl bromides led to mixtures
of isomers (Scheme 7). Again, the Z-configuration was the major
one in all cases.
Ar
XH
(Base)
R
L
H Pd L
X
L
Pd
X
F
H
H
L
L
PdL2
CO Me
2
Ar
R
A
ArX
H
E
H
5
+
+
B
L
Pd
L
Ar Pd L
X
X
Ar
R
Br
R
D
H
R
C
R = CHO (6d)
13d
13g
13h
72:28
80:20
78:22
14d
14g
14h
L
X
R
R = MeO C (6g)
2
Ar Pd L
R = CN (6h)
R
Scheme 7. Heck reaction of 5 with 4-bromobenzaldehyde (6d), methyl 4-bromo-
benzoate (6g) or 4-bromobenzonitrile (6h).
Scheme 8. General mechanism of the Heck coupling reaction.
3. Discussion
involved. For example, with 1,2-allenyl sulfones, Ma demonstrated
that the Heck reaction gave rise to polysubstituted 1,2-allenyl sul-
fones,26 according to the reactive way A–C, resulting from the co-
ordination of palladium to the central atom of the allene. In a few
other examples, the palladium was linked to one of the terminal
carbon atoms of the allene, and then, the mechanisms of the re-
actions involve intermediates E, F or G.18,19
In the case of the vinylidenecyclopropanes, the carbo-palladation
step occurs on the terminal double bond. Many electrophilic additions
and cycloadditions occurred in a similar manner. For example, the
The general mechanism for the Heck reaction involves the for-
mation of a palladium(II) species B (oxidative addition) from the
catalyst A, followed by the coordination of the alkene to give com-
plex C. Then, the insertion of this alkene in the Ar–Pd bond gives D.
Next, the change of the conformation gives E in order to allow a syn-
elimination of the product, and the formation of the palladium hy-
dride F. Finally, F undergoes a base assisted elimination which
regenerates the active palladium(0) catalyst A (Scheme 8).25
For the Heck reaction involving allenic compounds, previous
studies concerning a wide range of aryl and heteroaryl iodides have
demonstrated that these aryl halides undergo oxidative addition to
Pd(0) followed by addition of the resulting RPdX species to
the central carbon atom of the allene moiety. The formation of a
reported 2þ2 addition of chlorosulfonyl isocyanate leading to a
b-lac-
tam derivative confirms this polarization (Scheme 10a).8c,9,28 These
results contrast with the polar addition reactions of electrophilic re-
agents to 1. In most cases, an opening of the cyclopropane ring occurs
with the formation of an acetylenic bond (Scheme 10b).8c,29
p
-allylpalladium(II) species was assumed. In the absence of a suit-
able nucleophile, this allylic species undergoes a slow -hydride
elimination, generating a substituted 1,3-diene. It should be men-
tioned that the
3-coordination cannot be formed in the first step,
due to the orthogonal orbitals of the allene.26,28 The 1-allyl pre-
The Scheme 11 takes into account the general results. After the
oxidative addition of the aryl bromide to palladium, and co-
ordination of the alkenylidenecyclopropane 1, the insertion of 1 in
b
h
the Ar–Pd bond gives intermediate A. Then, the b-hydride elimi-
h
nation forms the products 7. As the reaction of Fischer chro-
miumcarbene complexes,17 the reaction described here is a formal
ene reaction involving the Ar–Pd bond. The catalytically active
Pd(0) species is regenerated by the base.
cursor complexes A or D that lacks the conjugation to the remaining
double bond are always formed first (Scheme 9).27 According to the
nature of the allene substituents, two major process can be

2184
Y. Fall et al. / Tetrahedron 66 (2010) 2181–2188
R1 PdX
R3
XPd
H
R3
R1
R2
R3
R4
H
R4
R2
R2
R4
R4
R1
H
C
A
B
R3
R1X
+
Pd(0) +
R4
R2
H
R1
H
R1
R1 PdX
R3
H
reported
protocol
R2
PdX
R2
R2
R4
R3
R4
R3
D
E
F
R1
XPd
Nu
R1
R2
R3
R4
F
H
G
R2
Nu
R4
R3
G
Scheme 9. General mechanisms for the Heck coupling reactions involving allene reagents.
a)
b)
2
1
O
+
ClSO2 N C O
N
SO2Cl
1
Nu
2
3
1
5
4
El
3
2
1
5
+
El-Nu
+
4
1
H(+)
El
(+)
(+)
H
H
Scheme 10. Previously reported electrophilic additions to alkenylidenecyclopropane 1.
Figure 2. ORTEP diagram of alkenylidenecyclopropane 1.
3
2
1
Table 2
Structure of alkenylidenecyclopropane 1
Pd(0)L2
1
Br
PdBrL2
Bond lengtha (Å)
Bond lengthb (Å)
X-ray measured
bond length (Å)
R
R
C(1)–C(2)bond
PdL2 Br
C(1)–C(2)
C(2)–C(3)
C(3)–C(4)
C(4)–C(4’)
C(4)–C(5)
C(1)–C(6)
1.314
1.288
1.490
1.552
1.524
1.524
1.323
1.298
1.488
1.545
1.519
1.511
1.306
1.291
1.488
1.546
1.512
1.497
+
H PdL2 Br
Base
Pd(0)L2
R
R
A
7a−n
Angle
Calcd anglea (ꢀ)
Calcd angleb (ꢀ)
X-ray measured
angle (ꢀ)
Scheme 11. Mechanism of the Heck coupling reaction involving alkenylidenecyclo-
propane 1.
C(6)–C(1)–C(60)
C(4)–C(3)–C(40)
C(3)–C(4)–C(40)
C(5)–C(4)–C(50)
118.6
62.8
58.6
116.6
62.6
58.7
116.0
62.6
58.7
Veryconstraint compounds 7, 9–14 have been obtained in similar
yields both from electron-poor aryl bromides such as 4-bromo-
benzaldehyde, 4-bromoacetophenone, 4-bromobenzo-phenone,
111.9
112.4
112.1
a
B3LYP/6.311Gþþ(d,p).
MP2/6.311Gþþ(d,p).
methyl
4-bromobenzoate,
4-nitrobromobenzene,
3-nitro-
b
bromobenzene, 4-bromobenzonitrile or 4-bromoisoquinoline and
from electron-rich aryl bromides such as 3-bromotoluene, 4-tert-
butylbromobenzene or 3-bromothiophene. This observation in-
dicates that the rate-limiting step of the reaction is probably not the
oxidative addition of the aryl bromide to the palladium complex, but
more likely the insertion of the C(1)–C(2) double bond in the Ar–Pd
bond. The reaction even occurs with the ortho-substituted aryl
bromide, 2-bromobenzonitrile 6i.
The structure of alkenylidenecyclopropane 1 has been calcu-
lated at the B3LYP/,30 and MP2/,31 levels using the 6.311Gþþ(p,d)
basis sets.32 This structure was confirmed by X-ray crystal analysis
(Fig. 2, and Table 2).
