An unexpected double-bond isomerization catalyzed by Crabtree's iridium(I) catalyst

Article abstract of DOI:10.1055/s-2005-871935

The first iridium-catalyzed isomerization of an exocyclic into an endocyclic double bond is described. A mechanism is proposed for this reaction. Crabtree's catalyst thus allows the migration of a double bond that does not occur under classical conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-871935

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LETTER
2043
An Unexpected Double-Bond Isomerization Catalyzed by Crabtree’s
Iridium(I) Catalyst
D
ouble-Bond Isomeriz
i
a
tion C
c
atalyze
d
by
h
C
rabtree’s
a
Iridium(I)
C
e
atalyst l Krel, Jean-Yves Lallemand, Catherine Guillou*
Institut de Chimie des Substances Naturelles, Bt 27, CNRS Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
Fax +33(1)69077247; E-mail: guillou@icsn.cnrs-gif.fr
Received 2 May 2005
Olefinic substrates 3 and 4 were readily obtained from the
appropriate ketones 10 and 13 via a Wittig reaction. These
ketones were prepared from of 1-methyl-5-methoxy-2-
tetralone (8).4 Bis-O-methylation (Me2SO4, NaOH, ace-
tone)5 of 1,6-dihydroxynaphthalene (5) gave dimethyl
ether 6 in 94% yield, which was then subjected to Bouvier
reduction under the conditions described by Cornforth
(Na, EtOH, concd HCl)6 to afford ketone 7 in 76% yield.
The desired 1-methyl derivative of the naphthalen-2-one
7 was then obtained by the use of an enamine alkylation
reaction: ketone 7 was converted into its pyrrolidine
enamine, which without isolation, was alkylated by re-
fluxing with methyl iodide in dry dioxane solution
(Scheme 2).
Abstract: The first iridium-catalyzed isomerization of an exocyclic
into an endocyclic double bond is described. A mechanism is pro-
posed for this reaction. Crabtree’s catalyst thus allows the migration
of a double bond that does not occur under classical conditions.
Key words: iridium, catalysis, isomerization, olefination, aldol-
like reaction
Heteroatom-directed homogeneous hydrogenation of ole-
fins in the presence of a transition metal catalyst provides
a powerful method for regio- and stereochemical control
in organic synthesis.1 The directing effects arise when the
heteroatom, hydrogen and the alkene bind simultaneously
to the transition metal, permitting exclusive syn delivery
of hydrogen to the unsaturated site. For this reaction,
Crabtree’s catalyst2 [Ir(cod)py(PCy3)]PF6 is effective
with a variety of directing groups such as hydroxyl, meth-
oxy, ester, carboxamide and carbalkoxy.3
OMe
OH
a
(94%)
OMe
OH
In a project aimed at the synthesis of natural products, we
planned to synthesize compounds 1 and 2 as useful syn-
thetic intermediates. The secondary methyl group of com-
pounds 1 and 2 could ideally be obtained by reduction of
the corresponding exo-double bond present in compounds
3 and 4 (Scheme 1).
5
6
(76%)
b
O
O
c
(88%)
R1
R1
OR2
OR2
OMe
OMe
8
7
H2, Crabtree's catalyst
Scheme 2 Reagents and conditions: (a) Me2SO4, NaOH, acetone,
reflux; (b) i) Na, EtOH reflux; ii) aq HCl reflux; (c) i) pyrrolidine,
toluene, reflux; ii) CH3I, dioxane.
OMe
OMe
3: R1 = CH3; R2 = H
4: R1 = OMe; R2 = (CH2)3OMe
1: R1 = CH3; R2 = H
2: R1 = OMe; R2 = (CH2)3OMe
Our strategy to form the critical quaternary center of the
target molecules 1 and 2 was based on an aldol-like alkyl-
ation reaction with acetals.7 A short synthesis of 1 is sum-
marized in Scheme 3. Ketone 8 was first converted into
the corresponding silyl enol ether 9. Reaction of 9 with 2-
methoxy-1,3-dioxolane in the presence of BF3·OEt2 af-
forded 10 in quantitative yield. Wittig olefination gave an
almost quantitative yield of exocyclic olefin 11. The diox-
olane group of 11 was removed with pyridinium para-tol-
uenesulfonate to give the aldehyde 12 in 89% yield.
