Reductive ring opening of dihydrodibenzothiepine and dihydrodinaphtho- oxepine and -thiepine

Article abstract of DOI:10.1016/j.tet.2005.07.042

The 4,4′di-tert-butylbiphenyl (DTBB)-catalysed lithiation of dihydrodibenzothiepine (1) at -78°C for 30 min followed by reaction with a carbonyl compound [^tBuCHO, Ph(CH₂)₂CHO, PhCHO, (n-C₅H₁₁)₂

Full text of DOI:10.1016/j.tet.2005.07.042

Tetrahedron 61 (2005) 9082–9096
Reductive ring opening of dihydrodibenzothiepine and
dihydrodinaphtho-oxepine and -thiepine
†
Francisco Foubelo, Benjamın Moreno, Tatiana Soler 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 31 March 2005; revised 7 July 2005; accepted 14 July 2005
Available online 3 August 2005
Dedicated to Professor Rafael Suau on the occasion of his 60th birthday
Abstract—The 4,40di-tert-butylbiphenyl (DTBB)-catalysed lithiation of dihydrodibenzothiepine (1) at K78 8C for 30 min followed by
reaction with a carbonyl compound [tBuCHO, Ph(CH2)2CHO, PhCHO, (n-C5H11)2CO, (CH2)5CO, (CH2)7CO, (K)-menthone] at the same
temperature leads, after hydrolysis with 3 M hydrochloric acid, to sulphanyl alcohols 2. If after addition of a carbonyl compound as the first
electrophile [Me2CO, (CH2)5CO, (K)-menthone], the resulting dianion of type II is allowed to react at room temperature for 30 min, a
second lithiation takes place to give an intermediate of type III, which by reaction with a second electrophile [Me2CO, Et2CO, (CH2)5CO,
ClCO2Et], yields, after hydrolysis, difunctionalised byphenyls 4. The cyclisation of the sulphanyl alcohol 2c under acidic conditions yields
the eight-membered sulphur containing heterocycle 3. The lithiation of dihydrodinaphthoheteroepines 7 and 10 with 2.2 equiv of lithium
t
naphthalenide in THF at K78 8C followed by reaction with different electrophiles [H2O, D2O, BuCHO, Me2CO, Et2CO, (CH2)4CO,
(CH2)5CO] at the same temperature leads, after hydrolysis, to unsymmetrically 2,20-disubstituted binaphthyls 9 and 12, respectively. When
the lithiation is performed with an excess of lithium in the presence of a catalytic amount of DTBB (10% molar), a double reductive cleavage
takes place to give the dianionic intermediate VII, which by reaction with different electrophiles [H2O, Me2CO, Et2CO, (CH2)4CO,
(CH2)5CO], followed by hydrolysis with water, yields symmetrically 2,20-disubstituted binaphthyls 8 and 11. In the case of starting from (R)-
or (S)-dihydrodinaphthoheteroepines 7 and 10, these methodologies allow us to prepare enantiomerically pure compounds 8, 11 and 12.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
chlorinated or brominated derivatives; Scheme 1, Method
A), (b) an oxygen– or sulphur–lithium exchange (Scheme 1,
Method B), or (c) a mercury– or tin–lithium transmetalla-
tion (Scheme 1, Method C) have been successfully used to
generate functionalised organolithium compounds, being
necessary to deprotonate the YH functionality before the
Among organometallic intermediates in synthetic organic
chemistry, organolithium compounds1 have become of
routine use due to their high reactivity even under mild
reaction conditions. When the organolithium compound
bears a functional group, this type of intermediates2 are
more interesting from a synthetic point of view because in
their reaction with an electrophile, the functionality is
transferred to this reagent, so polyfunctionalised molecules
can be prepared directly, creating at the same time in
general a new carbon–carbon bond. Some general pro-
cedures to prepare organolithium compounds are also
applicable to the corresponding functionalised systems,
namely (a) a halogen–lithium exchange (mainly from
Keywords: DTBB-catalysed lithiation; Sulphur–lithium exchange; Diben-
zothiepine; Dinaphthothiepine; Electrophilic substitution.
*
Corresponding author. Tel.: C34 965 909672; fax: C34 965 903549;
e-mail: foubelo@ua.es
†
´
Author responsible for X-ray studies. Present address: Servicios Tecnicos
de Investigacion, Planta Cero, Facultad de Ciencias, Universidad de
´
Alicante, Apdo. 99, 03080 Alicante, Spain.
Scheme 1.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.042

F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
9083
binaphthyls which are mainly prepared by metal-catalysed
coupling of aryl halides, triflates or stannanes with
appropriate counter pairs,10 as well as by nucleophilic
opening of dinaphthoazepinium11 and thiepinium12 salts.
2. Results and discussion
Scheme 2. Reagents and conditions: (i) Li, DTBB (5 mol %), THF,
K78 8C, 1 h; (ii) R1R2COZtBuCHO, Ph(CH2)2CHO, PhCHO, Me2CO,
(n-C5H11)2CO, (CH2)5CO, (CH2)7CO, (K)-menthone, K78 8C; (iii) HCl–
H2O, K78 8C to rt.
The reaction of 5,7-dihydrodibenzo[c,e]thiepine (1) with an
excess of lithium and a catalytic amount of 4,40-di-tert-
butylbiphenyl (DTBB; 5 mol%) in THF at K78 8C followed
by
treatment
with
a
carbonyl
compound
[R1R2COZtBuCHO, Ph(CH2)2CHO, PhCHO, Me2CO,
(n-C5H11)2CO, (CH2)5CO, (CH2)7CO, (K)-menthone] at
the same temperature led, after acid hydrolysis at K78 8C to
room temperature, to the corresponding hydroxy thiols 2
(Scheme 2 and Table 1). For prostereogenic carbonyl
compounds, such as pivalaldehyde, benzaldehyde,
3-phenylpropanal and (K)-menthone, the corresponding
1:1 mixture of diastereomers was obtained (Table 1, entries
1, 2, 3 and 8, respectively, and footnote c). In the case of
using (K)-menthone as the electrophile, the attack of the
nucleophile took place almost exclusively from the less
hindered face of the carbonyl group13 to give compound 2h
(Scheme 2).
lithiation step. On the other hand, the above mentioned
procedures are not very efficient from an atom economy
point of view.3 In order to solve this last disadvantage, in the
last few years a new methodology has been introduced for
the generation of functionalised organolithium compounds
consisting in a reductive opening of heterocycles (Scheme 1,
Method C).4 Since in many cases, the corresponding
organolithium intermediate is not stable at room tempera-
ture, it is necessary to perform the lithiation at low
temperature using, for that purpose, a high reactive
lithiation agent.5 For this reason, in the last few years our
group has intensively worked in the development of an
arene-catalysed lithiation,6 which, among other appli-
cations,7 can be used to the reductive opening of
heterocycles.8 In this paper we describe the application of
this methodology to the ring opening of benzo- and
naphtho-condensed sulphur-containing seven-membered
rings, comparing in the last case the reactivity of the
sulphur- and the oxygen-containing heterocycle.9 The
reaction of the resulting organolithium compounds with
electrophiles leads to funtionalised biphenyls and
Concerning possible intermediates involved in the
reaction shown in Scheme 2, in the lithiation step, a
reductive opening of the heterocycle takes place14 giving
intermediate I, which by reaction with the carbonyl
compound R1R2CO used as electrophile gives the second
intermediate II, precursor of products 2 by final acidic
hydrolysis.
Table 1. Preparation of compounds 2
Entry
R1R2CO
Producta
No.
R1
R2
Yield (%)b
1
2
3
4
5
6
7
8
tBuCHO
Ph(CH2)2CHO
PhCHO
Me2CO
(n-C5H11)2CO
(CH2)5CO
(CH2)7CO
(K)-Menthone
2a
2b
2c
2d
2e
2f
H
H
H
Me
tBu
Ph(CH2)2
Ph
Me
n-C5H11
71c
75c
82c
50
76
72
n-C5H11
(CH2)5
(CH2)7
—
2g
2h
47
55
d
a All products 2 wereO95% pure (GLC and/or 300 MHz 1H NMR).
b Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting material 1.
c Isolated as a ca. 1:1 diastereomeric mixture (NMR).
d See Scheme 2.
Scheme 3. Reagents and conditions: (i) H3PO4 (85%), PhMe, 110 8C.

9084
F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
one yielded almost exclusively the diastereomer 4g,
resulting from the attack of the organolithium intermediate
I to the first electrophile [(K)-menthone] at the less
hindered face, as it was above mentioned for compound
2h (Scheme 4, Table 2, entry 7).13
Compound 2 can be easily cyclised under acidic conditions
as is exemplified for the benzaldehyde derivative 2c.
Treatment of this compound with 85% phosphoric acid
under toluene reflux yielded the corresponding eight-
membered ring 3 in 74% isolated yield, whose structure
was determined by X-ray crystallography (Scheme 3).15
Compounds of type 4, especially those derived from
carbonyl compounds, could be adequate starting materials
for cyclisation processes (see above for compound 3).
However, treatment of compound 4e (derived from
cyclohexanone) with 85% phosphoric acid under toluene
reflux gave the corresponding diolefin 5 in 62% isolated
yield, without detection of any cyclisation products
(Scheme 5). In addition, hydroxyl ester 4f gave also the
dehydration product 6 in 50% yield upon treatment with a
catalytic amount of p-toluenesulphonic acid under toluene
reflux, also without formation of the desired lactone
(Scheme 5).
Starting material 1 was easily prepared from commercially
available 2,20-bis(bromomethyl)biphenyl by treatment with
sodium sulphide in DMF at 100 8C in almost quantitative
yield.12
From a synthetic point of view, an interesting variant of the
lithiation of the starting material 1 results when a second
electrophile is introduced in the molecule. It happens when
after the generation of the intermediate II instead of
hydrolysis a second lithiation took place at temperatures
ranging between K78 8C and room temperature. By this
treatment, a second carbon–sulphur bond cleavage took
place, so a new organolithium intermediate III was
generated, which by reaction with a second electrophile
{EZR3R4CO [Me2CO, Et2CO, (CH2)5CO], ClCO2Et} at
K78 8C gave, after hydrolysis, the expected products 4
(Scheme 4 and Table 2). Before the final hydrolysis
intermediates IV (for R3R4CO) or V (for ClCO2Et) are
probably involved in the process. Also here, the use of (K)-
menthone as the first electrophile and acetone as the second
Scheme 4. Reagents and conditions: (i) Li, DTBB (5 mol %), THF,
K78 8C, 1 h; (ii) R1R2COZMe2CO, (CH2)5CO, (K)-menthone, K78 8C;
(iii) K78 8C to rt; (iv) EZMe2CO, Et2CO, (CH2)5CO, ClCO2Et, K78 8C;
(v) H2O, K78 8C to rt.
Scheme 5. Reagents and conditions: (i) H3PO4 (85%), PhMe, 110 8C; (ii)
TsOH (cat.), PhMe, 110 8C.
Table 2. Preparation of compounds 4
Entry
R1R2CO
Electrophile E
Producta
No.
R1
R2
X
Yield (%)b
1
2
3
4
5
6
7
Me2CO
Me2CO
Me2CO
ClCO2Et
Me2CO
4a
4b
4c
4d
4e
4f
Me
Me
Me
Me
Me2COH
CO2Et
Me2COH
Et2COH
(CH2)5COH
CO2Et
40
36
45
46
38
41
35
(CH2)5CO
(CH2)5CO
(CH2)5CO
(CH2)5CO
(K)-Menthone
(CH2)5
(CH2)5
(CH2)5
(CH2)5
Et2CO
(CH2)5CO
ClCO2Et
Me2CO
c
—
4g
1
a All products 4 wereO95% pure (GLC and/or 300 MHz H NMR).
b Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting material 1.
c Isolated as a ca. 1:1 diastereomeric mixture (NMR); see Scheme 4.

