About the stereoselectivity control in reactions of chiral ortho-sulfinyl benzyl carbanions with aldehydes

Article abstract of DOI:10.1016/j.tet.2004.04.051

Reactions of aliphatic and aromatic aldehydes with the benzyllithium derived from 2-p-tolylsulfinyl ethylbenzene yield mixtures of mainly two compounds, anti-3 and syn-4, epimers at hydroxylic carbon, easily separated by chromatography and desulfinylated into enantiomerically pure 1-alkyl (or aryl)-2-phenyl-1-propanols. The observed stereoselectivity at C(1) and C(2) is analyzed to the light of the steric and electronic effects of the substituents.

Full text of DOI:10.1016/j.tet.2004.04.051

Tetrahedron 60 (2004) 5383–5392
About the stereoselectivity control in reactions of chiral
ortho-sulfinyl benzyl carbanions with aldehydes
†
*
Jose L. Garcıa Ruano, M. Teresa Aranda and Jose M. Aguirre
´
´
´
´ ´ ´
Departamento de Quımica Organica, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
Received 13 February 2004; revised 20 April 2004; accepted 22 April 2004
Abstract—Reactions of aliphatic and aromatic aldehydes with the benzyllithium derived from 2-p-tolylsulfinyl ethylbenzene yield mixtures
of mainly two compounds, anti-3 and syn-4, epimers at hydroxylic carbon, easily separated by chromatography and desulfinylated into
enantiomerically pure 1-alkyl (or aryl)-2-phenyl-1-propanols. The observed stereoselectivity at C(1) and C(2) is analyzed to the light of the
steric and electronic effects of the substituents.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
size of those substituents joined to the carbonyl group. Thus,
the reactions of compound 1 with 2-butanone in the
presence of LDA yielded almost equimolecular mixtures
of only two compounds, epimers at the hydroxylic carbon,
whereas with benzaldehyde the observed stereoselectivity is
clearly higher (around 70% de). Only one diastereoisomer
was obtained in reactions with enantiomerically pure
(2S,SR)-2-p-tolylsulfinyl cyclohexanone, which could be
the result of a double asymmetric induction process.4 A
similar situation was also observed in reactions of 1 with
optically pure N-sulfinyl imines, where the presence of the
chiral sulfoxide at the electrophile allowed the complete
control of the stereoselectivity when the proper matched
pair of the reagents was used.5 All the compounds obtained
in these reactions have the same configuration at the
benzylic carbon, which evidences the high stability that the
sulfinyl group confers to one of the two diastereomeric ortho
benzyl carbanions. The importance of this question in
asymmetric synthesis, which would provide an entry to
many fragments with two joined chiral centers (one of them
benzylic) supporting a variety of heteroatoms, prompted us
to check the validity of the stereochemical model so far
proposed.4 With this aim and to know the scope of reactions
of 1 with aldehydes for synthesizing optically pure 1,2-
disubstituted-1-propanols, we have studied and described in
this paper the behavior of a series of aromatic and aliphatic
aldehydes, containing substituents of different electronic
character and size.
Enantioselective deprotonation/substitution processes of
benzylic positions1 have been widely investigated in the
last years. Chiral auxiliaries have allowed the sterocon-
trolled functionalization of remote positions2 and the use of
sparteine as a chiral ligand3 has provided significant success
in the generation of chiral benzylic carbons. We have
recently reported the highly stereoselective generation of
benzylic stereocenters mediated by a remote sulfinyl group.4
The reactions of benzyl carbanions derived from enantio-
merically pure ortho-p-tolylsulfinyl compounds with dif-
ferent electrophiles, yielded compounds with an almost
complete control at the configuration of the benzylic centers
(Scheme 1).
In the case of reactions with prochiral carbonyl compounds,
we demonstrated that the influence of the sulfinyl group on
the stereoselectivity control at the electrophilic center was
also significant and, apparently, dependent on the relative
Scheme 1.
Keywords: Benzylic stereocenter; Chiral benzyllithium; Sulfoxide; Remote
stereocontrol; 1-Alkyl-2-phenyl-1-propanol; 1-Aryl-2-phenyl-1-propanol.
2. Results and discussion
*
Corresponding author. Tel.: þ34-914974701; fax: þ34-914973966;
The synthesis of the compound 1 was performed starting
from ortho-bromoethylbenzene according to the procedure
previously reported.4 The results obtained in reactions with
e-mail address: joseluis.garcia.ruano@uam.es
Present address: Departamento de Ciencias Basicas, Universidad
´ ´
Nacional de Lujan, Lujan, Argentina.
†
´
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.04.051

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5384
Table 1. Reactions of 1 with different aldehydes
Entry
Aldehyde (R)
Diastereomer ratio anti-3:syn-4
Isolated yield (%)
3
4
1a
2
3
4
5
6
7
8
2a (Ph)
85:15
84:16
65
68
—
12
2b (p-OMeC6H4)
2c (p-NO2C6H4)
2d (p-CNC6H4)
2e (p-CO2MeC6H4)
2f (2-Naphtyl)
2g (1-Naphtyl)
2h (2,6-DiMeC6H3)
2i (n-Bu)
b
—
b
—
b
—
85:15c
88:12
67:33
37:63
29:71
24:76
62
73
44
32
21
14
—
—
26
55
54
44
9
10
11
2j (i-Pr)
2k (t-Bu)
a
Data taken from Ref. 4.
Complex mixture (see text).
See text.
b
c
different aromatic (2a–h) and aliphatic (2i–k) aldehydes
are collected in Table 1.
2.1. Configurational assignment
The 1H NMR parameters, which are significant for the
configurational assignment of both diastereomers, are
depicted in Table 2. In general, anti isomers exhibit higher
We first investigated the behavior of the aromatic aldehydes
2a–f differing in the electronic density of the rings, and
2g–h with different sizes. When compound 1 was treated
with LDA in THF at 278 8C and then added compounds
2a–h, we observed that starting material disappears after a
few minutes. Aldehydes containing activated rings (2b, 2g
and 2h) afforded mixtures of only two alcohols anti-3 and
syn-4, whereas the less activated 2f yielded a 78:13:9
mixture of three alcohols (only 3f and 4f have been
indicated in entry 6). We have used the notation anti and syn
to design compounds 3 and 4, respectively (Table 1). A
detailed study of the reaction crude from 2a also revealed
the presence of a third stereoisomer‡ that it had not been
previously reported.4 The 3:4 ratio is almost identical
(85:15) for 2a, 2b and 2f, all of them with a similar size of
the aromatic ring, slightly increases to 88:12 for 2g but
significantly decreases (67:33) for 2h, which is the bulkiest
ring. This behavior will be later commented. The adducts
were easily isolated, purified by chromatography and
therefore completely characterized. Compounds 2c–e,
presumably the most reactive because they contain
electron-withdrawing groups, yielded complex mixtures
whose complete analysis was not possible in our hands.
Table 2. Significant 1H NMR parameters for the configurational assign-
ment of syn and anti epimers
a
a
b
b
Entry
Isomer
J1,2
J1,OH
dOH
dMe
1c
2c
3
4
5
anti-3a
syn-4a
anti-3b
syn-4b
anti-3f
syn-4f
anti-3g
syn-4g
anti-3h
syn-4h
anti-3i
syn-4i
9.7
4.9
9.7
5.6
9.7
5.3
9.3
5.6
10.1
10.1
8.9
5.2
10.1
4.8
8.9
2.4
7.0
—
3.81
3.26
3.66
3.27
4.14
3.50
3.75
2.86
3.09
2.52
2.38
1.88
2.83
1.71
2.65
1.59
0.75
1.10
0.75
1.10
0.76
1.14
0.75
1.27
0.79
1.61
1.01
1.20
0.84
1.21
1.01
1.25
6.5
2.4
7.3
2.0
6.5
2.7
4.4
2.4
7.3
4.4
7.7
—
6
7
8d
9
1
10
11
12e
13e
14
15
16
Nevertheless, the H NMR spectra of their crudes suggest
the presence of more than two alcohols.6 Finally, the
reaction of 1 with aliphatic aldehydes 2i–k yielded mixtures
only containing adducts 3 and 4 (entries 9–11). The
stereoselectivity is lower than that observed from the
aromatic aldehydes and it slightly increases when size of
the R group become larger.
anti-3j
syn-4j
anti-3k
syn-4k
7.7
6.5
a
Values of J measured in Hz.
