Diastereoselective remote C-H activation by hydroboration

Article abstract of DOI:10.1002/chem.200400023

Hydroboration of tetrasubstituted or trisubstituted alkenes with BH ₃ and subsequent thermolysis allows remote diastereoselective C-H activation of neighboring aryl rings. Tetrasubstituted and trisubstituted 1,1-diphenyl-ethylene derivatives undergo a highly stereoselective 1,2-rearrangement followed by remote C-H activation to lead, after oxidative workup, to a diol in which the relative stereochemistry of two stereocenters has been controlled. The mechanism of this remote activation has been studied and extended to related molecules that undergo this stereoselective C-H activation, namely alkenylbiphenyl systems or alkenes with only one phenyl ring, such as alkenylbenzenes. or bicyclic systems. We have shown that this reaction allows diastereoselective synthesis of molecules with up to three contiguous chiral centers.

Full text of DOI:10.1002/chem.200400023

FULL PAPER
À
Diastereoselective Remote C H Activation by Hydroboration
JesÇs A. Varela,*[a] Diego PeÊa,[a] Bernd Goldfuss,[b] Dmitri Denisenko,[c] Jiri Kulhanek,[d]
Kurt Polborn,[c] and Paul Knochel*[c]
Abstract: Hydroboration of tetrasubsti-
tuted or trisubstituted alkenes with
BH3 and subsequent thermolysis allows
in which the relative stereochemistry of
two stereocenters has been controlled.
The mechanism of this remote activa-
tion has been studied and extended to
related molecules that undergo this
À
stereoselective C H activation, namely
alkenylbiphenyl systems or alkenes
with only one phenyl ring, such as alke-
nylbenzenes, or bicyclic systems. We
have shown that this reaction allows di-
astereoselective synthesis of molecules
with up to three contiguous chiral cen-
ters.
À
remote diastereoselective C H activa-
tion of neighboring aryl rings. Tetrasub-
stituted and trisubstituted 1,1-diphenyl-
ethylene derivatives undergo a highly
stereoselective 1,2-rearrangement fol-
Keywords: C H
diastereoselective 1,2-migration
hydroboration organoboranes
thermal rearrangements
activation
¥
¥
¥
¥
À
lowed by remote C H activation to
lead, after oxidative workup, to a diol
Introduction
the preparation of cycloalkyl derivatives with three adjacent
stereocenters.[8] This rearrangement can also be performed
with acyclic tetrasubstituted olefins. It opens a new ap-
proach to acyclic control of two[9] or three[10] adjacent
The functionalization of unreactive carbon hydrogen bonds
is an active field of investigation.[1] Most of these carbon hy-
drogen activations have been performed with great success
by means of transition-metal-mediated reactions or transi-
tion-metal-catalyzed reactions.[2] Only a few examples in-
volving main group organometallic compounds have been
described.[3] Most organoboranes derived from disubstituted
olefins by hydroboration undergo thermal rearrangements
at elevated temperature.[4] Rickborn and Wood[5] as well as
Field and Gallagher[6] noted that cyclic tetrasubstituted al-
kenes undergo such a dyotropic rearrangement[7] under
much milder conditions. Recently, it was reported that an ef-
À
carbon centers. Remote C H activation can also be ach-
ieved with tetrasubstituted alkenes bearing bulky substitu-
ents, leading to boracycles with high stereoselectivity.[9,11,12]
À
Herein, we report detailed results on the remote C H acti-
vation of phenyl-substituted alkenes.
Results and Discussion
À
Mechanism of the remote C H activation of 1,1-diphenyl-
À
ficient allylic C H activation can be formally realized by hy-
droboration of tetrasubstituted cycloalkenes with BH3 in
THF followed by a smooth thermal rearrangement to allow
ethylene derivatives: Recently, we discovered that remote
À
C H activation can be performed with tetrasubstituted al-
kenes bearing bulky substituents, such as the 1,1-diphenylal-
kene 1.[9] Treatment of alkene 1 with BH3¥THF (508C, 12 h)
affords a cyclic organoborane 2, which, after oxidative
workup (NaOH, H2O2), produces diol 3 in 80% yield
(Scheme 1).
[a] Dr. J. A. Varela, Dr. D. PeÊa
Departamento de QuÌmica Orgµnica y Unidad Asociada al CSIC
Facultad de QuÌmica, Universidad de Santiago de Compostela
15782 Santiago de Compostela (Spain)
[b] Prof. Dr. B. Goldfuss
Institut f¸r Organische Chemie, Universit‰t zu Kˆln
Greinstrasse 4, 50939 Kˆln (Germany)
[c] Dipl. Chem. D. Denisenko, Dr. K. Polborn, Prof. Dr. P. Knochel
Department Chemie, Ludwig-Maximilians-Universit‰t
Butenandstrasse 5 13 (Haus F), 81377 M¸nchen (Germany)
E-mail: paul.knochel@cup.uni-muenchen.de
[d] Prof. Dr. J. Kulhanek
Department of Organic Chemistry, University of Pardubice
53210 Pardubice (Czech Republic)
À
Scheme 1. C H activation of 1.
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4252 4264
Remarkably, the conversion of alkene 1 to diol 3 produces
an intermediate cyclic organoborane 2 bearing the two
bulky substituents (Ph and tBu) in a cis arrangement. It
should also be noted that this high diastereoselectivity im-
plies that only one of the two diastereotopic aromatic rings
À
of 1 undergoes C H activation. To explain these results, we
have envisioned two reaction pathways A and B that lead to
Scheme 3. Conversion of 8 to 9.
the cyclic organoborane 2 (Scheme 2).
gave two products: the final diol 3 (25% yield) and the terti-
ary diol 10 (32% yield). Diol 10 is clearly the oxidation
product of the cyclic organoborane 5 postulated in path-
way A (Scheme 4). The relative stereochemistry of 3 and 10
was established by X-ray analysis (Figure 1).
Scheme 4.