F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
9085
THF at K78 8C, followed by reaction with the same
electrophile mentioned in Scheme 6 at the same temperature
gave, after hydrolysis under acidic conditions, the corre-
sponding monosubstituted products 9 (Scheme 7 and
Table 4, entries 1–4). In this case, and due to the less
energic reduction conditions, the first lithiation product VI
reacts with the electrophile giving an intermediate of type
IX, which by hydrolysis afforded sulphanyl alcohols 9.
Scheme 6. Reagents and conditions: (i) Li, DTBB (10 mol %), THF,
K78 8C; (ii) R1R2COZMe2CO, Et2CO, (CH2)4CO, (CH2)5CO, K78 8C;
(iii) HCl–H2O, K78 8C to rt.
Table 3. Preparation of compounds 8 and 11
Entry
Starting material
Electrophile E
Producta
No.
R1
R2
Yield (%)b
1
2
3
4
5
6
7
7
7
7
10
10
Me2CO
Et2CO
(CH2)4CO
(CH2)5CO
H2O
8a
8b
8c
8d
11
8a
Me
Et
Me
Et
52
57
31
38
96
48
(CH2)4
(CH2)5
—
c
Me2CO
Me
Me
1
a All products 8 and 11 wereO95% pure (GLC and/or 300 MHz H NMR).
b Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting material 7 or 10.
c See Scheme 8.
In the second part of this study, we will consider the
corresponding dinaphtho derivatives as a heterocycle to be
reductively opened, hoping that in this case functionalised
chiral binaphthyls could be accessible using this
methodology.
The reaction of 4,5-dihydro-3H-dinaphtho[2,1-c:10,20-e]
thiepine (7) with an excess of lithium and a catalytic
amount of DTBB, under the same reaction conditions shown
on Scheme 2 (THF, K78 8C), gave, after treatment with a
carbonyl compound as electrophile [R1R2COZMe2CO,
Et2CO, (CH2)4CO, (CH2)5CO] at the same temperature, and
final hydrolysis, the corresponding compounds 8, resulting
from a double condensation at both benzylic positions
(Scheme 6 and Table 3, entries 1–4). In contrast to the
behaviour observed for the starting material 1, in the case of
compound 7 it seems that here, after the first reductive ring
opening, the first organolithium intermediate VI suffers a
rapid second lithiation (even in the presence of the
electrophile: Barbier type reaction conditions) to give
the dilithium compound VII, which can survive under the
essayed conditions until the addition of the electrophile, so
giving the corresponding dialkoxide VIII, precursor of the
obtained products 8.
Different attempts to perform a second lithiation of
intermediate IX under catalytic conditions failed, so in
contrast to the results shown in Scheme 4 for the starting
material 1 we were not able to introduce two different
electrophiles at both benzylic positions (through an
intermediate of type X). For this reason we decide to
investigate for the first time, the behaviour of the
corresponding oxygen containing dinaphtho derivative 10
in an arene-promoted lithiation with concomitant ring
opening.
Actually, we found a similar behaviour starting from
compound 10 than from its sulphur analogue 7 (see
Schemes 6 and 7). Thus, using the DTBB-catalysed
lithiation (Scheme 6), as for compound 7, and using water
In order to avoid the mentioned second lithiation we used
the less active stoichiometric version of the arene-promoted
lithiation.16 Thus, treatment of the starting material 7 with a
THF solution of lithium naphthalene (1:2.2 molar ratio) in
Scheme 7. Reagents and conditions: (i) LiC10H8 (2.2 equiv), THF,
K78 8C; (ii) R1R2COZMe2CO, Et2CO, (CH2)4CO, (CH2)5CO, K78 8C;
(iii) HCl–H2O, K78 8C to rt.

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F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
Table 4. Preparation of compounds 9 and 12
Entry
Starting material
Electrophile E
Producta
No.
R1
R2
Yield (%)b
1
2
3
4
5
6
7
8
9
10
7
7
7
7
10
10
10
10
10
10
Me2CO
Et2CO
(CH2)4CO
(CH2)5CO
H2O
9a
9b
9c
9d
Me
Et
Me
Et
64
56
53
36
81
68c
48d
38
51
48
(CH2)4
(CH2)5
12a (XZH)
12b (XZD)
12c (XZtBuCHOH)
12d (XZMe2COH)
12e (XZEt2COH)
12f [XZ(CH2)5COH]
—
—
—
—
—
—
—
—
—
—
—
—
D2O
tBuCHO
Me2CO
Et2CO
(CH2)5CO
1
a All products 9 and 12 wereO95% pure (GLC and/or 300 MHz H NMR).
b Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting material 7 or 10.
c A ca. 70% deuterium incorporation was obtained (13C NMR).
d A ca. 1:1 diastereomeric mixture was obtained and separated by column chromatography (silica gel, hexane/ethyl acetate).
or acetone as electrophiles, compounds 11 and 8a were,
respectively, isolated (Scheme 8 and Table 3, entries 5 and
6). In addition, using the stoichiometric version of the
naphthalene-promoted lithiation (Scheme 7), and using
starting materials 7 and 10 in order to prepare chiral
products of type 8, 9, 11 and 12. Scheme 9 summarizes the
preparation of those heterocycles: commercially available
(R)- or (S)-binaphthol 14 (O99% ee) was treated with triflic
anhydride and pyridine in CH2Cl2 at K78 8C to yield the
corresponding bistriflate 15, which was then coupled with
methylmagnesium bromide in the presence of a catalytic
amount of (PPh3)2NiCl2 under ether reflux to yield the
corresponding chiral dimethyl derivative 11.20 After double
radical bromination with NBS catalyzed by AIBN in CCl4 at
80 8C to give the dibromoderivative 16, it was transformed
into the final compounds 7 and 10 as it was above mentioned
for the corresponding achiral systems. Alternatively,
compound 10 can be prepared from the dibromo compound
16 by first acetate nucleophilic substitution under PTC
reaction conditions to give the diacetate 17, followed by
basic hydrolysis to afford the diol 18 and final cyclisation
through a p-toluenesulphonic acid-promoted azeotropic
dehydration21 (Scheme 9).
t
different electrophiles [EZH2O, D2O, BuCHO, Me2CO,
Et2CO, (CH2)5CO] under the same reaction conditions than
for compound 9, the expected compounds 12 were isolated
(Scheme 8 and Table 4, entries 5–10).
Whereas possible intermediates involved in Scheme 8
would be successively XI, VII, X and VIII for compounds
8a, for compound 12 intermediates XI and XII (for
EZR1R2CO) are probably involved in their preparation.
Once chiral compound (R)-7 and (S)-7 or (R)-10 and (S)-10
were prepared, they were submitted to the same protocol
used for their racemic mixtures as shown in Schemes 6 and
8. Thus, the expected compounds 8, 11 and 12 were isolated
in high optical purity, the same than the starting materials,
so no racemisation occurred during the whole process of the
tandem lithiation-SE reaction. Optical purities of com-
pounds 7 and 10 were assigned on the basi0s of the starting
commercially available (R)- and (S)-1,1 -bi-2-naphthols
(Aldrich, 99% ee). In order to confirm the optical purity of
the reaction products, compounds (S)-12a and (S)-12f were
analysed by HPLC with a Daicel Chiralpack AS column,
along with racemic 12a and 12f. In both cases a 98% ee was
obtained (lZ254 nm, n-hexane/2-propanol, 1.0 mL/min;
12a trZ7.73 and 10.00 min; 12f trZ25.70 and 29.69 min).
Starting materials 7 and 10 were prepared in ca. 40% overall
yield from commercially available 1-bromo-2-methyl-
naphthalene (13) following the reaction sequence: (i)
homocoupling of its corresponding Grignard reagent in
the presence of a catalytic amount of (PPh3)2NiCl2 to give
compound 11;17 (ii) treatment with N-bromosuccinimide i0n
the presence of AIBN to give 2,20-bis(bromomethyl)-1,1 -
binaphthyl (16);18 (iii) reaction of the dibromo derivative
with sodium sulphide in DMF,12 or 5 M NaOH in dioxane in
the presence of 2,6-lutidine,19 to yield compound 7 or 10,
respectively, (Scheme 9).
In the last part of this work, we study the use of chiral
Scheme 8. Reagents and conditions: (i) Li, DTBB (10 mol %), THF, K78 8C; (ii) EZH2O, Me2CO, K78 8C; (iii) H2O, K78 8C to rt; (iv) LiC10H8 (2.2 equiv),
THF, K78 8C; (v) EZH2O, D2O, tBuCHO, Me2CO, Et2CO, (CH2)5CO, K78 8C.

F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
9087
Scheme 9. Reagents and conditions: (i) Mg, Et2O–PhH (1/1), 20 8C, 5 h; (ii) 13, (Ph3P)2NiCl2 (cat.), 40 8C, 15 h;(iii) (CF3SO2)2O, pyridine, CH2Cl2, K78 8C
to rt; (iv) MeMgBr (2.2 equiv), (Ph3P)2NiCl2 (cat.), Et2O, 0 8C to reflux; (v) NBS (2.5 equiv), AIBN (cat.), CCl4, 80 8C; (vi) Na2S$9H2O, DMF, reflux (for YZ
S) or 5 M NaOH, 2,6-lutidine, 80 8C (for YZO); (vii) KOAc, TBAB, DMF, 80 8C; (viii) 5 M NaOH, dioxane, 100 8C; (ix) TsOH (cat.), PhH, 80 8C.
In order to select representative examples, we chose the
starting materials (R)-7 or (S)-7 for preparing chiral products 8
and 11 (see Scheme 6; see also Scheme 8 for the structure of
compound 11) and (R)-10 or (S)-10 for achieving compounds
12 (see Scheme 8). The results were consistent and are
summarised in Table 5. For the case of using the starting
molecule (S)-10 and pivalaldehyde as electrophile a ca. 1:1
mixture of diastereomers was obtained, both of them being
separated and purified by column chromatography and
analysed (Table 5, entry 9 and footnote c). However, we are
not able to assign the absolute configuration of the newly
created stereocentre at both alcohol moieties.
Table 5. Preparation of chiral compounds 8, 11 and 12
Entry
Starting material
Electrophile E
Producta
No.
[a]rDt, c (solvent)
Yield (%)b
1
2
3
4
5
6
7
8
9
(R)-7
(S)-7
(R)-7
(S)-7
(R)-7
(S)-7
(R)-10
(S)-10
(S)-10
H2O
H2O
(R)-11c
(S)-11c
(R)-8b
(S)-8b
(R)-8d
K22.0, 0.37 (CH2Cl2)
C21.2, 0.74 (CH2Cl2)
K82.9, 1.38 (CH2Cl2)
C83.7, 1.40 (CH2Cl2)
K2.1, 1.51 (CH2Cl2)
C2.2, 1.69 (CH2Cl2)
K5.5, 1.00 (CHCl3)
C5.8, 1.00 (CHCl3)
K43.1, 1.65 (CH2Cl2)
K113.0, 1.40 (CH2Cl2)
C81.5, 1.00 (CH2Cl2)
K79.5, 0.76 (CH2Cl2)
C70.0, 0.80 (CH2Cl2)
K76.0, 0.91 (CH2Cl2)
91
85
39
42
38
40
80
78
13e
11e
46
28
49
46
Et2CO
Et2CO
(CH2)5CO
(CH2)5CO
H2O
(S)-8d
(S)-12ad
(R)-12ad
(R)-12cd
H2O
tBuCHO
10
11
12
13
(R)-10
(S)-10
(R)-10
(S)-10
Et2CO
Et2CO
(CH2)5CO
(CH2)5CO
(S)-12ed
(R)-12ed
(S)-12fd
(R)-12fd
a All products 8, 11 and 12 wereO95% pure (GLC and/or 300 MHz 1H NMR).
b Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting material 7 or 10.
c For structure of compound 11, see Scheme 8.
d For the meaning of X see Table 4.
e Both diastereomers were isolated and purified by column chromatography (silica gel, hexane/ethyl acetate). We do not know the absolute configuration of the
newly created stereocentres at both alcohol moieties.