Values of d expressed in ppm.
Data taken from Ref. 4.
b
c
d
e
‡
The 1H NMR signals presumably due to the forth diastereoisomer in less
than 3% ratio can also be detected.
Data taken from a mixture 3gþ4g.
The values of J were measured by double resonance experiments.

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5385
can see, the main difference between both diastereomers is
the value of their vicinal coupling constants between the
protons of the fragment H–C(1)–C(2)–H (J1,2). They are
usually $8.9 Hz for the isomers we have named as anti, but
#5.6 Hz for the syn ones. Taking into account that the steric
interactions must be the main factor controlling the
conformational stability of these compounds around the
C(1)–C(2) bond, the most populated rotamers for both
diastereoisomers must be those avoiding the gauche
interaction between the bulkiest substituents R and
2-p-tolylsulfinylphenyl (except in the case of t-Bu7) as
they have been depicted in Scheme 3. According to this, the
syn isomers must exhibit the lower values of J1,2 (#5.6 Hz)
because they display the protons in a gauche arrangement,
whereas the anti isomers will be those with higher J1,2
values ($8.9 Hz). The unequivocal configurational assign-
ment of compounds 3k and 4k by X-ray diffraction analysis
supports the validity of these criteria.8
Scheme 2.
J1,2, J1,OH and dOH but lower dMe values than their
corresponding syn epimers.
We first established that both epimers had identical
configuration at C(2). This had been previously demon-
strated for anti-3a and syn-4a.4 We have now checked the
same for the epimeric pair anti-3h and syn-4h. Their
independent oxidation with PCC afforded the same ketone 5
(Scheme 2), indicating both epimers only differs in the
configuration at hydroxylic carbon C(1). The reaction of
ortho-sulfinyl benzyl carbanions with any aldehyde fol-
lowed of the PCC oxidation of the resulting epimeric
mixture provides a very simple synthetic route to prepare
optically pure benzylic ketones.
The only pair of diastereoisomers than cannot be unequi-
vocally assigned from their vicinal coupling constant values
is that formed by anti-3h and syn-4h. These compounds
have identical value of J1,2 (10.1 Hz) suggesting that both
exhibit an anti relationship between the protons in their
most populated rotamers. Two different possibilities could
explain this result: (a) the two aryl groups adopt a gauche
arrangement in one of the epimers,9 and (b) both isomers
differ in the configuration at their two chiral carbons. To
clarify this point it was necessary to perform their oxidation
The configurational assignment of the other epimeric pairs
was made from the parameters collected in Table 2. As we
Scheme 3.
Table 3. Desulfinylation of alcohols or their derivatives with Ra-Ni
Entry
Starting compound
Reaction time (h)
Product (yield, %)
1
2
3
4
5
6
7
8
9
anti-8a
anti-8f
anti-8g
anti-3i
syn-4i
anti-3j
syn-4j
anti-3k
syn-4k
1
24
24
0.75
6
1.75
3
3.5
4
anti-9a (70)a (66)b
anti-9f (48)a (41)b
anti-9g (60)a (35)b
anti-6i (89)
syn-7i (95)
anti-6j (45)
syn-7j (47)
anti-6k (69)
syn-7k (75)
a
Isolated yield.
Overall yield from anti-3a,f,g (protectionþdesulfinylation).
b

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5386
(see above), which unequivocally disregarded the second
possibility.
obtain the corresponding 1-aryl (or alkyl)-2-phenyl 1-pro-
panols in optically pure form. In order to illustrate this
process we have studied the reactions of several sulfinyl
alcohols derived from both aromatic and aliphatic aldehydes
with Raney nickel and the results are indicated in Table 3.
Other significant spectroscopic value clearly different for
both epimers is the J1,OH parameter, which is higher for the
anti epimers (Table 2). Values lower than 4 Hz are
indicative of a predominance of rotamers exhibiting a
gauche arrangement between the involved protons. This is
only possible for intramolecularly associated species.10
Values around 5–7 Hz indicate free rotation around C–O
bonds and suggest the absence of intramolecular hydrogen
bonds.11 As it can be seen from Table 2, anti epimers show
J1,OH values of 7^1 Hz, whereas syn epimers have always
smaller values that, in the case of 1,2-diaryl propanols, are
even lower than 3 Hz. These are the expected results on the
basis that intramolecular association of the OH and the
sulfinylic oxygen must be easier for the syn-4 epimers than
anti-3, because it is strongly hindered by the steric (Tol/
CH2)1,3-parallel interaction (Scheme 3).
The reactions of alcohols derived from aliphatic aldehydes
evolve at room temperature in EtOH for those times
indicated in Table 3 towards the expected enantiomerically
pure propanols 6 and 7. The yields ranged between
moderate and very good although they have not been
optimized. The alcohols derived from aromatic aldehydes
(anti-3a, anti-3g and anti-3f) react with Ra-Ni yielding a
65:35 mixture of epimers at hydroxylic carbon. This
epimerization, which had been previously observed in the
desulfinylation of similar alcohols,12 can be avoided by
protecting the hydroxy groups as silyl derivatives before
their treatment with Raney nickel. Compounds anti-3a,
anti-3f and anti-3g were thus converted into their silyl
derivatives anti-8a, anti-8f and anti-8g, previous to their
desulfinylation. Enantiomerically pure compounds anti-6
can be easily obtained from anti-9 with TBAF.
The relationship of dOH and dMe values with the relative
configuration of the epimers, which is evident from the data
collected in Table 2, is more difficult to rationalize.
Anyway, it must be related to the anisotropic effects exerted
by the sulfinyl and aryl groups, which display a different
orientation in each diastereoisomer. The combined use of all
these criteria allows the assignment of compounds syn-4h
and anti-3h (the first one exhibits lower J1,OH and dOH but
higher dMe values), which have identical J1,2 values.
2.3. Stereochemical discussion
The stereochemical results deduced from Table 1 can be
summarized as follows.
Stereoselectivity at C(2). It is complete from aliphatic
(2i–k) and activated aromatic (2b, 2g, 2h) aldehydes, high
but incomplete for aromatic aldehydes lacking of electron
donating groups (2a and 2f), and low for deactivated aryl
aldehyde 2d (and probably 2e).
2.2. Desulfinylation reactions
Desulfinylation of compounds 3 and 4 was required to
Figure 1. Stereochemical course of the reaction.

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5387
Stereoselectivity at C(1). The sense of the stereoselectivity
depends on the nature of the aldehyde. anti-3 Epimers are
predominant from Ar–CHO, whereas syn-4 are the major
ones from R–CHO. The small variation of the de’s obtained
from aliphatic (2i–k) and aromatic (2a, 2b, 2f–h)
aldehydes suggests a scarcely significant role of the steric
effects on the stereoselectivity.
which always predicts the predominance of the anti-3
isomers due to steric reasons. Moreover, the small
differences in de observed for the aliphatic aldehydes are
not compatible with any explanation based on steric effects.
These results indicate that the stereochemical course must
account for the fact that aliphatic or aromatic nature of the
aldehydes is more important than their size in the control of
the stereoselectivity.k
These two facts are difficult to explain from the stereo-
chemical model proposed previously.4 This one suggested
that the reaction of 1 with LDA yields the chelated species A
(Fig. 1), with tolyl and methyl groups adopting a
pseudoaxial arrangement in order to avoid their interactions
with the ortho protons (allylic strain). In the reactions of
these species with aldehydes, the carbonyl oxygen is
associated with the lithium (B in Fig. 1) as a previous step
to the nucleophilic attack, which makes easier the reaction.
