Competition between novel 8-endo-dig and 6-trig cyclizations of samarium ketyls leading either to benzannulated cyclooctene or to hexahydronaphthalene derivatives

Article abstract of DOI:10.1016/S0040-4020(00)00353-7

Ketoesters 3a-3h with an alkynylaryl substituent were prepared by standard methods starting from siloxycyclopropanes 6a and 6b. Their reactions with 2.2 equiv. of samarium diiodide in the presence of hexamethyl phosphoramide either produced benzannulated

Full text of DOI:10.1016/S0040-4020(00)00353-7

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4267±4277
Competition between Novel 8-endo-dig and 6-trig Cyclizations of
Samarium Ketyls Leading either to Benzannulated Cyclooctene or
to Hexahydronaphthalene Derivatives
Erathodiyil Nandanan,a Chimmanamada U. Dineshb and Hans-Ulrich Reissiga,
*
a
È
È
Institut fur ChemieÐOrganische Chemie, Freie Universitat Berlin, Takustr. 3, D-14195 Berlin, Germany
È È
Institut fur Organische Chemie, Technische Universitat Dresden, Mommsenstrasse 13, D-01062 Dresden, Germany
b
Dedicated to Professor Rolf Huisgen on the occasion of his 80th birthday
Received 19 April 2000; accepted 28 April 2000
AbstractÐKetoesters 3a±3h with an alkynylaryl substituent were prepared by standard methods starting from siloxycyclopropanes 6a and
6b. Their reactions with 2.2 equiv. of samarium diiodide in the presence of hexamethyl phosphoramide either produced benzannulated
cyclooctenol derivatives 4b (or lactone 9), 4f, 4g, and 4h or hexahydronaphthalene derivatives 5a, 5c, and 5d. The competition between
8-endo-dig and 6-trig cyclizations strongly depends on the substitution pattern of 3. Plausible explanations for this competition and of the
diastereoselectivity observed are presented in this paper. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
interest since their transformation into intermediates
mimicking the BC rings of taxol derivatives is conceivable.6
We also tried to extend the cyclizations to alkynyl substi-
tuted arenes 3 but found in a preliminary study that the
anticipated 8-endo-dig reaction 3 to 4 proceeds only in
exceptional cases (R1ˆH). Most compounds 3 cyclized
under attack of the intermediate ketyl on the aromatic ring
giving hexahydronaphthalene derivatives 5 (Scheme 2).7
This 6-trig cyclization had not been observed before in
samarium chemistry and it should gain considerable
synthetic importance due to its ef®ciency and high
diastereoselectivity.8
Metal promoted radical cyclizations are gaining increasing
importance for the construction of ring compounds includ-
ing medium and large ring sizes.1 Signi®cant progress has
been made in recent years by application of samarium
diiodide introduced by Kagan et al. as selective one electron
transfer reagent.2 It has been demonstrated that samarium
diiodide in the presence of HMPA (hexamethyl phosphor-
amide) ef®ciently promotes cyclization of ketones with
ole®nic units giving not only ®ve- or six-membered rings3
but also larger rings including cyclooctanol derivatives
which may be monocyclic, fused bicyclic or bridged
bicyclic systems.4 We used this surprisingly smooth
8-endo-trig cyclization for the conversion of styrene
derivatives 1 into compounds 2 with benzannulated
cyclooctanol skeletons (Scheme 1).5 These products are of
Nevertheless we were still interested in 8-endo-dig cycliza-
tions and therefore describe our experiments providing ®rst
information about the dependence of the reactions depicted
in Scheme 2 on the substitution pattern of precursor 3.
Scheme 1.
Keywords: samarium(II) iodide; 8-endo-dig cyclization; cyclooctenols; hexahydronaphthalenes; Sonogashira reaction; siloxycyclopropanes.
* Corresponding author. Tel.: 149-30-838-55367;
e-mail: hans.reissig@chemie.fu-berlin.de
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00353-7

4268
E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
Scheme 2.
Synthesis of Starting Materials
substituent were further substituted by Sonogashira
reactions.12 Thus, from 8a alkynes 3a±3d and from 8b
compounds 3e±3h were smoothly available. The desilyl-
ation of 3a and 3e was carried out either by treatment
with potassium carbonate in methanol or tetrabutyl-
ammonium ¯uoride to form the terminal alkynes 3b
and 3f.13 It was found that the potassium carbonate/
methanol method resulted in better yields of the desilylated
product.
The model substrates 3a±3h for the SmI2 promoted cycliza-
tions were synthesized as illustrated in Scheme 3. Starting
from the known siloxycyclopropanes 6a and 6b9 their
deprotonation and alkylation10 with o-iodobenzyl iodide
furnished 7a and 7b, respectively, and these were ring
opened by treatment with triethylamine trishydro¯uoride.11
The two resulting ketoesters 8a and 8b with an iodobenzyl
I
1. LDA
Me3SiO
R1
CO2Me
2. o-iodobenzyl iodide
Me3SiO
R1
-78 ˚C, 48 h
CO2Me
6a R1 = Me
6b R1 = i-Pr
7a R1 = Me (68 %)
7b R1 = i-Pr (51 %)
.
NEt3 3HF
R2
I
R2
Pd(PPh3)2Cl2, CuI, Et2NH
H
O
O
R1
CO2Me
R1
CO2Me
8a R1 = Me (93 %)
8b R1 = i-Pr (95 %)
3a R1 = Me,
3b R1 = Me,
3c R1 = Me, R2 = n-Bu
R2 = SiMe3
R2 = H
87 %
K2CO3 / MeOH
98 %
76 %
79 %
80 %
41 %
74 %
71 %
R1 = Me, R2 = CH2OMe
3d
3e
3f
3g
3h
R2 = SiMe
1
R = i-Pr,
3
TBAF / THF
R1 = i-Pr, R2 = H
R1 = i-Pr,
2
R = n-Bu
R1 = i-Pr,
2
R = CH2OMe
Scheme 3.

E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
4269
SiMe3
MeO2C
O
2.2 equiv. SmI2
MeO2C
t-BuOH
THF/HMPA, rt, 15 h
52 %
H
SiMe3
OH
3a
5a
MeO2C
O
MeO2C
HO
2.2 equiv. SmI2
t-BuOH
+
O
O
THF/HMPA, rt, 15 h
H
4b
9
3b
13 %
61 %
MeO2C
O
2.2 equiv. SmI2
t-BuOH
MeO2C
H
THF/HMPA, rt, 15 h
55 %
OH
5c
3c
OMe
MeO2C
O
2.2 equiv. SmI2
MeO2C
t-BuOH
H
THF/HMPA, rt, 15 h
67 %
OH
MeO
5d
3d
Scheme 4.
SmI2 Promoted Cyclizations
the hexahydronaphthalene derivatives (Scheme 5). Whereas
the reaction of trimethylsilyl substituted alkyne 3e did not
give any de®nite product, the three substrates 3f±3h
with less shielded alkyne moieties afforded benzannu-
lated cyclooctenol derivatives 4f±4h in good yields.
Only one diastereomer was isolated in each of these
examples.
