Conformational Studies by Dynamic Nuclear Magnetic Resonance. 59. Stereodynamics of Conformational Enantiomers in the Atropisomers of Hindered Naphthylcarbinols

Article abstract of DOI:10.1021/jo970113+

Naphthyldialkylmethanols ArRR'COH (Ar = 1-naphthyl or 1-naphthyl-2-methyl) exist as a pair of atropisomers created by the restricted rotation about the Ar-COH bond.They can be detected by low-temperature NMR spectroscopy but can also be separated as stable compounds at room temperature if both the alkyl substituents are bulky tert-butyl groups (one such example is provided by compound 1, R = R' = Bu^t with Ar = 1-naphthyl).The free energies of activation (ΔG^%) for the interconversion of these atropisomers were found to vary between 7.6 kcal mol^-1 (as in 7, R = R' = Me, Ar = 1-naphthyl-2-methyl) and 32.9 kcal mol^-1 (as in 1).The syn-periplanar (sp) or anti-periplanar (ap) structires were assigned either by means of difference NOE experiments or by taking advantage of the H-8 chemical shifts which are vastly different in the two atropisomers.Depending on the substituents the more stable species at the equilibrium can be either the sp or the ap atropisomer.When R = R' = Prⁱ and R = R' = Et (respectively 2 and 3 if Ar = 1-naphthyl), the sp atropisomers adopt an asymmetric conformation, thus creating a pair of conformational enantiomers which interchange by rotating the isopropyl or the ethyl groups about the appropriate sp³-sp³ bonds, with ΔG^% values of 7.2 and 6.1 kcal mol^-1, respectively.On the contrary the corresponding 3-ap and 2-ap atropisomers adopt a symmetric (meso) conformation, as predicted by molecular mechanics calculations.In the case of R=Prⁱ, R'=Et, and Ar=1-naphthyl (10-sp atropisomer), two asymmetric conformers were found to be appreciably populated (ratio 9:1 at -135 deg C).

Full text of DOI:10.1021/jo970113+

J . Org. Chem. 1997, 62, 3315-3323
3315
Con for m a tion a l Stu d ies by Dyn a m ic Nu clea r Ma gn etic Reson a n ce.
1
5
9. Ster eod yn a m ics of Con for m a tion a l En a n tiom er s in th e
Atr op isom er s of Hin d er ed Na p h th ylca r bin ols
Daniele Casarini,* Lodovico Lunazzi, and Andrea Mazzanti2
Department of Organic Chemistry “A. Mangini”, University of Bologna,
Risorgimento, 4, Bologna 40136, Italy
Received J anuary 22, 1997X
Naphthyldialkylmethanols ArRR′COH (Ar ) 1-naphthyl or 1-naphthyl-2-methyl) exist as a pair of
atropisomers created by the restricted rotation about the Ar-COH bond. They can be detected by
low-temperature NMR spectroscopy but can also be separated as stable compounds at room
temperature if both the alkyl substituents are bulky tert-butyl groups (one such example is provided
t
q
by compound 1, R ) R′ ) Bu with Ar ) 1-naphthyl). The free energies of activation (∆G ) for the
-
1
interconversion of these atropisomers were found to vary between 7.6 kcal mol (as in 7, R ) R′
-
1
)
Me, Ar ) 1-naphthyl-2-methyl) and 32.9 kcal mol (as in 1). The syn-periplanar (sp) or anti-
periplanar (ap) structures were assigned either by means of difference NOE experiments or by
taking advantage of the H-8 chemical shifts which are vastly different in the two atropisomers.
Depending on the substituents the more stable species at the equilibrium can be either the sp or
i
the ap atropisomer. When R ) R′ ) Pr and R ) R′ ) Et (respectively 2 and 3 if Ar ) 1-naphthyl),
the sp atropisomers adopt an asymmetric conformation, thus creating a pair of conformational
enantiomers which interchange by rotating the isopropyl or the ethyl groups about the appropriate
3
3
q
-1
sp -sp bonds, with ∆G values of 7.2 and 6.1 kcal mol , respectively. On the contrary the
corresponding 3-ap and 2-ap atropisomers adopt a symmetric (meso) conformation, as predicted
i
by molecular mechanics calculations. In the case of R ) Pr , R′ ) Et, and Ar ) 1-naphthyl (10-sp
atropisomer), two asymmetric conformers were found to be appreciably populated (ratio 9:1 at -135
°
C).
In tr od u ction
isomer of a very similar compound (i.e., that having Ar
)
2-methyl-4-methoxyphenyl) indicated that a syn-
2
3
Restricted rotation about the sp -sp Ar-COH bond
periplanar (sp) structure is adopted. The OH group, in
fact, points toward the o-methyl substituent, with the
C-OH bond lying, in practice, on the same plane of the
aromatic ring, the corresponding dihedral angle deviating
only by 11.6° from a perfect coplanarity.6 In solution, of
course, a low-barrier libration process of (11.6° would
cause this plane to become a dynamic plane of symmetry.
Atropisomers of this type, with even larger interconver-
t
in carbinols of the type Ar-C(Bu )
2
OH (Ar being the
3
a
4
-methoxyphenyl moiety) was first reported by Stern-
hell and co-workers. They also identified the presence
of two syn and anti conformers when the Ar group (e.g.,
3
Ar ) 3,4-dimethoxyphenyl) bore substituents in positions
which destroyed the 2-fold Ar-COH symmetry axis of
the phenyl (or of the para-substituted phenyl groups).
The barrier for the Ar-COH rotation was measured
sion barriers, were observed for adamantyl (Ad) deriva-
-
1
1
(
about 20 kcal mol ) by variable temperature H NMR
t
tives such as Ar-C(Ad)
2
OH and Ar-CBu AdOH, Ar
3
spectroscopy. When less hindered carbinols (e.g., Ar-
being again the o-tolyl group.8
,9
In addition to the
t
i
CRBu OH, with R ) H, Me, Et, Pr ) were investigated,
2
3
mentioned rotational process about the sp -sp bond, a
the interconversion barriers were found, not unexpect-
3
q
second rotational process was detected about the sp -
edly, considerably lower (∆G in the range 8.7-13.0 kcal
mol ). Subsequently Lomas and Dubois were able to
3
t
t
-1
4
5,6
sp Bu -COH bonds in Ar-C(Bu ) OH (Ar ) o-tolyl). The
2
7
barriers for the rotation of the tert-butyl groups are not
equal in the two atropisomers, that of the syn-periplanar
isolate the rotational isomers (atropisomers ) of Ar-
t
C(Bu )
2
OH, by making use of a more hindered derivative
(
more stable) being higher than that for the anti-
(
i.e., the one with Ar ) o-tolyl) which has a significantly
larger interconversion barrier (25.9 kcal mol ). X-ray
diffraction of the thermodynamically more stable atrop-
q
-1
10
-
1
periplanar (∆G ) 10.3 and 9.3 kcal mol , respectively).
Carbinols bearing the 1-naphthyl substituent should also
display similar conformational properties, and an inves-
tigation on such derivatives (1-4) is the subject of the
present study.
X
Abstract published in Advance ACS Abstracts, April 1, 1997.
(
1) For part 58, see: Lunazzi, L.; Mazzanti, A.; Spagnolo, P.; Degl’
Innocenti, A. J . Org. Chem. 1997, 62, 2263.
