An environmentally friendly synthesis of functionalized indanes using electrochemical cyclization of ortho-halo-substituted homoallyl ethers and esters

Article abstract of DOI:10.1055/s-2006-948182

The electrochemical cyclization of a series of ortho-halo-substituted homoallyl ethers and esters to functionalized indanes catalyzed by Ni(II) catalyst precursors derived from Ni(cyclam)Br₂, (cyclam = 1,4,8,11-tetraazacyclotetradecane) and Ni(tmc)Br₂, (tmc = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) is reported. The starting homoallyl ethers were synthesized using either a one-pot method for allylation of aldehydes or by direct allylation of the corresponding acetals using bismuth triflate as a catalyst. The remarkably low toxicity, low cost and ease of handling of bismuth salts coupled with the mild nature of the electrochemical procedure makes this approach to indane synthesis especially environmentally friendly and attractive. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-948182

LETTER
2021
An Environmentally Friendly Synthesis of Functionalized Indanes Using
Electrochemical Cyclization of ortho-Halo-Substituted Homoallyl Ethers and
Esters
Synthesis of
F
a
unctionalize
n
d Indanes dra Olivero,a Rodolphe Perriot,a Elisabet Duñach,*a Ashvin R. Baru,b Eric D. Bell,b Ram S. Mohan*b
a
Laboratoire des Molécules Bioactives et des Arômes, CNRS, UMR 6001, Université de Nice-Sophia Antipolis, 06108 Nice Cedex 2,
France
E-mail: dunach@unice.fr
b
Laboratory for Environmentally Friendly Organic Synthesis, Department of Chemistry, Illinois Wesleyan University, Bloomington,
IL 61701, USA
E-mail: rmohan@iwu.edu
Received 3 February 2006
In the first approach, the acetal was reacted with allyl-
trimethylsilane or methallyltrimethylsilane in the pres-
ence of Bi(OTf)3·xH2O (1 < x < 4) to yield the homoallyl
ether (Method A). In the second approach, the acetal was
Abstract: The electrochemical cyclization of a series of ortho-
halo-substituted homoallyl ethers and esters to functionalized
indanes catalyzed by Ni(II) catalyst precursors derived from
Ni(cyclam)Br2, (cyclam = 1,4,8,11-tetraazacyclotetradecane) and
Ni(tmc)Br2, (tmc = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclo- generated in situ from the corresponding aldehyde and
tetradecane) is reported. The starting homoallyl ethers were synthe-
reacted with allyltrimethylsilane in the presence of
sized using either a one-pot method for allylation of aldehydes or by
Bi(OTf)3·xH2O (Method B). The third approach consisted
direct allylation of the corresponding acetals using bismuth triflate
of a one-pot method that involved the Bi(OTf)3·xH2O
as a catalyst. The remarkably low toxicity, low cost and ease of han-
catalyzed reaction of an aldehyde with an alkoxytrimeth-
dling of bismuth salts coupled with the mild nature of the electro-
ylsilane and allyltrimethylsilane (Method C). The ortho-
halo-substituted homoallyl acetates were generated by a
one-pot method in which the corresponding aldehyde was
reacted with allyltrimethylsilane in the presence of acetic
anhydride (Method D).
chemical procedure makes this approach to indane synthesis
especially environmentally friendly and attractive.
Key words: bismuth, electrochemical cyclization, homoallyl
ethers, indanes, Ni(II) cyclam
Electrochemical cyclization of 1a–i was carried out under
catalytic and mild conditions. Two stable and easily
available Ni(II) catalyst precursors, Ni(cyclam)Br2, Y
Intramolecular radical-type cyclizations constitute an
efficient method for the construction of carbocycles and
heterocycles.1 Generally, stoichiometric amounts of high-
ly toxic tin hydrides are used for these cyclizations, with
AIBN as an initiator.2 Electrochemistry provides a milder
alternative method for radical cyclization using catalytic
amounts of metal complexes, in particular of Ni(II) deriv-
atives.3 The electrochemical synthesis of benzofuran and
benzopyran structures have been reported via the cycliza-
tion of ortho-functionalized aryl halide substrates.4 In-
dane-derived skeletons are found in several compounds
possessing interesting biological5 and olfactory activi-
ties.6 We report here the use of a Ni-catalyzed electro-
chemical synthetic methodology for the construction of
functionalized indane skeletons.