Therefore it takes place intramolecularly with complete
retention of the configuration at the benzylic carbon that
becomes C(2) in the resulting propanol. The formation of
more than two isomers, observed in reactions with
aldehydes 2a, 2f, and 2d (and perhaps 2e too), means the
lost of configurational integrity at such a carbon during the
nucleophilic addition which must therefore take place with
partial racemization.§ The lost of stereoselectivity at C(2)
may be explained by assuming that they are less efficient in
the formation of the species B and a variable fraction of their
molecules (very low in 2a and 2f) evolves by association to
the less stable, but more reactive, species A0 (route c, Fig. 1)
without defined configuration. This fact would explain the
partial racemization observed at benzylic carbon.{
According to the expected tetrahedral structure of the
lithium, the species A has two coordinating vacancies,
which could be identified as pseudoequatorial (TS-I and
TS-II) and pseudoaxial (TS-III and TS-IV). As we can see,
from a steric point of view, TS-I and TS-IV are presumably
the most stable ones, respectively yielding anti-3 and syn-4
isomers. From the obtained results it seems that aliphatic
aldehydes prefer evolve through the axial vacancy (mainly
affording the syn isomers), whereas the association of the
aromatic aldehydes takes place mainly to the pseudoequa-
torial vacancy (the anti adducts are the mayor ones). The
reasons determining the preference of the aldehydes for the
pseudoaxial or pseudoequatorial approaches are not clear.pp
Taking into account that steric interactions are quite
important in the four-membered rings, they could determine
that TS-I and TS-IV were the only evolution ways through
the routes a and b, respectively. However, they must have
scarce significance in determining the pseudoequatorial or
pseudoaxial approach to the organolithium, which in its term
would be responsible of the stereoselectivity.
3. Conclusion
Concerning the stereoselectivity at C(1), the initial proposal
established that the intramolecular evolution of B occurred
via four-membered transition states (route a, Fig. 1). The
higher stability of TS-I with respect to TS-II, determined by
their steric interactions, was invoked to justify the 85:15
ratio of anti-3a:syn-4a observed in reaction with benz-
aldehyde. According to this model, steric interactions would
be responsible of the observed de. The fact that similar de
(70%) were obtained from 2a (entry 1), 2b (entry 2), and 2f
(entry 6) accounts for this proposal and suggests that
electronic grounds have scarce relevance in the stereo-
chemical course of the reaction. The slight improvement of
the stereoselectivity observed for 2g (76% de, entry 7) is
also consistent although a higher increase in de should
be expected on the basis of the quite higher size of the
1-naphtyl group with respect to the phenyl one. However,
the decrease of the de obtained from the bulkiest aldehyde
2h (34% de, entry 8) suggests something wrong in the initial
proposal. This failure is even more evident from the results
obtained with aliphatic aldehydes 2i–k. They show a very
low variation in their de despite the large differences in the
size of the aliphatic residues (n-Bu,i-Pr,t-Bu). Moreover,
they also show opposite stereoselectivity to that observed
with aromatic aldehydes. This inversion in the sense of the
stereoselectivity is not compatible with the initial model,
We have described the synthesis of enantiomerically pure
1-alkyl (or aryl)-2-pheny-1-propanols by reaction of
different aldehydes with the lithium 2-p-tolylsulfinyl benzyl
carbanions and further desulfinylation. Reactions from
aliphatic and aromatic aldehydes containing electron
donating groups are completely stereoselective at C(2),
but exhibit a moderate stereoselectivity at C(1) which is
mainly related to the aliphatic or aromatic character of the
aldehydes.
4. Experimental
4.1. General experimental methods
Solvents and aldehydes were purified according to standard
procedures. Reactions were monitored by TLC on commer-
cially available precoated plates (Merck silica gel 60 F254).
Flash chromatography was performed with Merck silica gel
k
Toru et al. (see Ref. 13 observed a similar situation in the reaction of
aldehydes with benzyllithium in the presence of bixoxazolines as chiral
ligands. The authors do not give any explanation about this fact.
We have investigated the stabilizing p-stacking interactions as a
pp
possible cause of the different behavior of aromatic and aliphatic
aldehydes. TS-III is less stable than TS-IV from a steric point of view,
but this situation can be inverted with aromatic aldehydes if we assume
that p-stacking interactions could stabilize TS-III (R¼Ar) with respect
to TS-IV. This assumption could not be strictly supported by the
experimental results because the stereoselectivity is scarcely modified
(de ranged between 60 and 70%) by the substituent of the aromatic ring.
§
The aldehydes showing this behavior are those with the lowest basicity at
the carbonyl group, that is, with the lowest ability to be associated with
{ the lithium.
It could also be explained by assuming the intermolecular attack of the
species A to these aldehydes (without previous association to the metal)
with inversion of the configuration at the benzylic carbon.

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5388
60 (230–400 mesh ASTM). Melting points were measured
using a Gallemkamp apparatus in open capillary tubes.
Specific rotations were measured at room temperature on a
Perkin–Elmer 241 MC polarimeter and concentrations are
expressed in g/100 mL. 1H and 13C NMR spectra were
recorded in CDCl3 on a Bruker AC-300 spectrometer (300
and 75 MHz, respectively) or Bruker WP-200-SY (200 and
50 MHz, respectively). Chemical shifts are reported in ppm
and J values are given in Hz. The attributions are supported
by double resonance experiments. IR spectra were obtained
in film with a Bruker Vector 22 spectrometer (4000–
400 cm21). Mass spectra were measured by electron impact
(EI, 70 eV) or FAB with a VG AutoSpec spectrometer.
Elemental analyses were obtained with a Perkin–Elmer
2400 CHNS/O series II. Diffractions of X-rays were taken
with a Siemens P4RA diffractometer.
158.7, 143.7, 142.5, 141.1, 140.8, 133.9, 131.3, 129.6,
128.0, 127.9, 127.2, 125.4, 113.0, 76.7, 55.0, 41.0, 21.2,
17.0. Anal. calcd for C23H24O3S: C, 72.60; H, 6.36; S, 8.43.
Found: C, 72.03; H, 6.29; S, 8.30. m/z (EIþ): 363 (Mþ2OH,
27), 225 (30), 152 (44), 135 (100), 91 (32), 77 (40). HRMS
calcd for C23H23O2S: 363.1419, found 363.1427.
4.2.3. (1S,2S,(S)S)-1-(2-Naphthyl)-2-[2-(p-tolylsulfinyl)-
phenyl)]-1-propanol (3f). Eluant for chromatography:
hexane/Et2O/CH2Cl2 1:2:1. Yield: 62%. Mp 190–191 8C
(Et2O–hexane). [a]2D0¼þ58.9 (c 1, CHCl3). IR: 3433, 2961,
1
1473, 1085, 1029 cm21. H NMR (300 MHz, CDCl3): d
7.88–7.73 (m, 5H0), 7.064–7.56 (m, 3H), 7.53–7.37 (m, 5H),
7.19 (part of AA BB system, 2H), 4.61 (dd, 1H, J¼7.3,
9.7 Hz, –CH–OH), 4.14 (d, 1H, J¼7.3 Hz, –OH), 3.87 (dq,
1H, J¼6.9, 9.7 Hz, CH3–CH–), 2.32 (s, 3H, CH3–Ar), 0.76
(d, 3H, J¼6.9 Hz, CH3–CH–). 13C NMR (75 MHz,
CDCl3): d 145.7, 142.8, 141.4, 141.1, 140.6, 133.1, 133.0,
132.6, 129.7, 128.7, 128.3, 128.1, 127.9, 127.6, 127.1,
126.0, 125.7, 124.7, 124.5, 80.2, 41.2, 21.2, 18.1. Anal.
calcd for C26H24O2S: C, 77.97; H, 6.04; S, 8.01. Found: C,
77.82; H, 5.82; S, 7.92.
4.2. General procedure for the reactions summarized in
Table 1
A solution of n-BuLi 2.3 M in hexane (260 mL, 0.60 mmol,
1.2 equiv.) was added over i-Pr2NH (126 mL, 0.90 mmol,
1.8 equiv.) in THF (3 mL) at 0 8C. After 45 min stirring, the
mixture was cooled at 278 8C and a solution of the
sulfoxide 1 (122 mg, 0.50 mmol, 1.0 equiv.) in THF (2 mL)
was then added. After 1 h stirring, the electrophile
(0.75 mmol, 1.5 equiv.) was added at 278 8C. When the
reaction was completed (15 and 30 min for aromatic and
aliphatic aldehydes, respectively) the mixture was hydro-
lyzed at that temperature (saturated NH4Cl), extracted
(CH2Cl2), dried (Na2SO4) and the solvent evaporated. The
residue was purified by flash column chromatography.