The very high regioselectivity of the carbo-palladation step is
certainly determined by electronic factors. Calculations have shown
that the HOMO’s of 1 and 4 are mainly localized on C(1)–C(2)
double bond [1,
(the LUMO is not clearly localized). The difference of positive
charges between C(1) and C(2) is important (1, q[C(1)]¼0.446;
q[C(2)]¼0.244). The HOMO-1 is localized on C(2)–C(3) double
bond. The palladium atom attacks the most charged carbon atom,
which also bears the largest relative sizes of component atomic
orbitals of the HOMO. The previously reported 2þ2 addition of
Satom. coef.(j2sj,j2pj), C(1)¼0.193; C(2)¼0.156]

Y. Fall et al. / Tetrahedron 66 (2010) 2181–2188
2185
chlorosulfonyl isocyanate leading to a
b
-lactam derivative is in ac-
complexes containing chelating diphosphines, might be less robust
than those containing monodentate phosphine ligands due to the
inability of the phosphorus donors to adopt the thermodynamically
more stable trans-geometry.25f More generally, small ring chelated
palladium species, such as with dppm, seems to be poor catalysts
for the Heck reaction.25a Concerning Tedicyp ligand, its complexa-
tion with Pd might led to 4 different rings types.36 We believe that,
according to the step of the catalytic cycle, the appropriate con-
formation of the Pd-Tedicyp complex will be formed to increase the
efficiency of the catalyst and this might help to obtain high turn-
over numbers (Scheme 13).
cordance with this polarization of the HOMO.8c,28
The preservation of the alkenylidenecyclopropane moiety
seems to reveal that a
p-allylpalladium intermediate, where the
carbon atom bears a positive charge leading to a nucleophilic at-
tack from nucleophiles as hydroxyl anion or acetate anion, is not
involved in the course of this reaction.4d To confirm the instability
of the cyclopropylallylique cation, we have calculated at the
B3LYP/6-311G(þþ)(d,p) level of theory, the total energies of the
two cations A (E¼ꢁ661.530658 hartrees, ZPE¼0.348932 hartree,
D
G¼ꢁ661.229640 hartrees) and
ZPE¼0.348887 hartree, G¼ꢁ661.250907 hartrees). The isomeri-
zation is an exothermic process by 13.3 kcal/mol33 (Scheme 12).
B
(E¼ꢁ661.553526 hartrees,
D
Pd
PPh2
Pd
Ph2P
Ph2P
PPh2
PPh2
Ph2P
Ph2P
PPh2
3
2
1
5
X
Pd(+)
HO(–)
+
Pd(II)
4
(+)Pd
7-members chelate
Pd
7-members chelate
1
Pd
products (alcohols)
Ph2P
Ph2P
Ph2P
Ph2P
PPh2
PPh2
PPh2
PPh2
(+)
(+)
8-members chelate
8-members chelate
A
B
Scheme 13. Chelation of palladium complex by Tedicyp.
Scheme 12. Stability of the allylcyclopropane cations.
4. Conclusion
The Heck reaction of vinylidenecyclopropanes 4 and 5 mainly
occurs on the most hindered face (face bearing the two methyl
groups) (syn-face preference). In fact, for 4, calculations at the
B3LYP/6-311G(þþ)(d,p) level of theory, shown that the HOMO
(38th OM) localized on C(1)–C(2) present an anisotropy. The orbital
is expanding on the face bearing the dimethyl groups including the
C(3)–C(4) bond (Fig. 3)(orbital distortions). In contrast, the LUMO
(39th OM) was relocalized on several atoms including carbon
atoms of the methyl. The complex PdArL2 adds to 4 or 5 in accor-
dance with the interaction of the LUMO of the Pd–Ar bond with the
HOMO of allenic compounds. So, the addition occurred according to
In conclusion, we have developed a simple access to highly
complex structures starting from simple molecules in four steps
from propargyl alcohols, alkenes and aryl bromides. Many methyl-
enecyclopropanes are interesting compounds, due to their biological
properties.37 Moreover, we have demonstrated that the Heck re-
action occurred on the terminal double bond of the allene moiety
without interaction with the internal one. Finally, the addition of the
complex PdArL2 corresponds to an electrophilic attack on the face of
the double bond, syn to the best electron-donor cyclopropyl
substituent.
the p
-facial selectivity of the electrophilic additions:34 it is observed
that the preferred direction of attack by the complex PdArL2 was syn to
the best electron-donor bond among the vicinal substituents.
4.1. X-ray crystallography
CCDC-751561 (for 1) and CCDC-752203 (for 7f) contain the
supplementary crystallographic data for this paper. These data can
be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrie-
ving.html [or from the Cambridge Crystallographic Data Center, 12
Union Road, Cambridge CB2 1EZ, UK; fax: (internet.) þ44 1223 336
033; or e-mail: deposit@ccdc.cam.ac.uk].
5. Experimental part
5.1. General information
All reactions were run under argon in oven-dried glassware.
Reagents and solvents were obtained from commercial sources and
used as received. Flash column chromatography (FC): Merck 230–
400 Mesh silica gel; EtOAc, Et2O and petroleum ether as eluents.
Thin-layer chromatography (TLC): Macherey–Nagel silica gel UV254
analytical plates; detection either with UV, or using revealing so-
Figure 3. HOMO (38th OM) of the alkenylidenecyclopropane 4.
The following step is the b-hydride elimination to give the 1,3-
diene and the palladium hydride F PdBrHL2 (Scheme 8). In the case
of the vinylidenecyclopropane 3, a mixture of the two 1,3-dienes 9
13
and 10 is obtained, but the major one correspond to the
b-elimi-
lution. 1H and C NMR spectra were recorded at 25 ꢀC in CDCl3
nation of the most acidic proton according to the Hoffmann rule,
affording the kinetic diene 9 at the detriment of the thermody-
namic diene 10.35 The orientation of the double bond might result
from the great size of the palladium complex.
This arylation reaction is catalyzed by a palladium associated to
the tetraphosphine ligand, Tedicyp. It is accepted that some metal
solutions at 500 or 300, and 125 or 75 MHz, respectively, using
a Bruker Advance DPX 500 or AC300 spectrometers. Chemical shift
in parts per million relative to CDCl3 (signals for residual CHCl3 in
the CDCl3: 7.24 ppm for 1H NMR and 77.16 ppm (central) for 13C
NMR). Carbon-proton couplings were determined by DEPT se-
quence experiments.

2186
Y. Fall et al. / Tetrahedron 66 (2010) 2181–2188
5.1.1. 1-(2-Methylpropenylidene)-2,2,3,3-tetramethylcyclo-propane
(1)5,7a 1H NMR (300 MHz, CDCl3) 1.72 (s, 6H), 1.20 (s, 12H); 13C
183.4 (s), 97.1 (s), 96.1 (s), 27.3 (s)(2C), 21.8
J¼1.48 Hz, 1H), 4.62 (br q, J¼0.8 Hz, 1H), 2.00 (br q, J¼0.6 Hz, 3H),
1.23 (s, 6H); 1.00 (s, 6H); 13C NMR (75 MHz, CDCl3)
192.3 (d), 148.2
(s), 143.6 (s), 134.7 (s), 131.3 (s), 129.7 (s), 129.5 (d)(4C), 114.8 (t),
22.3 (s), 22.1 (q), 21.8 (q)(2C), 21.0 (q)(2C), 20.5 (s). C18H22O (254.4):
C 84.99, H 8.72; found C 84.91, H 8.65.