As reported in our preliminary publication, 3a and
2.2 equiv. of samarium diiodide in the presence of HMPA
and t-butanol produced hexahydronaphthalene derivatives
5a in 52% yield as singular diastereomer (Scheme 4).7
The terminal alkyne moiety of 3b allowed attack of the
ketyl to the triple bond giving a mixture of the expected
benzannulated cyclooctenol derivative 4b (61% yield) and
lactone 9 which arises from the diastereomer of 4b. The two
substrates 3c and 3d with internal triple bonds behaved
similar to 3a giving again hexahydronaphthalene
derivatives 5c and 5d by attack on the aryl part.
We also investigated substrates 3i and 3j which were
prepared analogously to the route depicted in Scheme 3.
The two diastereomers of 3i provided an inseparable
mixture which apparently contains 5i but also the starting
material (Scheme 6). It will be necessary to separate the
diastereomers of 3i and to study the cyclization in single
experiments. By treatment under standard conditions
Surprisingly none of the isopropyl ketones 3e±3h furnished

4270
E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
Scheme 5.
Scheme 6.

E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
4271
R’
OSmI2
R
CO2Me
R’
R
11
MeO2C
R
MeO2C
R
H
R
I2SmO
R
OSmI2
R’
12
SmI2
13
SmI2
R’
MeO2C
R
MeO2C
R
_
H
R
SmI2
I2SmO
R’
SmI2
R
OSmI2
15
14
+
+
H
H
R’
MeO2C
R
MeO2C
R
H
R
HO
R’
R
OH
4
5
Scheme 7.
aldehyde 3j underwent a reductive cleavage and the ester 10
8-endo-dig cyclization occurs in the case that the alkyne
moiety is not blocked by a bulky substituent such as a
trimethylsilyl group in 3e. n-Butyl or methoxymethyl
groups are tolerated as substituent at the alkyne and 4f±4h
are formed in good yields. Methyl ketones 3a±3d generally
prefer 6-trig cyclization to produce hexahydronaphthalene
derivatives 5. Only compound 3b with a monosubstituted
alkyne unit gives the cyclooctenol derivative 4b and the
related lactone 9. Thus, an unhindered alkyne is required
for methyl ketones if the 8-endo-dig cyclization should have
a chance to compete with the 6-trig cyclization.
was isolated in moderate yield.14
Discussion
The reactions of 3 giving either 4 or 5 start with an electron
transfer from samarium diiodide to produce an intermediate
ketyl 11 (Scheme 7). The next step is crucial for the selec-
tivity of the sequence. 8-Endo-dig cyclization giving the
vinyl radical 12 will ®nally lead to 4, whereas formation
of 5 proceeds via cyclohexadienyl radical 13. Radicals 12
and 13 are converted into carbanionic species 14 or 15 by a
second electron transfer of samarium diiodide before proto-
nation by t-butanol furnishes the ®nal products 4 and 5.
Another point of concern is the stereoselectivity of these
reactions. The con®gurations of hexahydronaphthalene
derivatives 5a, 5c and 5d have been assigned in analogy
to an example determined with the help of an X-ray analy-
sis.15 A plausible explanation for the formation of these
compounds was presented in our preliminary communica-
tion.7 The 8-endo-dig cyclization leads to one diastereomer
in most cases, but ketone 3b provided a mixture of bicyclic
From the examples collected in Schemes 4 and 5 the follow-
ing conclusions can be drawn: an isopropyl substituted ketyl
moiety as derived from ketones 3e±3h is sterically too
hindered for an attack of the benzene ring. Hence, an

4272
E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
MeO2C
MeO2C
I2SmO
HO
R1
R2
R1
R2
cis-4
16
MeO2C
MeO2C
R1
R1
HO
R2
I2SmO
R2
trans-4
17
Scheme 8.
product 4b and lactone 9. We could not transform 4b into 9
and therefore we conclude that these two products should
have different relative con®gurations at the carbon atoms
bearing the carboxyl and the oxygen function. Since
compounds 4f±4h (Scheme 5) have very similar NMR
data they should also have trans location of the two
functional groups.
the scope and limitations and to understand their
surprisingly high stereoselectivities.
Experimental
General information
How do we explain the high stereoselectivity of the 8-endo-
dig cyclization? We assume a chair-like folding of the
¯exible chain with the methoxycarbonyl group occupying
an equatorial position.16 The ketyl unit may be arranged in
two variations: the oxygen (with the coordinated samarium
ion) in a pseudo-equatorial position and the substituent R1 in
an axial position (16 in Scheme 8) or in an inverted situation
(17 in Scheme 8). Reactive conformation 16 should provide
cis-4 whereas 17 will give trans-4. Small substituents R1
and R2 allow both arrangements as demonstrated by the
conversion of 3b (R1ˆMe and R2ˆH) into the mixture of
4b and 9. A larger substituent R2 seems to prefer the pseudo-
equatorial position as shown by the exclusive formation of
trans-isomers in the reactions of 3f, 3g and 3h. Of course,
this model is speculative and has to be con®rmed by further
investigations.
All reactions were performed under argon atmosphere in
¯ame dried ¯asks and the components were added by
means of syringes. All solvents were dried by standard
procedures. Tetrahydrofuran was freshly distilled from
potassium/benzophenone for each of the SmI2 reactions.
Thin layer chromatography (TLC) was carried out on
commercial Polygram Sil G/UV254 or Alox N/UV254
(MACHEREY-NAGEL). Neutral alumina (activity III, Fa.
MERCK) or ¯ash silica gel (E. MERCK) were used for
column chromatography. IR-spectra were measured on
1
Nicolet 205 FT-IR spectrometer. H and 13C NMR spectra
were recorded on Bruker AC 300 or Bruker DRX 500 MHz
instruments in CDCl3 solution. The chemical shifts are
given relative to the TMS or to the CDCl3 signals
(dHˆ7.27, dCˆ77.0). The missing signals of the minor
isomer are hidden by signals of the major isomer or they
could not be unambiguously identi®ed due to low intensity.
HRMS were determined by a Finnigan MAT 711 (8 kV)
instrument by direct evaporation method. Melting points
(uncorrected) were measured with BuÈchi (SMP-20) and
Gallenkamp (MPD 350). Samarium, hexamethyl phosphor-
amide, diiodoethane, t-butanol, Pd(PPh3)2Cl2, diethylamine,
copper(I) iodide and copper(II) acetate were commercially
available and were used as received. The starting
materials 6a,9 6b,9 7a18 and 8a18 were prepared by literature
procedures.