Scheme 2. Reaction pathways leading to the organoborane 2.
In pathway A, the initial hydroboration product 4, ob-
tained by the reaction of the tetrasubstituted alkene 1 with
[4,13]
À
BH3¥THF, can undergo C H activation of a phenyl ring.
This would lead to the cyclic five-membered boracycle 5.
This heterocycle then undergoes a 1,2-migration[14,15] leading
to the observed product 2 via borane-olefin complex 6. In-
terestingly, the coordination of boron to the olefin in aryl-
borane 6 during the entire migration process implies a cis-
relationship between the tBu and Ph substituents. The dia-
À
À
stereoselective C H activation of the aromatic C H bond
of 4 leading to 5 can be readily explained by steric consider-
ations: the bulky tert-butyl and phenyl groups are in a trans
relationship in the boracycle 5. An alternative pathway
(pathway B) is also possible. In this case, the first step is 1,2-
migration leading to the primary organoborane 7. This is
À
followed by C H activation of the aromatic ring to give
boracycle 2. Although the 1,2-migration process of the
borane 4 to 7 should readily occur under the reaction condi-
À
tions, the observed diastereoselectivity of the C H rear-
rangement is difficult to explain (cis arrangement of the sub-
stituents in boracycle 2).
A series of experiments that clearly prove the proposed
pathway A is presented below. The isomeric alkene 8 was
prepared and submitted to the same hydroboration condi-
tions as used for the thermal conversion of 1 to 2 (BH3¥THF
(3 equiv), 508C, 24 h). After oxidative workup (H2O2,
NaOH), we observed the formation of alcohol 9 in 63%
yield; however, there was no evidence for the formation of
diol 3 thus indicating that the organoborane 7 is not an in-
À
termediate in the C H activation process (Scheme 3).
Furthermore, interruption of the reaction before comple-
tion (one hour reaction time) and oxidative workup of the
hydroboration product of the diphenylethylene derivative 1
Figure 1. X-ray structure for diol 3 (a) and for the intermediate 10 (b).
Chem. Eur. J. 2004, 10, 4252 4264
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J. A. Varela, P. Knochel et al.
FULL PAPER
À
These results imply that the C H activation reaction is es-
pecially efficient if the boracyclopentane is formed. There-
fore, we prepared the trisubstituted alkene 11 and were
pleased to find that the hydroboration of 11 with BH3¥THF
and subsequent heating in THF at 508C for 24 h furnished,
after oxidative workup, the diastereomerically pure diol 12
in 60% yield (Scheme 5).
were employed to assess the relative energies of the transi-
tion structures.
From these results, the most favorable transition structure
is 4a-TS, in which the tert-butyl group is trans to the two hy-
drogens that undergo elimination and the phenyl group.
This transition structure would afford the intermediate bora-
cycle 5, which does indeed lead to the observed product 10.
IEF-PCM (THF) B3LYP/6-31G*//MNDOcomputations
have also been performed on the 1,2-migration step
(Scheme 8). They show that the dehydroboration and the re-
hydroboration steps have very similar activation energies
(TS-1 and TS-2); however, the six-membered boracycle 2 is
5.0 kcal¥molÀ1 more favorable than the corresponding five-
membered boracycle 5.
À
Scheme 5. C H activation of 11 followed by oxidative workup to give 12.
We have also prepared the (E)- and (Z)-tolyl-substituted
olefins (E)-13 and (Z)-13. As expected, in the case of (E)-
13, there was selective activation of the tolyl ring (14a:14b
= 4:1), whereas selective activation of the phenyl ring was
observed for Z-13 (14a:14b = 1:4). The formation of 20%
À
of the other isomeric C H activation product can be ex-
plained by assuming that the alkenes (E)-13 and (Z)-13
slowly isomerize under the reaction conditions at 508C
(Scheme 6).
Scheme 8. IEF-PCM (THF) B3LYP/6-31G*//MNDOcomputations on
the 1,2-migration step.
À
Scheme 6. C H activation of (E)-13 and (Z)-13 followed by oxidative
workup to give 14a and 14b.
À
Electronic effects on the phenyl ring for remote C H acti-
vation: Because we now know the mechanism of remote
To elucidate the origins of the diastereoselectivities in the
À
À
intramolecular C H activations of 4, four possible transition
C H activation of 1,1-diphenylethylene, we decided to study
structures of the dehydrogenation processes (cf. Scheme 1:
conversion of 4 to 5, Scheme 7)[13] were optimized and ana-
lyzed by frequency computations by means of the MNDO
method.[16,17] B3LYP/6-31G*[18] single-point computations
with the IEF-PCM[19] solvation model and THF as solvent
the remote activation of biphenyl systems bearing a double
bond in the ortho position. The treatment of 2-phenylstyr-
ene (15a) with BH3¥THF (3 equiv) at 908C for 12 h afforded
diol 16a in 80% yield after oxidative workup (H2O2,
NaOH). With this system, the preferential formation of a
À
five-membered boracycle is not possible, so that C H acti-
vation occurs through the six-membered boracycle 17a
(Scheme 9).
À
When the C H activation reaction was performed with
the methoxy- and trifluoromethyl-substituted biphenyls 15b
and 15c, diols 16b and 16c, were obtained respectively in
81% and 82% yield (Scheme 9). The fact that both biphen-
yls 15b and 15c, with a electron-donor group, such as MeO,
or an electron-attracting group, such as CF3, gave rise to the
same results clearly indicates that the reaction does not pro-
ceed through an electrophilic aromatic substitution, but
most likely through a four-center mechanism. When the pi-
nacolborane 18 was treated first with LiAlH4, to generate
Scheme 7. Possible transition structures of the dehydrogenation process
À
during the intramolecular C H activation of 4.