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F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
3. Conclusion
evaporated (15 Torr). The resulting residue was then
recrystallised (hexane) to yield pure compound 1 (2.0 g,
94% yield). Physical and spectroscopic data follow.
In conclusion, we have described here the use of
dihydrodibenzo- or dihydrodinaphthothiepine as starting
materials for the reductive ring opening using an arene-
promoted lithiation, so either functionalised organolithium
compounds or dilithium intermediates are generated, which
by reaction with electrophiles give polyfuncionalised
biphenyls or binaphthyls. In the second case, the oxygenated
analogue has also been studied in order to compare both
systems. The lithiation can be directed in the case of the
binaphtyl derivatives using either the stoichiometric or the
catalytic version of the arene-promoted lithiation. For
binaphthyl products, the chiral version of the reaction is
also studied, so chiral functionalised biaryl compounds are
prepared without observing any racemisation during the
tandem process lithiation-SE reaction. Finally, the reductive
opening of the binaphthyl derivatives takes place under
milder reaction conditions than in the case of the
corresponding biphenyl derivative. We think that this is
due to the lower energy of LUMO’s of naphthyl derivatives,
so electron transfer from the reducing reagent to the
substrates takes place easier.6g–k
4.2.1. 5,7-Dihydrodibenzo[c,e]thiepine (1). Pale yellow
solid; mp 95–96 8C (hexane) (lit. mp 89–90 8C);22 Rf 0.63
(hexane/ethyl acetate: 10:1); n (KBr) 3050, 3025 cmK1
(ArH); dH 3.27 (2H, d, JZ12.2 Hz, 2!CHH), 3.46 (2H, d,
JZ12.2 Hz, 2!CHH), 7.26–7.39 (8H, m, ArH); dC 31.3
(CH2), 127.7, 128.3, 128.4, 128.5, 135.6, 140.5 (ArC); m/z
212 (MC, 100%), 211 (28), 197 (19), 184 (21), 179 (67),
178 (53), 166 (37), 165 (61), 152 (15), 89 (26), 76 (20), 63
(13), 51 (10).
Isolation of compounds 7. General procedure. A mixture of
2,20-bis(bromomethyl)-1,10-binaphthyl (16) (2.20 g,
5.0 mmol) [easily prepared from 1-bromo-2-methyl-
bynaphthalene (13)17,18 for racemic 7 or from (R)- or (S)-
binaphthol (14)20 in the case of enantiomerically pure
derivatives 7] and sodium sulphide nonahydrate (3.55 g,
15.0 mmol) in DMF (20 mL) was stirred at 100 8C for 1 h.
After that, the reaction mixture was allowed to cool down to
room temperature, hydrolysed with water (200 mL),
extracted with ethyl acetate (3!200 mL) and the organic
layer was dried over anhydrous sodium sulphate and
evaporated (15 Torr). The resulting residue was then
recrystallised (acetone) to yield pure compounds 7
[1.28 g, 82% yield in the case of (G)-7]. Physical and
spectroscopic data follow.
4. Experimental
4.1. General
All reactions were carried out under an atmosphere of argon
in oven-dried glassware. All reagents were commercially
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 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
4.2.2. (G)-4,5-Dihydro-3H-dinaphtho[2,1-c:10,20-e]thie-
pine (7). Brown solid; mp 210–212 8C (hexane) (lit. mp
216–218 8C);12 Rf 0.83 (hexane/ethyl acetate: 2:1); n (KBr):
3049, 3008 cmK1 (ArH); dH 3.41 (4H, s, 2!CH2), 7.23–
7.30 (4H, m, ArH), 7.41–7.46 (2H, m, ArH), 7.93 (2H, dd,
JZ8.4, 3.6 Hz, ArH); dC 31.9 (CH2), 125.1, 125.7, 126.1,
126.4, 127.8, 128.9, 131.2, 132.5, 133.2, 133.4 (ArC); m/z
312 (MC, 100), 297 (15), 279 (79), 278 (27), 277 (37), 276
(43), 266 (49), 265 (50), 264 (24), 263 (39), 148 (21), 139
(26), 138 (82), 133 (32), 131 (85), 126 (17), 125 (25), 119
(20).
4.2.3. (R)-4,5-Dihydro-3H-dinaphtho[2,1-c:10,20-e]thie-
pine [(R)-7]. Physical and spectroscopic data were found
to be the same than for 7. [a]2D0 K259.2 (c 1.00, CH2Cl2)
{lit. [a]2D5 K276 (c 1.02, CHCl3)}.12
carrier gas, TinjectorZ275 8C, TdetectorZ300 8C, Tcolumn
Z
60 8C (3 min) and 60–270 8C (15 8C/min), PZ40 kPa.
HPLC analyses were performed on a Shimadzu LC-10
AD equipped with a chiral column (detailed in the main
text), by using mixtures of n-hexane/2-propanol as mobile
phase, at 25 8C. Specific rotations were determined with a
PerkinElmer 341 digital polarimeter.
4.2.4. (S)-4,5-Dihydro-3H-dinaphtho[2,1-c:10,20-e]thie-
pine [(S)-7]. Physical and spectroscopic data were found
to be the same than for 7. [a]2D0 C258.4 (c 1.00, CH2Cl2)
{lit. [a]2D3 C279 (c 0.20, CHCl3)}.12
4.2. Preparation of 5,7-dihydrodibenzo[c,e]thiepine (1),
4,5-dihydro-3H-dinaphtho[2,1-c:10,20-e]thiepine (7) and
4,5-dihydro-3H-dinaphtho[2,1-c:10,20-e]oxepine (10)
Isolation of compo0unds 10. Preparation from 2,20-
bis(bromomethyl)-1,1 -binaphthyl 16. General procedure.
To a 5 M aqueo0us NaOH solution (50 mL) was added a
solution of 2,2 -bis(bromomethyl)-1,10-binaphthyl (16)
(0.95 g, 2.24 mmol) in dioxane (5 mL). The resulting
mixture was stirred at 80 8C for 15 h. After that the reaction
mixture was allowed to cool down to room temperature,
hydrolysed with 3 M HCl (90 mL), extracted with ethyl
acetate (3!40 mL) and the organic layer was dried over
anhydrous sodium sulphate and evaporated (15 Torr). The
resultingresiduewasthenpurifiedbycolumnchromatography
Isolation of compound 1. A mixture of 2,20-bis(bromo-
methyl)biphenyl (3.4 g, 10 mmol) and sodium sulphide
nonahydrate (3.6 g, 15 mmol) in DMF (mL) was stirred at
100 8C for 1 h. After that the reaction mixture was allowed
to cool down to room temperature, hydrolysed with water
(20 mL), extracted with ethyl acetate (3!40 mL) and the
organic layer was dried over anhydrous sodium sulphate and

F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
9089
(silica gel, hexane/ethyl acetane, 20:1) to yield pure
compounds 10 [0.695 g, 78% yield in the case of (G)-10].
oil; Rf 0.58 (hexane/ethyl acetate: 4:1); n (KBr) 3310–3680
(OH), 3059, 3019 (ArH), 2575 cmK1 (SH); dH 0.67 [9H, s,
(CH3)3C], 0.69 [9H, s, (CH3)3C], 1.40–1.72 [4H, m, 2!
(OH, SH)], 2.25–2.32 (2H, m, ArCH2CHOH), 2.66 (1H, d,
JZ13.6 Hz, ArCHHCHOH), 2.87 (1H, d, JZ13.6 Hz,
ArCHHCHOH), 3.12–3.17 (2H, m, 2!CHOH), 3.42–3.63
(4H, m, 2!CH2SH), 7.10–7.45 (16H, m, 2!ArH); dC 25.3
[(CH3)3C], 25.35 [(CH3)3C], 26.3 (CH2SH), 34.6
[(CH3)3C], 34.65 [(CH3)3C], 35.5 (ArCH2CHOH), 35.7
(ArCH2CHOH), 79.1 (CHOH), 79.4 (CHOH), 126.0, 126.2,
126.6, 126.7, 127.6, 127.7, 128.0, 128.9, 129.2, 130.1,
130.15, 130.2, 130.35, 130.4, 130.5, 137.8, 138.6, 138.8,
139.9, 140.2 (ArC); m/z 282 (MCKH2O, 2%), 215 (10),
214 (68), 191 (20), 181 (90), 180 (100), 179 (79), 178 (38),
166 (29), 165 (55), 87 (17), 69 (18), 57 (48); HRMS: MCK
H2O, found 282.1440. C19H22S requires 282.1442.
Preparation from 2,20-bis(hydroxymethyl)-1,10-binaphthyl
(18). General procedure. A mixture of 2,20-bis(hydroxy-
methyl)-1,10-binaphthyl (0.95 g, 3.0 mmol) [easily prepared
from 2,20-bis(bromomethyl)-1,10-binaphthyl21] and
p-toluenesulphonic acid (0.095 g, 0.5 mmol) in benzene
(40 mL) was stirred at 80 8C for 48 h. After that the reaction
mixture was allowed to cool down to room temperature and
washed with a sodium carbonate saturated aqueous solution
(30 mL). Then, the organic layer was dried over anhydrous
sodium sulphate and evaporated (15 Torr). The resulting
residue was then purified by column chromatography (silica
gel, hexane/ethyl acetate: 20:1) to yield pure compounds 10
[0.49 g, 55% yield in the case of (G)-10]. Physical and
spectroscopic data follow.
4.3.2. 2-(2-Hydroxy-4-phenylbutyl)-20-sulphanylmethyl-
biphenyl (2b). Diastereomeric mixture: colourless oil; Rf
0.39 (hexane/ethyl acetate: 4:1); n (KBr) 3290–3650 (OH),
3060, 3025 (ArH), 2610 cmK1 (SH); dH 1.44–1.63 [8H, m,
2!(OH, SH), 2!CHCH2CH2], 2.43–2.80 (8H, m, 2!
ArCH2, 2!PhCH2), 3.39–3.65 (6H, m, 2!CHOH, 2!
CH2SH), 7.03–7.47 (26H, m, 2!Ph, 2!ArH); dC 26.3,
31.7, 38.2, 38.4, 41.4, 41.5 (CH2), 70.6, 71.1 (CHOH),
125.6, 126.2, 126.3, 126.7, 126.8, 127.7, 127.8, 128.0,
128.2, 128.3, 128.35, 129.0, 129.15, 130.0, 130.1, 130.2,
130.3, 136.4, 136.5, 138.7, 139.8, 140.35, 140.4, 141.7
(ArC); m/z 330 (MCKH2O, 6%), 214 (40), 182 (25), 181
(33), 180 (68), 179 (37), 178 (34), 166 (18), 165 (44), 105
(27), 91 (100), 77 (15), 44 (22); HRMS: MCKH2O, found
330.1139. C23H22S requires 330.1442.
4.2.5. (G)-4,5-Dihydro-3H-dinaphtho[2,1-c:10,20-e]oxe-
pine (10). White solid; mp 179–181 8C (hexane/dichloro-
methane) (lit. mp 188–188.5 8C);21 Rf 0.69 (hexane/ethyl
acetate: 2:1); n (KBr) 3042 cmK1 (ArH); dH 4.18 (2H, d, JZ
11.3 Hz, 2!CHHO), 4.63 (2H, d, JZ11.3 Hz, 2!CHHO),
7.24–7.31 (2H, m, ArH), 7.46–7.54 (4H, m, ArH), 7.61 (2H,
d, JZ8.3 Hz, ArH), 7.98 (4H, dd, JZ9.4, 8.6 Hz, ArH); dC
67.4 (CH2), 125.9, 126.0, 127.3, 127.6, 128.3, 129.1, 131.1,
133.5, 133.6, 135.4 (ArC); m/z 296 (MC, 100), 293 (11),
282 (11), 281 (30), 279 (22), 278 (28), 277 (70), 268 (20),
267 (40), 266 (36), 253 (54), 252 (67), 239 (37), 133 (33),
132 (48), 131 (27), 126 (37), 120 (30), 115 (33).
4.2.6. (R)-4,5-Dihydro-3H-dinaphtho[2,1-c:10,20-e]oxe-
pine [(R)-10]. Physical and spectroscopic data were found
to be the same than for 10. [a]2D0 K432.8 (c 1.00, CH2Cl2).
4.3.3. 2-(2-Hydroxy-2-phenylethyl)-20-sulphanylmethyl-
biphenyl (2c). Diastereomeric mixture: colourless oil; Rf
0.43 (hexane/ethyl acetate: 4:1); n (KBr) 3300–3645 (OH),
3055, 3022 (ArH), 2590 cmK1 (SH); dH 1.52–2.07 [4H, m,
2!(OH, SH)], 2.69–2.74 (3H, m, ArCH2CH, ArCHHCH),
2.97 (1H, dd, JZ13.9, 4.6 Hz, ArCHHCH), 3.36–3.57 (4H,
m, 2!CH2SH), 4.63–4.75 (2H, m, CHOH), 6.90–7.45
(26H, m, 2!Ph, 2!ArH); dC 26.3, 26.4, 43.4, 43.6 (CH2),
73.9, 74.4 (CHOH), 125.3, 125.5, 126.3, 126.5, 126.7,
127.2, 127.3, 127.7, 127.75, 128.0, 128.05, 128.2, 128.9,
129.2, 130.1, 130.2, 130.3, 130.6, 136.0, 136.1, 138.7,
138.9, 139.8, 140.3, 140.45, 143.9, 144.0 (ArC); m/z 302
(MCKH2O, 11%), 214 (86), 198 (22), 182 (11), 181 (75),
180 (100), 179 (86), 178 (53), 167 (18), 166 (26), 165 (80),
152 (17), 107 (80), 105 (70), 91 (47), 79 (84), 77 (93), 51
(32); HRMS: MCKH2O, found 302.1123. C21H18S requires
302.1129.
4.2.7. (S)-4,5-Dihydro-3H-dinaphtho[2,1-c:10,20-e]oxe-
pine [(S)-10]. Physical and spectroscopic data were found
to be the same than for 10. [a]2D0 C428.3 (c 1.00, CH2Cl2)
{lit. [a]2D8 C687 (c 1.4, benzene)}.21
4.3. Reductive lithiation of 5,7-dihydrodibenzo[c,e]-
thiepine (1) and reaction with electrophiles. Preparation
of compounds 2
Isolation of compounds 2. General procedure. To a cooled
(K78 8C) blue suspension of lithium powder (105 mg,
15.0 mmol) and a catalytic amount of DTBB (26 mg,
0.1 mmol) in THF (3 mL) was added dropwise a solution of
compound 1 (212 mg, 1.0 mmol) in THF (1 mL) under
argon and the mixture was stirred at the same temperature
for 30 min. Then the corresponding electrophile was added
dropwise (1.1 mmol) and after 5 min it was hydrolysed
carefully with 3 N HCl (5 mL). The resulting mixture was
allowed to reach room temperature, extracted with ethyl
acetate (3!15 mL) and the organic layer was dried over
anhydrous sodium sulphate and evaporated (15 Torr). The
residue was then purified by column chromatography (silica
gel, hexane/ethyl acetate) to yield pure compounds 2. Yields
are given in Table 1, physical, analytical and spectroscopic
data follow.
4.3.4. 2-(2-Hydroxy-2-methylpropyl)-20-sulphanyl-
methylbiphenyl (2d). Colourless oil; Rf 0.33 (hexane/
ethyl acetate: 4:1); n (KBr) 3280–3675 (OH), 3058, 3020
(ArH), 2545 cmK1 (SH); dH 0.98 (3H, s, CH3), 1.04 (3H, s,
CH3), 1.35–1.61 (2H, m, OH, SH), 2.54 (1H, d, JZ13.4 Hz,
CHHCOH), 2.75 (1H, d, JZ13.4 Hz, CHHCOH), 3.42–3.55
(2H, m, CH2SH), 7.13–7.47 (8H, m, ArH); dC 26.4, 29.2
(CH3), 29.8, 45.5 (CH2), 71.5 (COH), 126.3, 126.6, 127.3,
127.8, 128.9, 130.4, 130.7, 131.0, 135.8, 138.9, 140.4, 140.8
(ArC); m/z 254 (MCKH2O, 1%), 215 (11), 214 (64), 181
(65), 180 (83), 179 (67), 178 (35), 167 (11), 166 (28), 165
4.3.1. 2-(2-Hydroxy-3,3-dimethylbutyl)-20-sulphanyl-
methylbiphenyl (2a). Diastereomeric mixture: colourless

