Gold-catalyzed cycloisomerization of functionalized 1,5-enynes - An entry to polycyclic framework

Article abstract of DOI:10.1055/s-0031-1289867

The gold-catalyzed cycloisomerization reactions of variously functionalized 1,5-enynes are presented. The cyclization processes implying aryl- and 1,3-dicarbonyl-substituted skeletons are conducted under mild conditions and lead to cyclic structures obtai

Full text of DOI:10.1055/s-0031-1289867

74
CLUSTER
Gold-Catalyzed Cycloisomerization of Functionalized 1,5-Enynes – An Entry
to Polycyclic Framework
G
old-CatalyzedCy
l
cloisom
e
e
rization
x
of Functiona
a
lize
d
1,5-Enynes dre Pradal,a,b,1 Qian Chen,a,b,1 Pierre Faudot dit Bel,a,b Patrick Yves Toullec,*a,b Véronique Michelet*a,b
a
Chimie ParisTech, Laboratoire Charles Friedel (LCF), 11, rue P. et M. Curie, 75231 Paris Cedex 05, France
Fax +33(1)44071062; E-mail: patrick-toullec@chimie-paristech.fr; E-mail: veronique-michelet@chimie-paristech.fr
CNRS, UMR 7223, 75231 Paris Cedex 05, France
b
Received 12 September 2011
Abstract: The gold-catalyzed cycloisomerization reactions of vari-
ously functionalized 1,5-enynes are presented. The cyclization pro-
cesses implying aryl- and 1,3-dicarbonyl-substituted skeletons are
conducted under mild conditions and lead to cyclic structures ob-
tained according to 6-endo-dig or 5-endo-dig mode depending on
the involved nucleophilic partner. Some competitive pathways and
trapping of carbocationic intermediates are highlighted.
O
AuCl3 (10 mol%)
O
or
(1)
MeCN, 20°C
90–98%
H
Ph
Ph
Ph
2 for (Z)-1
3 for (E)-1
OH
as SM
as SM
1
OAc
[(Ph3PAu)3O]BF4
(1 mol%)
Key words: gold catalyst, cycloisomerization, 1,5-enynes, atom
economy, polycyclization
OAc
3
O
HO
O
(2)
(3)
O
1,4-dioxane, r.t.
71%
dr > 20:1
Gold-catalyzed cycloisomerization reactions of 1,n-
enynes have emerged as conceptually and chemically fas-
cinating processes as they offer the opportunity to develop
new atom-economical reactions.2,3 The recent emergence
of interest associated with the polycyclization processes
of enynes opened the way to the development of selective
gold catalysts.4,5 A wide variety of carbo- and heterocy-
cles presenting a high degree of structural complexity
were described using those new catalytic systems, which
made these methodologies competitive to previous effi-
cient reported catalytic systems for enynes.6 The field of
polycyclization of 1,5-enynes has received less attention.
5
4
HO
Ph3PAuNTf2
(1 mol%)
O
Br
Et2O, r.t.
1 h, 89%
Br
H
(E)-6
7
Scheme 1 Gold-catalyzed polycyclization of 1,5-enynes
rangements leading to cyclic derivatives and highlighting
various mechanistic pathways.
The Kozmin group described the formation of bicyclic
ethers upon cycloisomerization of 1,5-enynes possessing
an internal hydroxyl or amine function in the presence of
either Au(I) or Au(III) catalysts according to a 6-endo or
5-endo process, depending on the stereochemistry of the
alkene 1 (Scheme 1, equation 1).5e Later on, Toste et al.