4.2.4. (1R,2S,(S)S)-1-(2-Naphthyl)-2-[2-(p-tolylsulfinyl)-
phenyl)]-1-propanol (4f). Eluant for chromatography:
1
hexane/Et2O/CH2Cl2 1:2:1. [a]2D0¼266.8 (c 1, CHCl3). H
NMR (300 MHz, CDCl3): d 7.79 (m, 1H), 7.73–7.63 (m,
3H), 7.55 (m, 1H), 7.48–7.42 (m, 2H), 7.38–7.29 (m, 2H),
7.19 (dd, 1H, J¼1.6, 8.5 Hz), 7.13–7.05 (m, 5H), 5.00 (dd,
1H, J¼2.0, 5.3 Hz, –CH–OH), 3.97 (dq, 1H, J¼5.3,
6.9 Hz, CH3–CH–), 3.50 (m, 1H, –OH), 2.33 (s, 3H,
CH3–Ar), 1.14 (d, 3H, J¼6.9 Hz, CH3–CH–).
4.2.1. (1S,2S,(S)S)-1-(p-Methoxyphenyl)-2-[2-(p-tolylsul-
finyl)phenyl)]-1-propanol (3b). Eluant for chroma-
tography: hexane/Et2O/EtOAc 1:1:1. Yield: 68%. Mp
134–135 8C (Et2O–hexane). [a]2D0¼245.9 (c 1, CHCl3).
4.2.5. (1R,2R,(S)S)-1-(2-Naphthyl)-2-[2-(p-tolylsulfinyl)-
phenyl)]-1-propanol (30f). Eluant for chromatography:
hexane/Et2O/CH2Cl2 1:2:1. H NMR (300 MHz, CDCl3):
d 7.90–7.81 (m, 4H), 7.73 (d, 1H, J¼8.1 Hz), 7.59 (dd,0 1H,
J¼1.6, 8.5 Hz), 7.54–7.38 (m, 7H), 7.25 (part of AA BB0
system, 2H), 4.83 (dd, 1H, J¼4.4, 8.9 Hz, –CH–OH), 3.76
(dq, 1H, J¼6.9, 8.9 Hz, CH3–CH–), 2.71 (d, 1H, J¼
4.4 Hz, –OH), 2.36 (s, 3H, CH3–Ar), 0.84 (d, 3H, J¼
6.9 Hz, CH3–CH–).
1
1
IR: 3373, 2969, 1612, 1512, 1248, 1082, 1030 cm21. H
NMR (300 MHz, CDCl3): d 7.75 (d, 1H, J¼7.7 Hz), 7.55
(m, 2H), 7.46 (pa0rt of AA0BB0 system, 2H), 7.38 (m, 1H),
7.30 (part of AA BB0 system, 02H), 7.22 (part of AA0BB0
system, 2H), 6.89 (part of AA BB0 system, 2H), 4.41 (dd,
1H, J¼6.5, 9.7 Hz, –CH–OH), 3.81 (s, 3H, –OCH3), 3.73
(dq, 1H, J¼6.9, 9.7 Hz, CH3–CH–), 3.66 (d, 1H, J¼
6.5 Hz, –OH), 2.34 (s, 3H, CH3–Ar), 0.75 (d, 3H, J¼
6.9 Hz, CH3–CH–). 13C NMR (75 MHz, CDCl3): d 159.0,
145.7, 142.9, 141.5, 140.6, 135.8, 132.5, 129.7, 128.5,
127.9, 127.0, 124.9, 113.7, 79.5, 55.2, 41.5, 21.2, 18.2.
Anal. calcd for C23H24O3S: C, 72.60; H, 6.36; S, 8.43.
Found: C, 72.66; H, 6.25; S, 8.21.
4.2.6. (1S,2S,(S)S)-1-(1-Naphthyl)-2-[2-(p-tolylsulfinyl)-
phenyl)]-1-propanol (3g). Eluant for chromatography:
hexane/Et2O/CH2Cl2 1:1:1. Yield: 73%. Mp 186–187 8C
(Et2O–hexane). [a]2D0¼250.8 (c 1, CHCl3). IR: 3436, 2968,
1
1595, 1474, 1266, 1085, 1025 cm21. H NMR (300 MHz,
CDCl3): d 8.30 (d, 1H, J¼8.1 Hz), 7.88–7.67 (m, 5H), 7.61
(dt, 1H, 0J¼1.2, 7.7 Hz), 7.54–7.39 (m, 4H), 7.46 and 7.22
(AA0BB system, 4H), 5.37 (dd, 1H, J¼6.5, 9.3 Hz, –CH–
OH), 4.13 (dq, 1H, J¼6.9, 9.3 Hz, CH3–CH–), 3.75 (d, 1H,
J¼6.5 Hz, –OH), 2.33 (s, 3H, CH3–Ar), 0.75 (d, 3H,
J¼6.9 Hz, CH3–CH–). 13C NMR (75 MHz, CDCl3): d
145.5, 143.1, 141.3, 140.5, 139.3, 133.6, 132.4, 131.2,
129.5, 128.7, 128.3, 128.0, 127.9, 127.2, 125.8, 125.3,
124.8, 124.6, 123.5, 76.2, 41.4, 21.1, 18.5. m/z (EIþ): 383
(Mþ2OH, 3), 244 (44), 225 (34), 152 (70), 135 (100), 129
(63), 91 (38), 77 (22). HRMS calcd for C26H23OS:
383.1470, found 363.1457.
4.2.2. (1R,2S,(S)S)-1-(p-Methoxyphenyl)-2-[2-(p-tolylsul-
finyl)phenyl)]-1-propanol (4b). Eluant for chroma-
tography: hexane/Et2O/EtOAc 1:1:1. Yield: 12%. Mp
162–163 8C (Et2O–hexane). [a]2D0¼284.2 (c 0.5, CHCl3).
1
IR: 3383, 2931, 1611, 1512, 1247, 1083, 1031 cm21. H
NMR (300 MHz, CDCl3): d 7.65 (dd, 1H, J¼1.6, 7.7 Hz),
7.34 (d quint, 2H, J¼1.6, 7.7 Hz), 7.19 (s, 4H), 7.02 (dd, 1H,
J¼1.6, 7.3 Hz), 6.97 and 6.72 (AA0BB0 system, 4H), 4.80
(dd, 1H, J¼2.4, 5.6 Hz, –CH–OH), 3.81 (quint, 1H,
J¼6.9 Hz, CH3–CH–), 3.75 (s, 3H, –OCH3), 3.27 (d, 1H,
J¼2.4 Hz, –OH), 2.37 (s, 3H, CH3–Ar), 1.10 (d, 3H,
J¼6.9 Hz, CH3–CH–). 13C NMR (75 MHz, CDCl3): d
4.2.7. (1S,2S,(S)S)-1-(2,6-Dimethylphenyl)-2-[2-(p-
tolylsulfinyl)phenyl)]-1-propanol (3h). Eluant for

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5389
chromatography: hexane/EtOAc 3:1. Yield: 44%. Mp 158–
159 8C (Et2O–hexane). [a]2D0¼2138.3 (c 1, CHCl3). IR:
(84), 154 (13), 136 (15), 91 (11). HRMS calcd for
C20H27O2S: 331.1732, found 331.1730.
3343, 2972, 1474, 1264, 1084, 1008 cm21 1H NMR
.
(300 MHz, CDCl3): d 7.68 (d, 1H, J¼8.5 Hz), 7.64–7.57
(m, 2H), 7.52 and 7.24 (AA0BB0 system, 4H), 7.38 (ddd, 1H,
J¼2.4, 6.1, 8.5 Hz), 7.10–6.98 (m, 3H), 5.31 (dd, 1H,
J¼4.4, 10.1 Hz, –CH–OH), 4.29 (dq, 1H, J¼6.9, 10.1 Hz,
CH3–CH–), 3.09 (d, 1H, J¼4.4 Hz, –OH), 2.61 (bs, 3H,
CH3–Ph), 2.47 (bs, 3H, CH3–Ph), 2.36 (s, 3H, CH3–Ar),
0.79 (d, 3H, J¼6.9 Hz, CH3–CH–). 13C NMR (75 MHz,
CDCl3): d 146.6, 143.8, 141.8, 140.5, 137.9, 137.0, 136.4,
132.6, 130.7, 129.6, 128.6, 128.3, 127.5, 127.4, 127.3,
124.9, 76.4, 38.8, 21.5, 21.2, 21.1, 18.3. Anal. calcd for
C24H26O2S: C, 76.15; H, 6.92; S, 8.47. Found: C, 76.11; H,
6.96; S, 8.57.