9090
F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
(65), 152 (12), 59 (100); HRMS: MCKH2O, found
254.1126. C17H18S requires 254.1129.
(COH), 126.0, 126.2, 126.5, 126.8, 127.15, 127.2, 127.8,
127.9, 128.0, 128.9, 129.0, 130.3, 130.4, 130.8, 130.9,
131.3, 131.6, 135.6, 136.1, 139.2, 140.6, 141.2, 141.25
(ArC); m/z 350 (MCKH2O, 1%), 215 (16), 214 (99), 181
(52), 180 (90), 179 (47), 178 (24), 166 (15), 165 (33), 155
(50), 137 (35), 95 (40), 81 (100), 69 (40), 67 (14), 57 (14),
55 (48), 43 (59); HRMS: MCKH2O, found 350.2063.
C24H30S requires 350.2066.
4.3.5. 2-(2-Hydroxy-2-pentylheptyl)-20-sulphanylmethyl-
biphenyl (2e). Colourless oil; Rf 0.65 (hexane/ethyl acetate:
4:1); n (KBr) 3290–3650 (OH), 3058, 3020 (ArH),
2570 cmK1 (SH); dH 0.81–0.86 (6H, m, 2!CH3), 1.08–
1.29 (17H, m, OH, 8!CH2), 1.61 (1H, t, JZ7.7 Hz, SH),
2.53 (1H, d, JZ13.7 Hz, CHHCOH), 2.73 (1H, d, JZ
13.7 Hz, CHHCOH), 3.40–3.53 (2H, m, CH2SH), 7.14–7.47
(8H, m, ArH); dC 13.9 (CH3), 22.5, 22.55, 22.9, 23.1, 26.4,
32.2, 32.3, 38.8, 39.3, 41.7 (CH2), 74.9 (COH), 126.2,
126.7, 127.3, 127.8, 128.9, 130.3, 130.7, 131.2, 135.6,
138.9, 140.5, 141.1 (ArC); m/z 366 (MCKH2O, 2%), 215
(11), 214 (70), 191 (11), 181 (46), 180 (82), 179 (52), 178
(28), 167 (10), 166 (12), 165 (27), 97 (15), 83 (33), 71 (18),
69 (29), 57 (23), 55 (68), 43 (100); HRMS: MCKH2O,
found 366.2377. C25H34S requires 366.2381.
4.4. Sequential double lithiation of 5,7-dihydrodibenzo-
[c,e]thiepine (1) and reaction with electrophiles
Isolation of compounds 4. General procedure. To a cooled
(K78 8C) blue suspension of lithium powder (105 mg,
15.0 mmol) and a catalytic amount of DTBB (26 mg,
0.1 mmol) in THF (3 mL) was added dropwise a solution of
compound 1 (212 mg, 1.0 mmol) in THF (1 mL) under
argon and the mixture was stirred at the same temperature
for 30 min. Then the corresponding electrophile was added
dropwise (1.1 mmol) and after 5 min at K78 8C the cold
bath was removed and the reaction mixture was allowed to
react at 20 8C for 30 min. Then the reaction mixture was
cooled down to K78 8C and a second electrophile
(1.1 mmol) was added dropwise. After 5 min at this
temperature, the reaction mixture was hydrolysed with
water (4 mL), extracted with ethyl acetate (3!10 mL) once
at 20 8C, dried over anhydrous Na2SO4 and evaporated
(15 Torr). The residue was purified by column chromato-
graphy (silica gel, hexane/ethyl acetate) to yield pure
products 4. Yields are given in Table 2, physical, analytical
and spectroscopic data follow.
4.3.6. 2-(1-Hydroxycyclohexylmethyl)-20-sulphanyl-
methylbiphenyl (2f). Colourless oil; Rf 0.48 (hexane/ethyl
acetate: 4:1); n (KBr) 3275–3630 (OH), 3055, 3017 (ArH),
2610 cmK1 (SH); dH 1.05–1.49 (11H, m, OH, 5!CH2),
1.60 (1H, t, JZ7.7 Hz, SH), 2.53 (1H, d, JZ13.7 Hz,
CHHCOH), 2.73 (1H, d, JZ13.7 Hz, CHHCOH), 3.36–3.50
(2H, m, CH2SH), 7.14–7.48 (8H, m, ArH); dC 21.8, 21.9,
26.5, 26.4, 37.4, 37.8, 45.1 (CH2), 72.0 (COH), 126.3,
126.7, 127.1, 127.2, 127.9, 130.4, 130.8, 131.4, 135.3,
138.9, 140.6, 141.05 (ArC); m/z 294 (MCKH2O, 3%), 260
(10), 215 (13), 214 (59), 182 (14), 181 (69), 180 (100), 179
(74), 178 (48), 167 (16), 166 (20), 165 (57), 99 (87), 83 (33),
81 (79), 79 (15), 57 (12), 55 (43), 43 (38); HRMS: MCK
H2O, found 294.1441. C20H22S requires 294.1442.
4.4.1. 2,20-Bis-(2-hydroxy-2-methylpropyl)biphenyl (4a).
Colourless oil; Rf 0.13 (hexane/ethyl acetate: 4:1); n (KBr)
3220–3640 (OH), 3059, 3020 cmK1 (ArH); dH 0.96 (3H, s,
CH3), 1.05 (3H, s, CH3), 2.42 (2H, d, JZ13.4 Hz, 2!
CHHCOH), 2.49 (2H, br s, 2!OH), 2.89 (2H, d, JZ
13.4 Hz, 2!CHHCOH), 7.06–7.38 (8H, m, ArH); dC 31.1,
32.4 (CH3), 46.1, 46.4 (CH2), 71.8 (COH), 126.4, 126.9,
131.0, 131.5, 135.4, 141.5 (ArC); m/z 262 (MCK2H2O,
7%), 207 (57), 182 (17), 179 (49), 174 (54), 172 (25), 165
(15), 114 (27), 98 (27), 81 (19), 64 (18), 58 (42), 43 (47), 40
(100); HRMS: MCK2H2O, found 262.1714. C20H22
requires 262.1722.
4.3.7. 2-(1-Hydroxycyclooctylmethyl)-20-sulphanyl-
methylbiphenyl (2g). Colourless oil; Rf 0.49 (hexane/
ethyl acetate: 4:1); n (KBr) 3290–3660 (OH), 3059, 3019
(ArH), 2550 cmK1 (SH); dH 1.22–1.55 (15H, m, OH, 7!
CH2), 1.62 (1H, t, JZ7.8 Hz, SH), 2.56 (1H, d, JZ13.6 Hz,
CHHCOH), 2.72 (1H, d, JZ13.6 Hz, CHHCOH), 3.42–3.55
(2H, m, CH2SH), 7.14–7.86 (8H, m, ArH); dC 21.9, 22.2,
24.8, 26.4, 27.7, 28.2, 36.0, 36.2, 43.5 (CH2), 75.6 (COH),
126.1, 126.6, 127.2, 127.8, 128.9, 130.3, 130.8, 131.4,
135.6, 139.0, 140.5, 141.1 (ArC); m/z 322 (MCKH2O, 5%),
215 (14), 214 (50), 197 (11), 192 (10), 191 (12), 182 (13),
181 (57), 180 (100), 179 (95), 178 (67), 166 (25), 165 (64),
127 (52), 109 (32), 83 (11), 81 (18), 69 (27), 67 (70), 57
(19), 55 (82), 43 (42); HRMS: MCKH2O, found 322.1754.
C22H26s requires 322.1755.
4.4.2. 2-Ethoxycarbonylmethyl-20-(2-hydroxy-2-methyl-
propyl)biphenyl (4b). Colourless oil; Rf 0.17 (hexane/ethyl
acetate: 4:1); n (KBr) 3300–3690 (OH), 3059, 3020 (ArH),
1743 cmK1 (C]O); dH 0.91 (3H, s, CH3), 0.96 (3H, s,
CH3), 1.08 (3H, t, JZ6.7 Hz, CH3CH2), 2.30 (1H, br s, OH),
2.45 (1H, d, JZ13.4 Hz, CHHCOH), 2.67 (2H, d, JZ
13.4 Hz, CHHCOH), 3.30 (2H, s, CH2CO2), 3.95 (2H, q,
JZ6.7 Hz, CH2O), 7.04–7.38 (8H, m, ArH); dC 14.0, 29.3,
29.8 (CH3), 38.7, 45.2 (CH2), 60.6 (CH2O), 71.45 (COH),
126.2, 126.7, 127.2, 127.4, 129.9, 130.6, 130.7, 130.9,
132.5, 135.8, 141.1, 141.6 (ArC), 171.6 (C]O); m/z 294
(MCKH2O, 6%), 254 (37), 208 (40), 181 (31), 180 (65),
179 (70), 178 (38), 166 (29), 165 (56), 59 (100), 43 (44);
HRMS: MCKH2O, found 294.1586. C12H12O requires
294.1620.
4.3.8. (1R,2S,5R)-2-[(1-Hydroxy-2-isopropyl-5-methyl-
cyclohexyl)methyl]-20-sulphanylmethylbiphenyl (2h).
Diastereomeric mixture: colourless oil; Rf 0.71 (hexane/
ethyl acetate: 4:1); n (KBr) 3310–3620 (OH), 3058, 3018
(ArH), 2565 cmK1 (SH); dH 0.54–0.92 (10H, m, CH, 3!
CH3), 1.23–1.67 (8H, m, OH, SH, 3!CH2), 1.94–2.00 (1H,
m, CH), 2.02–2.11 (1H, m, CH), 2.25 (1H, d, JZ13.4 Hz,
CHHCOH), 2.51 (1H, d, JZ13.6 Hz, CHHCOH), 3.00 (1H,
d, JZ13.4 Hz, CHHCOH), 3.21 (1H, d, JZ13.6 Hz,
CHHCOH), 3.40–3.52 (2H, m, CH2SH), 7.11–7.47 (8H,
m, ArH); dC 17.7, 17.8 (CH3), 20.65, 20.7 (CH2), 22.3, 22.4
(CH3), 23.5, 23.6 (CH3), 25.8 (CH2), 26.4, 26.5, 27.5 (CH),
34.8, 34.9, 42.4, 46.9, 47.0 (CH2), 49.5, 50.1 (CH), 75.5
4.4.3. 2-(1-Hydroxycyclohexylmethyl)-20-(2-hydroxy-2-
methylpropyl)biphenyl (4c). Colourless oil; Rf 0.11