2) In partial fulfillment of the requirements for the Ph.D. degree
in Chemical Sciences, University of Bologna.
3) (a) Newsoroff, G. P.; Sternhell, S. Tetrahedron Lett. 1967, 2539.
b) Landman, D.; Newsoroff, G. P.; Sternhell, S. Aust. J . Chem. 1972,
5, 109.
4) Baas, J . M. A.; van der Toorn, J . M.; Wepster, B. M. Recl. Trav.
Chim. Pays-Bas 1974, 93, 173.
5) Lomas, J . S.; Dubois, J .-E. J . Org. Chem. 1976, 41, 3033.
6) Lomas, J . S.; Luong, P. K.; Dubois, J .-E. J . Org. Chem. 1977,
2, 3395.
7) This definition is taken from ref 5 and 6. (See also: Ikeda, Y.;
So far this type of atropisomerism was only observed
in the case of highly hindered carbinols, having a tert-
butyl or an adamantyl group as one of the substituents
R (there is also a case where both the substituents were
isopropyl groups ): compounds 3 and 4 (R ) Et and Me,
respectively) will show that this phenomenon is amenable
to observation also in less hindered systems. More
(
(
(
2
4
(
(
(
4
(
Kato, N.; Mori, A.; Takeshita, M. Magn. Reson. Chem. 1992, 30, 476.
Zoltewicz, J . A.; Maier, N. M.; Fabian, W. M. Tetrahedron 1996, 52,
(8) Lomas, J . S.; Dubois, J .-E. Tetrahedron 1981, 37, 2273.
(9) Lomas, J . S.; Anderson, J . E. J . Org. Chem. 1995, 60, 3246.
(10) Tiffon, B.; Lomas, J . S. Org. Magn. Reson. 1984, 22, 29.
8
703.)
S0022-3263(97)00113-8 CCC: $14.00 © 1997 American Chemical Society

3
316 J . Org. Chem., Vol. 62, No. 10, 1997
Casarini et al.
importantly, derivatives 2 and 3 are suited to investigate
a hitherto unreported feature in this type of carbinols,
i.e., the possible existence of conformational enantiomers
which, in principle, can be created by the restricted
rotation of the ethyl or isopropyl substituents: these
moieties lack, in fact, the local symmetric 3-fold rotational
axis of the tert-butyl (or methyl) group of 1 (or 4).
Resu lts a n d Discu ssion
The reaction employed (see the Experimental Section)
to obtain carbinol 1 (R ) tert-butyl) yields two compounds
(i.e., the two expected atropisomers), one being a liquid,
the other a solid. Although in the reaction mixture the
solid is present in a larger amount with respect to the
liquid, thermal equilibration (carried out at 116 °C in
DMSO) indicates, on the contrary, that the solid atropi-
somer is thermodynamically less stable, its proportion
at the equilibrium being about 2%. Obviously the
predominance of the solid atropisomer in the synthetic
process is the result of a kinetically controlled reaction.
The rate constant for transforming the more stable into
-6
-1
the less stable atropisomer was found to be 2.78 10
s ,
which corresponds (at 116 °C) to a free energy of
F igu r e 1. (Left) Experimental isopropyl methyl signals of 2
( C NMR, 75.5 MHz) as a function of temperature in CD Cl
2 2
showing, at -20 °C, a weaker pair of signals (downfield) for
the ap and a more intense pair of signals (upfield) for the sp
atropisomer. (Right) Computer simulation obtained with the
rate constants indicated.
1
3
q
-1
activation (∆G ) of 32.9 kcal mol (the rate constant for
the reverse process is 1.36 10 s-1; hence a ∆G ) 29.9
-
4
q
-1
kcal mol ). Of course the two atropisomers have differ-
ent 13C and H NMR spectra; in particular, the H-8 signal
of the liquid appears at much lower field (9.50 ppm) than
that of the solid compound (8.60 ppm).
1
Ta ble 1. NOE Effects Obser ved in th e Tw o
Atr op isom er s of 1 (in CDCl3 a t 22 °C) a n d th e Tw o
Atr op isom er s of 2 (in CD2Cl2 a t -70 °C)
Structural assignment of the two atropisomers of 1 was
achieved by difference NOE experiments. Irradiation of
the OH line enhances the H-2 but not the H-8 signal of
the solid, whereas the opposite occurs in the liquid
atropisomer. In addition, irradiation of the tert-butyl line
enhances the H-8 much more than the H-2 signal in the
solid, while the opposite trend is observed in the liquid
atropisomer (Table 1). Thus the syn-periplanar (sp)
structure can be unambiguously assigned to the more
stable (liquid) and the anti-periplanar (ap) structure to
the less stable (solid) atropisomer. The large low-field
shift of the H-8 signal in the NMR spectrum of atrop-
isomer 1-sp can be understood on the basis of an
intramolecular hydrogen bonding between the oxygen
and the H-8 atom (this being facilitated by the possibile
existence of a nearly planar six-membered ring), a feature
which is known to move significantly downfield the
chemical shifts of the hydrogens involved. This finding
can thus be used as a diagnostic tool for assigning the
sp or ap structures in other naphthylcarbinols of this
series.
observed NOE (%)
atropisomer
-sp
satd signal
H-2
H-8
1
OH
5
Me3
OH
25
8
10
1-ap
Me3
OH
6
18
12
2
2
-sp
-ap
CH(Me2)
OH
23
11
CH(Me2)
30
a unique pair of lines above 50 °C (this is not shown in
the picture because a solvent with a higher boiling point
than that of CD Cl had to be used). The methyl groups
2 2
within each of the two isopropyl substituents are, in fact,
diastereotopic since the local plane bisecting the Me-
CH-Me angle is not coincident with the plane of sym-
metry for the whole molecule.11 From the rate constants
needed to achieve the computer simulation (Figure 1,
q
right), the free energy of activation (∆G ) 14.9 kcal
-1
mol ) for the exchange between the major (2-sp) and the
In the case of 2 (R ) isopropyl) the two atropisomers
could not be separated, but their individual NMR spectra
were observed at low temperature, their signals having
minor (2-ap) atropisomer was obtained (Table 2). The
q
∆
G
values were found, within the errors ((0.2 kcal
-
1
mol ), independent of temperature, as often occurs in
the dynamics of intramolecular processes; thus, the free
energies of activation were considered throughout a
1
3
a 78:22 ratio in CD
2 2
Cl . In Figure 1 (left) the C NMR
spectra of the methyl signals of 2 are displayed as a
function of temperature. At -20 °C two widely separated
lines for the minor and two closely spaced lines for the
major atropisomer are visible. These lines broaden and
coalesce at higher temperatures, eventually displaying
(11) (a) Mislow, K.; Raban, M. Topics Stereochem. 1967, 1, 1. (b)
J ennings, W. B. Chem. Rev. 1975, 75, 307. (c) Eliel, E. L. J . Chem.
Educ. 1980, 57, 52.