4.2.11. (3R,4S,(S)S)-2-Methyl-4-[2-(p-tolylsulfinyl)-
phenyl]-3-pentanol (3j). Eluant for chromatography:
hexane/EtOAc 3:1. Yield: 21%. [a]2D0¼252.4 (c 0.5,
CHCl3). IR: 3396, 2930, 1469, 1129, 1082 cm21 1H
.
NMR (300 MHz, CDCl3): d 7.72 (dd, 1H, J¼1.2, 7.7 Hz),
7.53–7.30 (m, 3H), 7.40 and 7.23 (AA0BB0 system, 4H),
3.47 (m, 1H, CH3–CH–), 3.42 (m, 1H, –CH–OH), 2.83 (d,
1H, J¼7.7 Hz, OH), 2.35 (s, CH3–Ar), 1.88 (d quint, 1H,
J¼2.0, 6.9 Hz, –CH–(CH3)2), 0.98 (d, 3H, J¼6.9 Hz,
CH3–CH–CH3), 0.86 (d, 3H, J¼6.9 Hz, CH3–CH–CH3),
0.84 (d, 3H, J¼6.9 Hz, CH3–CH–). 13C NMR (75 MHz,
CDCl3): d 142.5, 141.8, 140.6, 132.7, 129.6, 128.7, 128.1,
126.7, 124.7, 80.4, 37.5, 29.7, 21.3, 20.5, 17.5, 13.5. m/z
(FABþ): 317 (MHþ, 100), 299 (39), 154 (41), 136 (30), 91
(11), 77 (13).
4.2.8. (1R,2S,(S)S)-1-(2,6-Dimethylphenyl)-2-[2-(p-tolyl-
sulfinyl)phenyl)]-1-propanol (4h). Eluant for chroma-
tography: hexane/EtOAc 3:1. Yield: 26%. Mp 180–
181 8C (Et2O–hexane). [a]2D0¼2196.2 (c 1, CHCl3). IR:
4.2.12. (3S,4S,(S)S))-2-Methyl-4-[2-(p-tolylsulfinyl)-
phenyl]-3-pentanol (4j). Eluant for chromatography:
hexane/EtOAc 3:1. Yield: 54%. [a]2D0¼275.7 (c 0.5,
1
3418, 2974, 1473, 1083, 1009 cm21. H NMR (300 MHz,
CDCl3): d 7.57 (dd, 1H, J¼1.2, 7.7 Hz), 7.41 (dt, 1H, J¼1.2,
8.1 Hz, 1H), 7.14 (dt, 1H, J¼1.2, 7.1 Hz), 7.01 (m, 4H), 6.85
(part of AA0BB0 system, 2H), 6.46 (d, 2H, J¼8.1 Hz), 5.32
(dd, 1H, J¼2.4, 10.1 Hz, –CH–OH), 4.61 (dq, 1H, J¼6.9,
10.1 Hz, CH3–CH–), 2.52 (d, 1H, J¼2.4 Hz, –OH), 2.32
(s, 3H, CH3–Ar), 2.27 (bs, 6H, 2£CH3–Ph), 1.61 (d, 3H,
J¼6.9 Hz, CH3–CH–). 13C NMR (75 MHz, CDCl3): d
145.0, 140.2, 138.4, 137.0, 131.5, 129.6, 129.3, 128.2,
128.1, 127.9, 127.4, 124.9, 75.2, 39.0, 21.2, 20.9, 19.5.
Anal. calcd for C24H26O2S: C, 76.15; H, 6.92; S, 8.47.
Found: C, 76.10; H, 6.91; S, 8.53.
CHCl3). IR: 3415, 2962, 1469, 1083, 1041 cm21 1H
.
NMR (300 MHz, CDCl3): d 7.75 (dd, 1H, J¼1.2, 7.3 Hz),
7.45–7.32 (m, 3H), 7.40 and 7.22 (AA0BB0 system, 4H),
3.53 (dq, 1H, J¼4.8, 6.9 Hz, CH3–CH–), 3.13 (m, 1H,
–CH–OH), 2.34 (s, 3H, CH3–Ar), 1.71 (bs, 1H, OH), 1.57
(sx, 1H, J¼6.5 Hz, –CH–(CH3)2), 1.21 (d, 3H, J¼6.9 Hz,
CH3–CH–), 0.83 (d, 3H, J¼6.9 Hz, CH3–CH–CH3), 0.71
(d, 3H, J¼6.5 Hz, CH3–CH–CH3). 13C NMR (75 MHz,
CDCl3): d 145.1, 142.1, 141.6, 141.3, 131.4, 129.9, 128.4,
127.4, 126.7, 126.3, 79.3, 36.9, 31.2, 21.3, 19.6, 17.8, 15.4.
m/z (FABþ): 317 (MHþ, 100), 299 (49), 154 (69), 136 (49),
91 (20), 77 (22).
4.2.9. (2S,3R,(S)S)-2-[2-(p-Tolylsulfinyl)phenyl]-3-hepta-
nol (3i). Eluant for chromatography: hexane/EtOAc 3:1.
Yield 32%. [a]2D0¼253.3 (c 0.5, CHCl3). IR: 3406, 2957,
4.2.13. (3S,4S,(S)S)-2,2-Dimethyl-4-[2-(p-tolylsulfinyl)-
phenyl]-3-pentanol (3k). Eluant for chromatography:
hexane/EtOAc 3:1. Yield: 14%. Mp 127–128 8C.
[a]2D0¼251.2 (c 0.5, CHCl3). IR: 3406, 2956, 1471, 1131,
1082, 1007 cm21. 1H NMR (300 MHz, CDCl3): 7.66 (d, 1H,
J¼7.5 Hz), 7.51 (m, 2H), 7.43 and 7.25 (AA0BB0 system,
4H), 7.32 (m, 1H), 3.64 (dq, 1H, J¼6.9, 8.9, Hz, CH3–CH–),
3.30 (dd, 1H, J¼7.7, 8.9 Hz, –CH–OH), 2.65 (d, 1H,
J¼7.7 Hz, OH), 2.38 (s, CH3–Ar), 1.01 (d, 3H, J¼6.5 Hz,
CH3–CH–), 0.97 (s, 9H, (CH3)3). 13C NMR (75 MHz,
CDCl3): d 148.1, 141.8, 141.3, 140.5, 132.4, 129.5, 128.6,
128.5, 126.5, 124.8, 83.2, 37.6, 36.1, 27.0, 21.2, 20.7. m/z
(FABþ): 331 (MHþ, 100), 313 (40), 154 (84), 139 (23), 91
(30), 77 (23), 57 (94). HRMS calcd for C20H27O2S:
331.1732, found 331.1725.
2931, 1595, 1440, 1083, 1024, 1011 cm21 1H NMR
.
(300 MHz, CDCl3): d 7.75 (d, 1H, J¼7.7 Hz), 7.52–7.42
(m, 2H), 7.44 and 7.23 (AA0BB0 system, 4H), 7.34 (m, 1H),
3.53 (m, 1H, –CH–OH), 3.42 (dq, 1H, J¼6.9, 8.9 Hz,
CH3–CH–), 2.38 (d, 1H, J¼7.3 Hz, OH), 2.36 (s, 3H,
CH3–Ar), 1.60–1.25 (m, 6H, (–CH2–)3), 1.01 (d, 3H,
J¼6.9 Hz, CH3–CH–), 0.89 (t, 3H, J¼7.3 Hz, CH3–CH2–).
13C NMR (75 MHz, CDCl3): d 145.8, 142.9, 141.8,
140.8, 132.2, 129.7, 127.9, 127.8, 126.9, 125.1, 76.1, 40.0,
34.6, 27.0, 22.7, 21.3, 18.2, 14.0. m/z (FABþ): 331 (MHþ,
100), 313 (71), 154 (59), 139 (16), 107 (22), 91 (28), 77
(22). HRMS calcd for C20H27O2S: 331.1732, found
331.1739.
4.2.10. (2S,3S,(S)S)-2-[2-(p-Tolylsulfinyl)phenyl]-3-hep-
tanol (4i). Eluant for chromatography: hexane/EtOAc 3:1.