F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
9091
(hexane/ethyl acetate: 4:1); n (KBr) 3250–3680 (OH), 3055,
3018 cmK1 (ArH); dH 0.80 (3H, s, CH3), 0.96 (3H, s, CH3),
0.98–1.46 (12H, m, 2!OH, 5!CH2), 2.46–2.62 (4H, m,
2!CH2), 7.10–7.34 (8H, m, ArH); dC 21.7, 21.9 (CH3),
25.5, 29.2, 29.8, 37.2, 37.9, 45.0, 45.5 (CH2), 71.5, 72.0
(COH), 126.2, 126.4, 126.9, 127.0, 127.6, 130.6, 131.0,
131.3, 135.1, 135.7, 142.3, 142.35 (ArC); m/z 302 (MCK
2H2O, 7%), 262 (21), 222 (46), 208 (13), 207 (76), 193 (12),
191 (19), 182 (77), 181 (31), 180 (27), 179 (99), 178 (41),
167 (27), 166 (23), 165 (41), 157 (21), 99 (100), 81 (70), 59
(76), 55 (36), 43 (50); HRMS: MCK2H2O, found
302.2039. C23H26 requires 302.2035.
3056, 3019 cmK1 (ArH); dH 0.40 (3H, d, JZ6.7 Hz,
CH3CH), 0.58–0.83 (6H, m, 2!CH3CH), 0.78 (3H, s,
CH3), 0.98 (3H, s, CH3), 1.15–1.66 (8H, m, 2!OH, 3!
CH2), 1.64–1.81 (1H, m, CH), 2.03–2.15 (1H, m, CH), 2.15
(1H, d, JZ13.4 Hz, CHHCOH), 2.37 (1H, d, JZ13.5 Hz,
CHHCOH), 2.50 (1H, d, JZ13.5 Hz, CHHCH3), 2.61 (1H,
d, JZ13.5 Hz, CHHCH3), 2.93 (1H, d, JZ13.5 Hz,
CHHCOH), 3.05 (1H, d, JZ13.4 Hz, CHHCOH), 7.08–
7.39 (8H, m, ArH); dC 17.6, 17.9 (CH3), 20.7, 20.75 (CH2),
22.2, 22.4 (CH3), 23.5, 23.7 (CH3), 25.8, 25.9 (CH2), 27.5,
27.55, 29.2 (CH), 29.6, 29.8, 34.8, 35.0, 42.2, 42.4, 45.5,
45.6, 46.9, 47.0 (CH2), 49.2, 50.4 (CH), 71.6, 75.2, 75.7
(COH), 126.1, 126.2, 126.3, 126.7, 126.8, 126.9, 127.2,
130.5, 130.7, 130.75, 131.2, 131.25, 131.3, 131.5, 131.7,
135.2, 135.65, 135.8, 136.0, 142.4, 142.6 (ArC); m/z 358
(MCK2H2O, 2%), 222 (46), 207 (51), 182 (34), 180 (15),
179 (68), 178 (23), 166 (12), 165 (21), 155 (50), 137 (34), 95
(35), 81 (78), 69 (40), 67 (16), 59 (68), 57 (16), 55 (63), 43
(100); HRMS: MCK2H2O, found 358.2651. C27H34
requires 358.2661.
4.4.4. 2-(1-Hydroxycyclohexylmethyl)-20-(2-hydroxy-2-
ethylbutyl)biphenyl (4d). Colourless oil; Rf 0.23 (hexane/
ethyl acetate: 4:1); n (KBr) 3360–3540, 3550–3640 (OH),
3056, 3019 cmK1 (ArH); dH 0.40 (3H, t, JZ7.3 Hz, CH3),
0.65 (3H, t, JZ8.0 Hz, CH3), 0.89–1.63 (16H, m, 2!OH,
7!CH2), 2.47–2.59 (4H, m, 2!CH2), 7.12–7.34 (8H, m,
ArH); dC 7.4, 7.8 (CH3), 21.7, 21.9, 25.5, 30.3, 31.0, 37.2,
37.9, 40.7 (CH2), 72.0, 75.25 (COH), 126.3, 126.5, 126.9,
130.9, 131.0, 131.15, 131.2, 131.25, 135.2, 135.4, 142.4,
142.6 (ArC); m/z 330 (MCK2H2O, 21%), 262 (29), 259
(19), 250 (18), 247 (15), 221 (22), 219 (15), 205 (19), 203
(14), 193 (16), 192 (20), 191 (82), 182 (40), 181 (37), 180
(27), 179 (99), 178 (48), 166 (19), 165 (48), 99 (58), 87 (66),
81 (65), 69 (19), 67 (16), 57 (37), 55 (63), 45 (68), 43 (56),
41 (100); HRMS: MCK2H2O, found 330.2332. C25H30
requires 330.2348.
4.5. Attempt of cyclisation of sulphanyl alcohol 2c, diol
4e and hydroxy ester 4f under acidic conditions
Isolation of compounds 3 and 5. General procedure. To a
solution of sulphanyl alcohol 2c or diol 4e (0.2 mmol) in
toluene (3 mL) was added 85% phosphoric acid (0.4 mL).
The reaction mixture was heated at 110 8C for 4 h, then the
toluene was removed by distillation and the resulting
residue 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 are given in the text, physical,
analytical and spectroscopic data for these compounds
follow.
4.4.5. 2,20-Bis-(1-Hydroxycyclohexylmethyl)biphenyl
(4e). Colourless oil; Rf 0.26 (hexane/ethyl acetate: 4:1); n
(KBr) 3350–3630 (OH), 3058, 3021 cmK1 (ArH); dH 0.92–
1.47 (20H, m, 10!CH2), 2.46 (2H, br s, 2!OH), 2.57 (2H,
d, JZ14.2 Hz, 2!ArCHH), 2.63 (2H, d, JZ14.2 Hz, 2!
ArCHH), 7.15–7.41 (8H, m, ArH); dC 21.7, 21.9, 25.5, 37.8,
38.7, 45.0 (CH2), 71.9 (COH), 126.3, 126.8, 131.0, 131.2,
135.1, 142.5 (ArC); m/z 342 (MCK2H2O, 22%), 259 (30),
217 (16), 203 (15), 192 (22), 191 (100), 179 (43), 178 (33),
166 (16), 165 (51), 95 (15), 81 (32), 79 (28), 67 (24), 55
(30), 41 (53); HRMS: MCK2H2O, found 342.2341. C26H30
requires 342.2348.
4.5.1. 7-Phenyl-7,8-dihydro-5H-dibenzo[c,e]thiocine (3).
Pale yellow solid; mp 143–144 8C (hexane); Rf 0.62
(hexane/ethyl acetate: 10:1); n (KBr) 3056, 3028 cmK1
(ArH); dH 2.94–3.03 (1H, m, CHHCH), 3.21 (1H, d, JZ
13.4 Hz, CHHCH), 3.43 (1H, d, JZ14.6 Hz, CHHS), 3.52
(1H, d, JZ14.6 Hz, CHHS), 4.15 (1H, d, JZ9.1 Hz, CHS),
7.12–7.34 (13H, m, ArH); dC 33.9 (CH2), 42.9 (CH2S), 51.2
(CHS), 126.4, 126.6, 127.4, 127.6, 128.4, 128.6, 128.9,
129.1, 129.6, 129.8, 139.4, 139.7, 140.1, 140.3, 142.6,
142.65, 143.1 (ArC); m/z 302 (MC, 57%), 198 (32), 197
(18), 180 (78), 179 (100), 178 (61), 165 (61), 91 (41);
HRMS: MC, found 302.1121. C21H18S requires 302.1129.
4.4.6. 2-Ethoxycarbonylmethyl-20-(1-hydroxycyclo-
hexylmethyl)biphenyl (4f). Colourless oil; Rf 0.33
(hexane/ethyl acetate: 4:1); n (KBr) 3360–3590 (OH),
3059, 3020 (ArH), 1740 cmK1 (C]O); dH 1.04–1.37
(11H, m, OH, 5!CH2), 1.08 (3H, t, JZ6.7 Hz, CH3),
2.43 (1H, d, JZ13.5 Hz, CHHCOH), 2.63 (1H, d, JZ
13.5 Hz, CHHCOH), 3.30 (2H, s, CH2CO2), 3.95 (2H, q,
JZ6.7 Hz, CH2CH3), 7.03–7.37 (8H, m, ArH); dC 14.0
(CH3), 21.75, 21.8, 25.5, 37.3, 37.7, 38.7, 44.8 (CH2), 60.5
(CH2O), 71.8 (COH), 126.0, 126.6, 127.0, 127.4, 129.8,
130.5, 130.7, 131.2, 135.3, 141.2, 141.7 (ArC), 171.6
(C]O); m/z 334 (MCKH2O, 8%), 254 (22), 208 (30), 181
(17), 180 (45), 179 (100), 178 (40), 166 (16), 165 (32), 99
(17), 81 (31), 79 (11), 55 (27), 41 (32); HRMS: MCKH2O,
found 334.1928. C23H26O2 requires 334.1933.
4.5.2. 2,20-Bis-(1-cyclohexenylmethyl)biphenyl (5). Pale
yellow oil; Rf 0.45 (hexane); n (film) 3055, 3030 cmK1
(ArH); dH 1.41–1.46 (4H, m, 2!CH2), 1.58–1.62 (2H, m,
CH2), 1.83–1.87 (2H, m, CH2), 2.85 (2H, d, JZ14.6 Hz,
2!ArCHH), 2.94 (2H, d, JZ14.6 Hz, 2!ArCHH), 5.07
(2H, br s, CH]C), 6.99–7.20 (8H, m, ArH); dC 22.4, 22.9,
25.3, 28.2 (CH2), 41.6 (CHS), 123.2, 125.2, 126.9, 129.1,
129.9, 136.6, 138.1, 141.3 (CH]C, ArC); m/z 342 (MC,
26%), 259 (33), 217 (13), 203 (14), 192 (18), 191 (100), 179
(59), 178 (34), 166 (16), 165 (51), 95 (12), 81 (44), 79 (22),
67 (29), 55 (37), 53 (19); HRMS: MC, found 342.2339.
C26H30 requires 342.2348.
4.4.7. (1R,2S,5R)-2-[(1-Hydroxy-2-isopropyl-5-methyl-
cyclohexyl)methyl]-20-(2-hydroxy-2-methylpropyl)-
biphenyl (4g). Diastereomeric mixture: colourless oil; Rf
0.42 (hexane/ethyl acetate: 4:1); n (KBr) 3340–3660 (OH),