Conformational Studies by Dynamic NMR
J . Org. Chem., Vol. 62, No. 10, 1997 3317
Ta ble 2. Ra tio of th e sp a n d a p Atr op isom er s a t
q
Equ ilibr iu m a n d F r ee En er gies of Activa tion (∆G , k ca l
-
1
m ol ) for Th eir In ter con ver sion in Der iva tives 1-8, 10
a n d 11
compd
sp:ap ratioa
∆Gq b
T range (°C)c
solvent
1
2
3
4
5
6
7
8
98:2 (116)
32.9
14.9
9.7
116
6-38
DMSO-d6
CD2Cl2
CD2Cl2
Me2O
DMSO-d6
CD2Cl2
Me2O
C2Cl4
CD2Cl2
CD2Cl2
78:22 (-20)
54:46 (-83)
92:8 (-133)
15:85 (23)
37:63 (-95)
30:70 (-130)
90:10 (-15)
30:70 (-62)
80:20 (-98)
-67 to -62
-109
8.4
17.2
10.0
7.6
16.4
12.3
9.7
70-100
-75 to -60
-125 to -115
30-75
1
1
0
1
-38 to -28
-83 to -62
a
In parentheses is the temperature (°C) at which the ratio was
b
measured. Barriers required to interconvert the more stable into
the less stable atropisomer. Range where line shape simulation
c
was performed (except for 1, see text).
reliable measure of the interconversion barrier. The sp
structure was assigned to the major atropisomer because
it exhibits the H-8 signals at a field much lower (9.45
ppm) than the minor one (8.27 ppm). Such a conclusion
was checked again by NOE measurements, which were
carried out at -70 °C in order to avoid possible saturation
q
transfer effects (from the measured ∆G value the
exchange rate between the two atropisomers was com-
puted to be too slow at that temperature to interfere with
the NOE effect). As shown in Figure 2, simultaneous
irradiation of the two OH signals enhances only the H-8
signal of the major (sp) and the H-2 signal of the minor
(ap) atropisomer. Conversely, simultaneous irradiation
of the two CH signals of the isopropyl groups only
enhances the H-8 signal of the minor (ap) and the H-2
signal of the major (sp) atropisomer (Table 1).
Analogous dynamic NMR spectra were observed for the
ethyl and methyl derivatives (3 and 4, respectively)
where the lower steric hindrance of these alkyl substit-
uents made the corresponding barriers (Table 2) even
q
-1
smaller (∆G ) 9.7 and 8.4 kcal mol , respectively). The
amount of the sp atropisomer at the equilibrium de-
creases regularly along the series R ) Bu , Pr , Et (i.e.,
8%, 78%, and 54% for 1-3, respectively). Strangely
t
i
2 2
F igu r e 2. Difference NOE spectra (in CD Cl at 300 MHz) of
the aromatic region of 2 at -70 °C. Simultaneous irradiation
of the isopropyl methine signals of both atropisomers enhances
the H-8 signal of the ap (minor) and the H-2 signal of the sp
9
enough its proportion, on the contrary, increases when
R ) methyl (it is 92% in 4, as shown in Table 2).
Although a simple explanation for such an irregular
trend is not available, MM calculations1 indicate indeed
that the amount of sp atropisomer in 4 is similar to that
of 1, and both are larger than the corresponding amounts
computed in the case of 2 and 3.
(major) atropisomer (top trace). On the contrary simultaneous
irradiation of the OH signals of both atropisomers enhances
the H-8 signals of the sp (major) and the H-2 signals of the ap
(minor) atropisomer (middle trace). The vertical scales of the
NOE spectra are amplified by a factor of 10 with respect to
that of the control spectrum (bottom trace).
2a
Introduction of a methyl group in position 2 of the
naphthalene ring modifies the steric requirements, thus
altering both the atropisomer ratio and the corresponding
interconversion barriers. The derivatives investigated
(5-7) are shown below. Unfortunately we have been
unable to prepare the analogous derivative having R )
tert-butyl, most likely owing to an exceedingly severe
steric hindrance.
In 5-7 the two atropisomers were detected by low-
temperature NMR, but contrary to what was observed
in 1-4, the ap was found more stable, in all three cases,
than the sp atropisomer. This assignment was based on
the values of the corresponding H-8 shifts, although in
the case of 5 this was further confirmed by the large,
reciprocal NOE effect observed between the H-8 and CH
isopropyl signals of the major atropisomer at -25 °C.
In addition to reversing the ratio of the atropisomers,
the methyl group in position 2 also modifies the inter-
conversion barriers by acting in two possible manners,
i.e., reducing mainly either the stability of the ground
state or that of the rotational transition state. In the
case of R ) isopropyl (5) the second possibility dominates;
(12) (a) The MMX force field (as implemented in the program PC
Model, Serena Software, Bloomington, IN) has been employed. (b)
These calculations indicate that the plane containing the C-OH bond
is tilted out of the naphthalene plane by 10° in 1-sp and 7° in 1-ap; cf.
the X-ray value of 11.6° reported in ref 6 for a similar compound.

3
318 J . Org. Chem., Vol. 62, No. 10, 1997
Casarini et al.
1
3
F igu r e 3. (Left) Experimental and computer-simulated methyl signals ( C NMR, 75.5 MHz) of atropisomer 1-sp as a function
of temperature in Me
2
O. (Right) Analogous spectra for the atropisomer 1-ap in the same conditions.
Ta ble 3. Ba r r ier s (∆G , k ca l m ol-1) for th e Rota tion a l
q
thus the barrier becomes larger than that of the unsub-
q
-1
stituted analog 2 (∆G ) 17.2 vs 14.9 kcal mol ). On
the contrary in the less hindered derivative 7 (R )
methyl) the first situation prevails, thus making the
corresponding barrier lower than that of the unsubsti-
P r ocess of Alk yl Gr ou p s (R) a bou t th e R-COH Bon d
compd R group ∆Gq
T range (°C)a
solvent
t
1
1
2-sp
3-sp
8
1
-sp
-ap
Bu
Bu
9.3 -88 to -78
8.6 -104 to -93
7.2 -125 to -120 Me O/CD Cl
2 2 2
6.1 -140
7.3 -125 to -120 Me2O
7.6 -110 CHF2Cl/Me2O/CD3OD
Me2O
Me2O
t
q
-1
i
tuted analog 4 (∆G ) 7.6 vs 8.4 kcal mol ). In the case
of 6 (R ) Et) the two effects are almost equally balanced,
thus leaving the barrier equal, within the errors ((0.2
q
Pr
Et
Bu
CHF2Cl/Me2O
t
-sp
0-sp
i
Pr
-
1
kcal mol ), to that of the unsubstituted analog 3 (∆G
)
10.0 and 9.7 kcal mol-1, respectively). The results are
a
Range where line shape simulation was performed.
collected in Table 2.
dihedral angle of about 30°. Clearly such an arrange-
ment would produce six C methyl lines (and two
A second motion, which occurs at much lower temper-
ature than required for interconverting the two atrop-
isomers, has been observed in 1. The 13C methyl signal
of each atropisomer (1-sp and 1-ap) splits into three lines
with a 1:1:1 relative intensity (Figure 3). By analogy
with previous results,10 this feature should be attributed
to the restricted rotation of the tert-butyl moieties, which
leads to a situation where the methyl groups occupy three
different environments. The barrier for such a process,
determined by computer line shape simulation (Figure
13
quaternary carbon lines) for each atropisomer, contrary
to the experimental evidence. Thus a 30° libration
process must still be fast, in order to exchange the
positions of the methyl groups on one side of the
naphthalene ring with the corresponding ones on the
opposite side. The barrier for such a motion must be
much lower than that for the 360° rotation which
exchanges the three methyl groups within each of the
two tert-butyl moieties and thus is NMR invisible.
