Reductive opening of 1H,3H-benzo[de]isochromene: Synthesis of 1,8-difunctionalised naphthalenes

Article abstract of DOI:10.1016/j.tet.2004.03.071

The lithiation of 1H,3H-benzo[de]isochromene (6) with lithium and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB, 5% molar) in THF at -50°C gives dianionic intermediate 7, which by reaction with different electrophiles {H₂O, D₂O, ^tBuCHO, PhCHO, Me ₂CO, (CH₃CH₂)₂CO, [CH ₃(CH₂)₄]₂CO, (CH₂) ₅CO, (CH₂)₇CO, (-)-menthone} at the same temperature followed by hydrolysis leads to functionalised alcohols 8. If after addition of a carbonyl compound as the first electrophile [^tBuCHO, (CH₂)₅CO, (-)-menthone], the resulting dialcoholate 9 is allowed to react at 0°C, a second lithiation takes place to give intermediate 10 which by reaction with a second electrophile [H₂O, ^tBuCHO, (CH₂)₅CO, CO₂], yields, after hydrolysis, 1,8-difunctionalised naphthalenes 11. Cyclization under acidic conditions of diols 8e-i gives oxygen-containing eight-membered heterocycles, which are homologous to the starting material 6.

Full text of DOI:10.1016/j.tet.2004.03.071

Tetrahedron 60 (2004) 4655–4662
Reductive opening of 1H,3H-benzo[de]isochromene:
synthesis of 1,8-difunctionalised naphthalenes
*
Francisco Foubelo, Benjamın Moreno and Miguel Yus
´
´ ´ ´ ´
Departamento de Quımica Organica, Facultad de Ciencias and Instituto de Sıntesis Organica (ISO), Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
Received 5 February 2004; revised 12 March 2004; accepted 24 March 2004
Dedicated to Professor Peter Stannety on the occasion of his 60th birthday
Abstract—The lithiation of 1H,3H-benzo[de]isochromene (6) with lithium and a catalytic amount of 4,40-di-tert-butylbiphenyl (DTBB, 5%
t
molar) in THF at 250 8C gives dianionic intermediate 7, which by reaction with different electrophiles {H2O, D2O, BuCHO, PhCHO,
Me2CO, (CH3CH2)2CO, [CH3(CH2)4]2CO, (CH2)5CO, (CH2)7CO, (2)-menthone} at the same temperature followed by hydrolysis leads to
functionalised alcohols 8. If after addition of a carbonyl compound as the first electrophile [tBuCHO, (CH2)5CO, (2)-menthone], the
resulting dialcoholate 9 is allowed to react at 0 8C, a second lithiation takes place to give intermediate 10 which by reaction with a second
t
electrophile [H2O, BuCHO, (CH2)5CO, CO2], yields, after hydrolysis, 1,8-difunctionalised naphthalenes 11. Cyclization under acidic
conditions of diols 8e–i gives oxygen-containing eight-membered heterocycles, which are homologous to the starting material 6.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
an efficient methodology to perform lithiation reactions
under very mild reaction conditions, which employs lithium
powder and a catalytic amount (,10%) of an arene,5–8
naphthalene and 4,40-di-tert-butylbiphenyl (DTBB) being
the most commonly used.9 For instance, the application of
this reductive methodology to the ring opening of
benzofused heterocycles, such as phthalan (1)10 or iso-
chroman (2)10e – n,11 allows the generation of the
corresponding functionalised organolithium intermediates
3, which can be trapped with different electrophiles, for
instance carbonyl compounds, to yield diols 4, suitable
precursors of the homologous heterocycles 5 (Scheme 1).
A useful and versatile methodology which can be applied in
the preparation of polyfunctionalised organic molecules
consists of the reaction of functionalised organometallic
compounds1 with electrophilic reagents. The organolithium
intermediates2 represent a special synthetic case due to their
high reactivity under mild reaction conditions, and they can
be generated using classical procedures (i.e., halogen–
lithium exchange or tin–lithium transmetallation)3 or
through the application of new methods. Amongst the
newer methods, the reductive ring opening of heterocycles4
has shown to be of wide application. Different oxygen-,
nitrogen- and sulfur-containing heterocycles of different
size (from three to seven-membered rings) have been used
to generate the corresponding functionalised organolithium
compounds. During the last few years, we have developed
Recently, Azzena et al. reported the use of the mentioned
arene catalysed lithiation methodology to study the ring
opening of some other benzannelated cyclic ethers and
amines and the reaction of the generated lithiated
Scheme 1.
Keywords: Reductive ring opening; Benzoisochromene; DTBB-catalysed lithiation; Electrophilic substitution; Oxygenated heterocycles.
*
Corresponding author. Fax: þ34-965-909672; e-mail address: foubelo@ua.es
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.03.071

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F. Foubelo et al. / Tetrahedron 60 (2004) 4655–4662
Scheme 2. Reagents and conditions: (i) Li, DTBB (5 mol%), THF, 250 8C, 6 h; (ii) Eþ¼H2O, D2O, tBuCHO, PhCHO, Me2CO, (CH3CH2)2CO,
[CH3(CH2)4]2CO, (CH2)5CO, (CH2)7CO, (2)-menthone, 250 8C, 15 min; (iii) H2O, 250 to 20 8C.
Table 1. Preparation of compounds 8
2. Results and discussion
Entry
Eþ
Producta
Starting material 6 was prepared from commercially
available 1,8-naphthalic anhydride by reduction with
LiAlH4 in a 3/1 diethyl ether/benzene mixture at 40 8C to
give first the corresponding diol13 which, after treatment
with 50% H3PO4 at 100 8C, led to the benzoisochromene 612
in 55% overall yield. The reaction of 1H,3H-benzo[de]iso-
chroman (6) with an excess of lithium (1/10 molar ratio) in
the presence of a catalytic amount of DTBB (5 mol%) in
THF at 250 8C led, after 6 h, to a solution of the dianion 7,
which reacted with different electrophiles {H2O, D2O,
tBuCHO, PhCHO, Me2CO, (CH3CH2)2CO, [CH3(CH2)4]2-
CO, (CH2)5CO, (CH2)7CO, (2)-menthone} at the same
temperature for 15 min yielding, after hydrolysis with
water, the expected functionalised alcohols 8 (Scheme 2
and Table 1). In the case of using (2)-menthone as
electrophile, the almost exclusive diastereomer is the one
resulting from the attack of the dianionic intermediate 7 to
the less hindered face of the carbonyl group (Fig. 1).