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À
Diastereoselective Remote C H Activation
4252 4264
À
in this case, remote C H activa-
tion takes place through the
preferred five-membered bora-
cycle 26, obtained from the ini-
tial hydroboration product 25
À
after 1,2-migration and C H ac-
tivation. This heterocycle then
undergoes another 1,2-migra-
tion leading to the six-mem-
bered boracycle 27 that, after
oxidative workup, affords the
observed diol 28 (Scheme 11).
Again, the preferred forma-
tion of the five-membered
À
boracycle for the C H activa-
tion was found when the hydro-
boration of 24 was interrupted
after 45 min. Oxidative workup
of the reaction mixture afford-
ed the alcohol 29, resulting
from the oxidation of the initial
hydroboration product 25, in
À
Scheme 9. C H activation of biphenyl systems 15 and 18, as well as of ferrocenes 20.
the corresponding borane, and then with BH3¥THF at 908C
for 12 h, the product of remote activation 19 is obtained in
16% yield. This shows that a benzylic borane ortho to a
À
phenyl ring is located close enough to the phenyl C H to
activate it under mild conditions (Scheme 9).
À
The C H activation can also be accomplished with other
molecules having a similar structure. Thus, the ferrocenes
20a and 20b, with disubstitution on one of the Cp rings, led
À
to the products of remote C H activation 22a and 22b
(yields of 45 and 47%, respectively) via the intermediate
boracycles 21a and 21b when treated with borane¥THF
(658C, 12 h) in (Scheme 9). The relative configuration of
22a was established by X-ray analysis of the corresponding
4-bromobenzoate 23 (Scheme 10, Figure 2).
Figure 2. Structure of the 4-bromobenzoate 23.
Scheme 10. Determination of the absolute configuration of 22a by con-
version to 23.
À
Remote C H activation of vinylbenzene derivatives:
À
Remote C H activation can also be accomplished on the
phenyl ring bearing the alkene. When the styrene derivative
24 was treated with BH3¥THF at 908C for 36 h, it led, after
oxidative workup, to diol 28 in 61% yield. We propose that,
À
Scheme 11. C H activation of styrene derivative 24 and conversion to
diol 28.
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J. A. Varela, P. Knochel et al.
FULL PAPER
À
47% yield and tertiary alcohol 30, resulting from the oxida-
tion of the boracycle 26, in 30% yield. Furthermore, treat-
ment of the isomeric alkenylbenzene 31 with BH3¥THF at
908C for seven days afforded, after oxidative workup, alco-
hol 32 in 49% yield and primary diol 28 in only 16% yield.
Alcohol 32 was obtained after oxidation of the initial hydro-
boration product, while diol 28 resulted from the oxidation
of the six-membered boracycle 27 (Scheme 11). The low
yield of diol 28 together with the long reaction time (7 days)
remote C H activation 38 in 17% yield. However, when the
À
tert-butyl group was replaced by a methyl group, C H acti-
vation products were not observed. In the case of the trisub-
stituted alkene 39, the only observed product was alcohol 40
in 81% yield. In this case, the observed alcohol is the oxida-
tion product of the borane resulting from two consecutive
1,2-migrations that place the boron in the most thermody-
namically stable position. With the styrene derivative 41, the
alcohol 42 was obtained in 64% yield from the oxidation of
the initial hydroboration product (Scheme 15).
À
demonstrates the difficulties in achieving remote C H acti-
vation through the boracycle 27 (Scheme 12).
These results clearly show that a bulky group, such as tert-
butyl, is necessary to promote
À
C H activation. This bulky
group probably forces the con-
formation of the hydroboration
product to place the boron
À
atom close to the C H of the
À
phenyl ring thus allowing C H
activation to proceed under
mild conditions. When this
group is replaced by
a less
bulky group, such as methyl, in
39 and 41, the conformation of
the hydroborated product is not
À
Scheme 12. C H activation of 24 and 31.
À
Cyclohexylidene derivative 33 also undergoes C H activa-
tion (Scheme 13). Only the trans-cyclohexanol product was
obtained. The relative configuration of 34 was established
by X-ray analysis of the corresponding 4-bromobenzoate 35
(Scheme 14, Figure 3).
À
Scheme 13. C H activation of 33.
Figure 3. Structure of the 4-bromobenzoate 35.
À
appropriate for the C H activation, which may occur only
at very high temperatures with a lack of selectivity.[4] In the
case of the styrene 36 bearing a tert-butyl in the ortho posi-
À
tion, the low yield of the C H activation product is attribut-
ed to the absence of the two methyl groups at the end of the
double bond. This leads to the other regioisomer in the ini-
tial hydroboration product in which the boron atom is not
close enough to the phenyl ring.
Scheme 14. Determination of the relative configuration of 34 by conver-
sion to 35.
À
We then decided to evaluate the influence of the different
Remote C H activation of bicyclic systems: From the above
studies, the presence of at least one bulky substituent is re-
À
alkenylbenzene substituents in the C H activation reaction.
À
Monosubstituted alkene 36 was submitted to the hydrobora-
tion conditions at 908C for 1.5 days. After oxidative workup,
alcohol 37 was obtained in a 40% yield and the product of
quired for mild remote C H activation (steric compression
activates the C H bond). We decided to turn our attention
to rigid bicyclic systems in which the rigidity of the system
À
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Diastereoselective Remote C H Activation
4252 4264
firmed by X-ray analysis, see
Figure 4) is attributed to the
fact that only the diastereotopic
hydrogen Hb undergoes the de-
hydroboration step leading to
the less sterically hindered
olefin 48. Other types of tetra-
substituted alkenes undergo the
À
C H activation reaction. Thus,
under the typical reaction con-
ditions (BH3¥THF (3 equiv),
508C, 24 h), alkene 49 afforded
diol 50 as one diastereoisomer
in 57% yield.
À
Scheme 15. C H activation of 36, 39, and 41.
will force the boron atom close to the phenyl ring in the hy-
À
droborated products in order to facilitate remote C H acti-
vation under mild conditions. Thus, the [2.2.1]bicycloalkene
43 reacts with BH3¥THF at 508C (36 h) and undergoes selec-
tive boron migration leading, after oxidative work-up, to pri-
mary alcohol 44. Further heating of alkene 43 and BH3¥THF
À
at 908C for 24 h leads to C H activation of the phenyl ring
and gives, after oxidation with H2O2/NaOH, diol 45
(Scheme 16).