Reaction of 12 with methyllithium afforded alcohol 3 as a
85:15 mixture of C13 epimers.8 Directed stereoselective
hydrogenation of the exocyclic double bond of 3 with
Crabtree’s catalyst furnished compound 1 in >90% de.8,9
Scheme 1
Contrary to expectation, the double bond of compound 4
was resistant to hydrogenation in the presence of
Crabtree’s catalyst. Only the migration of the double bond
into the six-membered ring was observed. In this letter we
wish to describe the influence of the environment around
the hydroxyl or the methoxy group in directed stereoselec-
tive hydrogenation of exocyclic olefins with Crabtree’s
catalyst.
SYNLETT 2005, No. 13, pp 2043–2046
Advanced online publication: 12.07.2005
1
9
.0
8
.2
0
0
5
DOI: 10.1055/s-2005-871935; Art ID: G15005ST
© Georg Thieme Verlag Stuttgart · New York

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2044
M. Krel et al.
LETTER
It should be noted that the migration of the double bond
under classical conditions failed (acidic or basic condi-
tions, Wilkinson catalyst, microwaves); the starting
material was transformed into 5-methoxy-1,2-dimethyl-
naphthalene. Moreover, hydrogenation of 4 in the
presence of palladium on charcoal afforded one diastereo-
isomer of 2 in quantitative yield.
O
O
O
O
OSiMe3
O
a
b
c
8
(94%)
(100%)
(97%)
OMe
OMe
OMe
9
10
11
These results led us to investigate more closely the reac-
tion of 4 with Crabtree’s catalyst. No deuterium incorpo-
ration was observed after exposure of 4 to deuterium in
the presence of iridium(I) catalyst. Only the double-bond
migration took place under these conditions. No double-
bond migration occurred when 4 was mixed with Crab-
tree’s catalyst in the absence of hydrogen. The following
mechanisms are proposed to rationalize these results.
Upon treatment with hydrogen, the cyclooctadiene is re-
duced, and the 12-electron ‘IrR2’ system is formed. The
OMe group and the neighboring exocyclic alkene bind to
the coordinatively unsaturated metal complex. The steric
hindrance of the side chain or another interaction with the
second OMe group prevents the oxidative addition of hy-
drogen to the iridium complex (Scheme 6). No directed
hydrogenation can occur under these conditions. Instead,
an insertion of the metal complex into the CH bond a to
the double bond is favored leading to the formation of an
h3-allyl hydride complex.11,12 Subsequent reductive elim-
ination affords the endocyclic alkene 15 under neutral
conditions. When the side chain is shorter the oxidative
addition of hydrogen to the iridium complex is possible
leading to the directed hydrogenation of the exo-double
bond present in compound 3.
d
(89%)
OH
OH
O
e
(90%)
f
(92%)
OMe
OMe
OMe
12
1
3
Scheme 3 Reagents and conditions: (a) ClSiMe3, Et3N, CH2Cl2, r.t.;
(b) 2-methoxy-1,3-dioxolane, BF3·OEt2, CH2Cl2, –78 °C; (c)
CH2=PPh3, THF, r.t.; (d) PPTS, acetone, reflux; (e) MeLi, THF,
–78 °C; (f) [Ir(cod)py(PCy3)]PF6, H2, CH2Cl2, r.t.
Compound 13, which possesses a longer side chain, was
synthesized by reaction of 9 with 1,1,4-trimethoxybutane.
A diastereoisomeric mixture of ketones 1310 and 1410 was
obtained, which was separated chromatographically. The
stereochemistry of 13 was determined by single-crystal
X-ray crystallography (Scheme 4).