Temperature of the lithiation step is very important in order
to achieve a good selectivity. Thus, the reductive opening of
the starting benzoisochromene 6 did not take place at
278 8C in a significant extension in the presence of the
same lithiation mixture, the starting heterocycle 6 being
recovered after hydrolysis. However, at 0 8C for 1 h, 1,8-
dimethylnaphthalene was isolated as the major reaction
product. Under these reaction conditions, after reductive
opening of the compound 6 giving the dianionic inter-
mediate 7, a second reductive cleavage of the remaining
carbon–oxygen bond took place to give a 1,8-bis(lithio-
methyl)naphthalene, which, after hydrolysis with water, led
to 1,8-dimethylnaphthalene. This result was in agreement
with those reported by Azzena et al.12 on the lithiation of the
compound 6 using as lithiating reagent lithium metal from a
30% weight dispersion in mineral oil in the presence of a
catalytic amount of naphthalene (10 mol%).
No.
E
Yield (%)b,c Rfd
1
2
3
4
5
6
7
8
9
10
H2O
D2O
8a
8b
8c
H
D
58 (.95)
42 (.95)e
34 (55)
0.46
0.46
0.33
0.16
0.14
0.38
0.58
0.36
0.37
0.37
tBuCHO
PhCHO
Me2CO
(CH3CH2)2CO
tBuCHOH
8d PhCHOH
8e
8f
34 (56)
43 (70)
45 (74)
Me2COH
(CH3CH2)2COH
[CH3(CH2)4]2CO 8g [CH3(CH2)4]2COH 34 (56)
(CH2)5CO
(CH2)7CO
(2)-Menthone
8h (CH2)5COH
(CH2)7COH
–
42 (68)
43 (70)
50 (82)
8i
8jf
a
All products were .95% pure (GLC and 300 MHz 1H NMR).
b
Isolated yield after column chromatography (silica gel, hexane/ethyl
acetate) based on the starting material 6.
In parenthesis GLC yield of compound 8.
Silica gel, hexane/ethyl acetate: 2/1.
55% deuterium from mass spectrometry and 13C NMR.
See Figure 1.
c
d
e
f
Figure 1.
intermediates mainly with water, deuterium oxide and alkyl
bromides, only one reaction with acetone with modest yield
being described.12 In this paper we report the ring opening
of 1H,3H-benzo[de]isochromene (6) using a DTBB-
catalysed lithiation with two synthetic purposes: (a) the
monolithiation reaction and trapping with carbonyl
compounds as electrophiles to get diols able to be cyclised
to the corresponding homologated heterocycles, and (b) the
sequential double lithiation in order to introduce two
different electrophiles, which for carbonyl compounds also
would be able to give the corresponding heterocycles by
acidic cyclisation.
Taking advantage of the unexpected easy reductive
cleavage of the carbon–oxygen bond in the dianionic
intermediate 7, the lithiation of 1H,3H-benzo[de]iso-
chromene (6) can be directed to the introduction of two
different electrophiles at both benzylic positions in a
Scheme 3. Reagents and conditions: (i) Li, DTBB (5 mol%), THF, 250 8C, 6 h; (ii) R1R2CO¼tBuCHO, (CH2)5CO, (2)-menthone, 250 8C, 15 min; (iii) 0 8C,
2 h; (iv) Eþ¼H2O, tBuCHO, (CH2)5CO, CO2, 270 8C, 15 min; (v) H2O, 270 to 20 8C.

F. Foubelo et al. / Tetrahedron 60 (2004) 4655–4662
Table 2. Preparation of compounds 11 from compound 6
4657
Entry
R1R2CO
Eþ
Producta
No.
R1
R2
E
Yield (%)b,c
Rfd
1
2
3
4
5
6
tBuCHO
H2O
tBuCHO
CO2
(CH2)5CO
CO2
CO2
11a
11b
11c
11d
11e
11ff
H
H
H
(CH2)5
(CH2)5
—
tBu
tBu
tBu
H
58 (.95)
49 (80)e
42 (.95)
45 (78)
43 (74)
41 (68)
0.33 (10/1)
0.31 (5/1)
0.18 (2/1)
0.21 (2/1)
0.24 (2/1)
0.13 (2/1)
tBuCHO
tBuCHOH
CO2H
tBuCHO
(CH2)5CO
(CH2)5CO
(2)-menthone
(CH2)5COH
CO2H
CO2H
a
1
All products were .95% pure (GLC and 300 MHz H NMR).
b
c
d
e
f
Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting material 6.
In parenthesis GLC yield of compound 11.
Silica gel, in parenthesis hexane/ethyl acetate ratio.
A ca. 1:1 mixture of diastereomers was obtained (300 MHz 1H NMR).
See Figure 2.
sequential manner. Thus, after reductive ring opening
lithiation to give the dianion 7 (Scheme 2) and reaction
with a carbonyl compound as the first electrophile
[tBuCHO, (CH2)5CO, (2)-menthone], the resulting
alcoholate 9 was stirred at 0 8C for 2 h, so a second
lithiation took place with the excess of lithium still present
in the reaction medium to give a new functionalised
organolithium compound 10 which, by reaction with a
Figure 2.
˚
Scheme 4. Reagents and conditions: (i) p-TsOH (cat.), MS 4 A, PhMe, 110 8C, 2 h.
Table 3. Preparation of compounds 12
Entry
Starting material 8
Producta
No.
R1
R2
Yield (%)b,c
Rfd
1
2
3
4
5
8e
8f
8g
8h
8i
12e
12f
12g
12h
12i
Me
Me
CH3CH2
CH3(CH2)4
.95
.95
89 (.95)
.95
56 (.95)
0.36
0.43
0.54
0.46
0.47
CH3CH2
CH3(CH2)4
(CH2)5
(CH2)7
a
1
All products were .95% pure (GLC and 300 MHz H NMR).
Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting material 8.
In parenthesis GLC yield of compound 12.
Silica gel, hexane/ethyl acetate: 10/1.
b
c
d

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F. Foubelo et al. / Tetrahedron 60 (2004) 4655–4662
spectrometers, respectively. The purity of volatile products
and the chromatographic analyses (GLC) were determined
with a flame ionisation detector and a 12 m capillary column
(0.2 mm diam., 0.33 mm film thickness), using nitrogen
(2 mL/min) as carrier gas, Tinjector¼275 8C, Tdetector¼300 8C,
Tcolumn¼60 8C (3 min) and 60–270 8C (15 8C/min),
P¼40 kPa. Specific rotations were determined with a
Perkin–Elmer 341 digital polarimeter.
Figure 3.