.
d
d
NMR (75 MHz, CDCl3)
(q)(2C), 21.6 (q)(4C).
d
5.1.2. 1-Cyclohexenylidene-2,2,3,3-tetramethylcyclopropane (2). 1H
NMR (300 MHz, CDCl3) 2.16–2.11 (m, 4H), 1.63–1.51 (m, 6H), 1.21
(s,12H); 13C NMR (75 MHz, CDCl3)
180.3 (s),104.6 (s), 96.4 (s), 32.7
d
5.1.11. 3-(4-Acetylphenyl)-2-methyl-3-(2,2,3,3-tetramethyl-cyclo-
d
propylidene)propene (7e). Yield 60%. 1H NMR (300 MHz, CDCl3)
(t)(2C), 27.8 (t)(2C), 27.2 (s)(2C), 26.5 (t), 21.6 (q)(4C). C14H22
(190.2): C 88.35, H 11.65; found C 88.22, H 11.75.
d
7.90 (d, J¼8.3 Hz, 2H), 7.29 (d, J¼8.3 Hz, 2H), 4.98 (br t, J¼1.5 Hz,
1H), 4.62 (br s,1H), 2.59 (s, 3H),1.98 (s, 3H),1.22 (s, 6H), 0.99 (s, 6H);
13C NMR (75 MHz, CDCl3)
198.1 (s), 147.7 (s), 146.7 (s), 143.7 (s),
d
5.1.3. 1-(2-Methylbutenylidene)-2,2,3,3-tetramethylcyclo-propane
135.3 (s), 131.3 (s), 129.1 (d)(2C), 128.1 (d)(2C), 114.7 (t), 26.7 (q),
22.3 (s), 22.1 (q), 21.8 (q)(2C), 21.0 (q)(2C), 20.5 (s). High resolution
ESI-MS calcd for [C19H24OþH]þ: 269.1899. Found: 269.1896.
(3). 1H NMR (300 MHz, CDCl3)
d
1.96 (q, J¼7.3 Hz, 2H), 1.74 (br s,
3H), 1.23 (s, 6H), 1.22 (s, 6H), 0.96 (t, J¼7.3 Hz, 3H); 13C NMR
(75 MHz, CDCl3)
d 182.4 (s), 103.9 (s), 98.4 (s), 27.7 (t), 27.2 (s), 21.5
(q)(4C), 20.5 (q), 12.5 (q). C12H20 (164.2): C 87.73, H 12.27; found C
87.82, H 12.05.
5.1.12. 3-(4-Benzoylphenyl)-2-methyl-3-(2,2,3,3-tetramethyl-cyclo-
propylidene)propene (7f). Yield 63%. 1H NMR (300 MHz, CDCl3)
d
7.80 (d, J¼8.5 Hz, 2H), 7.70 (d, J¼8.5 Hz, 2H), 7.56 (t, J¼7.4 Hz, 1H),
5.1.4. 1-(2-Methylpropenylidene)-2,2,3-trimethylcyclopropane
7.46 (t, J¼7.4 Hz, 2H), 7.33 (d, J¼8.2 Hz, 2H), 5.02 (br s, 1H), 4.70 (br
(4)5. 1H NMR (300 MHz, CDCl3)
d
1.72 (s, 6H), 1.20 (br s, 10H); 13C
s, 1H), 2.01 (s, 3H), 1.24 (s, 6H); 1.03 (s, 6H); 13C NMR (75 MHz,
NMR (75 MHz, CDCl3)
d
184.7 (s), 97.3 (s), 92.4 (s), 24.1 (s), 21.7 (q*,
CDCl3) d 196.6 (s), 147.6 (s), 146.0 (s), 143.7 (s), 138.0 (s), 135.4 (s),
d*), 21.5 (q*,d*), 18.9 (q), 13.2 (q).
132.2 (d), 131.4 (s), 130.0 (d)(2C), 129.9 (d)(2C), 128.7 (d)(2C), 128.3
(d)(2C), 114.7 (t), 22.2 (s), 22.1 (q), 21.8 (q)(2C), 21.0 (q)(2C), 20.5 (s).
C24H26O (330.5): C 87.23, H 7.93; found C 87.41, H 7.85.
5.1.5. 1-Cyclohexenylidene-2,2,3-trimethylcyclopropane (5). 1H NMR
(300 MHz, CDCl3)
d 2.17–2.12 (m, 4H), 1.60–1.50 (m, 7H), 1.20 (s,
3H), 1.14 (d, J¼4.9 Hz, 3H), 1.13 (3H, s); 13C NMR (75 MHz, CDCl3)
5.1.13. 3-(4-Methoxycarbonyl)phenyl-2-methyl-3-(2,2,3,3-tetrame-
d
181.5 (s), 104.9 (s), 92.6 (s), 32.8 (t), 32.5 (t), 27.7 (t), 27.6 (t), 26.5
thylcyclopropylidene)-propene (7g). Yield 52%. 1H NMR (300 MHz,
(q*), 26.5 (t), 26.3 (d*), 24.1 (s), 19.1 (q), 13.4 (q). C13H20 (176.3): C
88.57, H 11.43; found C 88.62, H 11.55.
CDCl3)
4.63 (br s, 1H), 3.90 (s, 3H), 1.99 (s, 3H), 1.23 (s, 6H), 0.99 (s, 6H); 13C
NMR (75 MHz, CDCl3) 167.4 (s), 147.5 (s), 146.5 (s), 143.7 (s), 131.4
d
7.97 (d, J¼8.3 Hz, 2H), 7.27 (d, J¼8.3 Hz, 2H), 4.99 (br s, 1H),
d
5.1.6. General procedure for the arylation of alkenylidenecyclo-
(s), 129.2 (d)(2C), 128.9 (d)(2C), 128.1 (s), 114.6 (t), 52.1 (q), 22.3 (s),
22.0 (q), 21.8 (q)(2C), 21.0 (q)(2C), 20.4 (s). C19H24O2 (284.4): C
80.24, H 8.51; found C 80.16, H 8.58.
propanes. As
a
typical experiment, 4-bromoacetophenone
(200 mg, 1.0 mmol), 1 (300 mg, 2.0 mmol) and K2CO3 (276 mg,
2.0 mmol) in DMAc (10 mL) in the presence of catalyst22
(0.004 mmol) are heated under argon for 20 h at 150 ꢀC. Usual
work-up gives rise to 161 mg of 7e (60% yield).