H
MeO
H
MeO
OMe
OMe
O
O
a
In summary, we describe here the first example of an effi-
cient iridium(I)-catalyzed isomerization of an exo- to an
endocyclic double bond. In addition, this method could
also be very useful when classical methods for isomeriza-
tion of double bonds fail. The general applicability of this
method is currently being investigated.
9
OMe
OMe
13 (76%)
14 (19%)
Scheme 4 Reagents and conditions: (a) 1,1,4-trimethoxybutane,
BF3·OEt2, CH2Cl2, –78 °C.
Acknowledgment
The exocyclic olefin 410 was synthesized in near quantita-
tive yield by Wittig olefination of the ketone 13.10 At-
tempts to hydrogenate 4 in the presence of Crabtree’s
catalyst were unsuccessful. Contrary to expectation, the
migration of the exo-double bond into the six-membered
ring occurred in quantitative yield (Scheme 5).10
The authors thank the CNRS for financial support and Robert Dodd
for carefully reading the manuscript and for helpful comments.
References
(1) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993,
93, 1307; and references therein.
H
MeO
H
MeO
(2) (a) Crabtree, R. H.; Felkin, H.; Morris, G. E. J. Organomet.
Chem. 1977, 141, 205. (b) Crabtree, R. H. Acc. Chem. Res.
1979, 12, 331. (c) Crabtree, R. H.; Demou, P. C.; Eden, D.;
Mihelnic, J. M.; Parnell, C. A.; Quirk, J. M.; Morris, G. E. J.
Am. Chem. Soc. 1982, 104, 6994.
(3) (a) Stork, G.; Kahne, D. E. J. Am. Chem. Soc. 1983, 105,
1072. (b) Schultz, A.; McCloskey, P. J. J. Org. Chem. 1985,
50, 5905. (c) Brown, J. M.; Hall, S. A. J. Organomet. Chem.
1985, 285, 333. (d) Brown, J. M.; Hall, S. A. Tetrahedron
Lett. 1984, 25, 1393. (e) Brown, J. M.; Naik, R. G. J. Chem.
Soc., Chem. Commun. 1982, 348. (f) Takagi, M.;
OMe
OMe
a
b
13
(97%)
(100%)
OMe
OMe
4
15
Scheme 5 Reagents and conditions: (a) CH2=PPh3, THF, r.t.; (b)
[Ir(cod)py(PCy3)]PF6, H2, CH2Cl2, r.t.
Yamamoto, K. Tetrahedron 1991, 47, 8869.
Synlett 2005, No. 13, 2043–2046 © Thieme Stuttgart · New York

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LETTER
Double-Bond Isomerization Catalyzed by Crabtree’s Iridium(I) Catalyst
2045
–
[Ir(cod)pyP(cy)3]+PF6
OMe
MeO
2H2
4
py
Ir+
R3P
–
PF6
15
reductive
elimination
(12e–)
MeO
OMe
OMe
MeO
py
OMe
MeO
H
Ir+
py
py
R3P
Ir+
Ir
+
R3P
R3P
H
H
(18e–)
η3 allyl
formation
(18e–)
CH
OMe
MeO
py
insertion
Ir+
R3P
H
(18e–)
Scheme 6
(4) (a) D’Angelo, J.; Revial, G.; Volpe, T.; Pfau, M.