developed a stereoselective efficient access to bicyclic
spiroketal frameworks starting from propargyl vinyl ether
4 (Scheme 1, equation 2).5f Our group5h and Gagné’s
group6d have recently extended the polycyclization meth-
odology to the intramolecular phenoxycyclization reac-
tions on 1,5-enynes under mild conditions following the
6-endo mode of cyclization (Scheme 1, equation 3).5h As
part of our ongoing research program on the gold activa-
tion of alkynes towards a variety of nucleophiles7 and on
cycloisomerization of 1,6-enynes,8,9 we decided to study
the gold-catalyzed cycloisomerization of functionalized
1,5-enynes focusing on aryl- and 1,3-dicarbonyl-function-
alized ones. In this paper, we describe their skeleton rear-
At the outset of our investigations, we turned our attention
to the known aryl-functionalized enynes 9 and 10, pre-
pared starting from allylic bromide 8 (Scheme 2). These
derivatives have indeed been cycloisomerized according
to an intramolecular domino Friedel–Crafts-type reac-
tion–cyclization by Nishizawa and co-workers in the pres-
ence of Hg(OTf)2 salt.6a–6c We also prepared two oxygen-
tethered analogues 116b and 12 via classical alkylation
reactions in the presence of 3,5-dimethoxyphenol and
4-methoxyphenol, respectively.
Anticipating the crucial importance of the substitution of
the alkenyl moiety, we also envisaged synthesizing 1,5-
enynes bearing a disubstituted exo-methylene moiety. For
this purpose, starting from 1-trimethylsilylpropyne 13 and
modifying the electrophilic partners compared to the liter-
ature,5b enynes 14–19 possessing an electron-rich and
electron-neutral aromatic nucleophile were obtained in
two to four steps. The alkenyl side chain was introduced
after propargylic deprotonation on 13 followed by the ad-
dition of 2-methyl-3-bromoprop-1-ene in 83% yield.5b
A
similar reaction conducted in the presence of a bromoben-
zyl derivative allowed the preparation of the desired
enynes 14 and 15 in 48% and 35% yield, respectively,
SYNLETT 2012, 23, 74–79
Advanced online publication: 11.11.2011
DOI: 10.1055/s-0031-1289867; Art ID: Y04611ST
x
x
.x
x
.2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

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Gold-Catalyzed Cycloisomerization of Functionalized 1,5-Enynes
75
over two steps. The silyl group could be deprotected, and
further Sonogashira cross-coupling10 in the presence of
phenyl iodide led to the desired enynes 18 and 19.
R1
refs. 6a,b
On the basis of our previous studies on intermolecular
domino Fridel–Crafts-type addition–cyclization,8b,e we
selected the PPh3AuCl/AgSbF6 system as the gold cation-
ic and carbophilic system in diethyl ether as the solvent.11
Results are presented in Table 1. Whereas the cyclo-
isomerization of enyne 9 led to several unidentified
byproducts (Table 1, entry 1), we were pleased to find that
substrate 10 reacted smoothly under mild conditions
(Table 1, entry 2) leading to the desired product in 92%
yield. The hexahydrophenanthrene 21 was isolated as a
single isomer, similarly as in the presence of Hg(OTf)2.
The cycloisomerization reactions of oxygen-tethered ana-
logues 11 and 12 were surprisingly much less effective.
As previously described with mercury salts,6b the cis iso-
mer was formed as the major product in the presence of
the commercially available Gagosz catalyst12
PPh3AuNTf2, but several other unidentified byproducts
were present: attempts to isolate some of them were un-
fortunately unsuccessful (Table 1, entry 3). The cycliza-
tion of the oxygen-tethered analogue 12 was sluggish, and
after prolonged reaction time (24 h) it did not give the ex-
pected product. Pleasingly, the major product could be
isolated this time, and 1H–13C COSY NMR spectroscopic
experiments confirmed the structure of 2313 (Table 1, en-
try 4), resulting from an intermolecular hydroxycylization
reaction, already observed for 1,5- and 1,6-enynes.8,9,14
R2
9 R1 = R2 = H
10 R1 = R2 = OMe
Br
8
for 11: ref. 6b
R1
R3
for 12: Cs2CO3, NaI,
4-methoxyphenol,
acetone, reflux, 47%
O
R2
11 R1 = R2 = OMe, R3 = H
12 R1 = R2 = H, R3 = OMe
R1
a, b
14 R1 = OMe, R2 = TMS
15 R1 = H, R2 = TMS
c
TMS
16 R1 = OMe, R2 = H
17 R1 = H, R2 = H
R1
R2
13
d
18 R1 = OMe, R2 = Ph
19 R1 = H, R2 = Ph
Scheme 2 Synthesis of 1,5-enynes. Reagents and conditions: a) n-
BuLi, 3-bromo-2-methylprop-1-ene, THF, 0 °C; b) n-BuLi, 3,5-dime-
thoxybenzylbromide or benzylbromide, THF, 0 °C, 48% (14), 35%
(15); c) TBAF, THF, 0 °C to r.t.; d) PdCl2(PPh3)2 (5 mol%), CuI (5
mol%), Et3N, PhI, 45 °C, 4 h, 61% (18), 42% (19).