4.2. Reductive lithiation of 1H,3H-benzo[de]iso-
chromene (6) and reaction with electrophiles.
Preparation of compounds 8
t
second electrophile [H2O, BuCHO, (CH2)5CO, CO2], and
final hydrolysis led to 1,8-difunctionalised naphthalenes 11
(Scheme 3 and Table 2). In the case of using prostereogenic
carbonyl compounds in both steps, such as pivaldehyde, an
almost 1:1 mixture of diastereomers was obtained (Table 2,
entry 2).
Isolation of compounds 8. General procedure. To a blue
suspension of lithium powder (35 mg, 5.0 mmol) and a
catalytic amount of DTBB (27 mg, 0.1 mmol; 5 mol%) in
dry THF (3 mL) under argon was added dropwise 1H,3H-
benzo[de]isochromene (6) (85 mg, 0.5 mmol) at 250 8C,
and the resulting mixture was stirred for 6 h (monitored by
GLC) at the same temperature. Then the corresponding
electrophile (1.0 mmol; 0.2 mL in the case of H2O and D2O)
was added dropwise and stirring was continued for 15 min.
After that, the reaction mixture was hydrolysed with water
(4 mL), extracted with ethyl acetate (3£10 mL), dried over
anhydrous Na2SO4 and evaporated (15 Torr). The residue
was purified by column chromatography (silica gel, hexane/
ethyl acetate) to yield pure products. Yields and Rf values
are given in Table 1, physical, analytical and spectroscopic
data follow.
Finally, intramolecular dehydration of diols 8e–i by
treatment with a catalytic amount of p-toluenesulfonic
˚
acid in the presence of 4 A molecular sieves in toluene at
110 8C gave the corresponding oxygen-containing seven-
membered heterocycle 12 in very high yields (Scheme 4 and
Table 3). In the case of diol 8j (Fig. 1), a complex mixture of
reaction products was obtained, probably involving the most
stable tertiary carbenium ion 15 (Fig. 3), which is
supposedly involved in this process. It is worthy to note
that the whole process 6!12 represents the homologation of
the starting heteroycle 6. Under the same reaction
conditions, hydroxyacid 11c gave the lactone 13 in almost
quantitative yield (Scheme 4). On the other hand, the diol
11d did not lead to the oxygen-containing eight-membered
heterocycle giving instead, among other products, the
conjugate hydroxyolefin 14 in 63% yield, after column
chromatography (Scheme 4).
4.2.1. 1-Hydroxymethyl-8-methylnaphthalene (8a).
White solid, mp 91–92 8C (pentane/dichloromethane) (lit.
mp 93–94.5 8C);14 n (KBr) 3480–3150 (OH), 3050, 3032
(ArH), 1085 cm21 (CO); dH 2.23 (1H, br s, OH), 3.02 (3H,
s, CH3), 5.22 (2H, s, CH2), 7.35–7.43 (3H, m, ArH), 7.54
(1H, d, J¼7.0 Hz, ArH), 7.71–7.74 (1H, m, ArH), 7.82 (1H,
d, J¼8.1 Hz, ArH); dC 24.1 (CH3), 66.4 (CH2OH), 124.9,
125.4, 127.9, 128.9, 130.2, 130.4, 131.5, 134.7, 135.6, 137.2
(ArC); m/z 172 (Mþ, 38%), 155 (11), 154 (69), 153 (100),
152 (20), 143 (11), 141 (13), 129 (13), 128 (31), 127 (10),
115 (19), 77 (16), 76 (36), 63 (13), 51 (12); HRMS: Mþ,
found 172.0874.C12H12O requires 172.0888.
3. Conclusion
In conclusion, we report here that the reductive opening
lithiation of 1H,3H-benzo[de]isochromene (6) at 250 8C
led to dianionic intermediate 7, which by reaction with
electrophiles and final hydrolysis gave functionalised
alcohols 8. It is worthy to note that it is possible to carry
out a sequential double lithiation-reaction with electrophiles
to prepare 1,8-difunctionalised naphthalene derivatives 11.
4.2.2. 8-Deuteromethyl-1-hydroxymethylnaphthalene
(8b). White solid, mp 91–92 8C (pentane/dichloro-
methane); n (KBr) 3485–3145 (OH), 3048, 3031 (ArH),
1064 cm21 (CO); dH 2.46 (1H, br s, OH), 3.02 (2H, s,
CH2D), 5.22 (2H, s, CH2), 7.35–7.43 (3H, m, ArH), 7.54
(1H, d, J¼7.0 Hz, ArH), 7.71–7.81 (1H, m, ArH), 7.84 (1H,
d, J¼8.1 Hz, ArH); dC 23.9 (t, JCD¼20.9 Hz), 66.3
(CH2OH), 124.9, 125.4, 127.8, 128.9, 130.2, 130.4, 131.5,
134.7, 135.6, 137.3 (ArC); m/z 173 (Mþ, 26%), 172 (24),
155 (40), 154 (99), 153 (100), 152 (19), 143 (11), 142 (12),
141 (13), 129 (28), 128 (45), 127 (16), 116 (12), 115 (25), 77
(24), 76 (29), 75 (11), 64 (11), 63 (21), 51 (19); HRMS: Mþ,
found 173.0934. C12H11DO requires 173.0950.
4. Experimental
4.1. General
All reactions were carried out under an atmosphere of
nitrogen in oven-dried glassware, except the preparation of
1H,3H-benzo[de]isochromene (6). All reagents were com-
mercially available (Acros, Aldrich) and were used without
further purification. Commercially available anhydrous
THF (99.9%, water content #0.006%, Acros) was used as
solvent in all the lithiation reactions. IR spectra were
measured (film) with a Nicolet Impact 400 D-FT
Spectrometer. NMR spectra were recorded with a Bruker
AC-300 or a Bruker ADVANCE DRX-500 using CDCl3 as
the solvent. LRMS and HRMS were measured with
Shimadzu GC/HS QP-5000 and Finingan MAT95 S
4.2.3. 1-[(2-Hydroxy-3,3-dimethyl)butyl]-8-hydroxy-
methylnaphthalene (8c). Colourless oil; n (film) 3410–
3160 (OH), 3048, 3029 (ArH), 1040 cm21 (CO); dH 1.06
[9H, s, (CH3)3C], 2.83 (2H, br s, 2£OH), 3.38–3.56 (3H, m,
CH2CH), 4.90 (1H, d, J¼12.40 Hz, CHHOH), 5.35 (1H, d,
J¼12.40 Hz, CHHOH), 7.36–7.44 (3H, m, ArH), 7.49 (1H,

F. Foubelo et al. / Tetrahedron 60 (2004) 4655–4662
4659
dd, J¼6.9, 1.25 Hz, ArH), 7.76–7.84 (2H, m, ArH); dC 25.9
[(CH3)3C], 35.2 [(CH3)3C], 36.9 (CH2CH), 66.4 (CH2OH),
83.4 (CHOH), 124.9, 125.2, 128.8, 130.7, 130.8, 131.0,
131.9, 135.9, 136.7, 136.9 (ArC); m/z 240 (Mþ2H2O,
24%), 207 (17), 183 (15), 172 (17), 168 (15), 155 (62), 154
(74), 153 (82), 152 (38), 151 (15), 141 (27), 129 (17), 128
(17), 115 (19), 76 (16), 75 (15), 57 (60), 55 (22), 45 (28), 41
(100); HRMS: Mþ2H2O, found 240.1510. C17H20O
requires 240.1514.