Yield: 55%. Mp 114–115 8C (Et2O–hexane). [a]2D0¼252.0
(c 0.5, CHCl3). IR: 3396, 2956, 2931, 1440, 1083,
4.2.14. (3R,4S,(S)S)-2,2-Dimethyl-4-[2-(p-tolylsulfinyl)-
phenyl]-3-pentanol (4k). Eluant for chromatography:
hexane/EtOAc 3:1. Yield: 44%. Mp 163–164 8C (Et2O–
hexane). [a]2D0¼295.8 (c 1, CHCl3). IR: 3443, 2953, 1487,
1305, 1147, 1089, 1047 cm21. 1H NMR (300 MHz, CDCl3):
d 7.66 (ddd, 2H,0 J¼1.6, 8.1, 12.5 Hz), 7.42 (m, 1H), 7.39
and 7.22 (AA0BB system, 4H), 7.32 (dt, 1H, J¼1.2, 7.7 Hz),
3.70 (dq, 1H, J¼2.4, 7.3 Hz, CH3–CH–), 3.35 (dd, 1H,
J¼2.4, 6.5 Hz, –CH–OH), 2.35 (s, CH3–Ar), 1.59 (d, 1H,
J¼6.5 Hz, OH), 1.25 (d, 3H, J¼7.3 Hz, CH3–CH–), 0.82
(s, 9H, (CH3)3). 13C NMR (75 MHz, CDCl3): d 147.8,
141.4, 141.3, 141.1, 131.8, 129.9, 128.4, 127.3, 126.7,
1
1006 cm21. H NMR (300 MHz, CDCl3): ( 7.93 (dd, 1H,
J¼2.4, 6.9 Hz), 7.43 and 7.21 (AA0BB0 system, 4H),
7.41–7.32 (m, 3H), 3.30 (m, 1H, –CH–OH), 3.23 (m,
1H, CH3–CH–), 2.36 (s, 3H, CH3–Ar), 1.88 (d, 1H, J¼
4.4 Hz, OH), 1.35–0.88 (m, 6H, (–CH2–)3), 1.20 (d, 3H,
J¼6.9 Hz, CH3–CH–), 0.79 (t, 3H, J¼7.3 Hz, CH3–CH2–).
13C NMR (75 MHz, CDCl3): d 144.1, 142.0, 141.7, 131.3,
129.9, 128.1, 127.1, 126.5, 126.0, 74.7, 40.0, 34.2, 28.4,
22.4, 21.3, 16.4, 13.9. m/z (FABþ): 331 (MHþ, 100), 313

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5390
126.2, 81.3, 36.5, 35.4, 26.6, 21.3, 16.9. Anal. calcd for
C20H26O2S: C, 72.69; H, 7.93; S, 9.70. Found: C, 72.55; H,
7.74; S, 9.39. m/z (FABþ): 331 (MHþ, 100), 313 (45), 243
(15), 154 (7), 139 (5), 91 (8), 77 (51), 57 (11).
Eluant for chromatography: hexane/AcOEt 1:1. Yield: 86%.
[a]2D0¼2237.2 (c 1, CHCl3). 1H NMR (200 MHz, CDCl3): d
7.86–7.27 (m, 13H), 7.13 (part of AA0BB0 system, 2H), 4.98
(d, 1H, J¼8.1 Hz, –CH–OTMS), 3.97 (quint, 1H, J¼
7.0 Hz, CH3–CH–), 2.35 (s, 3H, CH3–Ar), 1.19 (d, 3H,
J¼6.9 Hz, CH3–CH–), 20.22 (s, 9H, (CH3)3–Si).
4.2.15. (2S,(S)S)-1-(2,6-Dimethylphenyl)-2-[2-(p-tolylsul-
finyl)phenyl)]-propanone (5). The alcohol 3h or 4h was
dissolved in dry CH2Cl2 and PCC (1.5 equiv.) was added.
The mixture was stirred at room temperature during 4 h. The
solvent was partially evaporated and the residue was
chromatographed (hexane/EtOAc 1:1). Yield: 71%. Mp
106–107 8C (Et2O–hexane). [a]2D0¼248.2 (c 0.75, CHCl3).
4.3.4. (1S,2S)-1-(2-Naphthyl)-2-phenyl-1-trimethylsilyl-
oxypropane (9f). Yield: 48%. [a]2D0¼271.9 (c 0.75,
CHCl3). 1H NMR (300 MHz, CDCl3): d 7.84–7.76 (m,
3H), 7.63 (bs, 1H), 7.48–7.45 (m, 2H), 7.40 (dd, J¼1.6,
8.5 Hz, 1H) 7.30–7.18 (m, 5H), 4.75 (d, 1H, J¼7.7 Hz,
–CH–OTMS), 3.08 (quint, 1H, J¼7.3 Hz, CH3–CH–),
1.11 (d, 3H, J¼6.9 Hz, CH3–CH–), 20.19 (s, 9H, (CH3)3–
Si). 13C NMR (75 MHz, CDCl3): d 144.3, 141.3, 133.0,
132.9, 128.5, 127.9, 127.7, 127.6, 127.5, 126.1, 125.8,
125.6, 125.5, 125.1, 80.5, 48.1, 17.6, 20.2.
1
IR: 1698, 1466, 1085, 1033 cm21. H NMR (300 MHz,
CDCl3): d 7.57–7.51 (m, 2H), 7.47 (dt, 1H, J¼1.6, 8.1 Hz),
7.35 (dt, 1H,0J¼1.6, 8.1 Hz), 7.15 (t, 1H, J¼7.7 Hz), 7.03
and 6.92 (AA BB0 system, 4H), 6.84 (d, 2H, J¼8.1 Hz), 5.16
(q, 1H, J¼6.9 Hz, CH3–CH–), 2.32 (s, 3H, CH3–Ar), 2.00
(s, 6H, 2£CH3–Ph), 1.64 (d, 3H, J¼6.9 Hz, CH3–CH–).
13C NMR (75 MHz, CDCl3): d 208.2, 144.7, 141.4, 140.9,
140.6, 138.1, 133.4, 131.6, 129.7, 128.9, 128.6, 128.0,
127.3, 124.7, 48.1, 21.3, 19.5, 18.5. Anal. calcd for
C24H24O2S: C, 76.56; H, 6.42; S, 8.52. Found: C, 76.73;
H, 6.27; S, 8.06. m/z (EIþ): 376 (Mþ, 5), 243 (10), 225 (24),
133 (100), 105 (36), 91 (10), 77 (13). HRMS calcd for
C24H24O2S: 376.1497, found 376.1491.
4.3.5. (1S,2S)-1-(2-Naphthyl)-2-phenyl-1-propanol (6f).
This compound was obtained employing 9f, n-Bu4NþF2
(2 equiv.) and THF as solvent, under inert atmosphere, at
room temperature during 4 h. Eluant for chromatography:
hexane/EtOAc 6:1. Yield: 78%. [a]2D0¼241.7 (c 0.9,
CHCl3). IR: 3423, 2961, 1451, 1020 cm21 1H NMR
.
(200 MHz, CDCl3): d 7.88–7.80 (m, 4H), 7.55–7.46 (m,
3H), 7.38–7.28 (m, 5H), 4.83 (d, 1H, J¼8.6 Hz –CH–OH),
3.13 (dq, 1H, J¼6.9, 8.6 Hz, CH3–CH–), 1.96 (bs, 1H,
OH), 1.10 (d, 3H, J¼6.9 Hz, CH3–CH–). m/z (EIþ): 262
(Mþ, 2), 157 (100), 129 (61), 105 (13), 91 (8), 77 (12).
HRMS calcd for C19H18O: 262.1358, found 262.1354.
4.3. General procedure for desulfynilation of p-tolyl-
sulfoxides with Raney Nickel summarized in Table 3
The sulfoxide was dissolved in a minimal amount of ethanol
and excess of Raney Nickel was added. The reaction
mixture was vigorously stirred at room temperature and was
monitored by TLC. When no starting material remained,
stirring was stopped and the solvent was carefully decanted
and filtered on Celite. The solvent was evaporated and the
product was obtained from the residue in high purity.
4.3.6. (1S,2S,(S)S)-1-(1-Naphthyl)-2-[2-(p-tolylsulfinyl)-
phenyl)]-1-trimethylsilyloxypropane (8g). This com-
pound was obtained employing the alcohol 3g, trimethyl-
silyl chloride (2.0 equiv.), 2,6-lutidine (2.5 equiv.) and
dichloromethane as solvent at room temperature during
one hour. Eluant for chromatography: hexane/AcOEt 1:1.