Table 1 Gold-Catalyzed Cycloisomerization of 1,5-Enynes
Entry
Starting material Conditionsa
Product
Yield (%)b
1
9
A
A
20
21
–
H
MeO
OMe
2
10
92
H
MeO
OMe
3
11
12
Bc
22
23
71d
O
H
cis/trans = 80:20
HO
4e
B
40
O
OMe
© Thieme Stuttgart · New York
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76
A. Pradal et al.
CLUSTER
Table 1 Gold-Catalyzed Cycloisomerization of 1,5-Enynes (continued)
Entry
5
Starting material Conditionsa
Product
Yield (%)b
OMe
24
25
+
14
16
18
15
A
A
A
A
82
H
Ar
Ar
Ar
Ph
OMe
OMe
OMe
>1:10
OMe
24
25
6
7
8
90
92
57
+
H
1:4
OMe
26
27
+
Ph
Ph
23:77
28
29
+
H
1:>20
30
31
+
9
19
16
A
65
66
Ph
Ph
Ph
Ar
1:>20
MeO
32
33
Af
Ar
10
+
O
60:40
a Conditions A: 3 mol% PPh3AuCl, 3 mol% AgSbF6, Et2O, r.t., 1 h. Conditions B: 3 mol% PPh3AuNTf2, Et2O, r.t., 1 h.
b Isolated yields.
c CH2Cl2 was used in place of Et2O.
d Mixture of cis/trans isomers.
e Reaction time: 24 h.
f MeOH was used in place of Et2O. Isomeric ratio determined by 1H NMR spectroscopy. Ar = 2,4-(MeO)2C6H3.
We then tested the reactivity of substrates 14–19 in the and 25 during the reaction of 14 and 16 (Table 1, entry 5
presence of 3 mol% gold catalyst in diethyl ether for one vs. entry 6). It is noteworthy that free or substituted
hour, speculating that a similar Friedel–Crafts-type addi- alkynes reacted in a similar manner (Table 1, entry 6 vs.
tion–cyclization would occur. Surprisingly, no product entry 7, and entry 8 vs. entry 9). The competitive hy-
resulting from the domino process was formed in all cases droarylation reaction of the alkyne is only observed for
(Table 1,
entries
5–10).
The
formation
of electron-rich aromatic substrates (16 and 18) whereas it is
bicyclo[3.1.0]hexenyl adducts was the major competitive almost completely suppressed for benzyl-substituted
pathway, and bicyclic derivatives 25, 27, 29, and 31 were alkynes such as 15 and 19. We also envisaged challenging
detected without the intervention of the benzylic moiety. the hydroarylation and cycloisomerization pathways by
As minor products, the bicyclic derivatives 24, 26, 28, and conducting the reaction of 16 in the presence of an exter-
30, resulting from the gold-catalyzed hydroarylation of nal nucleophile (Table 1, entry 10). When methanol was
the alkynyl part,15 were also formed. Several attempts to used as solvent instead of diethyl ether, the expected
separate the respective mixtures were unfortunately un- methoxycyclization reaction leading to cyclohexene 32
successful.16 In the case of enynes 14 and 15, the TMS was observed, with no trace of product 24. The competi-
group was cleaved under these reaction conditions tive intermolecular Markovnikov addition of MeOH to
(Table 1, entries 5 and 8). This would presumably occur the alkyne moiety8c,7b,d,17and hydrolysis furnished ketone
after the cycloisomerization or hydroarylation processes, 33, the 60:40 mixture of 32 and 33 being isolated in 66%
considering the difference of the ratio for the products 24 yield (Table 1, entry 10).