5.1.14. 3-(4-Cyanophenyl)-2-methyl-3-(2,2,3,3-tetramethyl-cyclo-
propylidene)propene (7h). Yield 64%. 1H NMR (300 MHz, CDCl3)
d
7.57 (d, J¼8.3 Hz, 2H), 7.29 (d, J¼8.3 Hz, 2H), 4.99 (br s, 1H), 4.57
(br s, 1H), 1.97 (s, 3H), 1.22 (s, 6H); 0.99 (s, 6H); 13C NMR (75 MHz,
CDCl3) 148.5 (s), 146.4 (s), 143.4 (s), 131.8 (d)(2C), 130.9 (s), 129.6
(d)(2C), 119.4 (s), 114.9 (t), 110.0 (s), 22.4 (s), 22.0 (q), 21.8 (q)(2C),
21.0 (q)(2C), 20.5 (s). C18H21N (251.4): C 86.01, H 8.42; found C
85.92, H 8.48.
5.1.7. 3-Phenyl-2-methyl-3-(2,2,3,3-tetramethylcyclo-propylidene)-
propene (7a). Yield 46% . 1H NMR (300 MHz, CDCl3)
d
7.30–7.18 (m,
5H), 4.97 (t, J¼1.7 Hz, 1H), 4.66 (d, J¼1.5 Hz, 1H), 2.00 (br s, 3H), 1.23
(s, 6H), 1.00 (s, 6H); 13C NMR (75 MHz, CDCl3)
146.1 (s), 144.3 (s),
d
d
141.4 (s), 132.0 (s), 129.0 (d)(2C), 127.7 (d)(2C), 126.2 (d), 114.3 (t),
22.1 (s), 22.1 (q), 21.9 (q)(2C), 21.1 (q)(2C), 20.3 (s). C17H22 (226.4): C
90.20, H 9.80; found C 89.88, H 9.75.
5.1.15. 3-(2-Cyanophenyl)-2-methyl-3-(2,2,3,3-tetramethyl-cyclo-
propylidene)propene (7i). Yield 62%. 1H NMR (300 MHz, CDCl3)
5.1.8. 3-(3-Methylphenyl)-2-methyl-3-(2,2,3,3-tetramethyl-cyclo-
d
7.62 (dd, J¼7.8, 0.8 Hz, 1H), 7.52 (td, J¼7.7, 1.3 Hz, 1H), 7.34 (td,
J¼7.6, 1.3 Hz, 1H), 4.95 (t, J¼1.3 Hz, 1H), 4.28 (br s, 1H), 2.15 (s, 3H),
1.27 (s, 6H), 0.91 (s, 6H); 13C NMR (75 MHz, CDCl3)
148.8 (s), 146.0
propylidene)propene (7b). Yield 48%. 1H NMR (300 MHz, CDCl3)
d
7.15 (t, J¼7.2 Hz, 1H), 7.01 (m, 3H), 4.96 (sept., J¼1.2 Hz, 1H), 4.67
(t, J¼1.1 Hz, 1H), 2.32 (s, 3H), 1.98 (s, 3H), 1.22 (s, 6H), 1.00 (s, 6H);
13C NMR (75 MHz, CDCl3)
145.7 (s), 144.3 (s), 141.2 (s), 137.1 (s),
d
(s), 143.3 (s), 132.5 (d), 132.2 (d), 130.6 (d), 129.1 (s), 127.0 (d), 114.3
(t), 113.4 (s), 23.0 (s), 21.8 (q)(2C), 21.4 (q), 20.43 (s), 20.37 (q)(2C).
C18H21N (251.4): C 86.01, H 8.42; found C 86.12, H 8.40.
d
132.0 (s), 129.7 (d), 127.6 (d), 126.9 (d), 126.0 (d), 114.2 (t), 22.1 (q),
22.1 (s), 21.9 (q)(2C), 21.6 (q), 21.1 (q)(2C), 20.3 (s). C18H24 (240.4): C
89.94, H 10.06; found C 89.96, H 10.12.
5.1.16. 2-Methyl-3-(4-nitrophenyl)-3-(2,2,3,3-tetramethyl-cyclo-
propylidene)propene (7j). Yield 59%. 1H NMR (300 MHz, CDCl3)
5.1.9. 3-(4-tert-Butylphenyl)-2-methyl-3-(2,2,3,3-tetramethyl-cyclo-
d
8.15 (d, J¼8.8 Hz, 2H), 7.36 (d, J¼8.8 Hz, 2H), 5.02 (quint; J¼1.45,
1H), 4.59 (br s, 1H), 1.99 (s, 3H), 1.23 (s, 6H); 1.00 (s, 6H); 13C NMR
(75 MHz, CDCl3) 149.0 (s), 148.6 (s), 146.5 (s), 143.4 (s), 130.6 (s),
propylidene)propene (7c). Yield 48%. 1H NMR (300 MHz, CDCl3)
d
7.29 (d, J¼8.5 Hz, 2H), 7.14 (d, J¼8.5 Hz, 2H), 4.98 (br s, 1H), 4.72
(br s, 1H), 1.98 (s, 3H), 1.32 (s, 9H); 1.21 (s, 6H), 1.04 (s, 6H); 13C NMR
(75 MHz, CDCl3) 149.0 (s), 145.1 (s), 144.5 (s), 137.8 (s), 131.7 (s),
d
129.6 (d)(2C), 123.3 (d)(2C), 115.0 (t), 22.5 (s), 22.1 (q), 21.8 (q)(2C),
21.0 (q)(2C), 20.6 (s). C17H21NO2 (271.4): C 75.25, H 7.80; found C
75.15, H 7.88.
d
128.2 (d)(2C), 124.6 (d)(2C), 114.2 (t), 34.6 (s), 31.6 (q)(3C), 22.8 (s),
22.4 (q), 21.9 (q)(2C), 21.1 (q)(2C), 20.4 (s). C21H30 (282.5): C 89.29,
H 10.71; found C 89.21, H 10.78.
5.1.17. 2-Methyl-3-(3-nitrophenyl)-3-(2,2,3,3-tetramethyl-cyclo-
propylidene)propene (7k). Yield 55%. 1H NMR (300 MHz, CDCl3)
5.1.10. 3-(4-Formylphenyl)-2-methyl-3-(2,2,3,3-tetramethyl-cyclo-
d
8.09 (br s, 1H), 7.55–7.36 (m, 3H), 5.02 (br s, 1H), 4.59 (br s, 1H),
2.00 (s, 3H), 1.24 (s, 6H), 1.01 (s, 6H); 13C NMR (75 MHz, CDCl3)
148.6 (s), 148.3 (s), 143.4 (s), 143.2 (s), 135.0 (d), 130.3 (s), 128.7 (d),
propylidene)propene (7d). Yield 65%. 1H NMR (300 MHz, CDCl3)
d
10.00 (s), 7.81 (d, J¼8.3 Hz, 2H), 7.36 (d, J¼8.3 Hz, 2H), 5.00 (quint.
d

Y. Fall et al. / Tetrahedron 66 (2010) 2181–2188
2187
123.9 (d), 121.4 (d), 114.9 (t), 22.7 (s), 21.8 (q), 21.0 (q)(2C), 20.9
(q)(2C), 20.6 (s). C17H21NO2 (271.4): C 75.25, H 7.80; found C 75.31,
H 7.78.