(cyclam = 1,4,8,11-tetraazacyclotetradecane)
and
Ni(tmc)Br2, (tmc = 1,4,8,11-tetramethyl-1,4,8,11-
Z
tetraazacyclotetradecane)9 were used in 10.0 mol% for
cyclization of 1a–i (Figure 1). The electrochemical syn-
thesis was not efficient at less than 10% catalyst loading.
These two complexes, which generate Ni(I) intermediates
after a one-electron reduction,10 have been shown to be
efficient in reductive processes involving aryl halides.11
2+
2+
Me
Me
H
H
–
–
N
N
N
N
N
N
N
N
2 Br
2 Br
Ni
Ni
Me
The general strategy for the preparation of the starting
bromo- and chloroaryl derivatives 1a–i took advantage of
methodology previously developed using bismuth(III)
catalysts.7 Bismuth compounds are especially attractive
because of their remarkably low toxicity, low cost and
ease of handling.8 The desired substrates were synthesized
by one of the following methods (Scheme 1, Methods
A–D).
H
Me
H
Z = Ni(tmc)Br2
Y = Ni(cyclam)Br2
Figure 1
A preliminary screening of the experimental conditions to
determine the influence of the solvent, the supporting
electrolyte, and the nature of the electrodes on product
composition was carried out with substrate 1a. The key
findings are summarized in Table 1 (entries 1–5). The
electroreduction of 1a, conducted in DMF with tetrabutyl-
ammonium tetrafluoroborate as the supporting electro-
SYNLETT 2006, No. 13, pp 2021–2026
1
7
.0
8
.2
0
0
6
Advanced online publication: 09.08.2006
DOI: 10.1055/s-2006-948182; Art ID: S01306ST
© Georg Thieme Verlag Stuttgart · New York

2022
S. Olivero et al.
LETTER
R1
Method A
Br
SiMe3
Br
1.0 mol% Bi(OTf)3·xH2O
OR
CH2Cl2
OR
R1
OR
R = Me or Et
R
1 = H or Me
Method B
Cl
Cl
Cl
1.0 mol% Bi(OTf)3·xH2O
0.1 mol% Bi(OTf)3·xH2O
HC(OMe)3, MeOH
SiMe3
MeCN
OMe
CHO
OMe
OMe
Method C
X
X
1.0–3.0 mol% Bi(OTf)3·xH2O
SiMe3
CHO
ROSiMe3
CH2Cl2
0 °C
OR
X = Br or Cl
R = Bn or Et
Method D
X
X
1.0 mol% Bi(OTf)3·xH2O
SiMe3
CHO
(CH3CO)2O
MeCN
OAc
X = Br or Cl
0 °C
Scheme 1 Synthesis of the ortho-halo-substituted homoallyl ethers and esters
lyte, with a Mg anode and a carbon fiber cathode and lute ethanol, the cyclized 2a was obtained in 55% yield
catalyst Y, led to cyclized indane 2a in 58% yield (entry (entries 2, 3). The use of potassium bromide instead of
1), together with the dehalogenated compound 3a (26%). tetrabutylammonium tetrafluoroborate as the supporting
No cyclization to the six-membered ring was observed. electrolyte afforded the cyclized product in 76% yield
GC and NMR-COSY and NOESY experiments indicated (entry 4). The catalytic activity of Y and Z was found to
that the indane 2a was obtained as a 40:60 mixture of syn/ be similar for the cyclization of bromo derivative 1a
anti isomers. Although the syn/anti mixtures were not ful- (entries 4, 5). The cyclization of 1b–h with Y or Z as the
ly separable by flash column chromatography, some en- catalyst under the best conditions (DMF, KBr, r.t.) led to
richment of one isomer was seen in the isolated product the indane derivatives 2 as a mixture of syn/anti dia-
after chromatography. When the electrolysis of 1a was stereomers, as shown in Table 1.