Synlett 2012, 23, 74–79
© Thieme Stuttgart · New York

CLUSTER
Gold-Catalyzed Cycloisomerization of Functionalized 1,5-Enynes
77
Mechanistically, the cycloisomerization reactions of the
above-mentioned 1,5-enynes rely on an electrophilic car-
bon p-activation of the alkyne moiety in the presence of
the cationic gold complex such as depicted in Scheme 3
for derivatives 10, 11, 12, and 16. Depending on the sub-
stitution pattern of the alkenyl chain, various scenarios
may occur. In the case of enyne 10 and in line with
Nishizawa’s reports with mercury,6a–c a carbocationic-like
cascade would lead to intermediates A and B, the latter re-
sulting presumably from a concerted or stepwise addition
of the aromatic ring to the alkenyl part and the cyclization
process.18 The trapping of carbocation A by water was ev-
idenced in the case of 12, leading to alcohol 23. This may
be explained by a nonfavored chair-like intermediate
when Z is an oxygen atom instead of a CH2 group. The tri-
cyclic hexahydrophenanthrene 22 was therefore obtained
via a 6-endo-dig process, after re-aromatization and pro-
todemetalation steps. The cycloisomerization of 1,5-
enyne 16 was particularly interesting as it highlighted two
pathways depending on the ‘active’ nucleophile. The acti-
vation of the alkyne by the carbophilic gold complex
would lead either to the cation C or intermediates D/E, de-
pending on the relative nucleophilicity of the side chains
(alkene vs. aromatic ring). The formation of 24 would be
explained by the hydroarylation of the alkyne via interme-
diate C, which would evolve via re-aromatization and
protodemetalation towards the dihydronaphthalene. The
enyne 16 may react independently from the benzylic chain
and would give the cationic/carbenoid intermediates D/E.
The carbocation D could be trapped in the presence of
MeOH and after protodemetalation would afford ether 32.
In the absence of MeOH, the more pronounced carbenic
character of the Au(I) intermediate accounted for the for-
mation of bicyclic derivative 25, which is in full agree-
ment with the previous report from Toste’s group.5c
HO
(OMe)n
OAr
(OMe)n
b
H2O
23
a
a
(OMe)n
+
Z
[Au]+
b
Z
[Au]
+
H
22
24
A
Z
10
, 11 or 12
[Au]
H
B
OMe
+
a
b
H
OMe
b
[Au]
[Au]+
OMe
a
MeOH
C
OMe
16
Ar
+
32
25
[Au]
D
Ar
H
[Au]+
H
E
Scheme 3 Mechanism rationale
culiar as no ‘classic’ enol form was possible: the cyclo-
isomerization reaction unfortunately led to several
unidentified byproducts.