(s), 136.5 (s), 133.4 (s), 129.9 (d)(2C), 129.3 (d)(2C), 113.3 (d), 112.0
(t), 55.3 (q), 27.7 (t), 21.69 (s), 21.66 (d)(2C), 21.2 (d)(2C), 20.5 (s),
13.2 (q). 10o (37%): 1H NMR (300 MHz, CDCl3)
d
7.10 (d, J¼8.4 Hz,
2H), 6.83 (d, J¼8.4 Hz, 2H), 5.29 (q, J¼6.8 Hz, 1H), 3.80 (s, 3H), 1.86
5.1.18. 3-(4-Trifluoromethylphenyl)-2-methyl-3-(2,2,3,3-tetrame-
(s, 3H), 1.68 (d, J¼7.0 Hz, 3H), 1.22 (s, 6H), 1.01 (s, 6H); 13C NMR
thylcyclopropylidene)-propene (7l). Yield 57%. 1H NMR (300 MHz,
(75 MHz, CDCl3) d 158.0 (s), 151.0 (s), 142.7 (s), 134.1 (s), 132.7 (s),
CDCl3)
4.60 (br s, 1H), 2.00 (s, 3H), 1.24 (s, 6H); 1.00 (s, 6H); 13C NMR
(75 MHz, CDCl3)
131.1 (s), 129.2 (d)(2C), 128.4 (s, quadr. J(C–F)¼32.5 Hz), 124.8 (d,
quadr. J(C–F)¼3.8 Hz)(2C), 124.6 (s, quadr. J(C–F)¼272.0 Hz), 114.7
(t), 22.4 (s), 22.0 (q), 21.9 (q)(2C), 21.0 (q)(2C), 20.4 (s). C18H21F3
(294.3): C 73.45, H 7.19; found C 73.36, H 7.22.
d
7.55 (d, J¼8.1 Hz, 2H), 7.31 (d, J¼8.1 Hz, 2H), 5.00 (br s, 1H),
130.8 (d), 129.3 (d)(2C), 123.5 (d), 113.1 (d), 55.28 (q), 22.0 (q), 21.98
(s), 21.2 (d)(2C), 20.2 (s), 14.9 (q), 14.0 (q). C19H26O (270.4): C 84.39,
H 9.69; found C 84.45, H 9.76.
d
147.6 (s), 145.2 (s, quadr. J(C–F)¼1.1 Hz), 143.7 (s),
5.1.24. 3-(4-Formylphenyl)-2-methyl-3-(2,2,3-trimethylcyclo-propy-
lidene)propene (Z: 11d, 72%; E: 12d, 28%). Yield 63%. 1H NMR
(300 MHz, CDCl3)
d
10.00 (s, 1H), 7.81 (d, J¼8.2 Hz, 2H), 7.38 (d,
J¼8.2 Hz, 2H), 5.02 (br s, 1H), 4.69 (br s, 1H, minor iso.), 4.66 (br, s,
1H, major iso.), 2.03 (s, 3H, major iso.), 1.99 (s, 3H, minor iso.), 1.41
(q, J¼6.4 Hz, 1H), 1.19 (d, J¼6.4 Hz, 3H), 1.06 (s, 3H), 0.96 (s, 3H). 13C
5.1.19. 2-Methyl-3-(2,2,3,3-tetramethylcyclopropylidene)-3-(3-thie-
nyl)propene (7m). Yield 61%. 1H NMR (300 MHz, CDCl3)
d 7.24–
7.20 (m, 1H), 7.04–7.00 (m, 2H), 4.98 (br s, 1H), 4.82 (br s, 1H),
NMR (75 MHz, CDCl3) d 192.3 (d), 148.2 (s), 144.3 (s), 143.8 (s), 134.8
2.00 (s, 3H), 1.21 (s, 3H), 1.20 (s, 3H), 1.08 (s, 3H), 1.07 (s, 3H); 13C
(s), 131.9 (s), 129.6 (d)(2C), 129.5 (d)(2C), 114.9 (t), 26.1 (d), 22.4 (d),
22.2 (d), 18.6 (d), 18.1 (s), 13.4 (q). C17H20O (240.3): C 84.96, H 8.39;
found C 84.92, H 8.45.
NMR (75 MHz, CDCl3)
d 145.5 (s), 144.1 (s), 141.5 (s), 128.8 (d),
126.9 (s), 124.2 (d), 121.6 (d), 113.9 (t), 22.3 (q), 21.8 (q)(2C), 21.1
(q)(2C), 20.5 (s). C15H20S (232.4): C 77.53, H 8.67; found C 77.46,
H 8.62.
5.1.25. 3-(4-Acetylphenyl)-2-methyl-3-(2,2,3-trimethylcyclo-propyli-
dene)propene (Z: 11e, 72%; E: 12e, 28%). Yield 59%. 1H NMR
5.1.20. 3-(4-Isoquinolin)-2-methyl-3-(2,2,3,3-tetramethyl-cyclo-
(500 MHz, CDCl3)
d
major: 7.89 (d, J¼8.3 Hz, 2H), 7.30 (d, J¼8.3 Hz,
propylidene)propene (7n). Yield 65%. 1H NMR (300 MHz, CDCl3)
2H), 5.00 (br s, 1H), 4.66 (br s, 1H), 2.59 (s, 3H), 2.03 (s, 3H), 1.40 (q,
J¼6.2 Hz, 1H), 1.18 (d, J¼6.4 Hz, 3H), 1.05 (s, 3H), 0.95 (s, 3H); minor:
7.89 (d, J¼8.3 Hz, 2H), 7.36 (d, J¼8.3 Hz, 2H), 5.01 (br s, 1H), 4.69 (br
s, 1H), 2.58 (s, 3H), 1.99 (s, 3H), 1.40 (q, J¼6.2 Hz, 1H), 1.19 (d,
J¼6.4 Hz, 3H), 1.05 (s, 3H), 0.95 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
9.17 (s, 1H), 8.28 (s, 1H), 7.95 (d, J¼8.0 Hz, 1H), 7.69 (d, J¼8.0 Hz,
1H), 7.60–7.50 (m, 2H), 4.87 (br s, 1H), 4.27 (br s, 1H), 2.14 (s, 3H),
1.31 (s, 6H), 0.77 (s, 6H); 13C NMR (75 MHz, CDCl3)
151.1 (d), 149.7
d
(s), 143.7 (d), 142.8 (s), 135.5 (s), 132.8 (s), 130.2 (d), 127.1 (d), 127.0
(s), 126.9 (d), 126.5 (s), 125.5 (d), 114.8 (t), 23.2 (s), 22.1 (q)(2C), 21.4
(q), 20.4 (q)(2C), 20.3 (s). C20H23N (277.4): C 86.59, H 8.36; found C
86.54, H 8.28.