(72), 154 (30), 153 (63), 152 (68), 141 (27), 128 (17), 115
(16), 57 (29), 55 (50), 43 (100); HRMS: Mþ2H2O, found
324.2475. C23H32O requires 324.2453.
4.2.8. 1-[(1-Hydroxycyclohexyl)methyl]-8-hydroxy-
methylnaphthalene (8h). Colourless oil; n (film) 3535–
3140 (OH), 3058, 3036 (ArH), 1045 cm21 (CO); dH 1.27–
1.93 (12H, m, 5£CH2, 2£OH), 3.54 (2H, s, ArCH2COH),
5.16 (2H, s, CH2OH), 7.30 (1H, d, J¼5.9 Hz, ArH), 7.36–
7.42 (2H, m, ArH), 7.52 (1H, d, J¼5.8 Hz, ArH), 7.76–7.80
(2H, m, ArH); dC 22.0, 25.8, 37.4, 47.2 (CH2), 66.3
(CH2OH), 73.2 (COH), 124.4, 125.0, 129.1, 130.4, 131.6,
132.4, 132.5, 132.9, 135.7, 137.1 (ArC); m/z 252
(Mþ2H2O, 5%), 172 (19), 165 (20), 155 (15), 154 (100),
153 (75), 152 (36), 141 (12), 128 (19), 115 (15), 81 (18), 55
(30); HRMS: Mþ2H2O, found 252.1503. C18H20O requires
252.1514.
4.2.4. 1-Hydroxymethyl-8-[(2-hydroxy-2-phenyl)ethyl]-
naphthalene (8d). Colourless oil; n (film) 3510–3255
(OH), 3057, 3032 (ArH), 1092 cm21 (CO); dH 1.70 (2H, br
s, 2£OH), 3.65 (1H, dd, J¼14.6, 3.9 Hz, CHHCH), 3.87
(1H, dd, J¼14.6, 9.1 Hz, CHHCH), 4.89 (1H, dd, J¼9.1,
3.9 Hz), 5.11 (1H, d, J¼12.4 Hz, CHHOH), 5.37 (1H, d,
J¼12.4 Hz, CHHOH), 7.30–7.46 (6H, m, ArH), 7.57 (1H,
d, J¼7.0 Hz, ArH), 7.80–7.89 (4H, m, ArH); dC 45.3
(CH2CH), 66.7 (CH2OH), 77.1 (CHOH), 124.9, 125.2,
125.9, 128.5, 129.0, 129.1, 130.7, 130.9, 131.1, 131.6,
135.0, 136.0, 136.3, 143.9; m/z 260 (Mþ2H2O, 7%), 172
(15), 155 (14), 154 (100), 153 (76), 152 (23), 107 (10), 79
(11), 77 (18); HRMS: Mþ2H2O, found 260.1202. C19H16O
requires 260.1201.
4.2.9. 1-[(1-Hydroxycyclooctyl)methyl]-8-hydroxy-
methylnaphthalene (8i). Colourless oil; n (film) 3460–
3160 (OH), 3055, 3035 (ArH), 1045 cm21 (CO); dH 1.48–
1.64 (16H, m, 7£CH2, 2£OH), 3.54 (2H, s, ArCH2COH),
5.16 (2H, s, CH2OH), 7.29–7.43 (3H, m, ArH), 7.51–7.54
(1H, m, ArH), 7.76–7.81 (2H, m, ArH); dC 22.2, 25.0, 28.2,
35.6, 45.5 (CH2), 66.3 (CH2OH), 77.1 (COH), 124.4, 125.1,
129.1, 130.3, 131.6, 132.5, 132.7, 133.2, 135.7, 137.2
(ArC); m/z 280 (Mþ2H2O, 5%), 155 (16), 154 (100), 153
(53), 152 (15), 55 (11); HRMS: Mþ2H2O, found 280.1834.
C20H24O requires 280.1827.
4.2.5. 1-Hydroxymethyl-8-[(2-hydroxy-2-methyl)pro-
pyl]naphthalene (8e). Colourless oil; n (film) 3560–3275
(OH), 3055, 3033 (ArH), 1095 cm21 (CO); dH 1.25 [6H, s,
(CH3)2C], 2.17 (2H, br s, 2£OH), 3.57 (2H, s, CH2COH),
5.18 (2H, s, CH2OH), 7.33–7.45 (3H, m, ArH), 7.52–7.55
(1H, m, ArH), 7.78–7.83 (2H, m, ArH); dC 29.5 [(CH3)2C],
47.7 (CH2COH), 66.5 (CH2OH), 72.7 (COH), 124.6, 125.0,
129.2, 129.5, 130.5, 131.4, 132.6, 133.6, 135.8, 137.0
(ArC); m/z 212 (Mþ2H2O, 9%), 179 (18), 172 (22), 154
(92), 153 (100), 141 (17), 128 (27), 115 (17), 59 (47);
HRMS: Mþ2H2O, found 212.1196. C15H16O requires
212.1201.
4.2.10. (1R,2S,5R)-1-[(1-Hydroxy-2-isopropyl-5-methyl)-
cyclohexyl]methyl-8-hydroxymethylnaphthalene
(8j).