In conclusion, we have extended the methodology for the
use of a simple gold catalyst in cycloisomerization reac-
tions of 1,5-enynes. The design of 1,5-enynes bearing an
aromatic side chain highlighted various competitive
mechanistic pathways related to carbocationic-type cy-
clizations. Depending on the arrangement and substitution
of the alkenyl moiety, the formation of bicyclo[3.1.0]hex-
We finally envisaged studying the influence of the nucleo-
philic part on 1,5-enynes analogous to 10 and turned our
attention to the 1,3-dicarbonyl derivatives. Whereas the
Conia-ene reaction implying the addition of the enol form
of the carbonyl nucleophile (ketones, 1,3-diketones, and
b-keto esters) on the alkyne has been well documented in
the presence of gold,19 the implication of such nucleo-
philes has been scarcely studied on enynes.20 The prepara-
tion of enynes 34–36 was straightforward starting from
allylic bromide 8 and realizing nucleophilic substitution
in the presence of methyl 3-oxobutanoate, ethyl 2-methyl-
3-oxobutanoate, and 1,3-diphenylpropane-1,3-dione, re-
spectively, as 1,3-dicarbonyl partners (Scheme 4). Antic-
ipating a similar 6-endo-dig process as for analogue 11
implying the oxygen atom of the enol intermediate, we re-
markably observed the clean and stereoselective (dr >
95%) formation of dihydrofurans 37 and 38 in the pres-
ence of 1 mol% of PPh3AuNTf2 catalyst in 69% and 90%
isolated yields, respectively.21 These examples constitute
unique cases in addition with the one described by
Kozmin and co-workers (Scheme 1, compound 3),5e
where the substitution of the enyne changes the course of
the cyclization. The case of enyne 35 was particularly pe-
O
R1
a
R2
R3
Br
O
8
34 R1 = H, R2 = Me, R3 = OMe
35 R1 = Me, R2 = Me, R3 = OEt
36 R1 = H, R2 = R3 = Ph
O
b
b
H
CO2Me
R1
37, 69%
COR3
COR2
Ph
O
34 or 36
H
COPh
38, 90%
Scheme 4 Cyclosiomerization reactions of 1,3-dicarbonyl-functio-
nalized 1,5-enynes. Reagents and conditions: a) NaH, THF, 0 °C to
r.t., methyl 3-oxobutanoate, ethyl 2-methyl-3-oxobutanoate, or 1,3-
diphenylpropane-1,3-dione 85% (34), 57% (35), 80% (36); b)
PPh3AuNTf2 (1 mol%), Et2O, r.t., 2.5 h.
© Thieme Stuttgart · New York
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78
A. Pradal et al.
CLUSTER
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This work was supported by the Centre National de la Recherche
Scientifique and the Ministère de l’Education et de la Recherche.
Q.C. is grateful to the Ministère de l’Education et de la Recherche
for a grant (2006–2007). A.P. is grateful to National Research
Agency (ANR-09-JCJC-0078) for a grant (2009–2012). Johnson-
Matthey is acknowledged for a generous loan of HAuCl4.
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P. Y.; Marie, P.; Antoniotti, S.; Brancour, C.; Genêt, J.-P.;
Michelet, V. ARKIVOC 2007, (v), 67. (d) Genin, E.;
Toullec, P. Y.; Antoniotti, S.; Brancour, C.; Genêt, J.-P.;
Michelet, V. J. Am. Chem. Soc. 2006, 128, 3112.
(e) Antoniotti, S.; Genin, E.; Michelet, V.; Genêt, J.-P.
J. Am. Chem. Soc. 2005, 127, 9976.
(8) (a) Chao, C.-M.; Toullec, P. Y.; Michelet, V. Tetrahedron
Lett. 2009, 50, 3719. (b) Leseurre, L.; Chao, C.-M.; Seki, T.;
Genin, E.; Toullec, P. Y.; Genêt, J.-P.; Michelet, V.
Tetrahedron 2009, 65, 1911. (c) Genin, E.; Leseurre, L.;
Toullec, P. Y.; Genet, J.-P.; Michelet, V. Synlett 2007,
1780. (d) Leseurre, L.; Toullec, P. Y.; Genêt, J.-P.; Michelet,
V. Org. Lett. 2007, 9, 4049. (e) Toullec, P. Y.; Genin, E.;
Leseurre, L.; Genêt, J.-P.; Michelet, V. Angew. Chem. Int.
Ed. 2006, 45, 7427.
Synlett 2012, 23, 74–79
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CLUSTER
Gold-Catalyzed Cycloisomerization of Functionalized 1,5-Enynes
79
(9) For asymmetric cycloisomerization of 1,6-enynes, see:
(a) Pradal, A.; Toullec, P. Y.; Michelet, V. Synthesis 2011,
1501. (b) Pradal, A.; Chao, C.-M.; Vitale, M. R.; Toullec, P.