À
With this system, C H activation is not possible in the ini-
tial hydroboration product (trans arrangement of the boron
and the phenyl ring) and this does not allow the preferential
formation of a five-membered boracycle. Instead, boron mi-
À
gration occurs prior to C H activation. As observed in pre-
vious cases,[8,9,10] the corresponding ethyl-substituted alkene
46 undergoes a faster 1,2-migration and furnishes only one
diastereomeric diol (47) with a relative control of these ad-
jacent chiral centers. The observed diastereoselectivity (con-
Figure 4. Structure of the diol 47.
Conclusion
We have developed a method that allows the diastereoselec-
À
tive remote C H activation of aryl-substituted alkenes
under mild conditions. The mechanism of the diastereoselec-
tive remote activation was determined in the case of 1,1-di-
phenylethylene derivatives, and showed the preferred for-
mation of five-membered boracycles. This allows us to
expand this method to other tri- and tetrasubstituted al-
kenes, such as alkenes with a biphenyl group, alkenylben-
zene derivatives, or bicyclic systems, with the diastereoselec-
tive synthesis of up to three contiguous chiral centers.
Experimental Section
General: All commercial chemicals (Aldrich, Fluka, Lancaster) were of
the best available grade and used without further purification. 2,3,3-Tri-
À
Scheme 16. C H activation of 44, 46, and 49.
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J. A. Varela, P. Knochel et al.
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methyl-1,1-diphenyl-1-butene (1) was prepared according to published
procedures.[9] NMR spectra (1H, 13C and DEPT) were recorded on
Bruker AMX-300 instrument and the residual solvent peak was used as a
reference.
(43), 128 (17), 105 (22), 91 (19); HRMS for C19H21 ([M]+) calcd:
250.1721; found: 250.1703.
2-(2-Methyl-1-propenyl)biphenyl (15a, R = H)
Preparation of 2-biphenylcarboxaldehyde:[25] tBuLi (6.29 mL, 9.44 mmol,
2.2 equiv, 1.5m) was added to a solution of 2-bromobiphenyl (1.0 g,
4.2 mmol) in THF (10 mL) at À788C. After 30 min at this temperature
DMF (7 mL) was added and the reaction mixture was allowed to warm
to room temperature. HCl (10 mL, 3m) was added and the mixture was
extracted twice with ether (5 mL). The combined organic layers were
dried over MgSO4 and concentrated under the reduced pressure to give
2-biphenylcarboxaldehyde in quantitative yield (0.76 g). 1H NMR
(300 MHz, CDCl3): d = 9.90 (s, 1H), 7.96 7.94 (m, 1H), 7.58 7.53 (m,
1H), 7.44 7.35 (m, 5H), 7.36 7.29 ppm (m, 2H); 13C NMR (DEPT,
75 MHz, CDCl3): d = 191.4 (C), 144.9 (C), 136.7 (C), 132.7 (C), 132.5
(C), 129.7 (CH), 129.1 (2CH), 127.4 (2CH), 127.1 (CH), 126.7 (CH),
126.5 ppm (CH); MS (70 eV, EI): m/z (%): 182 (68, [M]+), 181 (100), 152
(53), 76 (14).
2-Benzhydryl-3,3-dimethyl-1-butene (8):[20] A solution of lithium bis(di-
phenylmethyl)cuprate was prepared by adding diphenylmethyllithium
(12 mmol), prepared by mixing diphenylmethane (2.0 g, 12 mmol) with
nBuLi (7.7 mL, 1.56m, 12 mmol) in THF at 08C, to a stirred slurry of
CuBr (1.17 g, 8.18 mmol) in THF (10 mL) at 08C. 3,3-Dimethyl-2-trifluoro-
methanesulfonyloxy-1-butene[21] (1.0 g, 4.31 mmol) in THF (10 mL) was
added, and the reaction mixture was stirred for 12 h at À158C. The mix-
ture was then diluted with hexane, filtered through a pad of celite, and
concentrated on a rotary evaporator. Purification of the residue by chro-
1
matography (silica gel, pentane) afforded olefin 8 (0.86 g, 80% yield). H
NMR (300 MHz, CDCl3): d = 7.28 7.12 (m, 10H), 5.34 (s, 1H), 5.09 (s,
1H), 4.58 (s, 1H), 1.09 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3):
d
= 159.6 (C), 144.4 (2C), 129.2 (4CH), 128.1 (4CH), 125.9 (2CH),
113.6 (CH2), 53.1 (CH), 37.0 (C), 29.9 ppm (3CH3); MS (70 eV, EI): m/z
(%): 250 (15, [M]+), 193 (100), 167 (98), 159 (29), 115 (33); HRMS for
C19H22 ([M]+) calcd: 250.1721; found: 250.1721.