9092
F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
Preparation of compound 6. A solution of hydroxy ester 4f
(70 mg, 0.2 mmol) in toluene (10 mL) in the presence of a
catalytic amount of p-toluenesulphonic acid (1 mg) was
heated at 110 8C in a Dean-Stark apparatus for 4 h, then the
toluene was removed by distillation and the resulting
residue was hydrolysed with a saturated solution of
CaCO3 (5 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) to yield pure product 6. Yield is given in the
text, physical, analytical and spectroscopic data for this
compound follow.
278 (26), 277 (23), 276 (42), 267 (20), 265 (39), 263 (36),
252 (20), 221 (15), 207 (176), 138 (19), 59 (100).
4.6.2. 2,20-Bis-(2-hydroxy-2-ethylbutyl)-1,10-binaphthyl
(8b). White solid; mp 121–122 8C (dichloromethane/
hexane) (found: C, 84.22; H, 8.43. C32H38O2 requires: C,
84.54; H, 8.42); Rf 0.58 (hexane/ethyl acetate: 2:1); n (KBr)
3677–3162 (OH), 3062 cmK1 (ArH); dH 0.13 (6H, t, JZ
7.5 Hz, 2!CH3), 0.63 (6H, t, JZ7.5 Hz, 2!CH3), 0.82–
1.09 (4H, m, 2!CH2CH3), 1.24–1.45 (4H, m, 2!
CH2CH3), 2.56 (2H, d, JZ14.0 Hz, 2!CHHAr), 2.72
(2H, d, JZ14.0 Hz, 2!CHHAr), 7.14–7.26 (2H, m, ArH),
7.37–7.42 (2H, m, ArH), 7.79–7.91 (8H, m, ArH); dC 7.3,
7.7 (CH3), 30.7, 31.7 (CH2CH3), 41.2 (CH2COH), 75.6
(COH), 125.3, 125.7, 127.4, 127.5, 127.9, 129.5, 132.3,
133.4, 135.3, 136.2 (ArC); m/z 436 [(MCKH2O), 0.1], 351
(10), 350 (34), 283 (37), 282 (100), 281 (17), 280 (12), 279
(41), 278 (10), 277 (13), 276 (10), 267 (18), 266 (30), 265
(37), 87 (23); HRMS, MCKH2O, found 436.2739.
C32H36O requires 436.2766.
4.5.3. Ethyl 2-[2-(1-cyclohexenylmethyl)phenyl]phenyl-
acetate (6). Colourless oil; Rf 0.50 (hexane/ethyl acetate:
10:1); n (film) 3050, 3027 (ArH), 1730 cmK1 (C]O); dH
1.16 (3H, t, JZ7.0 Hz, CH3), 1.47–1.51 (4H, m, 2!CH2),
1.61–1.66 (2H, m, CH2), 1.85–1.91 (2H, m, CH2), 2.90 (1H,
d, JZ15.0 Hz, CHHC]CH), 3.03 (1H, d, JZ15.0 Hz,
CHHC]CH), 3.30 (1H, d, JZ15.8 Hz, CHHCO), 3.38 (1H,
d, JZ15.8 Hz, CHHCO), 4.04 (2H, q, JZ7.0 Hz, CH2CH3),
5.06 (1H, br s, CH]C), 7.10–7.35 (8H, m, ArH); dC 14.1
(CH3), 22.3, 22.8, 25.3, 28.1, 38.8, 41.5 (CH2), 60.5
(CH2O), 121.2, 123.2, 126.5, 127.3, 127.35, 129.5, 129.6,
129.9, 130.0, 132.5, 136.4, 138.0, 140.5, 141.3, 142.9
(CH]C, ArC), 171.7 (C]O); m/z 334 (MC, 11%), 180
(15), 179 (100), 178 (32), 165 (22), 153 (44), 152 (13);
HRMS: MC, found 334.1926. C23H26O2 requires 334.1933.
4.6.3.
2,20-Bis-(1-hydroxycyclopentylmethyl)-1,10-
binaphthyl (8c). Pale yellow oil; Rf 0.39 (hexane/ethyl
acetate: 2:1); n (film) 3660–3180 (OH), 3060 cmK1 (ArH);
dH 1.28–1.65 (18H, m, 8!CH2, 2!OH), 2.66 (2H, d, JZ
14.5 Hz, 2!CHHAr), 2.89 (2H, d, JZ14.5 Hz, 2!CHHAr),
7.06 (2H, d, JZ8.4 Hz, ArH), 7.16–7.42 (2H, m, ArH), 7.85–
7.94 (8H, m, ArH); dC 23.0, 23.4, 40.2, 41.2, 43.8 (CH2), 82.7
(COH), 125.3, 126.0, 126.9, 127.5 127.9, 128.3 132.2, 133.3,
135.8, 135.9 (ArC); m/z 450 (MC, 0.3), 432 (4), 416 (15), 414
(21), 350 (26), 349 (18), 348 (52), 347 (13), 345 (13), 289 (11),
283 (26), 282 (100), 281 (56), 280 (27), 279 (65), 278 (23), 277
(34), 276 (26), 267 (28), 266 (41), 265 (56), 264 (14), 263 (18),
253 (12), 252 (23), 85 (21), 67 (20); HRMS, MC, found
450.2595. C32H34O2 requires 450.2559.
4.6. Double reductive lithiation of 4,5-dihydro-3H-
dinaphtho[2,1-c:10,20-e]thiepine (7) and 4,5-dihydro-3H-
dinaphtho[2,1-c:10,20-e]oxepine (10) and reaction with
electrophiles. Preparation of compounds 8 and 11
Isolation of compounds 8 and 11. General procedure. To a
cooled (K78 8C) blue suspension of lithium powder
(105 mg, 15.0 mmol) and a catalytic amount of DTBB
(26 mg, 0.1 mmol) in THF (3 mL) was added dropwise a
solution of compound 7 or 10 (0.5 mmol) in THF (1 mL)
under argon and the mixture was stirred at the same
temperature for 1 h. Then the corresponding electrophile
was added dropwise (0.6 mmol, 0.25 mL in the case of H2O)
and after 15 min it was hydrolysed with water (5 mL). The
resulting mixture was extracted with ethyl acetate (3!
15 mL) and the organic layer was dried over anhydrous
sodium sulphate and evaporated (15 Torr). The residue was
then purified by column chromatography (silica gel, hexane/
ethyl acetate) to yield pure compounds 8 and 11. Yields are
given in Tables 3 and 5, specific rotations are given in Table 5,
other physical, analytical and spectroscopic data follow.
4.6.4.
2,20-Bis-(1-hydroxycyclohexylmethyl)-1,10-
binaphthyl (8d). White solid; mp 142–143 8C (dichloro-
methane/hexane) (found: C, 84.98; H, 8.06. C34H38O2
requires: C, 85.31; H, 8.00); Rf 0.47 (hexane/ethyl acetate:
2:1); n (KBr) 3655–3145 (OH), 3058 cmK1 (ArH); dH 0.78–
1.68 (20H, m, 10!CH2), 2.57 (2H, d, JZ14.0 Hz, 2!
CHHAr), 2.74 (2H, d, JZ14.0 Hz, 2!CHHAr), 7.10–7.19
(2H, m, ArH), 7.36–7.41 (2H, m, ArH), 7.81–7.91 (8H, m,
ArH); dC 21.7, 22.0, 37.6, 37.7, 38.7 (CH2), 72.4 (COH),
125.2, 125.7, 127.3, 127.6, 127.9, 129.6, 132.3, 133.4,
135.0, 136.1 (ArC); m/z 460 [(MKH2O)C, 0.6], 362 (23),
283 (24), 282 (100), 281 (25), 279 (20), 267 (11), 266 (19),
265 (21), 99 (12), 81 (14); HRMS, MCKH2O, found
460.2771. C32H36O requires 460.2766.
4.6.5. 2,20-Dimethyl-1,10-binaphthyl (11).17 Colourless
oil; Rf 0.28 (hexane); n (film) 3053, 3003 cmK1 (ArH); dH
2.03 (6H, s, 2!CH3), 7.04 (2H, d, JZ8.4 Hz, ArH), 7.19
(2H, dd, JZ8.3, 7.0 Hz, ArH), 7.37 (2H, t, JZ7.1 Hz, ArH),
7.49 (2H, d, JZ8.4 Hz, ArH), 7.85–7.89 (4H, m, ArH); dC
20.0 (CH3), 124.9, 124.4, 125.6, 127.4, 127.9, 128.7, 132.2,
132.8, 134.2, 135.1 (ArC); m/z 282 (MC, 95%), 267 (40),
266 (20), 265 (30), 132 (100), 127 (15), 126 (62), 119 (23).
4.6.1. 2,20-Bis-(2-hydroxy-2-methylpropyl)-1,10-binaph-
thyl (8a). White solid; mp 78–79 8C (dichloromethane/
hexane) (lit. mp 80–81 8C);23 Rf 0.11 (hexane/ethyl acetate:
2:1); n (KBr): 3510–3390 (OH), 3053 cmK1 (ArH); dH 0.82
(6H, s, 2!CH3), 0.99 (6H, s, 2!CH3), 1.79 (2H, br s, 2!
OH), 2.56 (2H, d, JZ14.0 Hz, 2!CHH), 2.78 (2H, d, JZ
14.0 Hz, 2!CHH), 7.10–7.21 (4H, m, ArH), 7.37–7.42
(2H, m, ArH), 7.81–7.93 (6H, m, ArH); dC 29.8, 30.7 (CH3),
46.1 (CH2), 71.8 (COH), 125.3, 125.8, 127.5, 127.6, 127.9,
129.1, 132.2, 133.3, 135.4, 135.8 (ArC); m/z 362 (MCK
2H2O, 22), 323 (15), 322 (26), 320 (15), 319 (21), 294 (15),
293 (16), 292 (19), 289 (16), 283 (15), 282 (65), 279 (47),
4.6.6.
(R)-2,20-Bis-(2-hydroxy-2-ethylbutyl)-1,10-
binaphthyl [(R)-8b]. Physical and spectroscopic data
were found to be the same than for 8b.

F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
9093
4.6.7. (S)-2,20-Bis-(2-hydroxy-2-ethylbutyl)-1,10-bi-
naphthyl [(S)-8b]. Physical and spectroscopic data were
found to be the same than for 8b.
acetate: 2:1); n (KBr) 3709–3112 (OH), 3058 (ArH),
2546 cmK1 (SH); dH 0.56 (3H, t, JZ7.4 Hz, CH3), 0.73
(3H, t, JZ7.4 Hz, CH3), 1.40–1.61 (6H, m, 2!CH2, OH,
SH), 2.47 (1H, d, JZ14.2 Hz, CHHCOH), 2.65 (1H, d, JZ
14.2 Hz, CHHCOH), 3.29 (1H, d, JZ12.5 Hz, CHHSH),
3.34 (1H, d, JZ12.6 Hz, CHHSH), 7.03–7.08 (2H, m, ArH),
7.37–7.47 (3H, m, ArH), 7.62 (1H, d, JZ8.6 Hz, ArH),
7.79–8.02 (6H, m, ArH); dC 7.6, 8.1 (CH3), 30.4, 32.0, 41.9,
63.2 (CH2), 76.0 (COH), 125.5, 125.8, 126.1, 126.2, 126.3,
126.4, 126.8, 127.4, 127.5, 127.6, 127.9, 128.1, 128.4,
129.3, 132.3, 132.5, 133.0, 133.6, 134.2, 138.3 (ArC); m/z
382 [(MCKH2O), 0.1], 298 (31), 282 (27), 281 (18), 280
(58), 279 (100), 278 (19), 277 (24), 276 (16), 267 (13), 266
(21), 265 (39), 263 (14), 252 (19), 87 (11); HRMS, MCK
H2O, found 382.1755. C27H26S requires 382.1772.
4.6.8. (R)-2,20-Bis-(1-hydroxycyclohexylmethyl)-1,10-
binaphthyl [(R)-8d]. Physical and spectroscopic data
were found to be the same than for 8d.
4.6.9. (S)-2,20-Bis-(1-hydroxycyclohexylmethyl)-1,10-
binaphthyl [(S)-8d]. Physical and spectroscopic data were
found to be the same than for 8d.
4.6.10. (R)-2,20-Dimethyl-1,10-binaphthyl [(R)-11]. Physi-
cal and spectroscopic data were found to be the same than
for 11 {lit. [a]D22 K19.0 (c 1.3, ethanol)}.24
4.7.3. 2-(1-Hydroxycyclopentylmethyl)-20-sulphanyl-
methyl-1,10-binaphthyl (9c). Pale yellow oil; Rf 0.70
(hexane/ethyl acetate: 2:1); n (film) 3540–3360 (OH),
3058 (ArH), 2555 cmK1 (SH); dH 1.30–1.65 (10H, m, 4!
CH2, OH, SH), 2.68 (1H, d, JZ14.5 Hz, CHHCOH), 2.78
(1H, d, JZ14.5 Hz, CHHCOH), 3.39–3.54 (2H, m,
CH2SH), 7.03 (1H, d, JZ8.4 Hz, ArH), 7.09 (1H, d, JZ
8.6 Hz, ArH), 7.14–7.24 (2H, m, ArH), 7.28–7.51 (2H, m,
ArH), 7.70–7.76 (2H, m, ArH), 7.81–7.99 (4H, m, ArH); dC
23.1, 23.2, 27.3, 29.7, 31.4, 40.7 (CH2), 82.8 (COH), 125.5,
125.8, 126.2, 126.4, 126.7, 127.1, 127.8, 128.0, 128.1,
132.4, 132.6, 132.9, 133.0, 134.3, 134.7, 136.1, 137.3
(ArC); m/z 398 (MC, 0.5), 380 (17), 350 (11), 338 (24), 314
(20), 298 (14), 296 (13), 283 (25), 282 (100), 281 (57), 280
(34), 279 (74), 278 (24), 277 (38), 276 (23), 267 (35), 266
(41), 265 (62), 264 (16), 263 (27), 253 (16), 252 (36), 251
(10), 250 (11), 249 (14), 207 (13), 149 (17), 138 (11), 132
(13), 126 (14), 85 (18), 71 (14); HRMS, MC, found
398.1704. C27H26OS requires 398.1704.
4.6.11. (S)-2,20-Dimethyl-1,10-binaphthyl [(S)-11]. Physi-
cal and spectroscopic data were found to be the same than
for 11. {lit. [a]D23 C14.5 (c 1.0, toluene)}.25
4.7. Reductive lithiation of 4,5-dihydro-3H-dinaphtho[2,
1-c:10,20-e]thiepine (7) and 4,5-dihydro-3H-dinaphtho-
[2,1-c:10,20-e]oxepine (10) and reaction with electro-
philes. Preparation of compounds 9 and 12
Isolation of compounds 9 and 12. General procedure. To a
cooled (K78 8C) solution of compounds 7 or 10 (0.5 mmol)
in THF (2 mL) was added dropwise a 0.7 M THF solution
(1.6 mL, 1.1 mmol) of lithium naphthalenide and the
mixture was stirred at the same temperature for 1 h. Then
the corresponding electrophile was added dropwise
(0.6 mmol, 0.25 mL in the case of H2O and D2O) and
after 15 min it was hydrolysed with 3 M HCl (5 mL) for
compound 9 and with water in the case of 12. The resulting
mixture was extracted with ethyl acetate (3!15 mL) and
the organic layer was dried over anhydrous sodium sulphate
and evaporated (15 Torr). The residue was then purified by
column chromatography (silica gel, hexane/ethyl acetate) to
yield pure compounds 9 and 12. Yields are given in Tables 4
and 5, specific rotations are given in Table 5, other physical,
analytical and spectroscopic data follow.
4.7.4. 2-(1-Hydroxycyclohexylmethyl)-20-sulphanyl-
methyl-1,10-binaphthyl (9d). Pale yellow oil; Rf 0.70
(hexane/ethyl acetate: 2:1); n (film) 3600–3340 (OH), 3059
(ArH), 2570 cmK1 (SH); dH 1.18–1.73 (12H, m, 5!CH2,
OH, SH), 2.70 (1H, d, JZ14.0 Hz, CHHCOH), 2.79 (1H, d,
JZ14.0 Hz, CHHCOH), 3.41–3.60 (2H, m, CH2SH), 7.00–
7.24 (4H, m, ArH), 7.31–7.55 (2H, m, ArH), 7.74 (2H, m,
ArH), 7.80–8.01 (4H, m, ArH); dC 21.8, 21.9, 25.5, 31.8,
37.9, 38.9, 45.0 (CH2), 82.8 (COH), 124.9, 125.6, 126.0,
126.2, 126.5, 126.9, 127.6, 127.9, 128.0, 132.2, 132.3,
132.7, 132.9, 134.1, 134.5, 136.0, 137.1 (ArC); m/z 394
[(MCKH2O), 2], 328 (10), 315 (11), 314 (42), 312 (28), 297
(17), 296 (18), 295 (26), 282 (34), 281 (84), 280 (28), 279
(73), 278 (26), 277 (41), 276 (32), 267 (45), 266 (87), 265
(100), 253 (12), 252 (30), 239 (10), 138 (18), 132 (19), 131
(28), 126 (14); HRMS, MCKH2O, found 394.1760.
C28H26S requires 394.1755.
4.7.1. 2-(2-Hydroxy-2-methylpropyl)-20-sulphanyl-
methyl-1,10-binaphthyl (9a). Yellow oil; Rf 0.26 (hexane/
ethyl acetate: 2:1); n (KBr) 3510–3380 (OH), 3055 (ArH),
2560 cmK1 (SH); dH 0.98 (3H, s, CH3), 1.05 (3H, s, CH3),
1.55 (1H, dd, JZ9.1, 7.2 Hz, SH), 2.05 (1H, br s, OH), 2.63
(2H, dd, JZ24.2, 14.3 Hz, CH2COH), 3.42–3.53 (2H, m,
CH2SH), 7.03–7.10 (2H, m, ArH), 7.20–7.25 (1H, m, ArH),
7.40–7.47 (3H, m, ArH), 7.53 (1H, d, JZ8.5 Hz, ArH), 7.75
(1H, d, JZ8.5 Hz, ArH), 7.86–8.00 (4H, m, ArH); dC 27.3
(CH2), 30.0, 30.7 (CH3), 46.3 (CH2), 71.9 (COH), 125.6,
125.8, 126.2, 126.4, 126.6, 126.7, 126.9, 127.1, 127.7,
128.0, 128.1, 128.7, 129.0, 132.4, 132.6, 134.1, 134.8,
135.7, 137.4, 138.2 (ArC); m/z 372 (MC, 2), 354 (MCK
H2O, 8), 315 (13), 282 (24), 281 (71), 280 (38), 279 (89),
278 (28), 277 (34), 276 (39), 267 (22), 266 (47), 265 (63),
264 (22), 263 (25), 252 (17), 139 (9), 138 (22), 132 (11), 126
(8), 59 (100); HRMS, MC, found 372.1544. C25H24OS
requires 372.1548.
4.7.5. 2-Hydroxymethyl-20-methyl-1,10-binaphthyl (12a).
Colourless oil; Rf 0.17 (hexane/ethyl acetate: 5:1); n (film)
3570–3400 (OH), 3047 cmK1 (ArH); dH 1.54 (1H, br s,
OH), 2.05 (3H, s, CH3), 4.31 (1H, d, JZ12.9 Hz, CHHOH),
4.39 (1H, d, JZ12.9 Hz, CHHOH), 7.03 (1H, d, JZ8.4 Hz,
ArH), 7.09 (1H, d, JZ8.4 Hz, ArH), 7.18–7.27 (2H, m,
ArH), 7.37–7.52 (3H, m, ArH), 7.82 (1H, d, JZ8.4 Hz,
ArH), 7.88–7.95 (3H, m, ArH), 8.01 (1H, d, JZ8.6 Hz,
ArH); dC 20.2 (CH3), 63.4 (CH2), 125.1, 125.4, 125.8,
4.7.2. 2-(2-Hydroxy-2-ethylbutyl)-20-sulphanylmethyl-1,
10-binaphthyl (9b). Pale yellow oil; Rf 0.38 (hexane/ethyl