Conclusions
We could demonstrate that easily available ketoesters 3 with
an alkynylaryl substituent cyclize in the presence of
samarium diiodide to produce either benzannulated
cyclooctenol derivatives 4 or hexahydronaphthalene deriva-
tives 5. The competition between both reaction pathways
strongly depends on the substitution pattern of 3. In no
example both product types could be isolated. The smooth
formation of eight-membered rings is remarkable since not
many endo-dig cyclizations of samarium ketyls have been
reported.17 To the best of our knowledge, our examples are
the ®rst 8-endo-dig cyclizations employing Sm(II). The
peculiarity of the formation of hexahydronaphthalenes 5
has already been emphasized in our earlier publication.7
Both reactions will be further investigated to fully explore
Methyl 1-(2-iodobenzyl)-2-isopropyl-2-trimethylsiloxy-
cyclopropanecarboxylate (7b). To a stirred solution of
diisopropylamine (1.31 g, 13.0 mmol) in anhydrous THF
(25 mL) was added n-BuLi (5.54 mL of 2.35 M solution
in hexane, 13.0 mmol) dropwise at 2788C and was stirred
for 20 min under argon atmosphere. The cyclopropane
6b (2.50 g, 10.8 mmol) in dry THF (50 mL) was added

E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
4273
dropwise and stirring was continued for 1 h followed by the
dropwise addition of a solution of o-iodobenzyl iodide
(4.65 g, 13.5 mmol) in dry THF (50 mL). The mixture
was stirred for additional 48 h at 2788C. The reaction
mixture was quenched by saturated aqueous ammonium
chloride solution (25 mL) and allowed to warm to room
temperature. Water (50 mL) was added and the organic
phase was separated. The aqueous layer was extracted
with diethyl ether (3£75 mL) and the combined organic
extract was washed with water, brine and dried over
anhydrous sodium sulfate. Evaporation of the solvent
under reduced pressure gave a residue which was puri®ed
by column chromatography on neutral alumina using
hexane/ethyl acetate mixture (98:2) as eluent to afford a
diastereomeric mixture (90:10) of 7b (2.45 g, 51%) as a
colourless oil. IR (Neat): nˆ2965±2875 cm21 (C±H),
(374.2): C, 48.14%, H, 5.11%; Found: C, 48.13%, H,
5.39%.
General procedure A, Sonogashira reaction
A 50 mL two necked round bottom ¯ask was charged with
the iodo arene (1 equiv.) and diethylamine (approximately
8 mL/mmol) under argon atmosphere at room temperature.
The mixture was stirred for 5 min and then cooled to 08C in
an ice bath. Pd(PPh3)2Cl2 (0.010±0.017 equiv.) and
copper(I) iodide (0.020±0.026 equiv.) were added at once
followed by the corresponding alkyne (1.25±1.54 equiv.)
and stirring was continued at room temperature. After
completion of the reaction (2±6 h, monitored by TLC) the
solvent was evaporated under reduced pressure and the
residue was dissolved in diethyl ether (10 mL/mmol).
Water (10 mL/mmol) was added and the organic phase
was separated. The aqueous phase was extracted with
ether (3£10 mL/mmol). The combined ether extracts were
washed with saturated ammonium chloride solution
(10 mL/mmol), dried over anhydrous sodium sulfate,
®ltered and evaporated to get a residue which was puri®ed
by ¯ash column chromatography on silica gel with hexane/
ethyl acetate mixture (9:1) as eluent to furnish the corre-
sponding product.
1
1725 (CO2Me). trans-Isomer of 7b: H NMR (300 MHz,
CDCl3): dˆ7.63 (d, Jˆ7.7 Hz, 1H, Ar), 7.11±7.03 (m,
2H, Ar), 6.72±6.62 (m, 1H, Ar), 3.38 (s, 3H, OCH3), 3.37
(d, Jˆ18.0 Hz, 1H, CH2Ar), 2.56 (d, Jˆ18.0 Hz, 1H,
CH2Ar), 1.60 (dd, Jˆ1.4, 6.3 Hz, 1H, 3-H), 1.43 (hept.,
Jˆ6.9 Hz, 1H, CHMe2), 0.85 (d, Jˆ6.9 Hz, 3H, CH3),
0.79 (d, Jˆ6.3 Hz, 1H, 3-H), 0.75 (d, Jˆ6.9 Hz, 3H,
CH3), 0.00 (s, 9H, TMS); 13C NMR (75.5 MHz, CDCl3):
dˆ173.8 (s, CvO), 142.7, 139.3, 128.1, 127.5, 127.3,
101.7 (2s, 4d, Ar), 71.0 (s, C-2), 52.1 (q, OCH3), 40.3 (t,
CH2Ar), 34.4 (s, C-1), 31.9 (d, CHMe2), 25.1 (t, C-3), 19.6,
Methyl 4-oxo-2-(2-trimethylsilylethynylbenzyl)pentano-
ate (3a). The reaction was performed as described in general
procedure A. Thus, 8a (173 mg, 0.50 mmol), trimethylsilyl-
acetylene (62.0 mg, 0.60 mmol), Pd(PPh3)2Cl2 (4 mg,
0.005 mmol) and copper(I) iodide (2 mg, 0.099 mmol) in
diethylamine (4 mL) furnished 3a (138 mg, 87%) as a
pale yellow oil. IR (Neat): nˆ3020±2900 cm21 (vC±H,
C±H), 2155 (CuC), 1735 (CO2Me), 1720 (CvO); 1H
NMR (300 MHz, CDCl3): dˆ7.38 (dd, Jˆ1.3, 7.4 Hz, 1H,
Ar), 7.20±7.04 (m, 3H, Ar), 3.59 (s, 3H, OCH3), 3.28±3.18
(m, 1H, 2-H), 3.14 (dd, Jˆ5.9, 13.2 Hz, 1H, CH2Ar), 2.82
(dd, Jˆ9.4, 13.2 Hz, 1H, CH2Ar), 2.81 (dd, Jˆ9.3, 17.5 Hz,
1H, 3-H), 2.40 (dd, Jˆ3.6, 17.5 Hz, 1H, 3-H), 2.02 (s, 3H,
5-H), 0.20 (s, 9H, TMS); 13C NMR (CDCl3, 75.5 MHz):
dˆ206.3 (s, C-4), 175.1 (s, C-1), 140.9, 132.6, 129.5,
128.6, 126.5, 123.1 (2s, 4d, Ar), 103.3, 98.9 (2s, CuC),
51.7 (q, OCH3), 43.9 (t, CH2Ar), 41.1 (d, C-2), 36.2 (t,
C-3), 29.8 (q, C-5), 0.00 (q, TMS); Calcd for C18H24O3Si
(316.5): C, 68.31%, H, 7.64%; Found: C, 68.19%, H,
7.66%.
1
17.9 (2q, 2CH3), 1.8 (q, TMS). cis-Isomer of 7b: H NMR
(300 MHz, CDCl3): dˆ3.40 (s, 3H, OCH3), 2.36 (d,
Jˆ18.0 Hz, 1H, CH2Ar), 1.76 (d, Jˆ6.3 Hz, 1H, 3-H),
0.95 (d, Jˆ6.9 Hz, 3H, CH3), 0.89 (d, Jˆ6.9 Hz, 3H,
CH3), 0.01 (s, 9H, TMS); 13C NMR (75.5 MHz, CDCl3):
dˆ171.5 (s, CvO), 142.0, 139.4, 129.2, 128.8, 127.9,
101.0 (2s, 4d, Ar), 69.5 (s, C-2), 51.8 (q, OCH3), 40.0 (t,
CH2Ar), 37.1 (s, C-1), 33.4 (d, CHMe2), 23.6 (t, C-3), 19.3,
18.0 (2q, 2 CH3), 1.8 (q, TMS); Calcd for C18H27IO3Si
(446.4): C, 48.43%, H, 6.10%; Found: C, 48.54%, H,
6.16%.
Methyl 2-(2-iodobenzyl)-5-methyl-4-oxopentanoate (8b).