3
), is higher in the more stable (1-sp, liquid) than in the
13
The relatively high barriers for the rotation of the
q
less stable (1-ap, solid) atropisomer, the ∆G values being
respectively 9.3 and 8.6 kcal mol (Table 3). The
tert-butyl groups in 1-sp and 1-ap are a consequence of
the reciprocal interactions between two such substitu-
ents. If one of them is replaced by a less bulky substitu-
ent (e.g., a methyl group) the barrier should become
lower. To check this point we synthesized derivative 8
which displays, as usual, the spectra of the sp and ap
atropisomers at low temperature.
-
1
13
C
NMR spectra also indicate that in both atropisomers the
naphthalene ring is still a molecular plane of symmetry,
even when the rotation of the two tert-butyl groups is
slow. The six methyl groups display, in fact, only three
3
lines, and the two CMe quaternary carbons display a
single line. This requires that the two tert-butyl moieties
remain indistinguishable, even at such a low tempera-
ture. However, as suggested by common sense, the MM
calculations predict12 that the two tert-butyl groups are
not eclipsed but somehow staggered, with a reciprocal
The more stable atropisomer (about 90% at -15 °C) is
-sp, which interconverts into 8-ap with a ∆G ) 16.4
q
8
(
13) Anderson, J . E. In The Chemistry of Alkanes and Cycloalkanes;
Patai, S., Rappoport, Z., Eds.; Wiley: London, 1992; Chapter 3, p 95.

Conformational Studies by Dynamic NMR
J . Org. Chem., Vol. 62, No. 10, 1997 3319
Ch a r t 1. Sch em a tic Rep r esen ta tion 16 of th e Most
Sta ble Con for m er s of Atr op isom er 2-sp (ch ir a l,
left) a n d Atr op isom er 2-a p (Meso, r igh t)a
kcal mol-1. On further lowering the temperature the 13
C
single line corresponding to the three methyl groups of
the tert-butyl moiety of atropisomer 8-sp broadens and
1
4
eventually splits (at -135 °C) into three lines.
The
q
-1
corresponding rotational barrier (∆G ) 7.3 kcal mol
was found indeed lower (by 2 kcal mol ) than that
)
-
1
measured for the tert-butyl rotation in the more hindered
1
-sp derivative (the corresponding barrier for the 8-ap
atropisomer could not be measured since at very low
temperatures the weaker signal of its tert-butyl group is
overlapped by those of the major atropisomer).
a
Only the OH and the CH isopropyl hydrogens (the latter in
black) are reported.
this way the two isopropyl methyl groups avoid having
an unfavorable 1,3-parallel interaction. Such an ar-
rangement entails the existence of an asymmetric, thus
chiral, structure yielding a pair of conformational enan-
tiomers (i.e., a racemic conformer), and the C NMR
spectrum of 2-sp should therefore display two signals for
the two diastereotopic isopropyl CH carbons (and, for the
same reason, four signals for the diastereotopic methyl
groups) when the rotation is made sufficiently slow at
appropriate low temperature.
The same calculations predict, on the contrary, that
in the anti-periplanar (2-ap) atropisomer the most stable
conformation has the two isopropyl CH bonds forming a
much smaller dihedral angle than in 2-sp (i.e., 30° rather
than 110°). As shown in Chart 1 (right) the isopropyl
methyl groups do have, now, the unfavorable 1,3-parallel
interaction, but in 2-ap this is required to avoid the even
more unfavorable interaction of the methyl groups with
H-8 of the naphthalene ring. The situation encountered
in 2-ap somehow parallels that of the tert-butyl deriva-
tives 1: here too a low barrier libration process would
make equivalent (enantiotopic) the two isopropyl moi-
eties, with the naphthalene ring retained as a dynamic
plane of symmetry. Consequently the low-temperature
NMR spectrum of 2-ap should not display any splitting
of the 1 C lines when the isopropyl rotation is slow.
As anticipated in the Introduction, the substituents
lacking the symmetric local 3-fold rotational axis of the
tert-butyl group might produce conformers deprived of
any element of symmetry (i.e., conformational enanti-
omers). For instance, in each of the two atropisomers of
1
3
i
i
2
(R ) Pr ) and 3 (R ) Et), the two Pr -COH or the two
Et-COH bonds might be regarded as a pair of stereo-
genic axes,15 each being able to generate a chiral situation
which would therefore lead either to meso or to racemic
stereolabile diastereoisomers (conformers). As a conse-
quence when the rotation of the isopropyl groups in 2 or
of the ethyl groups in 3 is slow, each atropisomer of 2
and 3 might adopt conformations which retain a plane
of symmetry (meso) or conformations which lose any
element of symmetry (racemic). Molecular mechanics
calculations predict that both situations should be ob-
servable, depending on which atropisomer is examined,
and these predictions were, apparently, verified by our
experiments.
In the case of the syn-periplanar atropisomer of 2 (R
i
)
Pr ), the most stable conformer was computed to be
the one where the CH bonds of the two isopropyl groups
adopt a dihedral angle of about 110° (Chart 1, left). In
t
(
14) In the isomer of 8 having the MeC(OH)Bu moiety in position
3
1
3
2
of the naphthalene ring (compound 9), the C line of the tert-butyl
methyl group broadens at low temperature (in Me O) and subsequently
13
2
The C NMR spectra of 2 seem to agree well with these
hypotheses. As shown in Figure 4, where the C signals
of isopropyl CH are reported, two closely spaced lines are
visible at -93 °C, the one at lower field due to the major
2-sp) and that at higher field due to the minor (2-ap)
atropisomer. The downfield line is already broader than
the other and further broadens on lowering the temper-
ature, eventually splitting (at -130 °C) into a pair of
equally intense lines, as expected for an asymmetric
splits (at -110 °C) into two, with about a 1:1 ratio. These two groups
of lines are due to the spectra of the sp and ap atropisomers, which
have almost the same population, owing to the similarity of their steric
requirements. In the same temperature range one of these two lines
13
(that at lower field) broadens and splits into three (owing to a restricted
(
tert-butyl rotation, with a barrier almost equal to that responsible for
the atropisomer interconversion), whereas that at higher field remains
unsplit. This different behavior of the two atropismers could be due to
1
3
a separation of the three methyl C shifts too small to be observed.
(chiral) conformation like that in Chart 1 (left). On the
contrary, the upfield line of 2-ap does not undergo
exchange broadening, as conceivable for a symmetric
(
meso) conformation like that in Chart 1 (right). Accord-
(
15) (a) Casarini, D.; Foresti, E.; Gasparrini, F.; Lunazzi, L.;
Macciantelli, D.; Misiti, D.; Villani, C. J . Org. Chem. 1993, 58, 5674.
b) Casarini, D.; Lunazzi, L.; Gasparrini, F.; Villani, C.; Cirilli, M.;
ingly, the pair of lines corresponding to the diastereotopic
methyl groups of 2-sp also broadens and subsequently
splits into four lines at -135 °C, whereas that of the 2-ap
atropisomer does not. The process which exchanges one
conformational enantiomer into the other, by rotating the
(
Gavuzzo, E. J . Org. Chem. 1995, 60, 97. (c) Casarini, D.; Lunazzi, L.;
Alcaro, S.; Gasparrini, F.; Villani, C. J . Org. Chem. 1995, 60, 5515.