Yield: 59%. [a]D20¼2273.6 (c 1, CHCl3). 1H NMR
(200 MHz, CDCl3): d 8.22 (m, 1H), 7.87–7.22 (m, 14H),
5.65 (m, 1H, –CH–OTMS), 4.23 (m, 1H, CH3–CH–), 2.38
(s, 3H, CH3–Ar), 1.15 (m, 3H, CH3–CH–), 20.23 (s, 9H,
((CH3)3–Si).
4.3.1. (1S,2S,(S)S)-1-Phenyl-2-[2-(p-tolylsulfinyl)-
phenyl]-1-trimethylsilyloxypropane (8a). This compound
was obtained employing the alcohol 3a, trimethylsilyl
triflate (2.0 equiv.), 2,6-lutidine (2.5 equiv.) and dichloro-
methane as solvent at 0 8C during 20 min. Yield: 94%.
[a]2D0¼221.1 (c 1.68, CHCl3). 1H NMR (200 MHz, CDCl3):
d 7.66 (d, 1H, J¼7.6 Hz), 7.58–7.20 (m, 12H), 4.78 (d, 1H,
J¼7.0 Hz, –CH–OTMS), 3.85 (m, 1H, CH3–CH–), 2.40
(s, 3H, CH3–Ar), 1.13 (d, 3H, J¼7.0 Hz, CH3–CH–),
20.75 (s, 9H, (CH3)3–Si). 13C NMR: (75 MHz, CDCl3) d
144.5, 143.5, 142.1, 140.7, 131.1, 129.6, 128.1, 127.5,
126.9, 125.9, 125.6, 79.8, 43.1, 21.3, 19.8, 20.1.
4.3.7. (1S,2S,(S)S)-1-(1-Naphthyl)-2-phenyl-1-trimethyl-
silyloxypropane (9g). Yield: 60%. [a]2D0¼2134.8 (c 1,
CHCl3). 1H NMR (200 MHz, CDCl3): d 8.32 (m, 1H), 7.88
(dd, 1H, J¼1.6, 7.7 Hz), 7.75 (dd, 1H, J¼2.8, 6.5 Hz), 7.52
(dquint, 2H, J¼1.6, 6.5 Hz), 7.39–7.33 (m, 2H), 7.26–7.16
(m, 5H) 5.36 (m, 1H, –CH–OTMS), 3.30 (m, 1H, CH3–
CH–), 1.15 (m, 3H, CH3–CH–), 20.19 (s, 9H, ((CH3)3–
Si). 13C NMR (50 MHz, CDCl3): d 144.0, 139.6, 133.7,
130.7, 128.8, 128.6, 127.5, 126.0, 125.4, 125.1, 123.8, 77.6,
47.4, 18.3, 20.4.
4.3.2. (1S,2S)-1,2-Diphenyl-1-trimethylsilyloxypropane
(9a). Yield: 70%. [a]D20¼282.5 (c 0.71, CHCl3). H NMR
1
(200 MHz, CDCl3): d 7.35–7.15 (m, 10H), 4.60 (d, 1H,
J¼7.0 Hz, –CH–OTMS), 3.02 (quint, J¼7.0 Hz, 1H, CH3–
CH–), 1.12 (d, 3H, J¼7.0 Hz, CH3–CH–), 20.20 (s, 9H,
(CH3)3Si). 13C NMR (75 MHz, CDCl3): d 144.3, 143.7,
128.4, 127.6, 126.9, 126.8, 126.0, 82.2, 48.1, 17.5, 20.3.
4.3.8. (1S,2S)-1-(1-Naphthyl)-2-phenyl-1-propanol
(6g).14 This compound was obtained employing 9g,
n-Bu4NþF2 (2 equiv.) and THF as solvent, under inert
atmosphere, at room temperature during 4 h. Eluant
for chromatography: hexane/EtOAc 6:1.Yield: 89%.
[a]2D0¼282.0 (c 0.7, CHCl3). IR: 3443, 2964, 1494, 1453,
4.3.3. (1S,2S,(S)S)-1-(2-Naphthyl)-2-[2-(p-tolylsulfinyl)-
phenyl)]-1-trimethylsilyloxypropane (8f). This compound
was obtained employing the alcohol 3f, trimethylsilyl
chloride (2.0 equiv.), 2,6-lutidine (2.5 equiv.) and dichloro-
methane as solvent at room temperature during one hour.
1
1026 cm21. H NMR (200 MHz, CDCl3): d 8.34 (dd, 1H,
J¼2.1, 7.5 Hz), 7.92–7.79 (m, 2H), 7.60–7.25 (m, 9H),
5.47 (dd, 1H, J¼3.2, 8.1 Hz –CH–OH), 3.40 (quint, 1H,

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5391
J¼7.0 Hz, CH3–CH–), 1.97 (d, 1H, J¼2.7 Hz, OH), 1.14
(d, 3H, J¼7.0 Hz, CH3–CH–). m/z (EIþ): 262 (Mþ, 3), 157
(100), 129 (66), 105 (15), 91 (9), 77 (13). HRMS calcd for
C19H18O: 262.1358, found 262.1355.
4.3.14. (3R,4S)-2,2-Dimethyl-4-phenyl-3-pentanol (7k).17
Yield: 75%. [a]2D0¼þ41.5 (c 0.5, CHCl3). IR: 3442, 2957,
1
1640, 1453, 1364 cm21. H NMR (200 MHz, CDCl3): d
7.35–7.13 (m, 5H), 3.44 (dd, 1H, J¼3.8, 5.4 Hz –CH–
OH), 3.03 (dq, 1H, J¼3.8, 7.0 Hz, CH3–CH–), 1.49 (d, 1H,
J¼5.4 Hz, OH), 1.31 (d, 3H, J¼7.0 Hz, CH3–CH–), 0.94
(s, 9H, (CH3)3). 13C NMR (75 MHz, CDCl3): d 148.0,
128.4, 127.4, 126.0, 83.0, 41.1, 36.1, 26.8, 16.4. m/z (EIþ):
192 (Mþ, ,1), 149 (8), 135 (12), 106 (100), 91 (62), 77 (22),
57 (91).
4.3.9. (2S,3R)-2-Phenyl-3-heptanol (6i).15 Yield: 89%.
[a]2D0¼25.2 (c 0.5, CHCl3). IR: 3423, 2958, 1641, 1453,
1
1007 cm21. H NMR (300 MHz, CDCl3): d 7.34–7.19 (m,
5H), 3.64 (m, 1H, –CH–OH), 2.73 (quint, 1H, J¼7.3 Hz,
CH3–CH–), 1.63–1.25 (m, 7H, (–CH2–)3 and OH), 1.27
(d, 3H, J¼7.3 Hz, CH3–CH–), 0.89 (t, 3H, J¼7.3 Hz,
CH3–CH2-). 13C NMR (75 MHz, CDCl3): d 143.5, 128.5,
128.2, 126.6, 76.0, 46.1, 34.2, 27.9, 22.8, 18.0, 14.0. m/z
(FABþ): 175 (MHþ2H2O, 52), 154 (69), 137 (55), 105
(100), 91 (63), 77 (19).
Acknowledgements
We thank CAICYT (Grant BQU2003-04012) for financial
support.
4.3.10. (2S,3S)-2-Phenyl-3-heptanol (7i).15 Yield: 95%.
[a]2D0¼210.1 (c 0.5, CHCl3). IR: 3386, 2958, 1602,
1454 cm21 1H NMR (300 MHz, CDCl3): d 7.34–7.21
.
(m, 5H), 3.68 (m, 1H, –CH–OH), 2.79 (quint, 1H, J¼
6.9 Hz, CH3–CH–), 1.47–1.25 (m, 7H, (–CH2–)3 and
OH), 1.32 (d, 3H, J¼6.9 Hz, CH3–CH–), 0.88 (t, 3H,
J¼7.3 Hz, CH3–CH2–). 13C NMR (75 MHz, CDCl3): d
144.7, 128.5, 127.8, 126.4, 76.2, 45.5, 34.4, 28.2, 22.6, 15.3,
14.0. m/z (FABþ): 175 (MHþ2H2O, 75), 154 (18), 137
(22), 105 (100), 91 (53), 77 (11).