To a stirred solution of 7b (1.40 g, 3.14 mmol) in dry
dichloromethane (20 mL) was added triethylamine tris-
hydro¯uoride (750 mg, 4.70 mmol) at room temperature
under argon atmosphere. The reaction mixture was stirred
for 3 h. Water (25 mL) was added, the organic layer was
separated and the aqueous layer was extracted with
dichloromethane (2£10 mL). The combined organic phase
was washed with water, brine and dried over anhydrous
sodium sulfate. The solvent was evaporated under reduced
pressure and the crude residue was puri®ed by ¯ash column
chromatography on silica gel using hexane/ethyl acetate
(9:1) as eluent to afford 8b (1.11 g, 95%) as a colourless
oil. IR (Neat): nˆ2970±2875 cm21 (C±H), 1735 (CO2Me),
Methyl 4-oxo-2-(2-ethynylbenzyl)pentanoate (3b). A
¯ame dried 25 mL round bottom ¯ask was charged with
silyl compound 3a (590 mg, 1.86 mmol) and dry K2CO3
(309 mg, 2.24 mmol) in dry methanol (8 mL) under argon
atmosphere. The mixture was stirred at room temperature
for 2 h (monitored by TLC). The mixture was ®ltered
through a short pad of Celite, washed with diethyl ether
and the ®ltrate was evaporated to dryness to furnish the
desilylated product 3b (420 mg, 98%) as a colourless oil
which was used as obtained. IR (Neat): nˆ3280 cm21
(uC±H), 3090±2850 (vC±H, C±H), 2360 (CuC), 1740
(CvO), 1715 (CO2Me); 1H NMR (300 MHz, CDCl3):
dˆ7.48 (dd, Jˆ1.2, 7.5 Hz, 1H, Ar), 7.30±7.25 (m, 1H,
Ar), 7.22±7.14 (m, 2H, Ar), 3.65 (s, 3H, OCH3), 3.30 (s,
1H, CuCH), 3.33±3.23 (m, 1H, 2-H), 3.19 (dd, Jˆ6.3,
13.2 Hz, 1H, CH2Ar), 2.96 (dd, Jˆ8.7, 13.2 Hz, 1H,
1
1710 (CvO); H NMR (300 MHz, CDCl3): dˆ7.83±7.78
(m, 1H, Ar), 7.29±7.13 (m, 2H, Ar), 6.91 (td, Jˆ1.7, 7.6 Hz,
1H, Ar), 3.62 (s, 3H, OCH3), 3.31±3.20 (m, 1H, 2-H), 3.13
(dd, Jˆ7.1, 13.6 Hz, 1H, CH2Ar), 2.95 (dd, Jˆ8.2, 13.6 Hz,
1H, CH2Ar), 2.66±2.50 (m, 2H, 5-H and 3-H), 1.09 (d,
Jˆ7.0 Hz, 3H, CH3), 1.05 (d, Jˆ7.0 Hz, 3H, CH3); 13C
NMR (75.5 MHz, CDCl3): dˆ212.2 (s, C-4), 174.8 (s, C-
1), 141.4, 139.7, 130.1, 128.4, 128.2, 100.7 (2s, 4d, Ar), 51.7
(q, OCH3), 42.1 (t, CH2Ar), 41.0 (t, C-3), 40.7 (d, C-2), 40.6
(d, C-5), 18.1, 18.0 (2q, C-6 and C-7); Calcd for C15H19IO3

4274
E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
CH2Ar), 2.89 (dd, Jˆ9.4, 18.0 Hz, 1H, 3-H), 2.47 (dd,
Jˆ4.1, 18.0 Hz, 1H, 3-H), 2.10 (s, 3H, 5-H); 13C NMR
(CDCl3, 75.5 MHz): dˆ206.4 (s, C-4), 175.0 (s, C-1),
141.1, 133.1, 129.4, 128.9, 126.6, 122.1 (2s, 4d, Ar), 81.9,
81.5 (s, d, CuCH), 51.7 (q, OCH3), 44.0 (t, C-3), 41.1 (d,
C-2), 35.9 (t, CH2Ar), 29.9 (q, C-5); Calcd for C15H6O3
(242.3): C, 74.36%, H, 6.65%; Found: C, 73.79%, H,
6.83%.
3H, OCH3), 3.28±3.19 (m, 1H, 2-H), 3.13 (dd, Jˆ6.1,
13.0 Hz, 1H, CH2Ar), 2.88±2.80 (m, 2H, 3-H, CH2Ar),
2.48 (sept, Jˆ6.9 Hz, 1H, 5-H), 2.38 (dd, Jˆ3.7, 17.9 Hz,
1H, 3-H), 1.00 (d, Jˆ6.9 Hz, 3H, CH3), 0.96 (d, Jˆ6.9 Hz,
3H, CH3), 0.20 (s, 9H, TMS); 13C NMR (75.5 MHz,
CDCl3): dˆ212.4 (s, C-4), 175.2 (s, C-1), 141.1, 132.7,
129.5, 128.6, 126.5, 123.1 (2s, 4d, Ar), 103.4, 98.8 (2s,
CuC), 51.6 (q, OCH3), 41.0, 40.7 (2d, C-2, C-5), 40.9 (t,
C-3), 36.4 (t, CH2Ar), 18.2, 18.0 (2q, CH3), 0.00 (q, TMS);
Calcd for C20H28O3Si (344.5): C, 69.72%, H, 8.19%; Found:
C, 69.82%, H, 8.41%.
Methyl 2-(2-hex-1-ynylbenzyl)-4-oxopentanoate (3c).
The reaction was performed as described in general pro-
cedure A. Thus, 8a (500 mg, 1.44 mmol), 1-hexyne
(148 mg, 1.81 mmol), Pd(PPh3)2Cl2 (14 mg, 0.020 mmol)
and copper(I) iodide (6 mg, 0.030 mmol) in diethylamine
(6 mL) furnished 3c (330 mg, 76%) as pale yellow liquid.
IR (Neat): nˆ3065±2870 cm21 (C±H), 2200 (CuC), 1735
(CO2Me), 1720 (CvO); 1H NMR (300 MHz, CDCl3):
dˆ7.38 (dd, Jˆ1.4, 5.5 Hz, 1H, Ar), 7.23±7.08 (m, 3H,
Ar), 3.64 (s, 3H, OCH3), 3.30±3.27 (m, 1H, 2-H), 3.19
(dd, Jˆ5.9, 13.0 Hz, 1H, CH2Ar), 2.91 (dd, Jˆ7.5,
13.0 Hz, 1H, CH2Ar), 2.86 (dd, Jˆ9.2, 17.5 Hz, 1H, 3-H),
2.45 (t, Jˆ7.0 Hz, 2H, CH2), 2.40 (dd, Jˆ4.6, 17.5 Hz, 1H,
3-H), 2.06 (s, 3H, 5-H), 1.60±1.43 (m, 4H, 2 CH2), 0.95 (t,
Jˆ7.2 Hz, 3H, CH3); 13C NMR (75.5 MHz, CDCl3):
dˆ206.2 (s, C-4), 174.9 (s, C-1), 139.9, 132.1, 129.6,
128.7, 127.9, 123.8 (2s, 4d, Ar), 94.6, 78.5 (2s, CuC),
51.4 (q, OCH3), 43.5 (t, C-3), 41.5 (d, C-2), 35.9 (t,
CH2Ar), 30.5 (t, CH2), 29.6 (q, C-5), 21.8 (t, CH2), 18.9
(t, CH2), 13.3 (q, CH3); Calcd for C19H24O3 (300.4): C,
75.97%, H, 8.05%; Found: C, 76.35%, H, 8.28%.