17
1
2a
(16) Whereas in the ap atropisomers the MM calculations indicate
that the C-O-H moiety is essentially coplanar with the naphthalene
ring, the same calculations indicate that in the sp atropisomers there
is a deviation from coplanarity by a small dihedral angle, whose value
depends on the molecule investigated. Since the OH moiety experi-
ences, however, a low-barrier libration above and below the naphtha-
lene ring, the plane containing the C-O-H group has been drawn as
coplanar also in the case of the sp atropisomers, in order to somehow
visualize the consequence of this very fast process.
q
isopropyl groups of 2-sp, was found to have a ∆G ) 7.2
kcal mol (Table 3).
-1
(17) In practice only one of the two methyl lines of 2-ap could be
monitored down to -135 °C since the other was obscured by one of
the four methyl lines of the major atropisomer 2-sp.

3
320 J . Org. Chem., Vol. 62, No. 10, 1997
Casarini et al.
Ch a r t 2. Sch em a tic Rep r esen ta tion 16 of th e Most
Sta ble Con for m er s of Atr op isom er 3-sp (Ch ir a l,
left) a n d Atr op isom er 3-a p (Meso, r igh t)a
a
Only the OH and the CH2 hydrogens (the latter in black) are
reported.
1
3
F igu r e 4. Isopropyl methine signals of 2 ( C NMR, 75.5 MHz)
at different temperatures in Me O/CD Cl
2
2
2
. At -93 °C two lines
are observed for the minor (ap, upfield) and the major (sp,
downfield) atropisomer. The latter broadens and splits (at
-
130 °C) into two equally intense lines, whereas the other does
not. This is a consequence of the racemic conformation adopted
by 2-sp and the meso conformation adopted by 2-ap (Chart 1).
An analogous behavior had been anticipated by MM
calculations1 for 3 (R ) Et), since the conformation
having the lowest energy value was predicted to be
asymmetric (thus chiral) in 3-sp, whereas a symmetric
2a
(thus meso) conformation was predicted to have the
lowest energy value in 3-ap (Chart 2). Again the experi-
ment apparently supports the theoretical results, as
shown in Figure 5 where the 13C methylene signal of 3
is reported at various temperatures. The single line
observed when the two atropisomers are still in rapid
exchange (at -41 °C) broadens and splits into two lines
(
2 2
with an accidentally equal intensity in Me O/CHF Cl)
1
8
at -83 °C. The upfield line of the sp atropisomer then
broadens further and eventually splits into two at -146
°
C, whereas the downfield line of 3-ap does not. In 3-sp
1
3
F igu r e 5. Methylene signal of 3 ( C NMR, 75.5 MHz) as a
function of temperature in Me O/CHF Cl. The single line
the rotational barrier of the ethyl groups, which allows
2
2
observed at -41 °C broadens and subsequently splits (-83 °C)
into a pair of lines, with an accidentally equal intensity (see
ref 18), corresponding to the 3-ap (downfield) and the 3-sp
(
18) The upfield 13C line (in Me
atropisomer since in CD Cl (at -90 °C) this line is more intense than
that at lower field and, in the same sample, the H-8 proton signal at
.07 ppm (which corresponds to the sp atropisomer) is more intense
58%) than that (42%) at 8.08 ppm (corresponding to the ap atropiso-
mer). Apparently in Me O/CHF Cl the relative stability of atrop-
isomer 3-ap increases slightly with respect to the situation in CD Cl
2 2
O/CHF Cl) is attributed to the 3-sp
2
2
(upfield) atropisomer, respectively. The latter further broadens
9
(
and eventually splits (at -146 °C) into two lines, whereas the
other does not. This is because 3-sp adopts the racemic and
3-ap the meso conformation shown in Chart 2.
2
2
2
2
.

Conformational Studies by Dynamic NMR
J . Org. Chem., Vol. 62, No. 10, 1997 3321
Ch a r t 3. Sch em a tic Rep r esen ta tion 16 of th e Tw o
Most Sta ble Con for m er s (left a n d cen ter ) of
one conformational enantiomer to exchange into the
q
-1
other, was found to have a ∆G ) 6.1 kcal mol (Table
a
1
9
Atr op isom er 10-sp
3
).
Surprisingly, the corresponding derivatives with a
i
methyl group in position 2 (i.e., 5, R ) Pr ; 6, R ) Et) do
not display the effects due to R-COH rotational pro-
cesses in either of the two atropisomers. This might
depend upon a rotational barrier of the isopropyl and
ethyl moities too low to be detected by NMR. However
this seems quite unlikely, as bulkier compounds of this
type should experience an even higher hindrance to
rotation. MM calculations suggest an alternative expla-
nation for the absence of such an effect. In both atrop-
isomers of 5 and 6 the conformation having the lowest
computed energy turns out to be symmetric (meso) in that
both 5-sp and 6-sp maintain the naphthalene ring as a
plane of symmetry, as do 5-ap and 6-ap (this behavior,
therefore, differs from that of the less hindered analogs
a
The conformers differ by the relative position of the CH
isopropyl hydrogen. That on the left (E ) 0) is computed to be
more stable by 0.3 kcal mol than that in the center. On the
right is reported the most stable conformer of 10-ap.
-
1
2
and 3 where the sp atropisomers adopt an asymmetric
conformation). Thus, if these calculations have to be
trusted, the absence of line-broadening effects in 5 and
lations12a account for the presence of a single rotational
conformer by showing that in both atropisomers 11-sp
and 11-ap the most stable conformer has an energy
substantially lower than that of the next stable conformer
differing by the position of the isopropyl group (the
computed energy separation being respectively 1.2 and
6
is accounted for by the conservation of the molecular
symmetry.
The low-temperature NMR spectra of 2 and 3 show
that only a single conformation, respectively asymmetric
for the sp and symmetric for the ap atropisomers, is
observed although, in principle, more than one conforma-
tion (either symmetric or asymmetric) might have been
populated. In order to verify whether such a hypothetical
situation (i.e., the simultaneous presence of two or more
conformers) can, in practice, take place, we further
dissymmetrized these compounds, by preparing deriva-
tives 10 and 11. Here we have a configurationally stable
-
1
3
.1 kcal mol ).
The same calculations, on the other hand, suggest that
derivative 10 should be a good candidate for observing
two stereolabile diastereoisomers (i.e., two conformers)
since the two most stable rotational conformers of its 10-
sp atropisomer differ in the computed energy only by 0.3
-
1
kcal mol (their structures are reported in Chart 3).