catalyst (10 mg, 0.012 mmol) was added and the solution
degassed again under vacuum and filled with argon. The
mixture was allowed to warm to r.t. and the Schlenk tube
was linked to an hydrogenation apparatus. The system was
flushed ten times with hydrogen and stirred 12 h at r.t. under
an atmospheric pressure of hydrogen. The solvent was then
removed under vacuum and the resulting slurry dissolved in
Et2O and filtered on a short silica pad. Chromatography on
preparative TLC (elution with heptane–EtOAc, 85:15) of the
residue afforded 1 (26 mg, 92%) as a colorless oil. H NMR
(300 MHz, CDCl3): d = 7.19 (t, J = 7.9 Hz, 1 H, H7), 6.98 (d,
J = 8.0 Hz, 1 H, H6), 6.73 (d, J = 8.0 Hz, 1 H, H8), 5.13 (s,
1 H, 15%, H14a), 5.11 (s, 1 H, 85%, H14a), 5.00 (s, 1 H,
85%, H14b), 4.91 (s, 1 H, 15%, H14b), 4.13 (quad, J = 7.1
Hz, 1 H, 15%, H13), 4.06 (quad, J = 6.5 Hz, 1 H, 85%, H13),
3.83 (s, 3 H, H11), 3.10–2.95 (m, 1 H, H4a), 2.69–2.36 (m,
3 H, H4b-H3), 1.48 (s, 3 H, H12), 1.69 (d, J = 6.3 Hz, 3 H,
15%, H15), 1.02 (d, J = 6.4 Hz, 3 H, H15) ppm. 13C NMR
(75 MHz, CDCl3): d = 157.5 (C5), 151.0 (C2), 144.5 (C9),
127.2 (C7), 16.9 (C10), 119.6 (C8), 111.2 (C15), 108.1 (C6),
74.1 (C13), 56.1 (C11), 48.9 (C1), 32.7 (C3), 25.1 (C4), 23.1
(C12), 19.5 (C14) ppm. IR (CHCl3): n = 3453, 1579, 1459,
1254, 1062 cm–1. HRMS (ESI): m/z calcd for C15H22O2:
234.1620; found: 257.1492 [M + Na].
Tetrahedron Lett. 1988, 29, 4427. (b) Lundkvist, J. R. M.;
Johansson, A. M.; Arvidsson, L. E.; Hacksell, U. Acta Chem.
Scand., Ser. B 1986, 40, 508.
(5) Abell, A. D.; Phillips, A. J.; Budhia, S.; McNulty, A. N.;
Neubauer, B. L. Aust. J. Chem. 1998, 51, 389.
(6) Cornforth, J. W.; Robinson, R. J. Chem. Soc. 1949, 1855.
(7) (a) Karisami, K.; Koskinen, A. M. P.; Nissenen, M.;
Rissanen, K. Tetrahedron 2003, 59, 1421. (b) Müller, P.;
Nury, P.; Bernardinelli, G. Eur. J. Org. Chem. 2001, 4137.
(c) Longobardo, L.; Mobbili, G.; Tagliavini, E.; Trombini,
C.; Umari-Ronchi, A. Tetrahedron 1992, 48, 1299.
(8) Representative Procedures for the Synthesis of 3 and 1.
1-(5-Methoxy-1-methyl-2-methylene-1,2,3,4-
tetrahydronaphthalen-1-yl)ethanol (3).
To a solution of aldehyde 12 (83 mg, 0.38 mmol) in THF
was added methyllithium (1.6 N solution in hexane, 0.53
mL, 0.85 mmol) at –78 °C. The solution was stirred at
–78 °C for 2 h. The reaction mixture was quenched with aq
sat. NaHCO3 at –78 °C and extracted with CH2Cl2. The
combined organic layers were washed with H2O, brine, and
dried (Na2SO4), and the solvent was evaporated.