Methyl 5-methyl-4-oxo-2-(2-ethynylbenzyl)hexanoate (3f).
To a stirred solution of 3e (500 mg, 1.45 mmol) in anhy-
drous THF (20 mL) was added tetrabutylammonium
¯uoride (980 mg, 1.81 mmol, 1 M solution in THF) under
argon atmosphere at room temperature and the mixture was
stirred for 2 h. Water (10 mL) was added and the organic
layer was separated. The aqueous layer was extracted with
ether (2£10 mL). The combined organic layer was washed
with brine (10 mL) and dried over anhydrous sodium sul-
fate. Evaporation of the solvent and ¯ash column chromato-
graphy on silica gel using hexane/ethyl acetate (5:1)
afforded 3f (160 mg, 41%) as a light pink liquid. IR
(Neat): nˆ3260 cm21 (uC±H), 3060±2875 (vC±H,
C±H), 2360 (CuC), 1735 (CO2Me), 1710 (CvO); 1H
NMR (300 MHz, CDCl3): dˆ7.48 (dd, Jˆ1.2, 7.4 Hz, 1H,
Ar), 7.30±7.25 (m, 1H, Ar), 7.21±7.14 (m, 2H, Ar), 3.63 (s,
3H, OCH3), 3.29 (s, 1H, uCH), 3.34±3.25 (m, 1H, 2-H),
3.18 (dd, Jˆ6.5, 13.3 Hz, 1H, CH2Ar), 2.97 (dd, Jˆ8.7,
13.3 Hz, 1H, CH2Ar), 2.93 (dd, Jˆ9.3, 17.9 Hz, 1H, 3-H),
2.55 (sept., Jˆ6.9 Hz, 1H, 5-H), 2.50 (dd, Jˆ4.2, 17.9 Hz,
1H, 3-H), 1.07 (d, Jˆ6.9 Hz, 3H, CH3), 1.03 (d, Jˆ6.9 Hz,
3H, CH3); 13C NMR (75.5 MHz, CDCl3): dˆ212.4 (s, C-4),
175.1 (s, C-1), 141.2, 133.1, 129.4, 128.9, 126.6, 122.2 (2s,
4d, Ar), 82.0, 81.4 (s, d, CuCH), 51.7 (q, OCH3), 41.1, 40.7
(2d, C-2, C-5), 41.0 (t, C-3), 36.1 (t, CH2Ar), 18.1, 18.0 (2q,
C-6, C-7); Calcd for C17H20O3 (272.4): C, 74.97%, H,
7.50%; Found: C, 75.08%, H, 7.76%.
Methyl 2-[2-(3-methoxyprop-1-ynyl)benzyl]-4-oxopen-
tanoate (3d). The reaction was performed as described in
general procedure A. Thus, 8a (200 mg, 0.580 mmol),
propargyl methyl
ether (55.0 mg, 0.785 mmol),
Pd(PPh3)2Cl2 (7 mg, 0.010 mmol) and copper(I) iodide
(3 mg, 0.015 mmol) in diethylamine (4 mL) furnished 3d
(132 mg, 79%) as a pale yellow liquid. IR (Neat):
nˆ2975±2870 cm21 (C±H), 2320 (CuC), 1735
(CO2Me), 1720 (CvO); 1H NMR (300 MHz, CDCl3):
dˆ7.44 (dd, Jˆ1.4, 7.4 Hz, 1H, Ar), 7.26±7.13 (m, 3H,
Ar), 4.38 (s, 2H, OCH2), 3.66 (s, 3H, OCH3), 3.47 (s, 3H,
OCH3), 3.42±3.39 (m, 1H, 2-H), 3.20 (dd, Jˆ6.0, 13.0 Hz,
1H, CH2Ar), 2.91 (dd, Jˆ7.6, 13.0 Hz, 1H, CH2Ar), 2.85
(dd, Jˆ9.4, 18.0 Hz, 1H, 3-H), 2.49 (dd, Jˆ3.9, 18.0 Hz,
1H, 3-H), 2.11 (s, 3H, 5-H); 13C NMR (75.5 MHz, CDCl3):
dˆ206.6 (s, C-4), 175.1 (s, C-1), 140.6, 132.7, 129.5, 128.6,
126.7, 122.6 (2s, 4d, Ar), 89.5, 84.5 (2s, CuC), 60.5 (t,
OCH2), 57.7 (q, OCH3), 51.9 (q, OCH3), 43.9 (t, C-3),
41.1 (d, C-2), 36.1 (t, CH2Ar), 29.9 (q, C-5); Calcd for
C17H20O4 (288.3): C, 70.81%, H, 6.99%; Found: C,
71.08%, H, 6.96%.
Methyl 2-(2-hex-1-ynylbenzyl)-5-methyl-4-oxohexano-
ate (3g). The reaction was performed as described in general
procedure A. Thus, 8b (500 mg, 1.34 mmol), 1-hexyne
(139 mg, 1.69 mmol), Pd(PPh3)2Cl2 (10 mg, 0.014 mmol)
and copper(I) iodide (6 mg, 0.030 mmol) in diethylamine
(6 mL) furnished 3g (328 mg, 74%) as a colourless liquid.
IR (Neat): nˆ2965±2875 cm21 (C±H), 2360 (CuC), 1735
(CO2Me), 1715 (CvO); 1H NMR (300 MHz, CDCl3):
dˆ7.37 (dd, Jˆ1.3, 7.0 Hz, 1H, Ar), 7.19±7.11 (m, 3H,
Ar), 3.65 (s, 3H, OCH3), 3.35±3.22 (m, 1H, 2-H), 3.17
(dd, Jˆ6.0, 13.1 Hz, 1H, CH2Ar), 2.93 (dd, Jˆ7.6,
13.1 Hz, 1H, CH2Ar), 2.88 (dd, Jˆ9.8, 17.9 Hz, 1H, 3-H),
2.54 (m, 2H, 5-H and 3-H), 2.46 (t, Jˆ7.2 Hz, 2H, CH2),
1.66±1.43 (m, 4H, 2 CH2), 1.08 (d, Jˆ6.9 Hz, 3H, CH3),
1.03 (d, Jˆ6.9 Hz, 3H, CH3), 0.96 (t, Jˆ7.3 Hz, 3H, CH3);
13C NMR (75.5 MHz, CDCl3): dˆ212.7 (s, C-4), 175.4 (s,
C-1), 141.3, 132.3, 129.3, 127.6, 126.5, 124.0 (2s, 4d, Ar),
94.9, 78.7 (2s, CuC), 51.7 (q, OCH3), 40.9 (t, C-3), 40.7 (d,
C-2), 40.6 (d, C-5), 36.3 (t, CH2Ar), 30.8 (t, CH2), 22.1 (t,
CH2), 19.2 (t, CH2), 18.2 (q, CH3), 17.9 (q, CH3), 13.6 (q,
CH3); Calcd for C21H28O3 (328.5): C, 76.79%, H, 8.59%;
Found: C, 76.25%, H, 9.41%; HRMS (EI, 80 eV): Calcd for
C21H28O3, 328.20385; Found, 328.20413.