Furthermore, the calculations show that the two most
stable conformers of 10-sp differ indeed only by the
position of the isopropyl and not by that of the ethyl
moiety, as shown in Chart 3 where the CH
2
hydrogens
(
also indicated in black) occupy the same positions in the
-
1
two conformers having E ) 0 and 0.3 kcal mol . These
calculations also indicate that atropisomer 10-ap should
yield, on the contrary, the spectrum of a single conformer
(
Chart 3, right). This is because the two most stable
chiral center (i.e., the carbon atom bonded to OH) which
might couple its chirality with the second source of
chirality created, at low temperature, by the stereogenic
conformational axis15 corresponding to the Pr -COH
bond. As two sources of chirality are now available, two
stereolabile diastereoisomers (conformers) might become
observable.
conformers, differing by the position of the isopropyl
group, have a computed energy separation as large as
3
-1
.4 kcal mol
.
i
The low-temperature NMR spectra of 10 (Figure 6) are
in good agreement with such theoretical predictions. At
-62 °C the signals of the two atropisomers become
distinguishable, the major one (70%) having the ap
structure (contrary to the case of 11 where the sp
atropisomer was the more stable one). The interconver-
sion barrier (Table 2) between 10-ap and 10-sp has a
value (∆G ) 12.3 kcal mol ) which is in between that
of the more crowded diisopropyl derivative 2 and the less
crowded diethyl derivative 3 (14.9 and 9.7 kcal mol ,
respectively). This trend is analogous to that mentioned
above for the case of 10 with respect to 2 and 4 (for the
same reason the barrier of 10 is larger than that of the
less hindered derivative 11). At temperatures lower than
-
1
In the case of 11 (R ) Me) the experiment did not fulfill
such an expectation since both atropisomers 11-sp (more
stable) and 11-ap (less stable) displayed a spectrum due
to a single rotational conformer, even at -140 °C. Only
the interconversion barrier between the two atropisomers
q
-1
q
-1
could thus be measured (Table 2), and its value (∆G )
-
1
9
.7 kcal mol ) was found, as conceivable, intermediate
between those of the bulkier derivative 2 (where both the
R groups are isopropyl) and of the less crowded derivative
4
(where both the R groups are methyl). MM calcu-
70 °C some of the 13C lines of the minor atropisomer
0-sp (notably those corresponding to the CH of the
(19) It has to be pointed out that the interpretation we offered for
the apparent absence of dynamic processes in both 2-ap and 3-ap
cannot be considered completely unambiguous. If one neglects the
conclusions of the MM calculations and only relies upon the experi-
mental findings, the existence of asymmetric (racemic) conformations
also in 2-ap and 3-ap cannot be excluded in an absolute manner. In
this event the absence of dynamic effects might be attributed to
barriers too low to be detected by NMR. This is not totally unreasonable
in view of the lower tert-butyl rotational barriers measured in 1-ap
with respect to 1-sp.
isopropyl and the CH and CH of the ethyl moieties)
2
3
broaden considerably and sharpen again on further
cooling, a behavior typical for an exchange between two
strongly biased species having a substantial chemical
20
shift separation. Careful inspection of the spectra taken
at -135 °C (Figure 6) revealed the presence of a second
conformer in about a 10% proportion. The ∆G° at this

3
322 J . Org. Chem., Vol. 62, No. 10, 1997
Casarini et al.
i
created by the restricted rotation along the Pr -COH
stereogenic axis, have indeed been detected.
Exp er im en ta l Section
Ma ter ia ls. Naphthyldialkylmethanols 1-11 were prepared
according to the following general procedure. To a cooled (-50
°
C) solution of 1-naphthyllithium (15 mmol in 40 mL of
anhydrous THF under N ), obtained by halogen-metal ex-
2
change from 1-bromonaphthalene (15 mmol) and n-butyl-
lithium (16 mmol, 1.6 M in hexane), the appropriate ketone
(20 mmol in 5 mL of anhydrous THF) was added dropwise.
After stirring (30 min) at -50 °C, the mixture was allowed to
reach room temperature, and subsequently (1-20 h) the
reaction was quenched with a saturated aqueous solution of
NH
4
Cl and the mixture extracted with Et
2
O. The organic layer
was dried (Na
2
SO ) and concentrated in vacuo. Chromatog-
4
raphy of the crude on silica gel or preparative thin-layer
chromatography yielded the desired compounds.
2
,2,4,4-Tet r a m et h yl-3-(1-n a p h t h yl)p en t a n -3-ol,
sp
1
a tr op isom er (1-sp ): H NMR (CDCl
s, CMe
m, H-8); 13C NMR (CDCl
CMe ), 89.5 (C, COH), 122.5 (CH, Ar), 124.2 (CH, Ar), 125.0
3
, 300 MHz) δ 1.16 (18H,
3
), 2.35 (1H, s, OH), 7.35-7.75 (6H, m, Ar), 9.50 (1H,
3
3
, 75.5 MHz) δ 30.0 (CH ), 43.8 (C,
3
(CH, Ar), 127.7 (CH, Ar), 128.0 (CH, Ar), 128.9 (CH, Ar), 129.1
(
2
CH, Ar), 134.2 (C, Ar), 134.5 (C, Ar), 140.2 (C, Ar); MS m/ z
+
70 (M ). Anal. Calcd for C19
H
26O: C, 84.39; H, 9.69.
Found: C, 84.48; H, 9.52.
2
,2,4,4-Tet r a m et h yl-3-(1-n a p h t h yl)p en t a n -3-ol,
a p
, 300
1
a tr op isom er (1-a p ): mp 55-57 °C; H NMR (CDCl
MHz) δ 1.20 (18H, s, CMe
m, Ar), 8.60 (1H, m, H-8); 13C NMR (CDCl
3
3
), 2.20 (1H, s, OH), 7.42-8.25 (6H,
, 75.5 MHz) δ 31.0
3 3
CH ), 43.4 (C, CMe ), 87.5 (C, COH), 123.6 (CH, Ar), 124.6
3
(
(
(
(
CH, Ar), 125.5 (CH, Ar), 128.5 (CH, Ar), 128.8 (CH, Ar), 129.3
CH, Ar), 130.4 (CH, Ar), 133.5 (C, Ar), 134.4 (C, Ar), 145.2
C, Ar); MS m/ z 270 (M ). Anal. Calcd for C19
+
H
26O: C, 84.39;
H, 9.69. Found: C, 84.53; H, 9.47.
,4-Dim eth yl-3-(1-n a p h th yl)p en ta n -3-ol (2): 1H NMR
CDCl , 300 MHz) δ 0.95 (12H, bd, CH ), 1.82 (1H, bs, OH),
.65 (2H, bm, CHMe ), 7.45-7.85 (6H, Ar), 9.47 (1H, bs, H-8);
, 75.5 MHz) δ 17.7 (CH ), 35.7 (CH), 86.2 (C,
COH), 124.2 (CH, Ar), 124.8 (CH, Ar), 125.1 (CH, Ar), 126.6
2
(
3
3
2
2
1
3
C NMR (CDCl
3
3
(
CH, Ar), 128.2 (CH, Ar), 129.0 (CH, Ar), 129.1 (CH, Ar), 134.1
+
(C, Ar), 134.9 (C, Ar), 137.8 (C, Ar); MS m/ z 242 (M ). Anal.
Calcd for C17
-(1-Na p h th yl)p en ta n -3-ol (3): H NMR (CDCl
MHz) δ 0.78 (6H, t, J AB ) 7.1 Hz, CH ), 1.97 (1H, s, OH), 2.15
(2H, m, J AB ) 7.1 Hz, J gem ) 14.2 Hz, CHMe), 2.28 (2H, m,
AB ) 7.1 Hz, J gem ) 14.2 Hz, CHMe), 7.45-7.88 (6H, m, Ar),
H22O: C, 84.25; H, 9.15. Found: C, 84.40; H, 9.02.