Colourless oil; n (film) 3510–3190 (OH), 3055, 3032
(ArH), 1035 cm21 (CO); dH 0.64 (3H, d, J¼6.55 Hz,
CH3CH), 0.71–0.97 (m, 3 H), 1.01 (3H, d, J¼6.8 Hz,
CH3CH), 1.02 (3H, d, J¼6.8 Hz, CH3CH), 1.18–1.28 (2H,
m), 1.35–1.49 (1H, m), 1.53–1.60 (1H, m), 1.66–1.70 (1H,
m), 2.23 (2H, br s, 2£OH), 2.52–2.61 (1H, m), 2.89 (1H, d,
J¼14.4 Hz, ArCHHCOH), 4.40 (1H, d, J¼14.4 Hz, ArCH-
HCOH), 5.22 (2H, s, CH2OH), 7.34–7.42 (3H, m, ArH),
7.48–7.51 (1H, m, ArH), 7.76–7.81 (2H, m, ArH); dC 18.3
(CH3), 21.3 (CH2), 22.3 (CH3), 24.1 (CH3), 25.8 (CH), 27.8
(CH), 35.1 (CH2), 45.7 (CH2), 47.3 (CH2), 51.4 (CH), 66.4
(CH2OH), 77.2 (COH), 124.5, 124.8, 128.9, 130.3, 130.4,
132.1, 133.1, 134.0, 135.8, 137.5 (ArC); m/z 308
(Mþ2H2O, 2%), 172 (25), 155 (18), 154 (100), 153 (47),
152 (15), 128 (12), 95 (12), 81 (26), 69 (18), 55 (38);
HRMS: Mþ2H2O, found 308.2144. C22H28O requires
308.2140. [a]2D0¼258.4 [c¼1.0 (CH2Cl2)].
4.2.6. 1-[(2-Hydroxy-2-ethyl)butyl]-8-hydroxymethyl-
naphthalene (8f). Colourless oil; n (film) 3445–3185
(OH), 3050, 3030 (ArH), 1080 cm21 (CO); dH 0.90 (6H, t,
J¼6.9 Hz, 2£CH3), 1.38–1.57 (4H, m, 2£CH2), 2.18 (2H,
br s, 2£OH), 3.53 (2H, s, CH2COH), 5.17 (2H, s, CH2OH),
7.30–7.42 (3H, m, ArH), 7.50–7.53 (1H, m, ArH), 7.76–
7.81 (2H, m, ArH); dC 8.0 (CH3), 30.0 (CH2), 44.0 (CH2),
66.3 (CH2OH), 76.8 (COH), 124.5, 125.0, 129.1, 130.3,
131.4, 132.5, 132.7, 133.3, 135.8, 137.3 (ArC); m/z 240
(Mþ2H2O, 1%), 211 (10), 172 (28), 155 (18), 154 (100),
153 (75), 152 (20), 141 (13), 128 (17), 115 (11), 87 (19), 57
(22); HRMS: Mþ2H2O, found 240.1511. C17H20O requires
240.1514.
4.3. Sequential double lithiation of 1H,3H-benzo[de]iso-
chromene (6) and reaction with electrophiles
4.2.7. 1-Hydroxymethyl-8-[(2-hydroxy-2-pentyl)heptyl]-
naphthalene (8g). Colourless oil; n (film) 3430–3120
(OH), 3051, 3029 (ArH), 1105 cm21 (CO); dH 0.90 (6H, t,
J¼6.5 Hz, 2£CH3), 1.28–1.47 (18H, m, 8£CH2, 2£OH),
3.54 (2H, s, CH2COH), 5.18 (2H, s, CH2OH), 7.28–7.43
(3H, m, ArH), 7.53 (1H, d, J¼5.9 Hz, ArH), 7.77–7.81 (2H,
m, ArH); dC 14.0 (CH3), 22.6, 23.4, 32.3, 38.2, 44.9 (CH2),
66.3 (CH2OH), 77.2 (COH), 124.5, 125.0, 129.2, 130.3,
131.4, 132.5, 132.7, 133.3, 135.8, 137.4 (ArC); m/z 324
(Mþ2H2O, 9%), 253 (14), 236 (20), 235 (86), 193 (24), 181
(16), 179 (45), 178 (21), 169 (23), 167 (19), 166 (17), 165
Isolation of compounds 11. General procedure. To a blue
suspension of lithium powder (35 mg, 5.0 mmol) and a
catalytic amount of DTBB (27 mg, 0.1 mmol; 5 mol%) in
dry THF (3 mL) under argon was added dropwise 1H,3H-
benzo[de]isochromene (6) (85 mg, 0.5 mmol) at 250 8C,
and the resulting mixture was stirred for 6 h (monitored by
GLC) at the same temperature. Then the corresponding
carbonyl compound (0.7 mmol) was added dropwise and
stirring was continued for 15 min. After that, the reaction
mixture was allowed to rise to 0 8C and stirring was

4660
F. Foubelo et al. / Tetrahedron 60 (2004) 4655–4662
continued for 2 h at this temperature. Then, the reaction
mixture was cooled down to 270 8C and a second
electrophile (1.0 mmol, 0.2 mL in the case of H2O, carbon
dioxide was bubbled for 15 min) was added dropwise.
Finally it was hydrolysed with water (4 mL, 3 M HCl in the
case of using carbon dioxide as the second electrophile),
extracted with ethyl acetate (3£10 mL), dried over
anhydrous Na2SO4 and evaporated (15 Torr). The residue
was purified by column chromatography (silica gel, hexane/
ethyl acetate) to yield pure products. Yields and Rf values
are given in Table 2, physical, analytical and spectroscopic
data follow.
179 (14), 178 (10), 165 (24), 157 (13), 156 (100), 153 (30),
152 (11), 141 (10), 99 (35), 81 (34), 57 (10), 55 (38);
HRMS: Mþ22H2O, found 316.2184. C24H28 requires
316.2191.
4.3.5. 8-(1-Hydroxycyclohexylmethyl)-1-naphthylacetic
acid (11e). Pale yellow oil; n (film) 3645–3110 (OH),
3050 (ArH), 1714 (CvO), 1085 cm21 (CO); dH 1.29–1.55
(10H, m, 5£CH2), 3.30 (2H, s, CH2COH), 4.53 (2H, s,
CH2CO2H), 7.29–7.40 (4H, m, ArH), 7.76–7.79 (2H, m,
ArH); dC 21.9, 25.8, 29.7, 37.6, 43.5 (CH2), 72.3 (COH),
124.5, 124.8, 129.3, 129.9, 131.0, 132.1, 132.7, 132.8,
132.9, 135.9 (ArC), 176.2 (CO2H); m/z 280 (Mþ2H2O,
5%), 207 (13), 182 (100), 181 (11), 165 (21), 155 (12), 154
(18), 153 (27), 152 (29), 57 (10), 55 (15); HRMS:
Mþ2H2O, found 280.1452. C19H20O2 requires 280.1463.