Chromatography on preparative TLC (elution with heptane–
EtOAc, 85:15) of the residue afforded 3 (77 mg, 87%) as a
colorless oil. 1H NMR (300 MHz, CDCl3): d = 7.19 (t,
J = 7.9 Hz, 1 H, H7), 6.98 (d, J = 8,0 Hz, 1 H, H6), 6.73 (d,
J = 8,0 Hz, 1 H, H8), 5.13 (s, 1 H, 15%, H14a), 5.11 (s, 1 H,
85%, H14a), 5.00 (s, 1 H, 85%, H14b), 4.91 (s, 1 H, 15%,
H14b), 4.13 (q, J = 7.1 Hz, 1 H, 15%, H13), 4.06 (quad,
J = 6.5 Hz, 1 H, 85%, H13), 3.83 (s, 3 H, H11), 3.10–2.95
(m, 1 H, H4a), 2.69–2.36 (m, 3 H, H4b-H3), 1.48 (s, 3 H,
H12), 1.69 (d, J = 6.3 Hz, 3 H, 15%, H15), 1.02 (d, J = 6.4
Hz, 3 H, 85%, H15) ppm. 13C NMR (75 MHz, CDCl3): d =
157.5 (C5), 151.0 (C2), 144.5 (C9), 127.2 (C7), 126.9 (C10),
119.6 (C8), 111.2 (C15), 108.1 (C6), 74.1 (C13), 56.1 (C11),
48.9 (C1), 32.7 (C3), 23.1 (C12), 19.5 (C14) ppm. IR
(CHCl3): n = 1577, 1461, 1251, 1047 cm–1. HRMS (ESI):
m/z calcd for C15H20O2: 232.1463; found: 255.1374 [M + Na].
1-(5-Methoxy-1,2-dimethyl-1,2,3,4-
(9) When this reaction was conducted in the same conditions
with shorter time (1 h) no isomerization of 3 was observed.
(10) Representative Procedures for the Synthesis of 13, 14, 4
and 15.
1-(1,4-Dimethoxybutyl)-5-methoxy-1-methyl-3,4-
dihydro-1H-naphthalen-2-one (13).
To a solution of 9 (68 mg, 0.26 mmol) in CH2Cl2 580 mL
was added 1,1,4-trimethoxybutane (3.8 g, 26.2 mmol) at
–78 °C. The solution was stirred at –78 °C for 10 min then
BF3·OEt2 (2.94 mL, 23.2 mmol) was added. The reaction
mixture was stirred for 6 h at –78 °C. The residue was
diluted with CH2Cl2 and washed with sat. aq NaHCO3. The
combined organic layers were washed with H2O, brine, and
dried (Na2SO4), and the solvent was evaporated. Flash
chromatography on silica gel (elution with heptane–EtOAc,
90:10) of the residue afforded 13 (3.63 g, 76%) and 14 (907
mg, 19%) as white solids.
tetrahydronaphthalen-1-yl)ethanol (1).
A solution of alcohol 3 (28 mg, 0.12 mmol) in 2 mL of
CH2Cl2 in a Schlenk apparatus was cooled at –180 °C and
degassed under vacuum then filled with argon. Crabtree’s
Compound 13: 1H NMR (300 MHz, CDCl3): d = 7.21 (t,
J = 8.0 Hz, 1 H, H7), 6.91 (d, J = 8.0 Hz, 1 H, H8), 6.80 (d,
Synlett 2005, No. 13, 2043–2046 © Thieme Stuttgart · New York

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2046
M. Krel et al.
LETTER
J = 8.1 Hz, 1 H, H6), 3.85 (s, 3 H, H11), 3.66 (dd, J = 10.4,
2.2 Hz, 1 H, H13), 3.33–3.15 (m, 3 H, H16-H4a), 3.31 (s, 3
H, H17), 3.17 (s, 3 H, H18), 2.94 (ddd, J = 16.1, 11.8, 5.5
Hz, 1 H, H4b), 2.73 (ddd, J = 16.2, 5.3, 3.3 Hz, 1 H, H3a),
2.44 (ddd, J = 16.2, 11.7, 6.9 Hz, 1 H, H3b), 1.70–1.45 (m,
2 H, H14), 1.43 (s, 3 H, H12), 1.35–1.20 (m, 2 H, H15) ppm.
13C NMR (75 MHz, CDCl3): d = 213.9 (C2), 156.0 (C5),
142.2 (C9), 127.1 (C7), 125.1 (C10), 120.1 (C8), 107.8 (C6),
88.4 (C13), 72.7 (C16), 61.7 (C18), 58.5 (C17), 56.2 (C1),
55.4 (C11), 37.9 (C3), 29.5 (C14), 27.0 (C15), 23.4 (C12),
21.6 (C12) ppm. IR (CHCl3): n = 3155, 2985, 2255, 1805,
1794, 1643, 1470, 1382, 1167, 1096, 926 cm–1. HRMS
(ESI): m/z calcd for C18H26O4: 306.3966; found: 329.1734
[M + Na]. Anal. Calcd for C18H26O4 (%): C, 69.54; H, 7.30;
O, 23.16. Found: C, 69.48; H, 7.37; O, 23.15.