Y.; Michelet, V. Tetrahedron 2011, 67, 4371. (c) Pradal,
A.; Chao, C.-M.; Vitale, M.; Toullec, P. Y.; Michelet, V.
Beilstein J. Org. Chem. 2011, 7, 1021. (d) Andreiadis, E.;
Vitale, M. R.; Mézailles, N.; Le Goff, X.; Le Floch, P.;
Toullec, P. Y.; Michelet, V. Dalton Trans. 2010, 39, 10608.
(e) Chao, C.-M.; Vitale, M.; Toullec, P. Y.; Genêt, J.-P.;
Michelet, V. Chem. Eur. J. 2009, 15, 1319. (f)Chao,C.-M.;
Genin, E.; Toullec, P. Y.; Genêt, J.-P.; Michelet, V.
J. Organomet. Chem. 2009, 694, 538. (g) Chao, C.-M.;
Beltrami, D.; Toullec, P. Y.; Michelet, V. Chem. Commun.
2009, 6988.
(2 H, s), 3.33 (2 H, s), 3.79 (6 H, s), 5.72 (1 H, s), 6.26–6.37
(3 H, m), 7.15–7.31 (5 H, m). 13C NMR (75 MHz, CDCl3):
d = 18.6, 27.1, 30.4, 37.8, 43.0, 45.0, 55.2, 97.9, 106.8,
125.7, 128.0, 128.3, 133.4, 140.3, 141.3, 142.5, 160.8.
Compound 26: 1H NMR (300 MHz, CDCl3): d = 1.75 (3 H,
s), 1.70–1.84 (1 H, m), 2.20–2.28 (1 H, m), 2.50–2.70 (2 H,
m), 2.75–2.80 (1 H, m), 3.74 (3 H, s), 3.79 (3 H, s), 4.72 (1
H, br s), 4.82 (1 H, br s), 5.83–5.85 (1 H, m), 6.25–6.37 (2
H, m), 7.15–7.31 (5 H, m). 13C NMR (75 MHz, CDCl3): d =
22.3, 32.1, 36.6, 42.2, 55.1, 55.2, 97.3, 101.0, 104.8, 112.1,
125.2, 125.8, 126.8, 132.4, 137.6, 141.0, 143.5, 157.5,
158.1, 159.6. MS (CI): m/z = 321 [M + H]+.
3-Benzyl-5-methylbicyclo[3.1.0]hex-2-ene (29)
Colorless oil. 1H NMR (300 MHz, CDCl3): d = 0.09 (1 H, dd,
J = 3.4, 3.3 Hz), 0.67 (1 H, dd, J = 7.3, 3.5 Hz), 1.24 (3 H,
s), 1.41–1.43 (1 H, m), 2.25 (2 H, s), 3.28 (2 H, s), 5.56 (1 H,
br s), 7.12–7.30 (5 H, m). 13C NMR (75 MHz, CDCl3): d =
21.8, 22.6, 24.2, 29.9, 37.6, 43.9, 125.8, 128.2, 128.7, 130.0,
139.0, 142.0. MS (CI): m/z = 184 [M]+.
(10) (a) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874.
(b) Doucet, H.; Hierso, J.-C. Angew. Chem. Int. Ed. 2007,
46, 834.
(11) Typical Procedure for the Gold-Catalyzed Reactions of
1,5-Enynes
PPh3AuCl (3.3 mg, 0.0066 mmol) and AgSbF6 (2.3 mg,
0.0066 mmol) were added to a flask under argon atmos-
phere. Then, anhyd Et2O (0.44 mL) and 10 (60 mg, 0.22
mmol) were introduced, and the mixture was stirred for 1 h
at r.t. After filtration of the reactant, the solvent was
evaporated under reduced pressure. The residue was purified
by flash chromatography (cyclohexane–EtOAc, 100:1) on
silica gel to give 21 (55 mg, 92% yield) as a colorless oil.