d
198.1 (s), 146.7 (s), 143.9 (s), 143.7 (s), 135.3 (s), 131.9 (s), 129.0
(d)(2C), 128.1 (d)(2C), 114.7 (t), 26.7, 26.1, 22.4, 22.1, 18.6, 18.0 (s),
13.4. C18H22O (254.4): C 84.99, H 8.72; found C 85.06, H 8.75.
5.1.21. 1-[(4-Acetylphenyl)(cyclohexen-1-yl)]methylene-2,2,3,3-tet-
5.1.26. 3-(4-Cyanophenyl)-2-methyl-3-(2,2,3-trimethyl-cyclo-
ramethylcyclopropane (8). Yield 62%. 1H NMR (300 MHz, CDCl3)
propylidene)propene (Z: 11h, 80%; E: 12h, 20%). Yield 63%. 1H NMR
d
7.88 (d, J¼8.1 Hz, 2H), 7.27 (d, J¼8.1 Hz, 2H), 5.38 (br s, 1H), 2.58 (s,
(300 MHz, CDCl3)
d
7.58 (d, J¼8.2 Hz, 2H, major iso.), 7.37 (d,
3H), 2.35–2.0 (m, 2H), 1.85–1.55 (m, 4H), 1.20 (s, 6H), 1.09 (t,
J¼8.2 Hz, 2H, minor iso.), 7.31 (d, J¼8.2 Hz, 2H), 5.01 (br s, 1H), 4.65
(br s. 1H, minor iso.), 4.61 (br s, 1H, major iso.), 2.01 (s, 3H, major
iso.), 1.97 (s, 3H, minor iso.), 1.41 (q, J¼6.4 Hz, 1H), 1.18 (d, J¼6.4 Hz,
J¼5.8 Hz, 2H), 0.97 (s, 6H); 13C NMR (75 MHz, CDCl3)
d 198.2 (s),
147.3 (s), 147.1 (s), 144.7 (s), 137.2 (s), 135.1 (s), 129.2 (d)(2C), 128.0
(d)(2C), 126.8 (d), 27.1 (t), 26.7 (q), 25.9 (t), 23.2 (t), 22.4 (t), 22.1 (s),
22.0 (q)(2C), 21.1 (q)(2C), 20.3 (s). C22H28O (308.5): C 85.66, H 9.15;
found C 85.72, H 9.18.
3H), 1.04 (s, 3H), 0.94 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 146.4 (s),
144.5 (s), 143.6 (s), 131.8 (d)(2C), 131.5 (s, minor iso.), 129.5 (d)(2C),
119.4 (s), 114.9 (t), 110.1 (s), 26.6 (d,q, minor iso.), 26.1 (d,q), 22.4
(d,q), 22.1 (d,q),18.5 (d,q),18.1 (s), 13.3 (q). C17H20N (237.3): C 86.03,
H 8.07; found C 86.11, H 8.05.
5.1.22. 2-Ethyl-3-(4-formylphenyl)-3-(2,2,3,3-tetramethyl-cyclo-
propylidene)propene (9d) and 1-(4-formylphenyl)-2-methyl-1-
(2,2,3,3-tetramethylcyclopropylidene)-2-butene (10d). Overall yield
5.1.27. 1-[(Cyclohexen-1-yl)(4-formylphenyl)]methylene-2,2,3-trime-
62%. 9d (66%): 1H NMR (300 MHz, CDCl3)
d
9.97 (s, 1H), 7.80 (d,
thylcyclopropane (Z: 13d, 72%; E: 14d, 18%). Yield 64%. 1H NMR
J¼8.3 Hz, 2H), 7.39 (d, J¼8.3 Hz, 2H), 5.05 (q, J¼1.1 Hz, 1H), 4.76 (s,
(300 MHz, CDCl3) d 9.98 (s, 1H, major iso.), 9.95 (s, 1H, minor iso.),
1H), 2.24 (q, J¼7.5 Hz, 2H), 1.21 (br s, 12H), 1.05 (t, J¼7.5 Hz, 3H); 13C
7.80 (d, J¼8.2 Hz, 2H, major iso.), 7.75 (d, J¼7.7 Hz, minor iso.), 7.35
(d, J¼8.3 Hz, 2H), 5.46 (br s, 1H, minor iso.), 5.42 (br s, 1H, major
iso.), 1.75–1.55 (m, 2H), 1.35–1.0 (m, 3H), 1.17 (d, J¼6.6 Hz, 3H), 1.04
(s, 3H), 0.92 (s, 3H), 0.88–0.82 (m, 4H); 13C NMR (75 MHz, CDCl3)
NMR (75 MHz, CDCl3) d 192.1 (d), 149.9 (s), 147.6 (s), 147.5 (s), 134.6
(s), 130.8 (s), 129.7 (d)(2C), 128.7 (d)(2C), 112.9 (t), 27.7 (t), 21.9 (s),
21.5 (q)(2C), 21.1 (q)(2C), 20.9 (s), 13.1 (q). 10d (34%): 1H NMR
(300 MHz, CDCl3)
d
9.97 (s, 1H), 7.80 (d, J¼8.3 Hz, 2H), 7.33 (d,
d 192.3 (d), 148.6 (s), 141.3 (s), 137.3 (s), 134.6 (s), 132.3 (s), 129.54
J¼8.3 Hz, 2H), 5.21 (qq, J¼6.9, 1.3 Hz, 1H), 1.85 (s, 3H), 1.67 (d,
(d)(2C), 129.49 (d)(2C), 127.05 (d, major iso), 126.98 (d, minor iso.),
31.1 (q*,d*), 27.4 (t), 26.2 (d*,q*), 25.9 (t), 23.2 (t), 22.4 (t), 19.6 (q),
17.7 (s), 13.6 (q). C20H24O (280.4): C 85.67, H 8.63; found C 85.59, H
8.69.
J¼6.9 Hz, 3H), 1.21 (br s, 12H); 13C NMR (75 MHz, CDCl3)
d 192.2 (d),
148.5 (s), 145.7 (s), 135.7 (s), 134.6 (s), 132.6 (s), 129.5 (d), 129.4 (d),
124.4 (d), 28.1 (q), 22.1 (s), 21.9 (d)(2C), 21.1 (d)(2C), 20.5 (s), 15.0
(q). C19H24O (268.4): C 85.03, H 9.01; found C 84.82, H 9.08.