1
3
3
, 300
3
1
3
F igu r e 6. Methyl signals of the ethyl moiety of 10 ( C NMR,
5.5 MHz) as a function of temperature in Me O/CHF Cl/CD
7
2
2
3
-
J
1
3
OD (1:1:1). Two sharp lines (ratio 7:3) due respectively to the
major (10-ap) and the minor (10-sp) atropisomer are observed
at -62 °C. The line of the latter (upfield) broadens on further
lowering the temperature (the maximum line width being
observed at -107 °C) and sharpens again, eventually display-
ing, at -135 °C, two signals (ratio 1:9) for the pair of
conformers created by the restricted rotation of the isopropyl
group (Chart 3).
8.84 (1H, m, H-8); C NMR (CDCl
3
, 75.5 MHz) δ 8.2 (CH ),
3
33.7 (CH ), 79.1 (C, COH), 124.7 (CH, Ar), 124.9 (CH, Ar),
2
125.1 (CH, Ar), 126.3 (CH, Ar), 128.2 (CH, Ar), 129.3 (CH, Ar),
+
131.0 (C, Ar), 134.8 (C, Ar), 140.4 (C, Ar); MS m/ z 214 (M ).
Anal. Calcd for C15
H, 8.61.
H
18O: C, 84.07; H, 8.47. Found: C, 84.31;
1
2
-(1-Na p h th yl)p r op a n -2-ol (4): mp 94-96 °C; H NMR
(CDCl
3
, 300 MHz) δ 1.82 (6H, s, CH
3
), 2.08 (1H, s, OH), 7.40-
, 75.5
3
), 74.1 (C, COH), 122.6 (CH, Ar), 124.7 (CH,
7
.87 (6H, m, Ar), 8.84 (1H, dd, H-8); 13C NMR (CDCl
3
temperature is 0.6 kcal mol-1, which compares well with
MHz) δ 31.5 (CH
-
1
Ar), 125.1 (CH, Ar), 125.2 (CH, Ar), 127.2 (CH, Ar), 128.6 (CH,
the computed energy difference of 0.3 kcal mol (Chart
q
Ar), 129.0 (CH, Ar), 130.9 (C, Ar), 134.8 (C, Ar), 143.3 (C, Ar);
3
). The barrier for this dynamic process (∆G ) 7.6 kcal
mol ) is equal, within the errors ((0.2 kcal mol ), to
that (∆G ) 7.2 kcal mol ) for the dynamic process which
exchanges the conformational enantiomers of 3-sp by
rotating the isopropyl groups.21 We may thus conclude
that in the atropisomer 10-sp two different conformers,
+
MS m/ z 186 (M ). Anal. Calcd for C13
H
14O: C, 83.82; H, 7.58.
-
1
-1
Found: C, 83.65; H, 7.69.
q
-1
2
,4-Dim eth yl-3-(2-m eth yl-1-n a p h th yl)p en ta n -3-ol (5),
1
m a jor a tr op isom er : H NMR (CDCl
d, CH ), 1.20 (6H, d, CH ), 1.90 (1H, s, OH), 2.80 (3H, s, Ar-
3
, 300 MHz) δ 0.58 (6H,
3
3
CH
m, H-8); C NMR (Me
CH ), 19.7 (CH ), 26.1 (Ar-CH
3
3
), 2.98 (2H, m, CH-Me
2
), 7.34-7.73 (5H, m, Ar), 8.19 (1H,
O/C , -30 °C, 75.5 MHz) δ 18.7
), 37.7 (CH), 84.9 (C, COH),
1
3
2
6 6
D
(
3
3
(
20) Anet, F. A. L.; Basus, V. J . J . Magn. Reson. 1978, 32, 339. See
also: Sandstr o¨ m, J . Dynamic NMR Spectroscopy; Academic Press:
123.8 (CH, Ar), 124.3 (CH, Ar), 126.6 (CH, Ar), 126.9 (CH, Ar),
London, 1982; p 84.
(
129.0 (CH, Ar), 132.0 (CH, Ar), 132.7 (C, Ar), 133.8 (C, Ar),
21) The rotation of the ethyl group is expected to be too fast to be
+
1
35.5 (C, Ar), 142.2 (C, Ar); MS m/ z 256 (M ). Anal. Calcd
NMR detectable at -135 °C, as one can infer from the quite low
for C18
2,4-Dim eth yl-3-(2-m eth yl-1-n a p h th yl)p en ta n -3-ol (5),
m in or a tr op isom er : 1H NMR (CDCl
, 300 MHz) δ 0.78 (6H,
H24O: C, 84.32; H, 9.44. Found: C, 84.54; H, 9.52.
rotational barrier (observed below -140 °C) for the ethyl group in 3-sp
i.e., 6.1 kcal mol-1). Unfortunately at temperatures lower than -135
(
°
C compound 10 becomes insoluble.
3

Conformational Studies by Dynamic NMR
J . Org. Chem., Vol. 62, No. 10, 1997 3323
d, CH
CH ), 2.80 (2H, m, CH-Me
m, H-8); C NMR (Me
3
), 1.20 (6H, d, CH
3
), 2.10 (1H, s, OH), 2.62 (3H, s, Ar-
), 7.34-7.73 (5H, m, Ar), 9.26 (1H,
O/C , -30 °C, 75.5 MHz) δ 18.6
), 25.6 (Ar-CH ), 36.7 (CH), 84.9 (C, COH).
-(2-Meth yl-1-n aph th yl)pen tan -3-ol (6): H NMR (CDCl
00 MHz) δ 0.83 (6H, t, CH ), 1.88 (1H, s, OH), 2.02 (2H, m
), 7.20-7.73
, 75.5 MHz)
), 82.6 (C, COH), 124.4
CH, Ar), 124.9 (CH, Ar), 127.0 (CH, Ar), 127.7 (CH, Ar), 129.0
Ar), 124.8 (CH, Ar), 125.0 (CH, Ar), 125.6 (CH, Ar), 128.0 (CH,
3
2
Ar), 129.4 (CH, Ar), 130.9 (C, Ar), 134.9 (C, Ar), 140.7 (C, Ar);
1
3
+
2
6
D
3
6
MS m/ z 228 (M ). Anal. Calcd for C16
H
20O: C, 84.16; H, 8.83.
(CH
3
), 19.5 (CH
3
Found: C, 83.95; H, 8.62.