Methyl 5-methyl-4-oxo-2-(2-trimethylsilylethynylbenzyl)-
hexanoate (3e). The reaction was performed as described in
general procedure A. Thus, 8b (750 mg, 2.00 mmol),
trimethylsilylacetylene (250 mg, 2.50 mmol), Pd(PPh3)2Cl2
(14 mg, 0.020 mmol) and copper(I) iodide (8 mg,
0.040 mmol) in diethylamine (10 mL) furnished 3e
(550 mg, 80%) as a colourless oil. IR (Neat): nˆ3065±
2875 cm21 (vC±H, C±H), 2155 (CuC), 1735 (CO2Me),
1
1715 (CvO); H NMR (300 MHz, CDCl3): dˆ7.38 (dd,
Jˆ1.3, 7.5 Hz, 1H, Ar), 7.19±7.04 (m, 3H, Ar), 3.58 (s,

E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
4275
Methyl 2-[2-(3-methoxyprop-1-ynyl)benzyl]-4-oxohex-
anoate (3h). The reaction was performed as described in
general procedure A. Thus, 8b (180 mg, 0.480 mmol),
propargyl methyl ether (52 mg, 0.743 mmol), Pd(PPh3)2Cl2
(4 mg, 0.005 mmol) and copper(I) iodide (2 mg,
0.009 mmol) in diethylamine (4 mL) furnished 3h
(107 mg, 71%) as a colourless liquid. IR (Neat): nˆ
2970±2875 cm21 (C±H), 1735 (CO2Me), 1712 (CvO);
1H NMR (300 MHz, CDCl3): dˆ7.44 (d, Jˆ6.1 Hz, 1H,
Ar), 7.28±7.13 (m, 3H, Ar), 4.38 (s, 2H, OCH2), 3.63 (s,
3H, OCH3), 3.47 (s, 3H, OCH3), 3.41±3.24 (m, 1H, 2-H),
3.20 (dd, Jˆ6.4, 13.2 Hz, 1H, CH2Ar), 2.91 (dd, Jˆ9.3,
13.2 Hz, 1H, CH2Ar), 2.88 (dd, Jˆ9.4, 18.0 Hz, 1H, 3-H),
2.56±2.45 (m, 2H, 3-H and 5-H), 1.07 (d, Jˆ6.9 Hz, 3H,
CH3), 1.02 (d, Jˆ6.9 Hz, 3H, CH3); 13C NMR (75.5 MHz,
CDCl3): dˆ212.4 (s, C-4), 175.1 (s, C-1), 140.6, 132.6,
129.3, 128.5, 126.5, 122.5 (2s, 4d, Ar), 89.4, 84.5 (2s,
CuC), 60.3 (t, OCH2), 57.6 (q, OCH3), 51.7 (q, OCH3),
40.9 (d, C-5), 40.8 (t, CH2), 40.6 (d, C-2), 36.2 (t,
CH2Ar), 18.1 (q, CH3), 17.9 (q, CH3); HRMS (EI,
80 eV): Calcd for C19H24O4, 316.16746; Found,
316.16738.
(s, CvO), 140.6 (s, C-8a), 125.0, 122.7 (2d, C-5, C-6),
113.9 (s, C-8), 104.2, 97.4 (2s, CuC), 74.2 (s, C-4), 51.8
(q, OCH3), 49.1 (d, C-2), 43.8 (t, C-7), 40.3 (d, C-4a), 34.4,
31.0 (2t, C-1, C-3), 22.2 (q, CH3), 0.00 (q, TMS); Calcd for
C18H26O3Si (318.5): C, 67.88%, H, 8.23%; Found: C,
67.73%, H, 8.21%.
Methyl 8-hydroxy-8-methyl-5,6,7,8-tetrahydrobenzocyclo-
octene-6-carboxylate (4b) and 11-methyl-12-oxatri-
cyclo[9.2.1.03,8]tetradeca-3,5,7,9-tetraen-13-one (9). The
reaction was performed as described in general procedure
B. Thus, 3b (246 mg, 1.00 mmol), samarium (361 mg,
2.40 mmol), diiodoethane (620 mg, 2.20 mmol), HMPA
(3.22 g, 18.0 mmol) and t-BuOH (148 mg, 2.00 mmol) in
THF (40 mL) gave 4b (146 mg, 61%) and 9 (27 mg, 13%)
as colourless liquids. 4b: IR (Neat) nˆ3450 cm21 (OH),
3060±2880 (C±H), 1730 (CvO); 1H NMR (300 MHz,
CDCl3): dˆ7.23±7.11 (m, 4H, Ar), 6.31 (d, Jˆ12.6 Hz,
1H, 9-H), 5.71 (dd, Jˆ1.2, 12.6 Hz, 1H, 10-H), 3.71 (s,
3H, OCH3), 3.11 (bs, 3H, 5-H and 6-H), 1.84 (d,
Jˆ13.2 Hz, 1H, 7-H), 1.68±1.54 (m, 2H, 7-H and OH),
1.34 (s, 3H, CH3); 13C NMR (75.5 MHz, CDCl3):
dˆ175.5 (s, CO), 137.6, 137.1, 135.8, 129.7, 128.9,
127.4, 126.3, 125.4 (2s, 6d, Ar, C-9, C-10), 71.8 (s, C-8),
51.6 (q, OCH3), 40.8 (d, C-6), 36.3 (t, C-5), 33.1 (t, C-7),
20.3 (q, CH3); Calcd for C15H18O3 (246.3): C, 73.15%, H,
7.36%; Found: C, 72.69%, H, 7.38%. 9: IR (Neat):
nˆ3010±2875 cm21 (C±H), 1770 (CvO), 1630 (CvC);
1H NMR (300 MHz, CDCl3): dˆ7.29±7.26 (m, 3H, Ar),
7.18±7.15 (m, 1H, Ar), 6.52 (d, Jˆ12.6 Hz, 1H, 10-H),
5.86 (dd, Jˆ1.6, 12.6 Hz, 1H, 9-H), 3.25 (dd, Jˆ9.6,
13.3 Hz, 1H, CH2Ar), 2.95 (dt, Jˆ6.5, 9.5 Hz, 1H, 1-H),
2.76 (dd, Jˆ9.5, 13.3 Hz, 1H, CH2Ar), 1.95 (d,
Jˆ13.4 Hz, 1H, 14-H), 1.79±1.72 (m, 2H, OH and 14-H),
1.53 (s, 3H, CH3); 13C NMR (75.5 MHz, CDCl3): dˆ178.2
(s, CvO), 137.0, 136.2, 132.5, 129.3, 129.2, 128.3, 126.8
(2s, 5d, Ar, C-9 and C-10), 84.1 (s, C-11), 40.6 (d, C-1), 34.9
(t, C-2), 33.5 (t, C-14), 28.7 (q, CH3); Calcd for C14H14O2
(214.3): C, 78.48%, H, 6.59%; Found: C, 77.66%, H,
6.71%; HRMS (EI, 80 eV): Calcd for C14H14O2,
214.09938; Found, 214.09730.
General procedure B, SmI2 mediated ketone cyclization
Samarium (2.4 equiv.) was activated in a 50 mL two necked
round bottom ¯ask by heating with a hot air gun under
argon atmosphere. The ¯ask was cooled to room tempera-
ture and freshly distilled THF (5 mL/mmol) was added.