5.1.28. 1-[(Cyclohexen-1-yl)(4-methoxycarbonylphenyl)]-methylene-
5.1.23. 2-Ethyl-3-(4-methoxyphenyl)-3-(2,2,3,3-tetramethyl-cyclo-
propylidene)propene (9o) and 1-(4-methoxyphenyl)-2-methyl-1-
(2,2,3,3-tetramethylcyclopropylidene)-2-butene (10o). Overall yield
2,2,3-trimethylcyclopropane (Z: 13g, 80%; E: 14g, 18%). Yield 61%. 1H
NMR (300 MHz, CDCl3)
d
7.95 (d, J¼8.3 Hz, 2H, major iso.), 7.90
(minor iso.), 7.31 (minor iso.), 7.25 (d, J¼8.3 Hz, 2H, major iso.), 5.45
51%. 9o (63%): 1H NMR (300 MHz, CDCl3)
d
7.18 (d, J¼8.4 Hz, 2H),
(br, s,1H, minor iso.), 5.41 (br, s,1H, major iso.), 3.9 (s, 3H), 0.92–0.80
6.84 (d, J¼8.4 Hz, 2H), 5.00 (d, J¼1.4 Hz, 1H), 4.81 (d, J¼1.0 Hz, 1H),
(m, 10H); 13C NMR (75 MHz, CDCl3)
d 167.4 (s), 146.9 (s), 140.5 (s),
3.80 (s, 3H), 2.26 (q, J¼7.3 Hz, 2H), 1.20 (s, 6H), 1.10 (s, 6H), 1.05 (t,
137.4 (s), 132.4 (s), 129.2 (d)(2C), 129.0 (d)(2C), 128.0 (s), 126.85 (d,
major iso.), 126.78 (d, minor iso.), 52.1 (q), 27.3 (t), 26.2 (d,q), 25.9
J¼7.4 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
158.2 (s), 151.0 (s), 143.5

2188
Y. Fall et al. / Tetrahedron 66 (2010) 2181–2188
20. (a) Brown, S.; Grigg, R.; Hinsley, J.; Korn, S.; Sridharan, V.; Uttley, M. D. Tetra-
hedron 2001, 57, 10347–10355.
21. Bai, T.; Xue, L.; Xue, P.; Zhu, J.; Sung, H. H.-Y.; Ma, S.; Williams, I. D.; Lin, Z.; Jia, G.
(t), 23.2 (t), 22.7 (d,q), 22.4 (t), 18.6 (d,q), 17.5 (s), 13.7 (q). C21H26
(310.4): C 81.25, H 8.44; found C 81.52, H 8.49.
O
Organometallics 2008, 27, 2614–2626.
22. Laurenti, D.; Feuerstein, M.; Pe`pe, G.; Doucet, H.; Santelli, M. J. Org. Chem. 2001,
66, 1633–1637.
23. Doucet, H.; Santelli, M. Synlett 2006, 2001–2015.
5.1.29. 1-[(4-Cyanophenyl)(cyclohexen-1-yl)]methylene-2,2,3-trime-
thylcyclopropane (Z: 13h, 78%; E: 14h, 22%). Yield 65%. 1H NMR
(300 MHz, CDCl3)
d
7.56 (d, J¼8.4 Hz, 2H, major iso.), 7.51 (d,
24. (a) Feuerstein, M.; Doucet, H.; Santelli, M. J. Org. Chem. 2001, 66, 5923–5925; (b)
Feuerstein, M.; Doucet, H.; Santelli, M. Synlett 2001, 1980–1982; (c) Feuerstein,
M.; Doucet, H.; Santelli, M. Tetrahedron Lett. 2002, 43, 2191–2194; (d) Berthiol,
F.; Doucet, H.; Santelli, M. Tetrahedron Lett. 2003, 44, 1221–1225; (e) Berthiol, F.;
Doucet, H.; Santelli, M. Eur. J. Org. Chem. 2003, 1091–1096; (f) Berthiol, F.;
Doucet, H.; Santelli, M. Synlett 2003, 841–844; (g) Kondolff, I.; Doucet, H.;
Santelli, M. Tetrahedron Lett. 2003, 44, 8487–8491; (h) Kondolff, I.; Doucet, H.;
Santelli, M. Synlett 2004, 1561–1564; (i) Berthiol, F.; Doucet, H.; Santelli, M.
Tetrahedron Lett. 2004, 45, 5633–5636; (j) Battace, A.; Zair, T.; Doucet, H.;
Santelli, M. Tetrahedron Lett. 2006, 47, 459–462; (k) Kondolff, I.; Doucet, H.;
Santelli, M. Eur. J. Org. Chem. 2006, 765–774; (l) Berthiol, F.; Doucet, H.; Santelli,
M. Synthesis 2006, 1518–1536; (m) Battace, A.; Zair, T.; Doucet, H.; Santelli, M.
Synthesis 2006, 3495–3505; (n) Lemhadri, M.; Doucet, H.; Santelli, M. Synlett
2006, 2935–2940; (o) Berthiol, F.; Doucet, H.; Santelli, M. Tetrahedron 2006, 62,
4372–4383.
J¼8.4 Hz, 2H, minor iso.), 7.34 (d, J¼8.4 Hz, 2H, minor iso.), 7.28 (d,
J¼8.4 Hz, 2H), 5.42 (br s, 1H, minor iso.), 5.38 (br s, 1H, major iso.),
2.40–2.00 (m, 3H), 1.75–1.50 (m, 4H), 1.16 (d, J¼6.5 Hz, 3H), 1.02 (s,
3H), 0.91 (s, 3H), 0.85 (m, 2H); 13C NMR (75 MHz, CDCl3)
d 146.9 (s),
141.5 (s), 137.1 (s), 131.9 (s), 131.7 (d)(2C), 129.6 (d)(2C), 127.2 (d,
major iso.), 127.09 (d, minor iso.), 119.5 (s), 109.8 (s), 27.3 (t), 26.2
(q*,d*), 25.9 (t), 23.1 (t), 22.35 (q*,d*), 22.33 (t), 18.6 (q), 17.7 (s), 13.6
(q). C20H23N (277.4): C 86.59, H 8.36; found C 86.66, H 8.42.
Acknowledgements
25. (a) Knowles, J. P.; Whiting, A. Org. Biomol. Chem. 2007, 5, 21–44; (b) Alonso, F.;
Beletskaya, I.; Yus, M. Tetrahedron 2005, 61, 11771–11835; (c) Farina, V. Adv.
Synth. Catal. 2004, 346, 1553–1582; (d) Dounay, A. B.; Overman, L. E. Chem.
Rev. 2003, 103, 2945–2963; (e) Littke, A.; Fu, G. Angew. Chem., Int. Ed. 2002, 41,
4176–4211; (f) Withcombe, N.; Hii, K. K.; Gibson, S. Tetrahedron 2001, 57,
7449–7476; (g) Beletskaya, I.; Cheprakov, A. Chem. Rev. 2000, 100, 3009–
3066; (h) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33,
2379–2411.
Y.F. is grateful to the Mauritania Government for a grant. This
`
work was supported by the CNRS and the Ministere de l’Education
ˆ
´
Nationale. We thank Dr. M. Giorgi (Spectropole, Universite d’Aix-
Marseille) for the X-ray structure determinations and R. Rosas for
NMR spectroscopic studies. We are indebted to Dr. B. Vacher (Pierre
´
´
Fabre Medicaments, Castres, Fr) and Dr. N. Ferre for helpful com-
26. Fu, C.; Ma, S. Org. Lett. 2005, 7, 1605–1607.
ments and assistance.