1
3
3
,
3-Meth yl-2-(1-n a p h th yl)bu ta n -2-ol (11): mp 45-46 °C;
1
3
3
H NMR (CDCl
CH), 0.95 (3H, d, J ) 7.5 Hz, CH
(1H, bs, OH), 2.77 (1H, sept, J ) 7.5 Hz, CHMe
3
, 300 MHz) δ 0.75 (3H, d, J ) 7.5 Hz, CH
CH), 1.70 (3H, s, CH ), 1.96
), 7.32-7.86
(6H, m, Ar), 8.70-8.80 (1H, m, H-8); C NMR (CDCl , 75.5
MHz) δ 17.0 (CH ), 18.2 (CH ), 25.1 (CH ), 36.1 (CH), 78.9 (C,
3
-
CHMe), 2.55 (4H, m, CHMe), 2.74 (3H, s, Ar-CH
3
3
3
1
3
(5H, m, Ar), 8.56 (1H, m, H-8); C NMR (CD
2
Cl
2
2
1
3
δ 8.5 (CH ), 25.8 (Ar-CH ), 35.9 (CH
3
3
2
3
(
(
(
3
3
3
CH, Ar), 132.4 (CH, Ar), 132.6 (C, Ar), 134.0 (C, Ar), 135.4
C, Ar), 138.8 (C, Ar); MS m/ z 228 (M ). Anal. Calcd for
COH), 124.2 (CH, Ar), 124.5 (CH, Ar), 124.9 (CH, Ar), 127.1
(CH, Ar), 128.3 (CH, Ar), 129.1 (CH, Ar), 130.8 (C, Ar), 135.0
+
+
C
16
H
20O: C, 84.16; H, 8.83. Found: C, 84.02; H, 8.52.
(C, Ar), 143.2 (C, Ar); MS m/ z 214 (M ). Anal. Calcd for
1
2
-(2-Meth yl-1-n aph th yl)pr opan -2-ol (7): H NMR (CDCl
3
,
C
15
H
18O: C, 84.07; H, 8.47. Found: C, 83.94; H, 8.63.
3
00 MHz) δ 1.86 (1H, s, OH), 1.95 (6H, s, CH
3
), 2.68 (3H, s,
), 7.19-7.75 (5H, m, Ar), 8.71 (1H, m, H-8); C NMR
NMR Mea su r em en ts. The variable temperature NMR
1
3
1
13
Ar-CH
3
spectra were recorded at 300 MHz ( H) and 75.5 MHz ( C).
The computer simulation of the line shape was performed by
a computer program22 based on the Bloch equations, and the
best fit was visually judged by superimposing the plotted and
experimental traces. The samples for measurements below
-100 °C were prepared by connecting the NMR tubes,
containing a small amount of a deuterated compound for
locking purpose, to a vacuum line and condensing the gaseous
(CD
2
Cl
2
/Me ), 32.3 (CH ),
2
O, -15 °C, 75.5 MHz) δ 25.4 (Ar-CH
3
3
7
1
1
5.3 (C, COH), 124.1 (CH, Ar), 124.2 (CH, Ar), 127.3 (CH, Ar),
28.4 (CH, Ar), 128.5 (CH, Ar), 131.8 (CH, Ar), 132.7 (C, Ar),
+
34.0 (C, Ar), 134.1 (C, Ar), 142.9 (C, Ar); MS m/ z 200 (M ).
Anal. Calcd for C14
H, 8.22.
H16O: C, 83.96; H, 8.05. Found: C, 84.09;
3
,3-Dim et h yl-2-(1-n a p h t h yl)b u t a n -2-ol (8): 1H NMR
(
(
(
CDCl
3
, 300 MHz) δ 1.08 (9H, s, CMe
3
), 1.85 (3H, s, CH
3
), 1.98
2 2
solvents (Me O or CHF Cl) with liquid nitrogen. The tubes
1
3
1H, s, OH), 7.35-7.90 (6H, m, Ar), 9.36 (1H, m, H-8); C NMR
CDCl , 75.5 MHz) δ 26.8 (CH , CMe ), 29.4 (CH ), 39.7 (C,
), 83.7 (C, COH), 123.9 (CH, Ar), 124.7 (CH, Ar), 124.8
CH, Ar), 127.9 (CH, Ar), 128.4 (CH, Ar), 128.7 (CH, Ar), 129.8
CH, Ar), 133.2 (C, Ar), 134.7 (C, Ar), 141.5 (C, Ar); MS m/ z
were then sealed in vacuo and introduced in the precooled
probe of the spectrometer. The difference NOE measurements
were carried out in solutions purged from dissolved oxygen,
using a nitrogen stream, by presaturating the signal for about
10 s and acquiring the spectrum with the decoupler turned
off. The various lines of the multiplets were saturated by
cycling the irradiation frequencies about 40 times. A program
which accumulates the difference between the two FIDs (that
being irradiated and that acquired with the irradiation
frequency kept away from any signal) was employed. The
control spectrum was subsequently acquired with one-half the
number of scans.
3
3
3
3
CMe
(
(
3
+
2
28 (M ). Anal. Calcd for C16
Found: C, 84.01; H, 8.69.
,3-Dim eth yl-2-(2-n a p h th yl)bu ta n -2-ol (9) (obta in ed a s
H20O: C, 84.16; H, 8.83.
3
1
a secon d a r y p r od u ct fr om 8): H NMR (CDCl
δ 1.02 (9H, s, CMe
7
2
3
, 300 MHz)
), 1.81 (1H, s, OH), 7.41-
, 75.5 MHz) δ 25.4 (CH ),
), 78.7 (C, COH), 125.6 (CH,
3
), 1.73 (3H, s, CH
3
1
3
.96 (7H, m, Ar); C NMR (CDCl
5.8 (CH
3
3
3
, CMe
3
), 38.3 (C, CMe
3
Ar), 125.7 (CH, Ar), 125.8 (CH, Ar), 125.9 (CH, Ar), 126.3 (CH,
Ar), 127.3 (CH, Ar), 128.2 (CH, Ar), 132.0 (C, Ar), 132.3 (C,
Ar), 143.8 (C, Ar); MS m/ z 228 (M ). Anal. Calcd for
Ack n ow led gm en t. The authors thank Dr. F. Bolo-
gna for skillful assistance. This work was carried out
with the financial support of the National Research
Council (CNR) and of the Ministry the University and
Scientific Research (MURST), Rome.
+
16
C H20O: C, 84.16; H, 8.83. Found: C, 84.05; H, 8.95.
1
2
-Meth yl-3-(1-n aph th yl)pen tan -3-ol (10): H NMR (CDCl
00 MHz) δ 0.62 (3H, bt, J ) 7.4 Hz, CH CH ), 0.71 (3H, bd,
), 1.05 (3H, bd, J ) 6.8 Hz, CHCH ), 1.84
1H, bs, OH), 2.05 (1H, m, J gem ) 14.8 Hz, J AB ) 7.4Hz, CHMe),
3
,
3
2
3
J ) 6.8 Hz, CHCH
3
3
(
2
J O970113+
.40 (1H, m, J gem ) 14.8 Hz, J AB ) 7.4 Hz, CHMe), 2.62 (1H,
), 7.36-7.86 (6H, m, Ar), 8.54 (1H,
, 75.5 MHz) δ 8.3 (CH ), 16.9 (CH ),
), 36.1 (CH), 81.0 (C, COH), 124.7 (CH,
sept, J ) 6.8 Hz, CHMe
bs, H-8); C NMR (CDCl
7.5 (CH ), 30.8 (CH
2
(
22) (a) Casarini, D.; Lunazzi, L.; Macciantelli, D. J . Chem. Soc.
1
3
3
3
3
Perkin Trans. 2 1985, 1839. (b) Bonini, B. F.; Grossi, L.; Lunazzi, L.;
Macciantelli, D. J . Org. Chem. 1986, 51, 517.
1
3
2