Diiodoethane (2.2 equiv.) was added dropwise in THF
(15 mL/mmol) under a constant ¯ush of argon. The resultant
mixture was stirred for 1 h where it developed a dark bluish
green colour. Hexamethyl phosphoramide (18 equiv.) was
added in one portion, while the solution turned to deep
violet. The mixture was stirred for 5 min and a solution of
t-butanol (2 equiv.) and the alkynyl ketone (1 equiv.) in
THF (20 mL/mmol) was added dropwise over a period of
30 min. After 15 h the reaction was completed (monitored
by TLC) and quenched with a saturated aqueous solution of
ammonium bicarbonate solution (15 mL/mmol). The
organic layer was separated and the aqueous layer was
extracted with diethyl ether (3£25 mL). The combined
ether extracts were washed with brine (25 mL), water
(25 mL), dried over anhydrous sodium sulfate, ®ltered and
evaporated to get a crude residue which was puri®ed by
¯ash column chromatography on silica gel using hexane/
ethyl acetate mixture (17:3) as eluent to furnish the corre-
sponding cyclized products.
Methyl 8-(hex-1-ynyl)-4-hydroxy-4-methyl-1,2,3,4,4a,7-
hexahydronaphthalene-2-carboxylate (5c). The reaction
was performed as described in general procedure B. Thus,
3c (100 mg, 0.330 mmol), samarium (120 mg, 0.800 mmol),
diiodoethane (206 mg, 0.730 mmol), HMPA (1.10 g,
5.90 mmol) and t-BuOH (49 mg, 0.66 mmol) in THF
(25 mL) gave 5c (55 mg, 55%) as a colourless syrupy liquid.
IR (Neat): nˆ3450 cm21 (bs, OH), 3035±2865 (C±H),
Methyl 4-hydroxy-4-methyl-8-trimethylsilylethynyl-1,2,
3,4,4a,7-hexahydronaphthalene-2-carboxylate (5a). The
reaction was performed as described in general procedure
B. Thus, 3a (210 mg, 0.66 mmol), samarium (240 mg,
1.59 mmol), diiodoethane (420 mg, 1.45 mmol), HMPA
(2.14 g, 11.9 mmol) and t-BuOH (98 mg, 1.32 mmol) in
THF (35 mL) gave 5a (110 mg, 52%) as a colourless oil.
IR (Neat): nˆ3430 cm21 (br, OH), 3025±2825 (C±H),
1
2210 (CuC),1740 (CvO); H NMR (300 MHz, CDCl3):
dˆ5.82 (s, 2H, 5-H and 6-H), 3.71 (s, 3H, OCH3), 3.31
(ddd, Jˆ1.8, 4.0, 13.0 Hz, 1H, 1-H), 2.76 (bs, 3H, 7-H
and 4a-H), 2.45 (tt, Jˆ3.9, 13.0 Hz, 1H, 1-H), 2.34 (t,
Jˆ6.8 Hz, 2H, CH2), 2.10±1.74 (m, 4H, 2 CH2), 1.04 (s,
3H, CH3), 0.92 (t, Jˆ7.2 Hz, 3H, CH3); 13C NMR
(75.5 MHz, CDCl3): dˆ174.9 (s, CvO), 137.4 (s, C-8a),
125.1 (d, C-5), 122.9 (d, C-6), 114.1 (s, C-8), 93.5, 79.4 (2s,
CuC), 74.1 (s, C-4), 51.8 (q, OCH3), 48.9 (d, C-2), 43.8 (t,
C-7), 40.4 (d, C-4a), 34.1 (t, C-1), 31.5 (t, C-3), 30.9 (t,
CH2), 22.1 (q, CH3), 21.9 (t, CH2), 19.1 (t, CH2), 13.5 (q,
CH3); Calcd for C19H26O3 (302.4): C, 75.46%, H, 8.67%;
Found: C, 75.46%, H, 8.31%.
1
2140 (CuC), 1720 (CvO); H NMR (300 MHz, CDCl3):
dˆ5.62 (s, 2H, 5-H, 6-H), 3.51 (s, 3H, OCH3), 3.11 (ddd,
Jˆ1.7, 4.0, 13.5 Hz, 1H, 1-H), 2.61±2.53 (m, 3H, 7-H,
4a-H), 2.28 (tt, Jˆ3.9, 13.5 Hz, 1H, 1-H), 1.91±1.78 (m,
2H, 2-H, OH), 1.64±1.55 (m, 2H, 3-H), 0.84 (s, 3H, CH3),
0.00 (s, 9H, TMS); 13C NMR (75.5 MHz, CDCl3): dˆ174.8

4276
E. Nandanan et al. / Tetrahedron 56 (2000) 4267±4277
Methyl 4-hydroxy-8-(3-methoxyprop-1-ynyl)-4-methyl-
1,2,3,4,4a,7-hexahydronaphthalene-2-carboxylate (5d).
The reaction was performed as described in general proce-
dure B. Thus, 3d (100 mg, 0.346 mmol), samarium
(125 mg, 0.830 mmol), diiodoethane (220 mg, 0.780
mmol), HMPA (1.13 g, 6.30 mmol) and t-BuOH (52 mg,
0.70 mmol) in THF (40 mL) gave 5d (68 mg, 67%) as a
colourless liquid. IR (Neat): nˆ3445 cm21 (bs, OH),
CH3), 15.9 (q, CH3), 14.1 (q, CH3); Calcd for C21H30O3
(330.5): C, 76.33%, H, 9.15%; Found: C, 76.25%, H,
9.41%.
Methyl 8-hydroxy-8-isopropyl-9-methoxymethyl-5,6,7,
8-tetrahydrobenzocyclooctene-6-carboxylate (4h). The
reaction was performed as described in general procedure
B. Thus, 3h (90 mg, 0.290 mmol), samarium (103 mg,
0.680 mmol), diiodoethane (181 mg, 0.640 mmol), HMPA
(935 mg, 5.22 mmol) and t-BuOH (43 mg, 0.58 mmol) in
THF (20 mL) gave 4h (72 mg, 78%) as a colourless liquid.
IR (Neat): nˆ3480 cm21 (bs, OH), 3060±2820 (C±H),
1
2975±2825 (C±H), 2220 (CuC), 1735 (CvO); H NMR
(300 MHz, CDCl3): dˆ5.84 (s, 2H, 5-H and 6-H), 4.25 (s,
2H, OCH2), 3.71 (s, 3H, OCH3), 3.41 (s, 3H, OCH3), 3.32
(ddd, Jˆ2.4, 4.1, 13.5 Hz, 1H, 1-H), 2.80 (bs, 3H, 7-H and
4a-H), 2.46 (tt, Jˆ3.9, 13.5 Hz, 1H, 1-H), 2.11±1.68 (m,
4H, 2-H, 3-H and OH), 1.05 (s, 3H, CH3); 13C NMR
(75.5 MHz, CDCl3): dˆ174.7 (s, CvO), 139.8 (s, C-8a),
125.0 (d, C-5), 122.8 (d, C-6), 113.3 (s, C-8), 88.1, 85.2 (2s,
CuC), 74.1 (s, C-4), 60.5 (t, OCH2), 57.5 (q, OCH3), 51.9
(q, OCH3), 49.0 (d, C-2), 43.8 (t, C-7), 40.4 (d, C-4a), 34.3
(t, C-1), 31.2 (t, C-3), 22.1 (q, CH3); Calcd for C17H22O4
(290.4): C, 70.32%, H, 7.64%; Found: C, 70.08%, H,
7.21%; HRMS (EI, 80 eV): Calcd for C17H22O4,
290.15181; Found, 290.15119.