run in acetonitrile, the yield of 2a was 48%, and in abso-
Table 1 Electroreductive Cyclization of Derivatives 1 in the Presence of Ni(II) Catalystsa
X
OR
OR
e–, Ni(II)
(10 mol%)
+
25 °C
OR
1
2
3
Entry
Starting compoundb
Catalystc
Conditions
Productsd
2
3
(syn:anti)e
1
2
1a
R = Et
X = Br
Y
Y
DMF
n-Bu4NBF4
2a
3a
26%
58% (40:60)
1a
CH3CN
2a
3a
n-Bu4NBF4
48% (44:56)
50%
Synlett 2006, No. 13, 2021–2026 © Thieme Stuttgart · New York

LETTER
Synthesis of Functionalized Indanes
2023
Table 1 Electroreductive Cyclization of Derivatives 1 in the Presence of Ni(II) Catalystsa (continued)
X
OR
OR
e–, Ni(II)
(10 mol%)
+
25 °C
OR
1
2
3
Entry
Starting compoundb
Catalystc
Conditions
Productsd
2
3
(syn:anti)e
3
4
5
6
1a
1a
1a
Y
Y
Z
Z
EtOH
n-Bu4NBF4
2a
3a
15%
55% (47:53)
DMF
KBr
2a
3a
9%
76% (41:59)
DMF
KBr
2a
3a
17%
83% (45:55)
1b
R = Me
X = Br
DMF
KBr
2b
3b
22%
73% (48:52)
7
8
1c
R = Ac
X = Br
Z
DMF
KBr
2c
3c
2%
70% (43:57)
1d
R = Bn
X = Br
Z
DMF
KBr
2d
3d
22%
64% (44:56)
9
1e
R = Et
X = Cl
Z
DMF
KBr
2a
3a
20%
65% (44:56)
10
11
12
13
1e
R = Et
X = Cl
Y
Y
Yf
Yg
DMF
KBr
2a
3a
14%
68% (37:63)
1f
R = Me
X = Cl
DMF
KBr
2b
3b
22%
58% (46:54)
1g
R = Ac
X = Cl
DMF
KBr
2c
3c
12%
14% (47:53)
1h
R = Bn
X = Cl
DMF
KBr
2d
3d
18%
47% (47:53)
a General electrolysis conditions: under an inert gas at r.t., in a single-compartment cell fitted with a consumable sacrificial anode (Mg) and a
carbon fiber cathode, 2.0 mmol of 1 was added to 30 mL of solvent containing the supporting electrolyte (0.03 M; KBr or n-Bu4NBF4) and 0.2
mmol of Ni(II) catalyst (Y or Z). The electrolysis was carried out at a constant current of 30 mA (J = 0.15 A/dm2). The reaction was stopped
after complete consumption of 1 (1–3 F/mol), unless stated otherwise. After acidic hydrolysis and Et2O extraction, the crude compounds were
purified by column chromatography on silica gel, and characterized by NMR spectroscopy and mass spectrometry.
b The synthetic method used for preparation of the starting material along with the isolated yield and spectral data are given in ref.19 Synthetic
procedures for their preparation have been previously described (see ref. 7).
c Y = Ni(cyclam)Br2 and Z = Ni(tmc)Br2.
d All products 2a–i were characterized by 1H NMR and 13C NMR spectroscopy. Stereoisomers were identified by NOESY. Satisfactory HRMS
was obtained for all new compounds. Compounds 3a–c have been previously reported.16–18
e Ratios of syn/anti isomers were obtained by GC analysis of the crude reaction mixture. Refers to isolated yield after flash chromatographic
purification of the crude reaction product.
f The expected 2c was partially deacetylated to 1-methylindane, formed in 29% yield.
g The starting material 1h was recovered in 30% yield after 3.4 F/mol electrolysis.
Synlett 2006, No. 13, 2021–2026 © Thieme Stuttgart · New York

2024
S. Olivero et al.
LETTER
tion of the crude reaction product. The syn/anti isomers were not
fully separable by flash chromatography. The ratio of syn/anti iso-
mers in the crude product (determined by GC) is given in Table 1.
The electroreduction of aryl-bromo derivatives 1b–d car-
ried out with catalyst Z in DMF led to 64–73% yields of
the corresponding indanes 2b–d with syn:anti ratios of ca.
45:55 (entries 6–8). When the electroreduction using cat-
alyst Z was carried out in ethanol, double bond reduction
and debromination were observed. Interestingly, the ace-
tate group of 1c and the benzyloxy substituent in 1d were
compatible with the reductive reaction conditions. Com-
pound 1g gave a lower yield presumably due to the diffi-
culty of reducing a C–Cl bond compared to a C–Br bond.
The increased activation required to reduce the C–Cl bond
can lead to cleavage and/or reduction of the acetate group,
accounting for the low observed yield. The best yield of
2a from the cyclization of 1e was 68% with a syn:anti ra-
tio of 37:63. It is interesting to note that by using the elec-
trochemical methodology the Ar–Cl bonds could be
efficiently functionalized, which is not the case using the
more classical tin hydride methodology. The latter typi-
cally works only with more activated C–Br and C–I
bonds.2 Other chloro-aryl derivatives 1f–h underwent in-
tramolecular cyclization with catalyst Y (entries 11–13) to
1-Ethoxy-3-methyl indane (2a)
Mixture of two diastereomers (ratio 70:30). The syn/anti assign-
ments were determined by NOESY.