4.3.1. 1-[(3,3-Dimethyl-2-hydroxy)butyl]-8-methyl-
naphthalene (11a). Colourless oil; n (film) 3510–3230
(OH), 3047, 3027 (ArH), 1065 cm21 (CO); dH 0.96 [9H, s,
(CH3)3C], 1.72 (1H, br s, OH), 2.83 (3H, s, ArCH3), 3.06
(1H, dd, J¼14.0, 10.9 Hz, CHHCHOH), 3.41 (1H, dd,
J¼10.9, 2.1 Hz, CHHCHOH), 3.60 (1H, dd, 1H, J¼14.0,
2.1 Hz, CHHCHOH), 7.15–7.28 (4H, m, ArH), 7.59–7.66
(2H, m, ArH); dC 26.1 [(CH3)3C], 27.0 (CH3), 35.2
[(CH3)3C], 38.2 (CH2), 80.1 (CHOH), 124.8, 125.1, 128.3,
128.9, 130.3, 130.7, 132.7, 134.6, 135.9, 136.5 (ArC); m/z
242 (Mþ, 6%), 157 (13), 156 (100), 153 (25), 152 (14), 141
(40), 115 (12), 87 (11), 69 (14), 57 (19); HRMS: Mþ, found
242.1665. C17H22O requires 242.1671.
4.3.6. (1R,2S,5R)-8-[(1-Hydroxy-2-isopropyl-5-methyl-
cyclohexyl)methyl]-1-naphthylacetic acid (11f). Pale
yellow oil; n (film) 3580–2760 (OH), 3040 (ArH), 1709
(CvO), 1090 cm21 (CO); dH 0.62 (3H, d, J¼6.4 Hz,
CH3CH), 0.73–0.94 (m, 3H), 0.97 (3H, d, J¼6.8 Hz,
CH3CH), 1.01 (3H, d, J¼6.8 Hz, CH3CH), 1.22–1.68 (5H,
m), 2.45–2.52 (1H, m), 2.77 (1H, d, J¼14.6 Hz,
CHHCOH), 4.06 (1H, d, J¼17.8 Hz, CHHCO2H), 4.12
(1H, d, J¼14.6 Hz, CHHCOH), 5.10 (1H, d, J¼17.8 Hz,
CHHCO2H), 7.11 (2H, br s, 2£OH), 7.27–7.40 (4H, m,
ArH), 7.75–7.80 (2H, m, ArH); dC 18.1 (CH3), 21.0 (CH2),
22.2 (CH3), 23.9 (CH3), 25.7 (CH), 27.6 (CH), 35.0 (CH2),
43.6 (CH2), 45.4 (CH2), 47.4 (CH2), 51.2 (CH), 76.1 (COH),
124.6, 124.7, 129.1, 130.1, 130.7, 131.9, 132.6, 133.3,
133.7, 135.8 (ArC), 177.9 (CO2H); m/z 336 (Mþ2H2O,
0.5%), 183 (14), 182 (100), 154 (27), 153 (35), 152 (11), 55
(14), 44 (12); HRMS: Mþ2H2O, found 336.2070.
C23H28O2 requires 336.2089. [a]2D0¼249.4 [c¼0.95
(CH2Cl2)].
4.3.2. 1,8-Bis(2-hydroxy-3,3-dimethylbutyl)naphthalene
(11b). Diastereomeric mixture. Colourless oil; n (film)
3550–3310 (OH), 3050, 3030 (ArH), 1070 cm21 (CO); dH
1.07 [18H, s, 2£(CH3)3C], 1.46 (2H, br s, 2£OH), 3.08–
3.28 (2H, m, 2£CHH), 3.36–3.40 (2H, m, 2£CHH), 3.60–
3.66 (2H, m, 2£CH), 7.32–7.47 (4H, m, ArH), 7.71–7.80
(2H, m, ArH); dC 26.0, 26.1 [(CH3)3C], 35.1, 35.2
[(CH3)3C], 39.2, 39.3 (CH2), 79.2, 81.0 (CHOH), 129.0,
129.1, 130.9, 131.1, 135.9, 136.1, 136.2, 136.8 (ArC); m/z
328 (Mþ, 0.2%), 242 (10), 167 (11), 165 (10), 156 (10), 155
(16), 154 (11), 153 (25), 141 (10), 57 (54); HRMS: Mþ,
found 328.2372. C22H32O2 requires 328.2402.
4.4. Cyclisation of diols 8 and hydroxyacid 11c
Isolation of compounds 12, 13 and 14. General procedure.
To a solution of the corresponding diols 8 and 11d, or
hydroxyacid 11c (0.1 mmol) in toluene (1.5 mL) a catalytic
4.3.3. 8-(2-Hydroxy-3,3-dimethylbutyl)-1-naphthylacetic
acid (11c). Pale yellow oil; n (film) 3490–2820 (OH), 3063,
3034 (ArH), 1706 (CvO), 1084 cm21 (CO); dH 1.02 [9H, s,
(CH3)3C], 3.12 (1H, dd, J¼16.85, 10.9 Hz, CHHCHOH),
3.36 (1H, dd, J¼16.85, 2.3 Hz, CHHCHOH), 3.47 (1H, dd,
J¼10.8, 2.3 Hz, CHOH), 4.19 (1H, d, J¼17.7 Hz,
CHHCO2H), 4.19 (1H, d, J¼17.7 Hz, CHHCO2H), 7.15
(2H, br s, 2£OH), 7.24–7.38 (4H, m, ArH), 7.72–7.80 (2H,
m, ArH); dC 25.9 [(CH3)3C], 35.2 [(CH3)3C], 37.8, 43.0
(CH2), 81.0 (CHOH), 124.8, 125.1, 129.1, 130.0, 130.2,
131.1, 132.0, 132.2, 135.7, 136.0 (ArC), 177.3 (CO2H); m/z
268 (Mþ2H2O, 10%), 183 (13), 182 (86), 181 (14), 165
(17), 155 (29), 154 (59), 153 (100), 152 (71), 151 (18), 57
(51); HRMS: Mþ2H2O, found 268.1464. C18H20O2
requires 268.1463.
˚
amount of p-toluenesulfonic acid (30 mg) and 4 A molecular
sieves(30 mg)wereadded.Thereactionmixturewasheatedat
110 8C for 2 h, then toluene was removed by distillation and
the resulting residue was hydrolysed with water (mL),
extracted with ethyl acetate (3£10 mL), dried over anhydrous
Na2SO4 and evaporated (15 Torr). The residue was purified by
column chromatography (silica gel, hexane/ethyl acetate) to
yield pure products. Yields and Rf values are given in Table 3
for compounds 12, but in the case of compounds 13 and 14,
yields are given in the text, their Rf, analytical and spectro-
scopic data for all compounds follow.