1
1735 (CvO); H NMR (300 MHz, CDCl3): dˆ7.19±7.08
(m, 4H, Ar), 6.57 (s, 1H, 10-H), 4.58 (d, Jˆ11.0 Hz, 1H,
OCH2), 3.88 (d, Jˆ11.0 Hz, 1H, OCH2), 3.68 (s, 3H,
OCH3), 3.42 (s, 3H, OCH3), 3.32±3.07 (m, 3H, 5-H, 6-H),
2.01 (sept., Jˆ6.9 Hz, 1H, CHMe2), 1.78±1.22 (m, 3H, OH,
7-H), 0.97 (d, Jˆ6.7 Hz, 3H, CH3), 0.68 (d, Jˆ6.7 Hz, 3H,
CH3); 13C NMR (75.5 MHz, CDCl3): dˆ176.1 (s, CvO),
140.3, 137.6, 130.5, 129.3, 127.8, 127.2, 126.5, 126.2 (3s,
5d, Ar, C-9, C-10), 78.5 (s, C-8), 78.1 (t, OCH2), 58.1 (q,
OCH3), 51.5 (q, OCH3), 38.9 (d, C-6), 37.6 (d, CHMe2),
32.9 (t, C-5), 28.3 (t, C-7), 17.7 (q, CH3), 16.1 (q, CH3);
Calcd for C19H26O4 (318.4): C, 71.67%, H, 8.23%; Found:
C, 71.63%, H, 8.12%.
Methyl 8-hydroxy-8-isopropyl-5,6,7,8-tetrahydrobenzo-
cyclooctene-6-carboxylate (4f). The reaction was
performed as described in general procedure B. Thus, 3f
(100 mg, 0.370 mmol), samarium (132 mg, 0.880 mmol),
diiodoethane (230 mg, 0.814 mmol), HMPA (1.19 g,
6.66 mmol) and t-BuOH (55 mg, 0.74 mmol) in THF
(20 mL) gave 3f (62 mg, 61%) as a colourless liquid. IR
(Neat): nˆ3500 cm21 (br, OH), 3075±2875 (C±H), 1715
Methyl 3-(2-hex-1-ynylphenyl)propionate (10). The reac-
tion was performed as described in the general procedure B.
Thus, 3j (140 mg, 0.450 mmol), samarium (161 mg,
1.07 mmol), diiodoethane (279 mg, 0.990 mmol), HMPA
(1.45 g, 8.10 mmol) and t-BuOH (67 mg, 0.90 mmol) in
THF (25 mL) gave 10 (64 mg, 45%) as a colourless liquid.
IR (Neat): nˆ2975±2840 cm21 (C±H), 2205 (CuC), 1740
(CO2Me); 1H NMR (300 MHz, CDCl3): dˆ7.37 (d,
Jˆ7.2 Hz, 1H, Ar), 7.19±7.12 (m, 3H, Ar), 3.67 (s, 3H,
OCH3), 3.08 (t, Jˆ7.6 Hz, 2H, CH2), 2.66 (t, Jˆ7.6 Hz,
2H, CH2), 2.44 (t, Jˆ7.6 Hz, 2H, CH2), 1.62±1.44 (m,
4H, 2 CH2), 0.95 (t, Jˆ7.2 Hz, 3H, CH3); 13C NMR
(75.5 MHz, CDCl3): dˆ173.5 (s, CvO), 142.1, 132.2,
128.6, 127.7, 126.2, 123.5 (2s, 4d, Ar), 94.6, 78.7 (2s,
CuC), 51.5 (q, OCH3), 34.5 (t, CH2), 30.8 (t, CH2), 29.9
(t, CH2), 21.9 (t, CH2), 19.2 (t, CH2), 13.6 (q, CH3).
1
(CvO); H NMR (300 MHz, CDCl3): dˆ7.23±7.12 (m,
4H, Ar), 6.47 (d, Jˆ12.6 Hz, 1H, 9-H), 5.61 (d,
Jˆ12.6 Hz, 1H, 10-H), 3.70 (s, 3H, OCH3), 3.12 (bs, 3H,
5-H and 6-H), 1.71 (sept., Jˆ6.9 Hz, 1H, CHMe2), 1.66±
1.44 (m, 3H, OH and 7-H), 0.87 (d, Jˆ6.9 Hz, 3H, CH3),
0.85 (d, Jˆ6.9 Hz, 3H, CH3); 13C NMR (75.5 MHz, CDCl3):
dˆ175.8 (s, CvO), 137.4, 135.6, 135.1, 129.8, 128.3,
127.9, 127.3, 126.4 (2s, 6d, Ar, C-9, C-10), 76.0 (s, C-8),
51.4 (q, OCH3), 41.5, 40.2 (2d, C-6, CHMe2), 33.4, 31.1 (2t,
C-5, C-7), 17.3 (q, CH3), 16.5 (q, CH3); Calcd for C17H22O3
(274.4): C, 74.42%, H, 8.08%; Found: C, 74.41%, H,
8.00%.
Methyl 9-butyl-8-hydroxy-8-isopropyl-5,6,7,8-tetrahydro-
benzocyclooctene-6-carboxylate (4g). The reaction was
performed as described in general procedure B. Thus, 3g
(100 mg, 0.310 mmol), samarium (110 mg, 0.730 mmol),
diiodoethane (192 mg, 0.680 mmol), HMPA (1.00 g,
5.60 mmol) and t-BuOH (46 mg, 0.62 mmol) in THF
(20 mL) gave 4g (78 mg, 76%) as a colourless crystalline
solid. Mp: 96±998C; IR (KBr): nˆ3505 cm21 (OH), 3055±
Acknowledgements
E. N. and C. U. D. thank the Alexander-von-Humboldt
foundation for research fellowships. Support by the
Volkswagen-Stiftung and the Fonds der Chemischen
Industrie is most gratefully acknowledged. We thank Dr
È
R. Zimmer (Freie Universitat Berlin) for helpful discussions
and Dr M. Gruner (Technische Universitat Dresden) for
È
1
2840 (C±H), 1720 (CvO); H NMR (300 MHz, CDCl3):
NMR spectra measurements and their interpretations.
dˆ7.26±7.09 (m, 4H, Ar), 6.36 (s, 1H, 10-H), 3.69 (s, 3H,
OCH3), 3.10±3.06 (m, 3H, 5-H and 6-H), 2.38±2.28 (m, 1H,
7-H), 2.19±2.04 (m, 1H, 7-H), 2.01 (sept., Jˆ7.0 Hz, 1H,
CHMe2), 1.69±1.34 (m, 7H, OH, 3 CH2), 0.95 (t, Jˆ7.2 Hz,
3H, CH3), 0.91 (d, Jˆ7.0 Hz, 3H, CH3), 0.70 (d, Jˆ7.0 Hz,
3H, CH3); 13C NMR (75.5 MHz, CDCl3): dˆ176.1 (s,
CvO), 146.2, 139.4, 135.1, 129.1, 128.1, 126.5, 126.2,
125.4 (3s, 5d, Ar, C-9, C-10), 79.1 (s, C-8), 51.6 (q,
OCH3), 38.9 (d, C-6), 37.2 (d, CHMe2), 34.6 (t, C-5), 33.4
(t, C-7), 30.8 (t, CH2), 29.4 (t, CH2), 23.0 (t, CH2), 17.8 (q,
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