1
syn Isomer: H NMR (200 MHz): d = 7.40–7.00 (m, 4 H), 4.85–
4.70 (dd, J = 6.35, 2.25 Hz, 1 H), 3.60–3.40 (q, J = 7 Hz, 2 H),
3.50–3.25 (m, 1 H), 2.40–2.20 (ddd, J = 13.5, 7.2, 2.3 Hz, 1 H),
1.85–1.60 (ddd, J = 13.7, 7.6, 6.3 Hz, 1 H), 1.25–1.15 (d, J = 7.0
Hz, 3 H), 1.20–1.05 (t, J = 7.0 Hz, 3 H). 13C NMR (12 peaks): d =
149.8, 142.8, 129.0, 126.7, 125.7, 124.1, 82.4, 64.2, 42.3, 37.4,
20.4. 16.0. MS (70 eV): m/z (%) = 176 (17) [M+], 175 (22), 147 (38),
132 (44), 131 (100), 130 (60), 129 (41), 115 (40), 91 (62), 77 (26).
1
anti Isomer: H NMR (200 MHz): d = 7.40–7.00 (m, 4 H), 4.90–
4.75 (t, J = 7 Hz, 1 H), 3.70–3.50 (m, 2 H), 3.10–2.85 (m, 1 H),
2.70–2.50 (dt, J = 12.5, 7.1 Hz, 1 H), 1.60–1.40 (ddd, J = 12.5, 8.2,
7.1 Hz, 1 H), 1.35–1.20 (d, J = 6.9 Hz, 3 H), 1.25–1.15 (t, J = 6.8
Hz, 3 H). 13C NMR (12 peaks): d = 148.0, 143.7, 128.4, 127.0,
124.7, 123.7, 82.3, 64.8, 42.4, 37.0, 20.9, 16.1. MS (70 eV): m/z
(%) = 176 (8) [M+], 175 (15), 147 (24), 132 (34), 131 (100), 130
(71), 129 (40), 115 (35), 91 (64), 77 (20).
afford the corresponding indanes 2 in 14–58% yields. COSY (500 MHz) of 2a (70:30): expected correlations were ob-
tained for both syn and anti isomers. NOESY (500 MHz) of 2a
Compound 1i, prepared according to method A, was re-
(70:30): H4 and H2 strong NOESY effect for the syn isomer, no cor-
relation H4 and H2 for the anti isomer.
ductively electrolyzed to the indane structure 2i, with both
catalysts, Y and Z, as shown in Scheme 2. The yields were
only moderate (35–36%); presumably the steric hindrance
of the methallyl group makes the molecule less prone to
HRCIMS of 2a: m/z calcd for C12H17O: 177.1274; found: 177.1274
[M + H]+.
cyclization. The major product 3i arose from a protode-
halogenation of the starting material.
1-Methoxy-3-methylindane (2b)
Mixture of two diastereomers (ratio: 64:36). The syn/anti assign-
ments were made by comparison with literature spectra.12
In conclusion, the Ni-catalyzed reductive cyclization of o-
syn Isomer: 1H NMR (200 MHz): d = 7.40–7.00 (m, 4 H), 4.75–4.6
(dd, J = 6.2, 1.9 Hz, 1 H), 3.45–3.20 (m, 1 H), 3.35–3.20 (s, 3 H),
2.40–2.25 (ddd, J = 13.5, 7.1, 2 Hz, 1 H), 1.85–1.65 (ddd, J = 13.8,
7.8, 6.2 Hz, 1 H), 1.25–1.15 (d, J = 7.0 Hz, 3 H). 13C NMR (11
peaks): d = 149.9, 142.2, 129.2, 126.7, 125.7, 124.1, 83.8, 56.4,
41.9, 37.4, 20.3. MS (70 eV): m/z (%) = 162 (25) [M+], 161 (51),
131 (100), 130 (91), 129 (65), 115 (67), 91 (77), 77 (30).