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F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
125.9, 126.0, 126.4, 126.5, 127.9, 128.1, 128.2, 128.7,
132.2, 132.4, 133.1, 133.2, 133.5, 134.6, 134.7, 136.5
(ArC); m/z 298 (MC, 35), 281 (14), 280 (51), 279 (100), 278
(22), 277 (50), 276 (30), 268 (25), 267 (19), 266 (15), 265
(51), 264 (18), 263 (36), 254 (19), 253 (21), 252 (35), 240
(15), 239 (31), 128 (15), 127 (40), 126 (44), 119 (15), 115
(26), 86 (15), 77 (27), 51 (29), 50 (22), 44 (46); HRMS: MC,
found 298.1346. C22H18O requires 298.1358.
(ArC); m/z 384 (MC, 0.5), 366 (4), 350 (0.2), 298 (36), 281
(29), 280 (66), 279 (100), 278 (18), 277 (22), 276 (15), 267
(17), 266 (25), 265 (44), 264 (10), 263 (14), 252 (22);
HRMS: MC, found 384.2090. C27H28O2 requires 384.2089.
4.7.8. 2-(2-Hydroxy-2-methylpropyl)-20-hydroxymethyl-
1,10-binaphthyl (12d). Colourless oil; Rf 0.18 (hexane/ethyl
acetate: 2:1); n (KBr) 3663–3130 (OH), 3058 cmK1 (ArH);
dH 1.06 (3H, s, CH3), 1.17 (3H, s, CH3), 2.05 (2H, br s, 2!
OH), 2.55 (1H, d, JZ14.2 Hz, CHHCOH), 2.65 (1H, d, JZ
14.2 Hz, CHHCOH), 4.28 (1H, d, JZ12.9 Hz, CHHOH),
4.32 (1H, d, JZ12.9 Hz, CHHOH), 7.02 (1H, d, JZ8.6 Hz,
ArH), 7.09 (1H, d, JZ8.6 Hz, ArH), 7.19–7.27 (2H, m,
ArH), 7.40–7.47 (2H, m, ArH), 7.66 (1H, d, JZ8.6 Hz,
ArH), 7.82 (1H, d, JZ8.6 Hz, ArH), 7.89–7.94 (3H, m,
ArH), 7.99 (1H, d, JZ8.6 Hz, ArH); dC 28.8, 31.7 (CH3),
46.7, 63.1 (CH2), 72.0 (COH), 125.5, 125.8, 126.1, 126.3,
126.4, 126.7, 127.5, 127.9, 128.0, 128.1, 128.4, 129.4,
132.2, 132.4, 132.9, 133.5, 134.1, 135.1, 135.2, 138.2
(ArC); m/z 356 (MC, 0.5), 338 (1), 320 (0.4), 298 (28), 296
(19), 281 (21), 280 (52), 279 (100), 278 (30), 277 (50), 276
(20), 267 (17), 266 (17), 265 (45), 264 (12), 263 (21), 253
(17), 252 (34); HRMS: MC, found 356.1800. C25H24O2
requires 356.1776.
4.7.6.
2-Deuteromethyl-20-hydroxymethyl-1,10-bi-
naphthyl (12b). Colourless oil; Rf 0.17 (hexane/ethyl
acetate: 5:1); n (film) 3570–3400 (OH), 3047 cmK1
(ArH); dH 1.50 (1H, br s, OH), 2.05 (2H, s, CH2D), 4.32
(1H, d, JZ12.95 Hz, CHHOH), 4.38 (1H, d, JZ12.95 Hz,
CHHOH), 7.03 (1H, d, JZ8.4 Hz, ArH), 7.09 (1H, d, JZ
8.4 Hz, ArH), 7.18–7.27 (2H, m, ArH), 7.37–7.52 (3H, m,
ArH), 7.82 (1H, d, JZ8.4 Hz, ArH), 7.86–7.95 (3H, m,
ArH), 8.01 (1H, d, JZ8.4, ArH); dC 20.0 (t, JCDZ19.7 Hz,
CH2D), 63.4 (CH2OH), 125.1, 125.4, 125.8, 125.9, 126.0,
126.4, 126.5, 127.9, 128.0, 128.2, 128.7, 132.1, 132.4,
133.0, 133.2, 133.5, 134.6, 134.7, 136.4 (ArC); m/z 299
(MC, 41), 298 (27), 281 (35), 280 (73), 279 (88), 278 (39),
277 (27), 266 (30), 265 (39), 264 (23), 263 (17), 254 (12),
253 (22), 252 (46), 250 (10), 240 (10), 143 (17), 142 (14),
141 (12), 140 (12), 139 (32), 138 (18), 133 (11), 132 (100),
129 (14), 128 (10), 127 (45), 126 (69), 125 (12), 121 (11),
120 (15), 119 (13), 115 (12), 114 (13), 113 (24); HRMS:
MC, found 299.1420. C18H17DO requires 299.1419.
4.7.9. 2-(2-Hydroxy-2-ethylbutyl)-20-hydroxymethyl-1,
10-binaphthyl (12e). Colourless oil; Rf 0.26 (hexane/ethyl
acetate: 2:1); n (KBr) 3681–3103 (OH), 3053 cmK1 (ArH);
dH 0.56 (3H, t, JZ7.5 Hz, CH3), 0.73 (3H, t, JZ7.5 Hz,
CH3), 1.20–1.26 (2H, m, CH2CH3), 1.39–1.56 (2H, m,
CH2CH3), 1.98 (2H, br s, 2!OH), 2.46 (1H, d, JZ14.2 Hz,
CHHCOH), 2.65 (1H, d, JZ14.2 Hz, CHHCOH), 4.28 (1H,
d, JZ12.7 Hz, CHHOH), 4.32 (1H, d, JZ12.7 Hz,
CHHOH), 7.03–7.08 (2H, m, ArH), 7.20–7.24 (2H, m,
ArH), 7.40–7.47 (2H, m, ArH), 7.62 (1H, d, JZ8.6 Hz,
ArH), 7.81–8.00 (5H, m, ArH); dC 7.6, 8.1 (CH3), 30.4,
32.0, 41.9, 63.2 (CH2), 75.9 (COH), 125.5, 125.8, 126.1,
126.2, 126.3, 126.4, 126.8, 127.5, 127.9, 128.1, 129.3,
132.2, 132.5, 133.0, 133.6, 134.1, 134.7, 135.7, 138.4
(ArC); m/z 366 [(MCKH2O), 0.2], 298 (34), 281 (14), 280
(61), 279 (100), 278 (16), 277 (19), 276 (12), 267 (10), 266
(16), 265 (34), 263 (12), 252 (16); HRMS: MC, found
384.2094. C27H28O2 requires 384.2089.
4.7.7. 2-(2-Hydroxy-3,3-dimethylbutyl)-20-hydroxy-
methyl-1,10-binaphthyl (12c). First diastereoisomer:
white solid; mp 190–191 8C (hexane/ethyl acetate) (found:
C, 84.11; H, 7.44. C27H28O2 requires: C, 84.34; H, 7.34); Rf
0.14 (hexane/ethyl acetate: 5:1); n (film) 3649–3139 (OH),
3062 cmK1 (ArH); dH 0.66 [9H, s, (CH3)3], 2.25 (1H, dd,
JZ14.3, 11.0 Hz, CHHCHOH), 2.44 (2H, br s, 2!OH),
2.61 (1H, dd, JZ14.3, 2.2 Hz, CHHCHOH), 3.64 (1H, dd,
JZ11.0, 2.2 Hz, CHOH), 4.26 (2H, d, JZ12.2 Hz,
CHHOH), 4.33 (1H, d, JZ12.2 Hz, CHHOH), 7.00–7.04
(2H, dd, JZ8.4, 3.1 Hz, ArH), 7.19–7.25 (2H, m, ArH),
7.40–7.46 (2H, m, ArH), 7.62 (1H, d, JZ8.6 Hz, ArH), 7.79
(1H, d, JZ8.4 Hz, ArH), 7.89–8.00 (4H, m, ArH); dC 25.3
(CH3), 30.9 [C(CH3)3], 34.9, 63.1 (CH2), 80.0 (COH),
125.4, 125.7, 126.0, 126.2, 126.4, 126.5, 126.6, 127.3,
127.9, 128.0, 128.2, 128.3, 132.1, 133.0, 133.5, 134.2,
134.9, 136.5, 137.4 (ArC); m/z 384 (MC, 0.5), 366 (4), 350
(0.2), 298 (36), 281 (29), 280 (66), 279 (100), 278 (18), 277
(22), 276 (15), 267 (17), 266 (25), 265 (44), 264 (10), 263
(14), 252 (22); HRMS: MC, found 384.2090. C27H28O2
requires 384.2089. Second diastereoisomer: colourless oil;
Rf 0.13 (hexane/ethyl acetate: 5:1); n (film) 3630–3125
(OH), 3060 cmK1 (ArH); dH 0.53 [9H, s, (CH3)3], 2.28 (1H,
dd, JZ14.0, 10.7 Hz, CHHCHOH), 2.44 (2H, br s, 2!OH),
2.59 (1H, dd, JZ14.0, 2.2 Hz, CHHCHOH), 3.15 (1H, dd,
JZ10.7, 2.2 Hz, CHOH), 4.32 (1H, d, JZ13.1 Hz,
CHHOH), 4.36 (1H, d, JZ13.1 Hz, CHHOH), 7.12 (1H,
d, JZ8.6 Hz, ArH), 7.18 (1H, d, JZ8.4 Hz, ArH), 7.23–
7.31 (2H, m, ArH), 7.41–7.49 (2H, m, ArH), 7.61 (1H, d,
JZ8.4 Hz, ArH), 7.81 (1H, d, JZ8.6 Hz, ArH), 7.91–7.96
(3H, m, ArH), 8.02 (1H, d, JZ8.4 Hz, ArH); dC 25.1 (CH3),
34.6 [C(CH3)3], 36.5, 63.3 (CH2), 78.9 (COH), 125.4, 125.5,
125.9, 126.0, 126.5, 126.6, 128.0, 128.1, 128.2, 128.5,
129.1, 132.2, 132.4, 133.1, 133.2, 133.9, 134.1, 134.5, 137.2
4.7.10. 2-(1-Hydroxycyclohexylmethyl)-20-hydroxy-
methyl-1,10-binaphthyl (12f). Colourless oil; Rf 0.28
(hexane/ethyl acetate: 2:1); n (KBr) 3672–3148 (OH),
3062 cmK1 (ArH); dH 0.85–1.57 (10H, m, 5!CH2), 1.90
(2H, br s, 2!OH), 2.46 (1H, d, JZ14.2 Hz, CHHCOH),
2.58 (1H, d, JZ14.2 Hz, CHHCOH), 4.27 (1H, d, JZ
12.5 Hz, CHHOH), 4.33 (1H, d, JZ12.5 Hz, CHHOH),
7.00–7.09 (2H, m, ArH), 7.19–7.24 (2H, m, ArH), 7.39–
7.46 (2H, m, ArH), 7.62 (1H, d, JZ8.6 Hz, ArH), 7.83 (1H,
d, JZ8.6 Hz, ArH), 7.88–7.93 (3H, m, ArH), 7.99 (1H, d,
JZ8.4 Hz, ArH); dC 21.8, 21.9, 25.5, 36.8, 39.6, 63.2 (CH2),
72.6 (COH), 125.5, 125.8, 126.1, 126.2, 126.3, 126.4, 126.9,
127.4, 127.9, 128.1, 128.4, 128.5, 132.2, 132.4, 133.0,
133.6, 134.2, 134.5, 135.5, 138.5 (ArC); m/z 396 (MC, 0.1),
378 (0.6), 360 (1), 299 (10), 298 (42), 281 (17), 280 (70),
279 (100), 278 (16), 277 (19), 276 (12), 266 (11), 265 (29),
263 (11), 252 (16); HRMS: MC, found 396.2077. C28H28O2
requires 396.2089.