Preparation of 2-(2-methyl-1-propenyl)biphenyl (15a, R = H): To the
suspension of isopropyltriphenylphosphonium iodide (0.42 g, 1 mmol,
1 equiv) in THF (4 mL) at 08C was added nBuLi (0.62 mL, 1 equiv,
1.6m). After 30 min, 2-biphenylcarboxaldehyde (0.182 g, 1 mmol) in THF
(5 mL) was added and the reaction mixture was allowed to warm to
room temperature. Water (10 mL) was added and the mixture was ex-
tracted with ether (2î5 mL). The combined organic phases were dried
over MgSO4 and concentrated under reduced pressure. The residue was
purified by flash chromatography (pentane) to afford 15a (0.17 g, R =
3,3-Dimethyl-1,1-diphenyl-1-butene (11):[22] To
a mixture of nBuLi
(7.22 mL, 11 mmol, 1.61m) and THF (7 mL) at 08C was added dropwise
a solution of diethyl benzhydrylphosphate (3.53 g, 11 mmol) in THF
(14 mL). The ice bath was removed, and the mixture was stirred at room
temperature for 1 h. To the resulting mixture was added dropwise a solu-
tion of pivalaldehyde (1.0 g, 11 mmol) in THF (7 mL). The reaction mix-
ture was stirred for 2 h and treated with saturated aqueous NH4Cl solu-
tion (15 mL). The aqueous layer was washed with ether, the combined or-
ganic layers were dried with MgSO4, and the solvent was removed under
reduced pressure. Purification by flash chromatography (pentane/ether
9:1) afforded the olefin 16 (2.16 g; 79%). IR (film): n˜ = 2958, 1493,
1
H, 80% yield). H NMR (300 MHz, CDCl3): d = 7.80 7.30 (m, 9H), 6.14
(m, 1H), 1.84 (d, J = 1.1 Hz, 3H), 1.83 ppm (d, J = 1.1 Hz, 3H); 13C
NMR (DEPT, 75 MHz, CDCl3): d = 141.6 (C), 141.1 (C), 136.7 (C),
134.7 (C), 130.2 (CH), 129.7 (CH), 129.6 (2CH), 128.7 (CH), 127.8
(2CH), 126.7 (CH), 126.6 (CH), 126.4 ppm (CH); MS (70 eV, EI): m/z
(%): 208 (26, [M]+), 193 (100), 178 (66), 165 (45); HRMS for C16H16
([M]+) calcd: 208.1252, found: 208.1247.
1475, 1443, 702 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.25 7.07 (m,
;
10H), 6.00 (s, 1H), 0.88 ppm (s, 3H); 13C NMR (DEPT, 75 MHz,
CDCl3): d = 144.1 (C), 140.8 (C), 140.1 (CH), 139.1 (C), 130.3 (2CH),
128.0 (2CH), 127.7 (2CH), 126.8 (2CH), 126.7 (CH), 126.5 (CH), 33.9
(C), 31.3 ppm (3CH3); MS (70 eV, EI): m/z (%): 236 (66, [M]+), 221
(100), 191 (16), 178 (27), 165 (30), 143 (81), 128 (33), 91 (44); HRMS for
C18H20 ([M]+) calcd: 236.1565; found: 236.1555.
2-(2-Methyl-1-propenyl)-4’-methoxybiphenyl (15b, R = OMe)
Preparation of 2-bromo-4’-methoxybiphenyl: To a solution of p-methoxy-
iodobenzene (2.55 g, 10 mmol) in THF (10 mL) at À788C was added
tBuLi (10.9 mL, 16 mmol, 1.5m). After 1 h, the solution was warmed to
À458C and a solution of ZnBr2 (8.3 mL, 12 mmol, 1.5m) was added.
After stirring at room temperature for 30 min, a solution of [Pd(dba)2]
(0.22 g, 0.38 mmol), PPh3 (0.37 g, 1.4 mmol), and ortho-iodobromoben-
zene (2.20 g, 7.78 mmol) in THF (6 mL) was added. Stirring was main-
tained overnight. Saturated aqueous NH4Cl (15 mL) was added, and the
mixture was extracted with ether. The extracts were dried over MgSO4
and concentrated under reduced pressure. Purification of the residue by
flash chromatography (silica gel, pentane) afforded 2-bromo-4’-methoxy-
biphenyl (2.0 g, 97% yield). 1H NMR (300 MHz, CDCl3): d = 7.59 7.50
(m, 1H), 7.31 7.22 (m, 5H), 6.90 6.83 (m, 2H), 3.81 ppm (s, 3H); 13C
NMR (DEPT, 75 MHz, CDCl3): d = 159.0 (C), 142.2 (C). 133.5 (C),
133.1 (CH), 131.3 (CH), 130.5 (2CH), 128.4 (CH), 127.3 (CH), 122.9
(CH), 113.3 (2CH), 55.2 ppm (CH3); MS (70 eV, EI): m/z (%): 264 (100,
[M]+), 262 (100), 249 (22), 247 (22), 221 (18), 219 (18), 139 (53).
(E)-3,3-Dimethyl-1-(4-methylphenyl)-1-phenyl-1-butene ((E)-13): To
a
solution of 1-bromo-4-methylbenzene (0.79 g, 4.61 mmol) in THF (4 mL)
at À788C was added nBuLi (2.86 mL, 4.61 mmol, 1.61m). After 1 h, the
solution was warmed to À458C and a solution of ZnBr2 (3.35 mL,
5 mmol, 1.5m in THF) was added. After stirring at room temperature for
30 min,
a solution of [Pd(dba)2] (0.12 g, 0.2 mmol), PPh3 (0.20 g,
0.8 mmol), and (E)-1-(tert-butyl)-2-(4-methylphenyl)-1-ethenyl iodide
(1.2 g, 4.19 mmol) (prepared by Sonogashira cross-coupling between io-
dobenzene and 3,3-dimethyl-1-butyne[23] followed by treatment with
DIBAL-H and iodine[24]) in THF (4 mL) was added. Stirring was main-
tained overnight. Saturated aqueous NH4Cl (15 mL) was added and the
mixture was extracted with ether, dried over MgSO4, and concentrated
under reduced pressure. Purification of the residue by flash chromatogra-
phy (silica gel, pentane) afforded the alkene (E)-13 (1.00 g, 98% yield).