27. The regioselectivity on catalyst dependence of condensation of phenylethyne
and methyl 2,3-pentadienoate has been justified by a different Pd catalyst
double bond coordination (h
1 precursor complexes as D (Scheme 9)), see: Trost,
References and notes
B. M.; Kottirsch, G. J. Am. chem. Soc. 1990, 112, 2816–2818.
28. Pasto, D. J.; Chen, A. F.-T.; Ciurdaru, G.; Paquette, L. A. J. Org. Chem. 1973, 38,
1015–1026.
29. Pasto, D. J.; Miles, M. F.; Chou, S.-K. J. Org. Chem. 1977, 41, 3098–3101.
30. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652; (b) Lee, C.; Yang, W.; Parr, R.
G. Physiol. Rev. 1988, B37, 785–789.
1. (a) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518–5542; (b) Heck, R. F. J. Am. Chem.
Soc. 1969, 91, 6707–6714; (c) Heck, R. F. J. Am. Chem. Soc. 1971, 93, 6896–6901;
(d) Heck, R. F.; Nolley, J. P. J. Org. Chem. 1972, 37, 2320–2322; (e) Heck, R. F. Ann.
N.Y. Acad. Sci. 1977, 295, 201–224.
2. Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. 1971, 44, 581.
3. For preliminary results, see: Fall, Y.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2007, 48, 3579–3581.
4. (a) Ma, S. Acc. Chem. Res. 2009, 42, 1679–1688; (b) Ma, S. Chem. Rev. 2005, 105,
2829–2871; (c) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem. Rev.
2000, 100, 3067–3125; (d) Lu, J.-M.; Shi, M. Tetrahedron 2006, 62, 9115–9122;
(e) Li, W.; Shi, M. Eur. J. Org. Chem. 2009, 270–274.
5. Patrick, T. B.; Schmidt, D. J. J. Org. Chem. 1977, 42, 3354–3356.
6. Hartzler, H. D. J. Am. Chem. Soc. 1961, 83, 4990–4996.
7. (a) Crandall, J. K.; Paulson, D. R. J. Am. Chem. Soc. 1966, 88, 4302–4303; (b)
Paulson, D. R.; Crandall, J. K.; Bunnell, C. A. J. Org. Chem. 1970, 35, 3708–3714.
8. (a) Crandall, J. K.; Paulson, D. R.; Bunnell, C. A. Tetrahedron Lett. 1968, 5063–
5066; (b) Leandri, G.; Santelli-Rouvier, C. Bull. Soc. Chim. Fr. 1970, 1515–1520; (c)
Poutsma, M. L.; Ibarbia, P. A. J. Am. Chem. Soc. 1971, 93, 440–450.
9. Pasto, D. J.; Miles, M. F. J. Org. Chem. 1976, 41, 425–432.
10. Crandall, J. K.; Schuster, T. J. Org. Chem. 1990, 55, 1973–1975.
11. Pasto, D. J.; Miles, M. F. J. Org. Chem. 1976, 41, 2068–2070.
12. Sasaki, T.; Eguchi, S.; Ogawa, T. J. Am. Chem. Soc. 1975, 97, 4413–4414.
13. Santelli, M.; Bertrand, M. Bull. Soc. Chim. Fr. 1973, 2340–2343.
14. (a) Lu, J.-M.; Shi, M. Org. Lett. 2008, 10, 1943–1946; (b) Lu, J.-M.; Shi, M. Chem.d Eur.
J. 2009, 15, 6065–6073.
15. Lu, B.-L.; Lu, J.-M.; Shi, M. Tetrahedron 2009, 65, 9328–9335.
16. Su, C.; Huang, X.; Liu, Q.; Huang, X. J. Org. Chem. 2009, 74, 8272–8279.
17. Hwu, C.-C.; Wang, F.-C.; Yeh, M.-C. P.; Sheu, J.-H. J. Organomet. Chem. 1994, 474,
123–128.
18. (a) Ma, S.; Negishi, E.-i J. Am. Chem. Soc. 1995, 117, 6345–6357; (b) Gardiner, M.;
Grigg, R.; Sridharan, V.; Vicker, N. Tetrahedron Lett. 1998, 39, 435–438; (c)
Knoke, M.; de Meijere, A. Eur. J. Org. Chem. 2005, 2259–2268; (d) Ma, S. Pure
Appl. Chem. 2006, 78, 197–208.
31. Møller, C.; Plesset, M. S. Phys. Rev. 1934, 46, 618–622.
32. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G.
A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Fores-
man, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.;
Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P.
M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03, revision E.01; Gaussian: Pittsburgh, PA, 2004.
33. Vinylcyclopropyl tosylate underwent Pd(0) catalysed regioselective sub-
stitution at the terminal vinylic position with stabilized C-nucleophiles. An
unsymmetric
p-allyl palladium complex where the palladium would be posi-
tioned closer to the cyclopropyl carbon has been invoked. In fact, the opening
of the cyclopropane to give 2-vinylallyl cation is weakly exothermic, dDG¼–2.
06 kcal/mol (B3LYP/6-311G(þþ)(d, p)), see: Stolle, A.; Ollivier, J.; Piras, P. P.;
Salau¨n, J.; de Meijere, A. J. Am. Chem. Soc. 1992, 114, 4051–4067.
34. (a) For reviews on diastereoselection, see a thematic issue: Chem. Rev. 1999, 99,
1069–1480; (b) Ohwada, T. Chem. Rev. 1999, 99, 1337–1375; (c) Mehta, G.;
Singh, S. R.; Gagliardini, V.; Priyakumar, U. D.; Sastry, G. N. Tetrahedron Lett.
2001, 42, 8527–8530; (d) Moraleda, D.; Ollivier, C.; Santelli, M. Tetrahedron Lett.
2006, 47, 5471–5474.
35. Smith, M. B.; March, J. March’s Advanced Organic Chemistry, 6th ed.; John Wiley
& Sons: New York, NY, 2007; p 1497.
36. Reynaud, C.; Fall, Y.; Feuerstein, M.; Doucet, H.; Santelli, M. Tetrahedron 2009,
65, 7440–7448.
19. (a) Grigg, R.; Brown, S.; Sridharan, V.; Uttley, M. D. Tetrahedron Lett. 1998, 39,
3247–3250; (b) Chang, H.-M.; Cheng, C.-H. J. Org. Chem. 2000, 65, 1767–1773;
(c) Brown, S.; Grigg, R.; Hinsley, J.; Koen, S.; Sridharan, V.; Uttley, M. D. Tetra-
hedron 2001, 57, 10347–10355; (d) Oh, C. H.; Jung, S. H.; Bang, S. Y.; Park, D. I.
Org. Lett. 2002, 4, 3325–3327; (e) Fu, C.; Ma, S. Org. Lett. 2002, 4, 1707–1709.
37. (a) Brandi, A.; Goti, A. Chem. Rev. 1998, 98, 589–635; (b) Brandi, A.; Cicchi, S.;
Cordero, F. M.; Goti, A. Chem. Rev. 2003, 103, 1213–1269.