H3a, H4b), 2.50–2.40 (m, 1 H, H3b), 1.85–1.70 (m, 2 H,
H15), 1.44 (s, 3 H, H12), 1.35–1.15 (m, 2 H, H14) ppm. 13
C
NMR (75 MHz, CDCl3): d = 156.3 (C5), 151.8 (C2), 143.6
(C9), 127.2 (C10), 125.9 (C7), 119.9 (C8), 109.1 (C9), 107.0
(C6), 90.8 (C13), 73.0 (C16), 61.5 (C18), 58.5 (C17), 55.4
(C11), 48.1 (C1), 32.7 (C3), 28.2 (C14), 27.2 (C15), 26.2
(C12), 24.6 (C4) ppm. Anal. Calcd for C19H28O3 (%): C,
74.96; H, 9.27; O, 15.77. Found: C, 74.75; H, 9.09; O, 16.01.
IR (CHCl3): n = 1577, 1461, 1433, 1367, 1254, 1047 cm–1.
HRMS (ESI): m/z calcd for C19H28O3: 304.2038; found:
327.1894 [M + Na].
1-(1,4-Dimethoxybutyl)-5-methoxy-1,2-dimethyl-1,4-
dihydronaphthalene (15).
A solution of alkene 4 (98 mg, 0.32 mmol) in 3 mL of
CH2Cl2 in a Schlenk apparatus was cooled at –180 °C and
degassed under vacuum then filled with argon. Crabtree’s
catalyst (11 mg, 0.012 mmol) was added and the solution
degassed again under vacuum and filled with argon. The
mixture was allowed to warm to r.t. and the Schlenk tube
was linked to an hydrogenation apparatus. The system was
flushed ten times with hydrogen and stirred 12 h at r.t. under
an atmospheric pressure of hydrogen. The solvent was then
removed under vacuum and the resulting slurry dissolved in
Et2O and filtered on a short silica pad. Chromatography on
preparative TLC (elution with heptane–EtOAc, 85:15) of the
residue afforded 1 (90 mg, 92%) as a colorless oil. 1H NMR
(300 MHz, CDCl3): d = 7.27 (dd, J = 8.0, 1.1 Hz, 1 H, H8),
7.17 (t, J = 8.0 Hz, 1 H, H7), 6.71 (dd, J = 7.9, 1.0 Hz, 1 H,
H6), 5.59 (dqd, J = 2.7, 1.7, 0.6 Hz, 1 H, H3), 3.83 (s, 3 H,
H11), 3.51 (s, 3 H, H18), 3.26 (s, 3 H, H18), 3.30–3.20 (m,
4 H, H4a, H13, H16), 3.08 (dq, J = 22.4, 2.6 Hz, 1 H, H4b),
1.88 (dd, J = 2.6, 1.7 Hz, 3 H, H19), 1.65–1.60 (m, 2 H,
H14), 1.55 (s, 3 H, H12), 1.45–1.38 (m, 1 H, H15), 1.00–
0.90 (m, 1 H, H15) ppm. 13C NMR (75 MHz, CDCl3): d =
155.9 (C5), 141.3 (C9), 136.2 (C2), 125.9 (C7), 124.0 (C10),
122.6 (C3), 120.5 (C8), 106.9 (C6), 88.4 (C13), 73.1 (C16),
61.8 (C18), 58.5 (C17), 55.2 (C11), 47.1 (C1), 28.9 (C15),
27.2 (C14), 25.1 (C4), 23.3 (C12), 20.5 (C19). IR (CHCl3):
n = 1582, 1462, 1423. HRMS (ESI): m/z calcd for C19H28O3:
304.2038; found: 327.1950 [M + Na].