1
IR (film): n˜ = 2957, 1510, 816, 701 cmÀ1; H NMR (300 MHz, CDCl3): d
Preparation of 4’-methoxybiphenyl-2-carboxaldehyde: tBuLi (12.2 mL,
18 mmol, 1.5m) was added to a solution of 2-bromo-4’-methoxybiphenyl
(2.18 g, 8.3 mmol) in THF (15 mL) at À788C. After 30 min at this tem-
perature, DMF (2 mL) was added and the reaction mixture was allowed
to warm to room temperature. HCl (15 mL, 3m) was added, and the mix-
ture was extracted twice with diethyl ether (10 mL). The combined or-
ganic phases were dried over MgSO4 and concentrated under reduced
pressure to give 4’-methoxybiphenyl-2-carboxaldehyde (1.5 g, 85%
= 7.36 7.05 (m, 9H), 6.09 (s, 1H), 2.33 (s, 3H), 0.99 ppm (s, 9H); 13C
NMR (DEPT, 75 MHz, CDCl3): d = 141.3 (C), 142.0 (C), 139.2 (CH),
138.8 (C), 136.2 (C), 130.3 (2CH), 128.7 (2CH), 127.7 (2CH), 126.7
(2CH), 126.6 (CH), 33.9 (C), 31.3 (3CH3), 20.9 ppm (CH3); MS (70 eV,
EI): m/z (%): 250 (61, [M]+), 235 (100), 157 (42), 143 (50), 128 (20), 105
(28), 91 (25); HRMS for C19H22 ([M]+) calcd: 250.1721; found: 251.1752.
(Z)-3,3-Dimethyl-1-(4-methylphenyl)-1-phenyl-1-butene ((Z)-13): Analo-
gous procedure was used as described for (E)-1-(4-methylphenyl)-1-
phenyl-1-propene (E-18) from bromobenzene (0.47 g, 3 mmol), nBuLi
(1.86 mL, 3 mmol, 1.61m), ZnBr2 (2.18 mL, 3.3 mmol, 1.5m), [Pd(dba)2]
(0.08 g, 0.14 mmol, 5%), PPh3 (0.128 g, 0.49 mmol, 18%), and (Z)-1-(tert-
butyl)-2-phenyl-1-ethenyl iodide (0.82 g, 2.73 mmol) afforded (Z)-13
1
yield). H NMR (300 MHz, CDCl3): d = 9.91 (s, 1H), 7.93 7.91 (m, 1H),
7.56 7.51 (m, 1H), 7.44 7.33 (m, 2H), 7.25 7.18 (m, 2H), 6.94 6.91 (m,
2H), 3.79 ppm (s, 3H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 192.6
(C), 159.7 (C), 145.6 (C), 133.7 (C), 133.5 (CH), 131.2 (2CH), 130.7
(CH), 130.0 (C), 127.6 (CH), 127.3 (CH), 113.9 (2CH), 55.3 ppm (CH3);
MS (70 eV, EI): m/z (%): 212 (100, [M]+), 197 (19), 181 (23), 169 (38),
141 (43), 115 (29); HRMS for C14H12O2 ([M]+) calcd: 212.0837, found:
212.0836.
(0.45 g, 67% yield). IR (film): n˜ = 2958, 1444, 737, 697 cmÀ1 1H NMR
;
(300 MHz, CDCl3): d = 7.16 6.98 (m, 9H), 5.99 (s, 1H), 2.30 (s, 3H),
0.89 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 144.3 (C),
140.0 (CH), 139.1 (C), 137.7 (C), 136.2 (C), 130.2 (2CH), 128.4 (2CH),
127.9 (2CH), 126.8 (2CH), 126.4 (CH), 33.9 (C), 31.3 (3CH3), 21.2 ppm
(CH3); MS (70 eV, EI): m/z (%): 250(60, [M]+), 235 (100), 157 (36), 143
Preparation of 2-(2-methyl-1-propenyl)-4’-methoxybiphenyl (15b, R
=
OMe): To the suspension of isopropyltriphenylphosphonium iodide
(2.9 g, 6.71 mmol) in THF (10 mL) at 08C was added nBuLi (4.5 mL,
4258
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2004, 10, 4252 4264

À
Diastereoselective Remote C H Activation
4252 4264
6.71 mmol, 1.5m). After 30 min, 4’-methoxybiphenyl-2-carboxaldehyde
(1.42 g, 6.71 mmol) in THF (15 mL) was added and the reaction mixture
was allowed to warm to room temperature. Water (25 mL) was added,
and the mixture was extracted with ether (2î10 mL). The combined or-
ganic phases were dried over MgSO4 and concentrated under reduced
pressure. The residue was purified by flash chromatography (pentane/di-
ethyl ether 9:1) to afford 15b (1.45 g, R = OMe, 91% yield). 1H NMR
(300 MHz, CDCl3): d = 7.25 7.10 (m, 6H), 6.86 6.80 (m, 2H), 5.97 (m,
1H), 3.76 (s, 3H), 1.71 (d, J = 1.3 Hz, 3H), 1.68 ppm (d, J = 1.3 Hz,
3H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 158.5 (C), 140.6 (C), 136.6
(C), 134.4 (C), 134.0 (C), 130.7 (2CH), 130.2 (CH), 129.6 (CH), 126.3
(2CH), 125.2 (CH), 113.2 (2CH), 55.2 (CH2), 26.1 (CH2), 19.3 ppm
(CH3); MS (70 eV, EI): m/z (%): 238 (32, [M]+), 223 (100), 208 (57), 165
(26), 152 (16); HRMS for C17H18O([ M]+) calcd: 238.1358, found:
238.1371.
20 mL). The combined organic phases were dried over MgSO4 and con-
centrated under reduced pressure. The residue was purified by flash chro-
matography (pentane/ether 9:1) to afford 18 (0.13 g, 15% yield). IR
(KBr): n˜
= ;
3030, 2979, 2930, 1738, 1610, 1361, 1144 cmÀ1 1H NMR
(300 MHz, CDCl3): d = 8.09 7.70 (m, 2H), 7.67 7.63 (m, 3H), 7.50 7.33
(m, 4H), 1.39 ppm (m, 12H); MS (70 eV, EI): m/z (%): 280 (91, [M]+),
265 (27), 194 (88), 180 (100), 152 (16); HRMS for C18H21BO2 ([M]+)
calcd: 280.1635, found: 280.1624.