but-3-enyl-functionalized aryl halides to the correspond-
ing indane structures was carried out in moderate to good
yields. The yields of cyclization of bromo derivatives
were higher than those of chloro analogues, for which
catalyst Y showed a better efficiency. The compatibility
of the reaction with acetate and benzyloxy functional
groups allows the further introduction of different func-
tionalities in the molecules. The combination of non-toxic
bismuth-based catalysts for the synthesis of the substrates
and a subsequent mild electrochemical cyclization
1
anti Isomer: H NMR (200 MHz): d = 7.40–7.00 (m, 4 H), 4.80–
4.65 (t, J = 6.8 Hz, 1 H), 3.45–3.35 (s, 3 H), 3.10–2.90 (six line mul-
tiplet, J = 6.8 Hz, 1 H), 2.75–2.50 (ddd, J = 13.0, 7.0, 6.8 Hz, 1 H),
1.60–1.40 (ddd, J = 13.0, 7.8, 6.7 Hz, 1 H), 1.35–1.25 (d, J = 6.9
method makes this approach to the synthesis of indane Hz, 3 H). 13C NMR (11 peaks): 149.9, 142.2, 128.6, 126.9, 124.8,
123.9, 83.9, 56.8, 41.5, 37.0, 21.0. MS (70 eV): m/z (%) = 162 (58)
skeletons particularly environmentally friendly and
[M+], 161 (87), 131 (100), 130 (85), 129 (65), 115 (66), 91 (81), 77
attractive.
(30).
3-Methylindyl Acetate (2c)
Spectral Data
Mixture of two diastereomers (ratio: 46:54). The syn13/anti14 assign-
All spectra were recorded in CDCl3. The diastereomeric ratios re-
ported below refer to ratio obtained by NMR analysis after purifica-
ments were made by comparison with literature data.
OEt
Me
OEt
OEt
Br
Me
e–, Y or Z (10 mol%)
+
DMF, KBr
Me
Mg/C, 25 °C
Me
1i
2i
with Y : 35%
with Z : 36%
3i 60%
42%
Scheme 2 Electrochemical cyclization of methallyl derivative 1i
Synlett 2006, No. 13, 2021–2026 © Thieme Stuttgart · New York

LETTER
Synthesis of Functionalized Indanes
2025
syn Isomer: 1H NMR (500 MHz): d = 7.45–7.40 (d, J = 7.6 Hz, 1
H), 7.40–7.20 (m, 3 H), 6.20–6.15 (dd, J = 6.6, 2.0 Hz, 1 H), 3.50–
3.40 (six line multiplet, J = ca. 7.1 Hz, 1 H), 2.40–2.30 (ddd,
J = 14.0, 7.2, 2.1 Hz, 1 H), 2.05–2.00 (s, 3 H), 2.05–1.90 (ddd,
J = 14.1, 7.3, 6.7 Hz, 1 H), 1.35–1.25 (d, J = 7.0 Hz, 3 H). 13C NMR
(12 peaks): d = 171.5, 150.2, 141.1, 129.7, 127.2, 126.3, 123.9,
77.8, 42.0, 37.4, 21.8, 20.2. MS (70 eV): m/z (%) = 190 (1) [M+],
148 (25), 131 (50), 130 (100), 129 (50), 115 (60), 91 (46), 77 (41).
References and Notes
(1) (a) Giese, B. In Radicals in Organic Synthesis: Formation of
Carbon–Carbon Bonds; Pergamon Press: Oxford, 1986.
(b) Stork, G. In Radical-Mediated Cyclization Processes – A
Goal for Synthetic Efficiency; Bartmann, W.; Trost, B. M.,
Eds.; Verlag Chemie: Basel, 1984.
(2) (a) Majumdar, K. C.; Basu, P. K.; Mukhopadhyay, P. P.
Tetrahedron 2004, 60, 6239. (b) Davies, A. G. Organotin
Chemistry, 2nd ed.; Wiley and Sons: London, 2004.
(3) Duñach, E.; Franco, D.; Olivero, S. Eur. J. Org. Chem. 2003,
1605.
1
anti Isomer: H NMR (500 MHz): d = 7.40–7.20 (m, 4 H), 6.20–
6.10 (t, J = 6.6 Hz, 1 H), 3.20–3.10 (ca. six line multiplet, J = 7.0
Hz, 1 H), 2.85–2.75 (dt, J = 13.4, 7.45 Hz, 1 H), 2.15–2.05 (s, 3 H),
1.70–1.60 (ddd, J = 13.1, 6.8, 6.1 Hz, 1 H), 1.40–1.30 (d, J = 6.9
Hz, 3 H). 13C NMR (12 peaks): d = 171.6, 148.8, 141.2, 129.2,
127.3, 125.2, 124.0, 77.6, 41.7, 37.4, 21.4, 20.2. MS (70 eV): m/z
(%) = 190 (0) [M+], 131 (38), 130 (100), 129 (43), 115 (46), 91 (33),
77 (30).