References and notes
1. Ahlbrecht, H. Methods of Organic Chemistry (Houben-Weyl).
Additional and Supplementary Volumes to the 4th Edition;
Helmchen, G., Hoffmann, R. W., Mulzer, J., Schaumann, E.,
Eds.; Thieme: Stuttgart, 1995; Vol. E21a, pp 664–695.
2. (a) Linnane, P.; Magnus, N.; Magnus, P. Nature 1997, 385,
799–801. (b) Magnus, N.; Magnus, P. Tetrahedron Lett. 1997,
38, 3491–3494. (c) Myers, A. G.; Yang, B. H.; Chen, H.;
McKinstry, L.; Kopecky, D. J.; Gleason, J. L. J. Am. Chem.
Soc. 1997, 119, 6496–6511. (d) For recent review, see:
Mikami, K.; Shimizu, M.; Zhang, H. C.; Maryanoff, B. E.
Tetrahedron 2001, 57, 2917–2951.
4.3.11. (3R,4S)-2-Methyl-4-phenyl-3-pentanol (6j).16
Yield: 45%. [a]2D0¼216.9 (c 0.5, CHCl3). IR: 3474, 2963,
1
1494, 1453 cm21. H NMR (300 MHz, CDCl3): d 7.36–
7.21 (m, 5H), 3.44 (m, 1H, –CH–OH), 2.85 (quint, 1H,
J¼7.3 Hz, CH3–CH–), 1.80 (d sx, 1H, J¼4.4, 6.9 Hz,
–CH–(CH3)2), 1.26 (d, 3H, J¼6.9 Hz, CH3–CH–),
1.20 (d, 1H, J¼4.4 Hz, OH), 1.03 (d, 3H, J¼6.9 Hz,
CH3–CH–CH3), 0.95 (d, 3H, J¼6.9 Hz, CH3–CH–CH3,).
13C NMR (75 MHz, CDCl3): d 144.1, 128.6, 128.1,
126.6, 80.4, 43.4, 29.9, 20.4, 18.6, 15.3. m/z (EIþ): 178
(Mþ, 4), 160 (10), 145 (27), 135 (10), 106 (100), 91 (88), 77
(27), 57 (79). HRMS calcd for C12H18O: 178.1358, found
178.1358.
3. (a) Hoppe, D.; Hense, T. Angew. Chem. Int. Ed. 1997, 36,
2282–2316. (b) Beak, P.; Basu, A.; Gallagher, D. J.; Park,
Y. S.; Thayumanavan, A. Acc. Chem. Res. 1996, 29, 552–560.
For recent uses of (2)-sparteine, see: (c) Johnson, T. A.; Jang,
D. O.; Slafer, B. W.; Curtis, M. D.; Beak, P. J. Am. Chem. Soc.
2002, 124, 11689–11698. (d) Jang, D. O.; Kim, D. D.; Pyun,
D. K.; Beak, P. Org. Lett. 2003, 5, 4155–4157.
´
4. Garcıa Ruano, J. L.; Carren˜o, M. C.; Toledo, M. A.; Aguirre,
J. M.; Aranda, M. T.; Fisher, J. Angew. Chem. Int. Ed. 2000,
39, 2736–2737.
4.3.12. (3S,4S)-2-Methyl-4-phenyl-3-pentanol (7j).16
Yield: 47%. [a]2D0¼þ11.5 (c 0.5, CHCl3). IR: 3426, 2963,
´ ´
5. (a) Garcıa Ruano, J. L.; Aleman, J.; Soriano, J. F. Org. Lett.
´ ´
2003, 5, 677–680. (b) Garcıa Ruano, J. L.; Aleman, J. Org.
1
1494, 1453 cm21. H NMR (300 MHz, CDCl3): d 7.35–
7.21 (m, 5H), 3.41 (m, 1H, –CH–OH), 2.90 (quint, 1H,
J¼6.9 Hz, CH3–CH–), 1.60 (m, 1H, –CH–(CH3)2), 1.40
(bs, 1H, OH), 1.31 (d, 3H, J¼6.9 Hz, CH3–CH–), 0.94 (d,
3H, J¼6.5 Hz, CH3–CH–CH3); 0.91 (d, 3H, J¼6.5 Hz,
CH3–CH–CH3,). 13C NMR (75 MHz, CDCl3): d 145.1,
128.5, 127.7, 126.2, 81.1, 42.7, 30.1, 19.9, 16.7, 15.6. m/z
(EIþ): 178 (Mþ, 4), 160 (15), 145 (41), 106 (100), 91 (86),
77 (28), 57 (45). HRMS calcd for C12H18O: 178.1358,
found 178.1360.
Lett. 2003, 5, 4513–4516.
6. In the crude obtained from 2c, the identification of any
compound was not possible. The signals of several alcohols,
probably more than two, could be recognized in the 1H NMR
spectrum of the crude came from 2e. They are not the major
components and the products could not be isolated. Only the
crude obtained from nitrile 2d showed the presence of an
18:22:9:51 mixture of the four possible alcohols, according to
eluting order, as major components (72%). Their relative
1
stereochemistry was established by H NMR (ratio anti–syn,
4.3.13. (3S,4S)-2,2-Dimethyl-4-phenyl-3-pentanol (6k).17
Yield: 69%. [a]2D0¼þ8.0 (c 0.5, CHCl3). IR: 3451, 2958,
69:31). Nevertheless, their complete configurational assign-
ment was not established because only the first and the last
compounds could be separated.
1
1642, 1453, 1365 cm21. H NMR (300 MHz, CDCl3): d
7.35–7.18 (m, 5H), 3.41 (m, 1H, –CH–OH), 3.05 (dq, 1H,
J¼4.0, 7.3 Hz, CH3–CH–), 1.43 (bs, 1H, OH), 1.39 (d, 3H,
J¼7.3 Hz, CH3–CH–), 0.86 (s, 9H, (CH3)3). 13C NMR
(75 MHz, CDCl3): d 144.1, 128.9, 128.3, 126.4, 83.4, 41.7,
35.9, 26.7, 22.4. m/z (EIþ): 192 (Mþ, ,1), 149 (43), 105
(25), 91 (23), 77 (18), 57 (100).
7. Hirota, M.; Sekiya, T.; Abe, K.; Tashiro, H.; Karatsu, M.
Tetrahedron 1983, 39, 3091–3099.
8. Crystallographic data (excluding structure factors) for the
structures 3k and 4k have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
numbers CCDC 221162 and 221163. Copies of the data can be

´
J. L. Garcıa Ruano et al. / Tetrahedron 60 (2004) 5383–5392
5392
obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge, CB2 1EZ, UK [fax: þ44(0)-1223-336033
13. (a) Nakamura, S.; Nakagawa, R.; Watanabe, Y.; Toru, T.
J. Am. Chem. Soc. 2000, 122, 11340–11347. (b) Nakamura,
S.; Nakagawa, R.; Watanabe, Y.; Toru, T. Angew. Chem. Int.
Ed. 2000, 39, 353–355.
or e-mail: deposit@ccdc.cam.ac.uk].
9. The fact that the preferred conformation of one of these
epimers displays the high sterically demandant 2,6-dimethyl-
phenyl ring in gauche arrangement with respect to the
sulfinylated ring suggests some kind of p-stacking interaction
between the aromatic rings exhibiting complementary elec-
tronic density (donor–acceptor interaction).
14. Piazza, C.; Millot, N.; Knochel, P. J. Organomet. Chem. 2001,
624, 88–95.
15. Reetz, M. T.; Stanchev, S.; Haning, H. Tetrathedron 1992, 48,
6813–6820.
16. Alonso, E.; Guijarro, D.; Yus, M. Tetrahedron 1995, 51,
11457–11464.
´ ´
17. Alonso, E.; Guijarro, D.; Martınez, P.; Ramon, D. J.; Yus, M.
10. Abraham, R. J.; Bakke, J. M. Tetrahedron 1978, 34, 2947–2951.
11. Moniz, W. B.; Poranski, Jr. C. F.; Hall, T. N. J. Am. Chem.
Soc. 1966, 88, 190–192.
Tetrahedron 1999, 55, 11027–11038.
´ ´
12. Garcıa Ruano, J. L.; Garcıa Paredes, C.; Hamdouchi, C.
Tetrahedron: Asymmetry 1999, 10, 2935–2944.