1-Phenyl-2-(2-methyl-1-propenyl)ferrocene (20a): 2-Phenylferrocenecar-
boxaldehyde was prepared from the ferrocenecarboxaldehyde dimethyl-
acetal and iodobenzene, according to the literature procedure[27] in 65%
yield. nBuLi in hexane (1.6m, 6.3 mL, 10 mmol) was added to the stirred
suspension of isopropyltriphenylphosphonium iodide (4.32 g, 10 mmol) in
THF (15 mL) at 08C. The mixture was stirred for 30 min, then a solution
of 2-phenylferrocenecarboxaldehyde (2.90 g, 10 mmol) in THF (10 mL)
was added. The mixture was allowed to warm to room temperature. 1m
HCl (30 mL) was added, and the organic phase was separated. The aque-
ous phase was extracted with pentane (20 mL). The combined organic
phases were washed (water, NaHCO3 solution, and brine) and dried over
Na2SO4. The solvent was removed under reduced pressure. The residue
was purified by flash chromatography (silica gel, pentane) to afford
2.05 g (65% yield) of 20a as an orange oil. IR (KBr): n˜ = 3092, 2910,
2-(2-Methyl-1-propenyl)-4’-trifluoromethylbiphenyl (15c, R = CF3)
Preparation of 2-bromo-4’-trifluoromethylbiphenyl: To a solution of 4-io-
dotrifluoromethylbenzene (2.32 g, 8.5 mmol) in THF (10 mL) at À788C
was added tBuLi (11 mL, 18 mmol, 1.7m). After 1 h the solution was
warmed to À458C, and a solution of ZnBr2 (9.3 mL, 14 mmol, 1.5m) was
added. After the mixture had been stirred at room temperature for
30 min,
a solution of [Pd(dba)2] (0.22 g, 0.38 mmol), PPh3 (0.37 g,
2854, 1601, 1505, 818, 763, 699 cmÀ1 1H NMR (CDCl3, 300 MHz): d =
;
1.4 mmol), and 2-iodobromobenzene (2.20 g, 7.78 mmol) in THF (6 mL)
was added. Stirring was maintained overnight. Saturated aqueous NH4Cl
(15 mL) was added, and the mixture was extracted with ether. Extracts
were dried over MgSO4 and concentrated under reduced pressure. Purifi-
cation of the residue by flash chromatography (silica gel, pentane) afford-
ed 2-bromo-4’-trifluoromethylbiphenyl (2.22 g, 95% yield). 1H NMR
(300 MHz, CDCl3): d = 7.91 7.00 ppm (m, 8H); 13C NMR (75 MHz,
CDCl3): d = 144.5, 141.2, 140.3, 133.3, 132.7, 131.0, 129.9, 129.8, 129.5,
129.4, 128.3, 127.6, 127.5, 125.9, 125.0, 122.3, 122.2 ppm; MS (70 eV, EI):
m/z (%): 302 (100, [M]+), 300 (100), 201 (47), 152 (31); HRMS for
C13H8BrF3 ([M]+) calcd: 299.9761, found: 299.9750.
7.62 7.59 (m, 2H), 7.37 7.31 (m, 2H), 7.28 7.23 (m, 1H), 6.17 (s, 1H),
4.51 4.47 (m, 2H), 4.31 4.29 (m, 1H), 4.08 (s, 5H), 1.86 (s, 3H),
1.81 ppm (s, 3H); 13C NMR (DEPT, CDCl3, 75 MHz): d = 139.1 (C),
134.0 (C), 129.1 (2CH), 127.8 (2CH), 125.9 (CH), 120.8 (CH), 86.5 (C),
82.3 (C), 70.4 (5CH), 69.6 (CH), 69.0 (CH), 66.9 (CH), 26.6 (CH3),
19.6 ppm (CH3); MS (70 eV, EI): m/z (%): 316 (100, [M]+); HRMS for
C20H20Fe ([M]+) calcd: 316.0914, found: 316.0931.
1-(4-Methylphenyl)-2-(2-methyl-1-propenyl)ferrocene (20b): 2-(4-Meth-
ylphenyl)ferrocenecarboxaldehyde was prepared in 70% yield from the
ferrocenecarboxaldehyde dimethylacetal and 4-iodotoluene using the
procedure for the preparation of 2-phenylferrocenecarboxaldehyde.
nBuLi in hexane (1.6m, 3.1 mL, 5 mmol) was added to the stirred suspen-
sion of isopropyltriphenylphosphonium iodide (2.16 g, 5 mmol) in THF
(10 mL) at 08C. The reaction mixture was stirred for 30 min, and then a
solution of 2-(4-methylphenyl)ferrocenecarboxaldehyde (1.52 g, 5 mmol)
in THF (10 mL) was added. The mixture was allowed to warm to room
temperature. 1m HCl (30 mL) was added, and the organic phase was sep-
arated. The aqueous phase was extracted with pentane (20 mL). The
combined organic phases were washed (water, NaHCO3 solution, and
brine) and dried over Na2SO4. The solvent was removed under reduced
pressure. The residue was purified by flash chromatography (silica gel,
pentane) to afford 1.22 g (74% yield) of 20b as an orange oil. IR (KBr):
Preparation of 4’-trifluoromethylbiphenyl-2-carboxaldehyde: tBuLi
(10.7 mL, 16 mmol, 1.5m) was added to a solution of 2-bromo-4’-trifluor-
omethylbiphenyl (2.19 g, 7.3 mmol) in THF (15 mL) at À788C. After
30 min at this temperature, DMF (2 mL) was added, and the reaction
mixture was allowed to warm to room temperature. HCl (15 mL, 3m)
was added, and the mixture was extracted with ether (2î10 mL). The
combined organic phases were dried over MgSO4 and concentrated
under reduced pressure to give 4’-trifluoromethylbiphenyl-2-carboxalde-
hyde (1.12 g, 62% yield). 1H NMR (300 MHz, CDCl3): d = 10.00 (s,
1H), 8.08 8.06 (m, 1H), 7.83 7.68 (m, 1H), 7.60 7.44 ppm (m, 4H); 13C
NMR (75 MHz, CDCl3): d
= 191.5, 144.1, 141.6, 133.7, 133.6, 130.6,
1
n˜ = 3093, 2966, 2920, 2857, 1523, 1438, 1106, 817 cmÀ1; H NMR (CDCl3,
130.5, 130.5, 130.3, 130.2, 129.9, 128.5, 128.1, 125.4, 125.3 ppm; MS
(70 eV, EI): m/z (%): 250 (93, [M]+), 249 (100), 201 (51), 181 (65), 152
(53), 104 (23); HRMS for C14H9OF3 ([M]+) calcd: 250.0605, found:
250.0587.