Compound 14: 1H NMR (300 MHz, CDCl3): d = 7.21 (t,
J = 8.0 Hz, 1 H, H7), 6.91 (d, J = 8.0 Hz, 1 H, H8), 6.80 (d,
J = 8.1 Hz, 1 H, H6), 3.85 (s, 3 H, H11), 3.66 (dd, J = 10.4,
2.2 Hz, 1 H, H13), 3.33–3.15 (m, 3 H, H16, H4a), 3.31 (s, 3
H, H17), 3.17 (s, 3 H, H18), 2.94 (ddd, J = 16.1, 11.8, 5.5
Hz, 1 H, H4b), 2.73 (ddd, J = 16.2, 5.3, 3.3 Hz, 1 H, H3a),
2.44 (ddd, J = 16.2, 11.7, 6.9 Hz, 1 H, H3b), 1.70–1.45 (m,
2 H, H14), 1.43 (s, 3 H, H12), 1.35–1.20 (m, 2 H, H15) ppm.
13C NMR (75 MHz, CDCl3): d = 215.2 (C2), 156.1 (C5),
140.4 (C9), 126.6 (C7), 125.5 (C10), 120.6 (C8), 108.3 (C6),
88.5 (C13), 72.7 (C16), 61.2 (C18), 58.6 (C17), 56.3 (C1),
55.4 (C11), 37.8 (C3), 28.4 (C14), 26.9 (C15), 20.3 (C4),
20.2 (C12) ppm. IR (CHCl3): n = 3155, 2984, 2254, 1794,
1706, 1642, 1469, 1382, 1261, 1167, 1096 cm–1.
1-(1,4-Dimethoxybutyl)-5-methoxy-1-methyl-2-
methylene-1,2,3,4-tetrahydronaphthalene (4).
To a solution of ketone 12 (3.3 g, 10.7 mmol) in THF were
successively added at r.t. methyltriphenylphosphonium
bromide (19.1g, 54 mmol) and potassium tert-butoxide (6 g,
54 mmol). The reaction mixture was stirred at r.t. for 48 h.
The reaction mixture was diluted with Et2O and washed with
sat. aq NaHCO3. The combined organic layers were washed
with H2O, brine, and dried (Na2SO4), and the solvent was
evaporated. Flash chromatography on silica gel (elution with
heptane–EtOAc, 90:10) of the residue afforded 4 (3.17g,
97%) as a white solid. 1H NMR (300 MHz, CDCl3): d =
7.22–7.15 (m, 2 H, H7, H8), 6.69 (dd, J = 7.3, 1.8 Hz, 1 H,
H6), 5.03 (q, J = 1.3 Hz, 1 H, H19a), 4.85 (d, J = 1.3 Hz, 1
H, H19b), 3.82 (s, 3 H, H11), 3.39 (dd, J = 10.2, 2.0 Hz, 1 H,
H13), 3.34 (t, J = 6.7 Hz, 2 H, H16), 3.31 (s, 3 H, H18), 3.17
(s, 3 H, H18), 2.95–2.80 (m, 1 H, H4a), 2.80–2.55 (m, 2 H,
(11) For isomerization of allylamides see: Neugnot, B.; Cintrat, J.
C.; Rousseau, B. Tetrahedron 2004, 60, 3575.
(12) For the isomerization of allyl ethers see: (a) Nelson, S. G.;
Bungard, C. J.; Wang, K. J. Am. Chem. Soc. 2003, 125,
13000. (b) Ohmura, T.; Yamamoto, Y. Y.; Miyaura, N.
Organometallics 1999, 18, 413; and references therein.
Synlett 2005, No. 13, 2043–2046 © Thieme Stuttgart · New York