(12) Mézailles, N.; Ricard, L.; Gagosz, F. Org. Lett. 2005, 7,
4133.
3-Benzyl-5-methyl-1-phenylbicyclo[3.1.0]hex-2-ene (31)
Colorless oil. 1H NMR (300 MHz, CDCl3): d = 0.63 (1 H, d,
J = 4.1 Hz), 0.95 (3 H, s), 1.34 (1 H, d, J = 4.1 Hz), 2.40 (2
H, s), 3.39 (2 H, s), 5.67 (1 H, s), 7.18–7.22 (6 H, m), 7.26–
7.31 (4 H, m). 13C NMR (75 MHz, CDCl3): d = 18.6, 27.2,
30.4, 37.4, 43.0, 45.1, 125.7, 125.9, 127.9, 128.3, 128.8,
133.2, 140.0, 140.4, 141.8. MS (CI): m/z = 260 [M]+.
(17) Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem. Int. Ed.
1998, 37, 1415.
(18) (a) Koh, J. H.; Gagné, M. R. Angew. Chem. Int. Ed. 2004, 43,
3459. (b) Feducia, J. A.; Gagné, M. R. J. Am. Chem. Soc.
2008, 130, 592; and references cited therein.
(13) 2-[(4-Methoxyphenoxy)methyl]-1,3-dimethylcyclohex-3-
enol (23)
1H NMR (400 MHz, CDCl3): d = 1.27 (6 H, m), 1.76–1.75
(4 H, m), 2.50 (1 H, m), 3.77 (3 H, s), 3.94–3.92 (1 H, dd,
J = 5.8, 7.3 Hz), 4.12–4.08 (1 H, dd, J = 3.0, 7.3 Hz), 5.50 (1
H, t, J = 1.2 Hz), 6.87–6.77 (4 H, m). 13C NMR (100 MHz,
CDCl3): d = 22.3, 23.0, 24.8, 33.7, 50.5, 55.8, 68.9, 71.6,
76.8, 77.1, 77.4, 114.7, 115.7, 123.7, 131.6, 152.7, 154.2.
MS (CI): m/z = 245 [M – H2O + H]+, 262 [M – H2O + NH4]+,
263 [M + H]+, 280 [M + NH4]+.
(19) (a) Conia, J. M.; Le Perchec, P. Synthesis 1975, 1.
(b) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am.
Chem. Soc. 2004, 126, 4526. (c) Staben, S. T.; Kennedy-
Smith, J. J.; Toste, F. D. Angew. Chem. Int. Ed. 2004, 43,
5350. (d) Ochida, A.; Ito, H.; Sawamura, M. J. Am. Chem.
Soc. 2006, 128, 16486. (e) Ito, H.; Makida, Y.; Ochida, A.;
Ohmiya, H.; Sawamura, M. Org. Lett. 2008, 10, 5051.
(20) (a) Amijs, C. H. M.; López-Carrillo, V.; Raducan, M.; Pérez-
Galán, P.; Ferrer, C.; Echavarren, A. M. J. Org. Chem. 2008,
73, 7721. (b) Yao, T.; Zhang, X.; Larock, R. C. J. Am. Chem.
Soc. 2004, 126, 11164. (c) Teng, T.-M.; Lin, M.-S.; Vasu,
D.; Bhunia, S.; Liu, T.-.; Liu, R.-S. Chem. Eur. J. 2010, 16,
4744. (d) For a recent interesting contribution on allylic
alcohols, see: Chiarucci, M.; Locritani, M.; Cera, G.;
Bandini, M. Beilstein J. Org. Chem. 2011, 7, 1198.
(21) Methyl 5-(1,2-dimethylcyclopent-2-en-1-yl)-2-methyl-
4,5-dihydrofuran-3-carboxylate (37)
(14) Buzas, A. K.; Istrate, F. M.; Gagosz, F. Angew. Chem. Int.
Ed. 2007, 46, 1141.
(15) Nevado, C.; Echavarren, A. M. Synthesis 2005, 167; and
references cited therein.