F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
9095
4.7.11. (S)-2-Hydroxymethyl-20-methyl-1,10-binaphthyl
[(S)-12a]. Physical and spectroscopic data were found to
be the same than for 12a.
´
Tetrahedron 2005, 61, 3125–3450. (Guest editors: Najera,
C.; Yus, M.).
3. For reviews, see: (a) Trost, B. M. Science 1991, 254,
1471–1477. (b) Trost, B. M. Angew. Chem., Int. Ed. Engl.
1995, 34, 259–281. (c) Trost, B. M. Acc. Chem. Res. 2002, 35,
695–705.
4.7.12. (R)-2-Hydroxymethyl-20-methyl-1,10-binaphthyl
[(R)-12a]. Physical and spectroscopic data were found to
be the same than for 12a.
4. For reviews, see: (a) Yus, M.; Foubelo, F. Rev. Heteroat.
Chem. 1997, 17, 73–107. (b) Yus, M.; Foubelo, F. In Attanasi,
O. A., Spinelli, D., Eds.; Targets in Heterocycic Systems;
Italian Society of Chemistry: Rome, 2002; Vol. 6, pp 136–171.
(c) Yus, M. Pure Appl. Chem. 2003, 75, 1453–1475.
5. For monographs on metal activation, see: (a) Cintas, P.
Activated Metals in Organic Synthesis; CRC: Boca Raton,
1993. (b) Active Metals; Fu¨rstner, A., Ed.; VCH: Weinheim,
1996.
4.7.13.
(R)-2-(2-Hydroxy-3,3-dimethylbutyl)-20-
hydroxymethyl-1,10-binaphthyl [(R)-12c]. Two diastereo-
isomers were isolated in enantiomericaly pure form and
their physical and spectroscopic data were found to be the
same than for those isolated in the racemic 12c.
4.7.14. (S)-2-(2-Hydroxy-2-ethylbutyl)-20-hydroxy-
methyl-1,10-binaphthyl [(S)-12e]. Physical and spectro-
scopic data were found to be the same than for 12e.
6. 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. Lat. J. Chem. 2002, 79–92. (e) Ramon, D. J.;
Yus, M. Rev. Cubana Quim. 2002, 14, 75–115. (f) Yus, M. In
Rappoport, Z., Marek, I., Eds.; The Chemistry of Organo-
lithium Compounds; Wiley: Chichester, 2004; Vol. 1,
pp 647–747. For mechanistic studies, see: (g) Yus, M.;
Herrera, R. P.; Guijarro, A. Tetrahedron Lett. 2001, 42,
3455–3458. (h) Yus, M.; Herrera, R. P.; Guijarro, A. Chem.
Eur. J. 2002, 8, 2574–2584. (i) Yus, M.; Herrera, R. P.;
Guijarro, A. Tetrahedron Lett. 2003, 44, 1309–1312. (j) Yus,
M.; Herrera, R. P.; Guijarro, A. Tetrahedron Lett. 2003, 44,
1313–1316. (k) Yus, M.; Herrera, R. P.; Guijarro, A.
Tetrahedron Lett. 2003, 44, 5025–5027. For a polymer
supported arene-catalized version of this reaction, see: (l)
4.7.15.
(R)-2-(2-Hydroxy-2-ethybutyl)-20-hydroxy-
methyl-1,10-binaphthyl [(R)-12e]. Physical and spectro-
scopic data were found to be the same than for 12e.
4.7.16. (S)-2-(1-Hydroxycyclohexylmethyl)-20-hydroxy-
methyl-1,10-binaphthyl [(S)-12f]. Physical and spectro-
scopic data were found to be the same than for 12f.
4.7.17. (R)-2-(1-Hydroxycyclohexylmethyl)-20-hydroxy-
methyl-1,10-binaphthyl [(R)-12f]. Physical and spectro-
scopic data were found to be the same than for 12f.
´
Gomez, C.; Ruiz, S.; Yus, M. Tetrahedron Lett. 1998, 39,
´
1397–1400. (m) Gomez, C.; Ruiz, S.; Yus, M. Tetrahedron
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This work was generously supported by the current Spanish
´
Ministerio de Educacion y Ciencia (MEC; grant no.
BQU2001-0538) and the Generalitat Valenciana (project
no. GRUPOS03/135). B.M. thanks the MEC for a
predoctoral fellowship.
´
1081–1083. (p) Alonso, F.; Gomez, C.; Candela, P.; Yus, M.
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Asymmetry 1992, 3, 1365–1368.

9096
F. Foubelo et al. / Tetrahedron 61 (2005) 9082–9096
solved by direct methods and refined to all 2901 unique F2o by
full matrix least squares (SHELX97). All the hydrogen atoms
were placed at idealised positions and refined as rigid atoms.
Final wR2Z0.1032 for all data and 199 parameters; R1Z
0.0685 for 972 FoO4s(Fo). (b) SAINT version 6.02A: Area-
Detector Integration Software; Siemens Industrial Automation
Inc.: Madison, WI, 1995. (c) Sheldrick, G. M. SADABS: Area-
´ ´
´ ´
12. Stara, I. G.; Stary, I.; Tichy, M.; Zavada, J.; Fiedler, P. J. Org.
Chem. 1994, 59, 1326–1332.
13. This selectivity has been observed in other cases using
different functionalised organolithium compounds and
prostereogenic cyclic carbonyl compounds. See, for instance:
(a) Soler, T.; Bachki, A.; Falvello, L. R.; Foubelo, F.; Yus, M.
Tetrahedron: Asymmetry 1998, 9, 3939–3943. (b) Soler, T.;
Bachki, A.; Falvello, L. R.; Foubelo, F.; Yus, M. Tetrahedron:
Asymmetry 2000, 11, 493–517. (c) Foubelo, F.; Saleh, S. A.;
Yus, M. J. Org. Chem. 2000, 65, 3478–3483. (d) Falvello,
L. R.; Foubelo, F.; Soler, T.; Yus, M. Tetrahedron: Asymmetry
2000, 11, 2063–2066. (e) Foubelo, F.; Yus, M. Tetrahedron
Lett. 2000, 41, 5047–5051. (f) Yus, M.; Soler, T.; Foubelo, F.
Tetrahedron: Asymmetry 2001, 12, 801–810. (g) Yus, M.;
Moreno, B.; Foubelo, F. Synthesis 2004, 1115–1118.
¨
Detector Absorption Correction; Gottingen University:
¨
Gottingen, Germany, 1996 (d) SHELX97 [Includes
SHELXS97, SHELXL97 and CIFTAB]—Programs for Crystal
Structure Analysis (Release 97-2). Sheldrick, G. M., Institu¨t
¨
fu¨r Anorganische Chemie der Universitat: Tammanstrasse 4,
¨
D-3400 Gottingen, Germany, 1998.
16. (a) Screttas, C. G.; Micha-Screttas, M. J. Org. Chem. 1978, 43,
1064–1071. (b) Screttas, C. G.; Micha-Screttas, M. J. Org.
Chem. 1979, 44, 713–719. (c) Cohen, T.; Bhupathy, M. Acc.
Chem. Res. 1989, 22, 152–161.
14. For a related ring opening of the corresponding oxygen- and
nitrogen-containing heterocycles, see: Azzena, U.; Demartis,
S.; Pilo, L.; Piras, E. Tetrahedron 2000, 56, 8375–8382.
15. (a) Crystal data (excluding structure factors deposited at the
Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 265391): C21H18S, MZ302.41;
17. Maigrot, N.; Mazaleyrat, J.-P. Synthesis 1985, 317–320.
18. Bestmann, H. J.; Both, W. Chem. Ber. 1974, 107, 2926–2930.
19. Kirmse, W.; Kund, K. J. Org. Chem. 1990, 55, 2325–2332.
20. Xiao, D.; Zhang, Z.; Zhang, X. Org. Lett. 1999, 1, 1679–1681.
21. Mislow, K.; Glass, M. A. W.; O’Brien, R. E.; Rutkin, P.;
Steinberg, D. H.; Weiss, J.; Djerassi, C. J. Am. Chem. Soc.
1962, 84, 1455–1478.
˚
˚
˚
monoclinic, aZ12.968(7) A, bZ13.179(7) A, cZ9.942(5) A,
3
˚
bZ107.473(10)8; VZ1620.7(15) A ; space group P2(1)/c;
ZZ4; DcZ1.239 Mg mK3; lZ0.71073 A; mZ0.194 mm
;
K1
˚
F(000)Z640; TZ24G1 8C. Data collection was performed on
a Bruker Smart CCD diffractometer, based on three u-scan
runs (starting uZK348) at values fZ08, 1208, 2408 with the
detector at 2qZK328. For each of these runs, 606 frames were
collected at 0.38 intervals and 30 s per frame. An additional run
fZ08 of 100 frames was collected to improve redundancy.
The diffraction frames were integrated using the program
SAINT and the integrated intensities were corrected for
Lorentz-polarisation effects with SADABS. The structure was
22. Truce, W. E.; Emrick, D. D. J. Am. Chem. Soc. 1956, 78,
6130–6137.
23. Chong, J. M.; MacDonald, G. K.; Park, S. B.; Wilkinson, S. H.
J. Org. Chem. 1993, 58, 1266–1268.
24. Miyano, S.; Okado, S.; Suzuki, T.; Handa, S.; Hashimoto, H.
Bull. Chem. Soc. Jpn. 1986, 59, 2044.
25. Junge, K.; Hagemann, B.; Enthaler, S.; Spannenberg, A.;
Michalik, M.; Oehme, G.; Monsees, S.; Riermeier, T.; Beller,
M. Tetrahedron: Asymmetry 2004, 15, 2621–2631.