(4) Olivero, S.; Rolland, J.-P.; Duñach, E. Organometallics
1998, 17, 3747.
(5) (a) Hong, B.-C.; Sarshar, S. Org. Prep. Proced. Int. 1999, 1,
1. (b) Wickens, P.; Cantin, L.-D.; Chuang, C.-Y.; Dai, M.;
Hentemann, M. F.; Kumarasinghe, E.; Liang, S. X.; Lowe,
D. B.; Shelekhin, T. E.; Wang, Y.; Zhang, C.; Zhang, H.-J.;
Zhao, Q. PCT Int. Appl., WO 2004011446, 2004.
(c) Sekiguchi, T.; Nakagawa, S.; Fujikura, Y. JP 03044337,
1991. (d) Meakins, S. E.; Motion, K. R. Eur. Pat. Appl., EP
393742, 1990. (e) Frank, W. C. USA, US 93-79008, 1994.
(f) Ohnuma, H.; Fujikura, Y.; Fujita, M.; Toi, N. Eur. Pat.
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Belko, R. P.; Molner, E. A. USA, US 6342612, 2002.
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Hentemann, M. F.; Kumarasinghe, E.; Liang, S. X.; Lowe,
D. B.; Shelekhin, T. E.; Wang, Y.; Zhang, C.; Zhang, H.-J.;
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4, 1109.
1-Benzyloxy-3-methylindane (2d)
Mixture of two diastereomers (ratio: 55/45). The syn/anti assign-
ments were made by comparison with spectrum of 2a.
syn Isomer: 1H NMR (200 MHz): d = 7.40–6.90 (m, 4 H and 5 H),
4.95–4.80 (m, 1 H), 4.55–4.45 (s, 2 H), 3.50–3.25 (m, 1 H), 2.45–
2.25 (ddd, J = 13.5, 7.2, 2.2 Hz, 1 H), 1.85–1.60 (ddd, J = 13.7, 7.6,
6.3 Hz, 1 H), 1.25–1.15 (d, J = 7.0 Hz, 3 H). 13C NMR (15 peaks):
d = 149.9, 142.6, 139.3, 129.2, 128.8, 128.1, 127.9, 126.8, 125.8,
124.2, 81.8, 70.8, 42.2, 37.5, 20.5. MS (70 eV): m/z (%) = 238 (0)
[M+], 147 (50), 131 (30), 115 (14), 105 (21), 92 (40), 91 (100), 77
(34), 65 (26).
anti Isomer: 1H NMR (200 MHz): d = 7.40–6.90 (m, 4 H and 5 H),
4.95–4.8 (m, 1 H), 4.70–4.50 (2 d, J = 11.9 Hz, 2 H), 3.10–2.85 (m,
1 H), 2.70–2.45 (dt, J = 12.6, 7.1 Hz, 1 H), 1.65–1.45 (ddd, J = 12.6,
8.0, 7.0 Hz, 1 H), 1.35–1.20 (d, J = 6.9 Hz, 3 H). 13C NMR (15
peaks): d = 148.1, 143.5, 139.3, 128.8, 128.6, 128.1, 127.9, 127.0,
124.9, 123.8, 81.9, 71.3, 42.3, 37.1, 21.0. MS (70 eV): m/z (%) =
238 (0) [M+], 147 (50), 131 (30), 115 (14), 105 (21), 92 (40), 91
(100), 77 (34), 65 (26). HRMS: m/z calcd for C17H18ONa: 261.1259;
found: 261.1263 [M + Na]+.
1-Ethyloxy-3,3-dimethylindane (2i)
1H NMR (200 MHz): d = 7.42–7.15 (m, 4 H), 4.92 (dd, J = 6.7, 5.3
Hz, 1 H), 3.77–3.59 (m, 2 H), 2.30–2.19 (dd, J = 13.0, 6.7 Hz, 1 H),
1.98–1.89 (dd, J = 12.9, 5.3 Hz, 1 H), 1.21–1.29 (m, 3 H), 1.23 (s,
6 H). 13C NMR (13 peaks): d = 152.2, 141.9, 128.5, 125.3, 124.9,
122.3, 81.2, 64.3, 48.3, 42.4, 30.1, 29.8, 15.8. MS (70 eV): m/z
(%) = 190 (22) [M+], 188 (21), 175 (11), 161 (17), 146 (53), 145
(100), 131 (75), 129 (50), 128 (32), 105 (10), 91 (27), 77 (18).