(16) 3-(3,5-Dimethoxybenzyl)-5-methylbicyclo[3.1.0]hex-2-
ene (25) and 1,2-Dihydro-5,7-dimethoxy-2-(2-
methylallyl)naphthalene (24)
Compound 25: 1H NMR (300 MHz, CDCl3): d = 0.09 (1 H,
dd, J = 3.4, 2.4 Hz), 0.67 (1 H, dd, J = 7.2, 3.5 Hz), 1.24 (3
H, s), 1.41–1.44 (1 H, m), 2.25 (2 H, s), 3.22 (2 H, s), 3.78 (6
H, s), 5.60 (1 H, d, J = 1.7 Hz), 6.30 (3 H, s). 13C NMR (75
MHz, CDCl3): d = 21.8, 22.6, 24.1, 29.9, 37.9, 43.8, 55.2,
97.9, 106.8, 130.3, 141.4, 142.6, 160.7.
1H NMR (300 MHz, CDCl3): d = 1.07 (3 H, s), 1.60–1.67 (4
H, m), 1.87 (1 H, m), 2.16 (3 H, s), 2.16–2.25 (2 H, m), 2.65–
2.81 (2 H, m), 3.71 (3 H, s), 4.59 (1 H, t, J = 10.2 Hz), 5.40
(1 H, br s). 13C NMR (75 MHz, CDCl3): d = 12.9, 14.1, 21.5,
29.0, 31.7, 32.3, 50.6, 53.1, 86.6, 101.9, 126.1, 143.2, 166.7,
168.7. MS (CI): m/z = 237 [M + H]+.
Compound 24: 1H NMR (300 MHz, CDCl3): d = 1.73 (3 H,
s), 1.70–1.84 (1 H, m), 2.10–2.15 (1 H, m), 2.50–2.70 (2 H,
m), 2.75–2.80 (1 H, m), 3.80 (6 H, s), 4.72 (1 H, br s), 4.82
(1 H, br s), 5.75–5.85 (1 H, m), 6.30–6.36 (2 H, m), 6.70–
6.77 (1 H, m). 13C NMR (75 MHz, CDCl3): d = 22.2, 31.3,
34.4, 42.5, 55.0, 55.5, 96.3, 105.1, 112.1, 115.6, 120.6,
129.4, 137.5, 143.5, 156.0, 159.0. MS (CI): m/z = 245 [M +
H]+.
1,2-(Dimethylcyclopent-2-en-1-yl)-2-phenyl-4,5-
dihydrofuran-3-yl)(phenyl)methanone (38)
1H NMR (300 MHz, CDCl3): d = 1.17 (3 H, s), 1.67 (1 H, m),
1.74 (3 H, s), 2.04 (1 H, m), 2.23–2.27 (2 H, m), 3.19, 3.14
(2 H, 2 dd, J = 15.0, 10.3 Hz), 4.83 (1 H, t, J = 10.3 Hz), 5.43
(1 H, br s), 6.99–7.20 (8 H, m), 7.39 (2 H, dd, J = 1.4, 8.4
Hz). 13C NMR (75MHz, CDCl3): d = 13.3, 21.6, 29.1, 33.0,
34.8, 53.2, 86.8, 112.7, 126.3, 127.5, 127.6, 128.8, 129.3,
129.8, 130.3, 130.9, 139.3, 143.2, 166.7, 193.7. MS (CI):
m/z = 345 [M + H]+.
3-(3,5-Dimethoxybenzyl)-5-methyl-1-phenylbicyclo-
[3.1.0]hex-2-ene(27) and 1,2-Dihydro-5,7-dimethoxy-2-
(2-methylallyl)-4-phenylnaphthalene (26)
Compound 27: 1H NMR (300 MHz, CDCl3): d = 0.64 (1 H,
d, J = 4.1 Hz), 0.96 (3 H, s), 1.35 (1 H, d, J = 4.1 Hz), 2.40
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Synlett 2012, 23, 74–79

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