4.4.1. 3,3-Dimethyl-3,4-dihydro-1H-naphtho[1,8-cd]-
oxepine (12e). Pale yellow oil; n (film) 3054, 3035 (ArH),
1065 cm21 (CO); dH 1.34 [6H, s, (CH3)2], 3.32 (2H, s,
CH2CO), 5.03 (2H, s, CH2O), 7.16–7.40 (4H, m, ArH), 7.71
(2H, d, J¼8.4 Hz, ArH); dC 27.6 (CH3), 46.9 (CH2), 67.2
(CH2O), 77.5 (CO), 124.8, 124.9, 125.4, 125.5, 127.5,
128.2, 128.3, 135.1, 135.6, 139.6 (ArC); m/z 212 (Mþ,
11%), 165 (12), 154 (71), 153 (100), 152 (32), 151 (11);
HRMS: Mþ, found 212.1217. C15H16O requires 212.1201.
4.3.4. 1,8-Bis(1-hydroxycyclohexylmethyl)naphthalene
(11d). Colourless oil; n (film) 3580–3310 (OH), 3055,
3035 (ArH), 1055 cm21 (CO); dH 1.43–1.56 (22H, m,
10£CH2, 2£OH), 3.64 (4H, s, 2£ArCH2), 7.26–7.37 (4H,
m, ArH), 7.74 (2H, d, J¼8.0 Hz, ArH); dC 21.9, 25.9, 37.7,
49.1 (CH2), 72.4 (COH), 124.4, 129.2, 132.9, 133.7, 134.2,
135.9 (ArC); m/z 334 (Mþ2H2O, 0.5%), 236 (32), 221 (21),

F. Foubelo et al. / Tetrahedron 60 (2004) 4655–4662
4661
4.4.2. 3,3-Diethyl-3,4-dihydro-1H-naphtho[1,8-cd]-
oxepine (12f). Pale yellow oil; n (film) 3052, 3036 (ArH),
1071 cm21 (CO); dH 0.91 (6H, t, J¼7.5 Hz, 2£CH3), 1.51–
1.67 (4H, m, 2£CH2CH3), 3.27 (2H, s, CH2CO), 5.02 (2H, s,
CH2O), 7.16–7.22 (2H, m, ArH), 7.25–7.34 (2H, m, ArH),
7.67–7.73 (2H, m, ArH); dC 8.3 (CH3), 28.7 (CH2), 42.9
(CH2), 67.0 (CH2O), 82.0 (CO), 125.0, 125.2, 125.4, 127.4,
128.0, 128.2, 132.4, 135.1, 135.8, 139.7 (ArC); m/z 240
(Mþ, 5%), 155 (20), 154 (100), 153 (90), 152 (32), 57 (14);
HRMS: Mþ, found 240.1517. C17H20O requires 240.1514.
3.09 (1H, d, J¼16.5 Hz, ArCHH), 3.41 (1H, br s, OH), 5.33
(1H, br s, ArCHvC), 7.22–7.25 (2H, m, ArH), 7.35–7.41
(2H, m, ArH), 7.66 (2H, d, J¼8.1 Hz, ArH); dC 21.8, 22.0,
22.5, 23.3, 25.5, 26.5, 35.5, 35.9, 36.5 (CH2), 77.2 (COH),
124.7, 124.9, 125.3, 125.8, 129.6, 133.0, 134.5, 138.3, 140.1
(CvCH, ArC); m/z 316 (Mþ2H2O, 29), 234 (15), 233 (60),
221 (24), 220 (100), 219 (18), 203 (14), 202 (10), 191 (30),
179 (38), 178 (38), 166 (11), 165 (48), 153 (22), 152 (17), 81
(24), 79 (10), 67 (11), 55 (23); HRMS: Mþ2H2O, found
316.2183. C24H28 requires 316.2191.
4.4.3. 3,3-Dipenthyl-3,4-dihydro-1H-naphtho[1,8-cd]-
oxepine (12g). Colourless oil; n (film) 3050, 3032 (ArH),
1066 cm21 (CO); dH 0.86–0.90 (6H, t, J¼6.8 Hz, 2£CH3),
1.27–1.56 (16H, m, 8£CH2), 3.27 (2H, s, CH2CO), 5.02
(2H, s, CH2O), 7.14–7.23 (2H, m, ArH), 7.30–7.35 (2H, m,
ArH), 7.67–7.71 (2H, m, ArH); dC 14.0 (CH3), 22.6, 23.6,
32.4, 36.8, 43.7(CH2), 66.9 (CH2O), 81.6 (CO), 125.0,
125.2, 125.5, 127.4, 128.0, 128.1, 132.5, 135.1, 135.8, 139.8
(ArC); m/z 324 (Mþ, 2%), 155 (25), 154 (100), 153 (44),
152 (13); HRMS: Mþ, found 324.2448. C23H32O requires
324.2453.
Acknowledgements
´
This work was generously supported by the Direccion
General de Ensen˜anza Superior (DGES) of the current
Spanish Ministerio de Ciencia y Tecnologıa (MCyT; grant
no. BQU2001-0538) and the Generalitat Valenciana
(projects no. GV01-443 and CTIDIB/2002/318). B. M.
thanks the MCyT for a scholarship.
´
4.4.4. 3-Cyclohexyl-3,4-dihydro-1H-naphtho[1,8-cd]-
oxepine (12h). Pale yellow oil; n (film) 3052, 3035
(ArH), 1064 cm21 (CO); dH 1.27–1.76 (10H, m, 5£CH2),
3.29 (2H, s, CH2CO), 5.05 (2H, s, CH2O), 7.17–7.36 (4H,
m, ArH), 7.68–7.72 (2H, m, ArH); dC 22.4, 25.9, 36.1, 45.5
(CH2), 66.7 (CH2O), 78.0 (CO), 124.9, 125.3, 125.4, 127.4,
128.0, 128.1, 132.4, 135.1, 135.4, 140.0 (ArC); m/z 252
(Mþ, 5%), 155 (15), 154 (100), 153 (63), 152 (21); HRMS:
Mþ, found 252.1537. C18H20O requires 252.1514.
References and notes
1. For a review, see: Boudier, A.; Bromm, L. O.; Lotz, L.;
Knochel, P. Angew. Chem. Int. Ed. 2000, 39, 4414–4435.