HRMS: m/z calcd for C13H18O: 190.1353; found: 190.1351 [M+].
(10) Gosden, C.; Healy, K. P.; Pletcher, D. J. Chem. Soc., Dalton
Trans. 1978, 8, 972.
(11) Duñach, E.; Esteves, A. P.; Medeiros, M. J.; Olivero, S. New
J. Chem. 2005, 4, 633.
(12) Armstrong, D. W.; Gahm, K. H.; Chang, L. W. Microchem.
J. 1997, 57, 149.
(13) Izumi, T.; Murakami, S. J. Chem. Technol. Biotechnol.
1994, 60, 23.
(14) Miura, M.; Yoshida, M.; Nojima, M.; Kusabayashi, S. J.
Chem. Soc., Perkin Trans. 1 1982, 1, 79.
(15) Yadav, J. S.; Subba Reddy, V. B.; Srihari, P. Synlett 2001,
673.
(1-Ethoxy-3-methyl)but-3-enylbenzene (3i)
1H NMR (500 MHz): d = 7.35–7.23 (m, 5 H), 4.76 (br s, 1 H), 4.69
(br s, 1 H), 4.38 (dd, J = 8.0, 5.3 Hz, 1 H), 3.37 (dq, J = 7.3, 6.8 Hz,
1 H), 3.32 (dq, J = 7.3, 6.8 Hz, 1 H), 2.54 (dd, J = 14.4, 8.0 Hz, 1
H), 2.29 (dd, J = 14.4, 5.3 Hz, 1 H), 1.72 (s, 3 H), 1.16 (dd, J = 7.3,
6.8 Hz, 3 H). 13C NMR (11 peaks): d = 142.8, 142.6, 128.7, 127.4,
126.6, 112.4, 80.9, 64.1, 46.6, 29.9, 15.3. MS: m/z (%) = 190 (0)
[M+], 134 (8), 107 (59), 106 (33), 91 (8), 70 (100), 77 (61).
(16) Watahiki, T.; Akabane, Y.; Mori, S.; Oriyama, T. Org. Lett.
2003, 5, 3045.
(17) Hosomi, A.; Masahiko, E.; Sakurai, H. Chem. Lett. 1976,
941.
Acknowledgment
Elisabet Duñach would like to acknowledge funding from CNRS,
Université de Nice-Sophia Antipolis. Ram Mohan would like to
acknowledge The National Science Foundation for a RUI grant
(0350216). Ram Mohan would also like to acknowledge The
Camille and Henry Dreyfus Foundation for a Teacher-Scholar
Award.
(18) Aggarwal, V. K.; Vennall, G. P. Synthesis 1998, 1822.
(19) (a) Compound 1a (Method A, 76%): 1H NMR: d = 1.79 (t, 3
H, J = 7.2 Hz), 2.42–2.46 (m, 2 H), 3.35–3.39 (m, 2 H),
4.72–4.73 (m, 1 H), 5.01–5.10 (m, 2 H), 5.83–5.89 (m, 1 H),
7.25–7.52 (m, 4 H). 13C NMR (12 peaks): d = 14.8, 40.7,
64.1, 79.4, 116.4, 122.5, 127.1, 127.2, 128.2, 132.1, 134.2,
Synlett 2006, No. 13, 2021–2026 © Thieme Stuttgart · New York

2026
S. Olivero et al.
LETTER
139.6. HRMS: m/e calcd for C12H15ClO: 210.0811 [M];
141.1. HRMS: m/e calcd for C12H15BrO: 254.0306 [M];
found: 253.0231 [M – 1]. (b) Compound 1b (Method A,
88%): 1H NMR: d = 2.45 (m, 2 H), 3.24 (s, 3 H), 4.65 (dd, 1
H), 5.07 (m, 2 H), 5.85 (dp, 1 H), 7.42 (m, 4 H). 13C NMR
(11 peaks): d = 41.0, 50.9, 81.7, 117.0, 123.1, 127.5, 127.6,
128.8, 132.6, 134.4, 140.7. HRMS: m/e calcd for
found: 209.0740 [M – 1]. (f) Compound 1f (Method B,
81%): this compound has been reported previously.15 The
spectral data are given here. 1H NMR: d = 2.46 (m, 2 H), 3.22
(s, 3 H), 4.70 (dd, 1 H, J = 7.3, 4.9 Hz), 5.02 (m, 2 H), 5.86
(m, 1 H), 7.32 (m, 4 H). 13C NMR: (11 peaks): d = 40.9, 56.9,
79.4, 116.9, 126.9, 127.2, 128.3, 129.3, 132.8, 134.3, 139.1.