´
2. For reviews, see: (a) Najera, C.; Yus, M. Trends Org. Chem.
´
1991, 2, 155–181. (b) Najera, C.; Yus, M. Recent Res. Dev.
´
Org. Chem. 1997, 1, 67–96. (c) Najera, C.; Yus, M. Curr. Org.
´
Chem. 2003, 7, 867–926. (d) Najera, C.; Sansano, J. M.; Yus,
M. Tetrahedron 2003, 59, 9255–9303. (e) Chinchilla, R.;
4.4.5. 3-Cyclooctyl-3,4-dihydro-1H-naphtho[1,8-cd]-
oxepine (12i). Colourless oil; n (film) 3051, 3035 (ArH),
1054 cm21 (CO); dH 1.52–1.68 (14H, m, 7£CH2), 3.27
(2H, s, CH2CO), 5.00 (2H, s, CH2O), 7.18 (2H, t, J¼6.6 Hz,
ArH), 7.26–7.36 (2H, m, ArH), 7.70 (2H, d, J¼8.4 Hz,
ArH); dC 22.4, 25.3, 28.4, 33.9, 44.6 (CH2), 66.3 (CH2O),
82.0 (CO), 124.9, 125.3, 125.4, 127.4, 128.05, 128.1, 132.4,
135.1, 135.7, 139.9 (ArC); m/z 280 (Mþ, 3%), 155 (16), 154
(100), 153 (62), 152 (22), 55 (19); HRMS: Mþ, found
280.1812. C20H24O requires 280.1827.
´
Najera, C.; Yus, M. Chem. Rev. 2004, in press.
3. (a) Wakefield, B. J. Organolithium methods; Academic:
´
London, 1988. (b) Sapse, A. M.; von Rague Schleyer, P.
Lithium chemistry: a theoretical and experimental overview;
Wiley: New York, 1995. (c) Gray, M.; Tinkel, M.; Sniekus, V.
Comprehensive organometallic chemistry II; Abel, E. W.,
Stone, F. G. A., Wilkinson, G., McKillop, A., Eds.; Pergamon:
Oxford, 1995; Vol. 11, pp 1–92. (d) Clayden, J. Organo-
lithiums: selectivity for synthesis; Pergamon: Oxford, 2002.
4. For reviews, see: (a) Yus, M.; Foubelo, F. Rev. Heteroatom.
Chem. 1997, 17, 73–107. (b) Yus, M.; Foubelo, F. Targets
Heterocycl. Syst. 2002, 6, 136–171. (c) Yus, M. Pure Appl.
Chem. 2003, 75, 1453–1475.
4.4.6. 4-(tert-Butyl)-1,2,4,5-tetrahydronaphtho[1,8-
de]oxocin-2-one (13). Pale yellow oil; Rf 0.50 (hexane/
ethyl acetate: 2/1); n (film) 3055, 3030 (ArH), 1721 (CvO),
1065 cm21 (CO); dH 1.12 [9H, s, (CH3)3C], 3.46 (1H, dd,
J¼15.9, 6.2 Hz CHHCH), 3.88 (1H, dd, J¼15.9, 7.8 Hz,
CHHCH), 4.29–4.34 (2H, m, CHO, CHHCO), 4.47 (d, 1H,
J¼13.9 Hz, CHHCO), 7.37–7.48 (4H, m, ArH), 7.76–7.82
(2H, m, ArH); dC 26.2 [(CH3)3C], 36.8 [(CH3)3C], 37.0,
44.8 (CH2), 88.7 (CHO), 125.5, 125.7, 128.8, 129.5, 129.6,
130.6, 130.7, 132.2, 134.1, 135.2 (ArC), 171.7 (CO2); m/z
268 (Mþ, 5%), 183 (15), 182 (70), 181 (15), 165 (17), 155
(32), 154 (84), 153 (100), 152 (69), 76 (12), 57 (52); HRMS:
Mþ, found 268.1483. C18H18O2 requires 268.1463.
5. For reviews, see: (a) Yus, M. Chem. Soc. Rev. 1996, 25,
´
155–161. (b) Ramon, D. J.; Yus, M. Eur. J. Org. Chem. 2000,
225–237. (c) Yus, M. Synlett 2001, 1197–1205. (d) Yus, M.;
´
´
Ramon, D. J. Latv. J. Chem. 2002, 79–92. (e) Ramon, D. J.;
Yus, M. Rev. Cubana Quim. 2002, 14, 75–115. (f) Yus, M. In
The chemistry of organolithium compounds; Rappoport, Z.,
Marek, I., Eds.; Wiley: Chichester, 2004; Chapter 11.
´
6. For polymer versions of this reaction, see: (a) Gomez, C.;
Ruiz, S.; Yus, M. Tetrahedron Lett. 1998, 39, 1397–1400.
´
(b) Gomez, C.; Ruiz, S.; Yus, M. Tetrahedron 1999, 55,
´
7017–7026. (c) Yus, M.; Candela, P.; Gomez, C. Tetrahedron
2002, 58, 6207–6210. (d) Arnauld, T.; Barret, A. G. M.;
Hopkins, B. T. Tetrahedron Lett. 2002, 43, 1081–1083.
7. For mechanistic studies, see: (a) Yus, M.; Herrera, R. P.;
Guijarro, A. Tetrahedron Lett. 2001, 42, 3455–3458. (b) Yus,
M.; Herrera, R. P.; Guijarro, A. Chem. Eur. J. 2002, 8,
2574–2584. (c) Herrera, R. P.; Guijarro, A.; Yus, M.
4.4.7. 1-Cyclohexylidenemethyl-8-(1-hydroxycyclohexyl-
methyl)naphthalene (14). Pale yellow oil; Rf 0.79 (hexane/
ethyl acetate: 10/1); n (film) 3570–3270 (OH), 3050, 3030
(ArH), 1060 cm21 (CO); dH 1.05–1.64 (18H, m, 9£CH2),
1.84–1.96 (2H, m, CH2), 2.98 (1H, d, J¼16.5 Hz, ArCHH),

4662
F. Foubelo et al. / Tetrahedron 60 (2004) 4655–4662
Tetrahedron Lett. 2003, 44, 1309–1312. (d) Herrera, R. P.;
Guijarro, A.; Yus, M. Tetrahedron Lett. 2003, 44, 1313–1316.
8. For the last paper on this topic from our laboratory, see:
41, 1589–1592. (h) Pastor, I. M.; Yus, M. Tetrahedron 2001,
57, 2365–2370. (i) Pastor, I. M.; Yus, M. Tetrahedron 2001,
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