(g) Compound 1g (Method D, 33%): this compound has
been reported previously.15 The spectral data are given here.
1H NMR: d = 2.09 (s, 3 H), 2.54–2.62 (m, 2 H), 5.03–5.10 (t,
2 H, J = 6.18 Hz), 5.68–5.81 (m, 1 H), 6.18–6.23 (dd, 1 H,
J = 7.7, 2.5 Hz), 7.19–7.41 (m, 4 H). 13C NMR (12 peaks):
d = 20.9, 39.4, 71.6, 118.1, 126.8, 127.1, 128.7, 129.5, 132.0,
132.9, 137.9, 169.7. (h) Compound 1h (Method C, 35%): 1H
NMR: d = 2.50 (app t, 2 H), 4.38 (dd, 2 H), 4.91 (t, 1 H,
J = 6.2 Hz), 5.02 (m, 1 H), 5.90 (dquar, 2 H), 7.30 (m, 9 H).
13C NMR (15 peaks): d = 41.1, 70.9, 77.2, 117.0, 127.0,
127.5, 127.6, 127.7, 128.3, 128.4, 129.3, 132.9, 134.4,
138.2, 139.4. HRMS: m/e calcd for C17H17ClO: 272.0968
[M]; found: 271.0894 [M – 1]. (i) Compound 1i (Method A,
43%): 1H NMR: d = 1.18 (t, 3 H, J = 7.18 Hz), 1.84 (s, 3 H),
2.26–2.42 (m, 2 H), 3.32–3.42 (m, 2 H), 4.78–4.85 (m, 3 H),
7.08–7.52 (m, 4 H). 13C (13 peaks): d = 15.3, 22.9, 45.2,
64.6, 79.1, 112.4, 123.0, 127.6, 127.7, 128.6, 132.6, 142.1,
142.6. HRMS: m/e calcd for C13H17BrO: 268.0463 [M];
found: 267.0379 [M – 1].
C11H13BrO: 240.0150 [M]; found: 239.0066 [M – 1].
(c) Compound 1c (Method D, 27%): 1H NMR: d = 2.09 (s, 3
H), 2.55–2.60 (m, 2 H), 5.04–5.10 (t, 2 H, J = 6.43 Hz),
5.72–5.78 (m, 1 H), 6.12–6.15 (dd, 1 H, J = 7.67, 2.73 Hz),
7.09–7.54 (m, 4 H). 13C NMR (12 peaks): d = 21.0, 39.5,
73.8, 118.1, 122.0, 127.2, 127.4, 129.0, 132.7, 132.9, 139.6,
169.7. HRMS: m/e calcd for C12H13BrO2: 268.0099 [M];
found: 268.0098 [M – 1]. (d) Compound 1d (Method C,
27%): 1H NMR: d = 2.48 (t, 2 H, J = 6.9 Hz), 4.28–4.48 (dd,
2 H), 4.86 (t, 1 H, J = 6.18 Hz), 5.02–5.10 (m, 2 H), 5.81–
5.94 (m, 1 H), 7.12–7.55 (m, 9 H). 13C NMR (15 peaks): d =
41.2, 70.9, 79.6, 117.1, 123.1, 127.6, 127.7 (2 peaks), 127.9,
128.3, 128.9, 132.7, 134.5, 138.2, 141.0. HRMS: m/e calcd
for C17H17BrO: 316.0463 [M]; found: 315.0381 [M – 1].
(e) Compound 1e (Method C, 77%): 1H NMR: d = 1.18 (t, 3
H, J = 7.18 Hz), 2.42–2.46 (m, 2 H), 3.36–3.39 (m, 2 H),
4.76–4.80 (m, 1 H), 5.00–5.10 (m, 2 H), 5.79–5.92 (m, 1 H),
7.16–7.50 (m, 4 H). 13C NMR (12 peaks): d = 14.7, 40.6,
64.1, 77.1, 116.3, 126.5, 126.9, 127.8, 128.8, 132.3, 134.2,
Synlett 2006, No. 13, 2021–2026 © Thieme Stuttgart · New York