300 MHz): d = 7.46 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.12
(m, 1H), 4.46 (m, 2H), 4.27 (m, 1H), 4.06 (s, 5H), 2.37 (s, 3H), 1.84 (d,
J
= 1.3 Hz, 3H), 1.79 ppm (d, J =
0.9 Hz, 3H); 13C NMR (DEPT,
Preparation of 2-(2-methyl-1-propenyl)-4’-trifluoromethylbiphenyl (15c,
R = CF3): To the suspension of isopropyltriphenylphosphonium iodide
(1.87 g, 4.34 mmol) in THF (6 mL) at 08C was added nBuLi (2.7 mL,
4.34 mmol, 1.6m). After 30 min, 4’-trifluoromethylbiphenyl-2-carboxalde-
hyde (1.09 g, 4.34 mmol) in THF (10 mL) was added and the mixture was
allowed to warm to room temperature. Water (25 mL) was added and
the mixture was extracted with ether (2î10 mL). The combined organic
phases were dried over MgSO4 and concentrated under reduced pressure.
The residue was purified by flash chromatography (pentane) to afford
15c (0.88 g, R = CF3, 74% yield). 1H NMR (300 MHz, CDCl3): d =
7.50 (m, 2H), 7.30 (m, 2H), 7.28 7.20 (m, 4H), 5.90 (m, 1H), 1.70 (d, J
CDCl3, 75 MHz): d = 135.9 (C), 135.5 (C), 133.8 (C), 129.0 (2CH), 128.5
(2CH), 120.9 (CH), 86.8 (C), 82.3 (C), 70.4 (5CH), 69.4 (CH), 68.9 (CH),
66.9 (CH), 26.6 (CH3), 21.1 (CH3), 19.6 ppm (CH3); MS (70 eV, EI): m/z
(%): 330 (100, [M]+); HRMS for C21H22Fe ([M]+) calcd: 330.1071,
found: 330.1060.
1-(tert-Butyl)-2-(2-methyl-1-propenyl)benzene (24): tBuLi (11.3 mL,
17 mmol, 1.5m) was added to a solution of 1-(tert-butyl)-2-iodobenzene
(2 g, 7.7 mmol) in THF (10 mL) at À788C. After 30 min at this tempera-
ture, DMF (2 mL) was added, and the reaction mixture was allowed to
warm to room temperature. HCl (15 mL, 3m) was added, and the mixture
was extracted with ether (2î10 mL). The combined organic phases were
dried over MgSO4 and concentrated under reduced pressure to yield 2-
(tert-butyl)benzaldehyde[28] (1.11 g, 89% yield). 1H NMR (300 MHz,
CDCl3): d = 10.80 (s, 1H), 7.96 7.91 (m, 1H), 7.50- 7.48 (m, 2H), 7.36
7.32 (m,1H), 1.54 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d =
191.8 (C), 151.1 (C), 134.5 (C), 132.3 (CH), 129.3 (CH), 125.3 (2CH),
34.8 (C), 32.0 ppm (CH3); MS (70 eV, EI): m/z (%): 162 (10, [M]+), 147
(100), 129 (100).
=
0.9 Hz, 3H), 1.65 ppm (d, J =
0.9 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d = 145.3, 139.6, 136.7, 135.6, 130.4 129.8, 129.6, 127.5, 126.6,
124.7, 124.6, 124.5, 26.0, 19.3 ppm; MS (70 eV, EI): m/z (%): 276 (47,
[M]+), 261 (100), 246 (38), 233 (29), 192 (33), 165 (24); HRMS for
C17H15F3 ([M]+) calcd: 276.1126, found: 276.1152.
Biphenyl dioxaborolane (18): A solution of 2-biphenyllithium (prepared
from 2-bromobiphenyl (0.83 g, 3.6 mmol) and tBuLi 4.8 mL, 7.2 mmol,
1.5m) was added to (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl
chloride[26] (0.52 g, 3 mmol) in diethyl ether (36 mL) at À788C. The reac-
tion mixture was allowed to warm to room temperature overnight. Water
was added (35 mL), and the mixture was extracted with ether (2î
To
a suspension of isopropyltriphenylphosphonium iodide (2.88 g,
6.6 mmol) in THF (10 mL) at 08C was added nBuLi (2.66 mL, 6.6 mmol,
2.5m). After 30 minm 2-(tert-butyl)benzaldehyde (1.08 g, 6.6 mmol) in
THF (10 mL) was added, and the reaction mixture was allowed to warm
Chem. Eur. J. 2004, 10, 4252 4264
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4259

J. A. Varela, P. Knochel et al.
FULL PAPER
to room temperature. Water (25 mL) was added, and the mixture was ex-
tracted with ether (2î10 mL). The combined organic phases were dried
over MgSO4 and concentrated under reduce pressure. The residue was
purified by flash chromatography (pentane) to afford 24 (0.96 g, 77%
yield). 1H NMR (300 MHz, CDCl3): d = 7.32 7.29 (m, 1H), 7.11 7.02
(m, 2H), 6.93 6.91 (m, 1H), 6.48 (m, 1H), 1.80 (d, J = 1.3 Hz, 3H),
1.47 ppm (d, J = 0.9 Hz, 1H); 13C NMR (DEPT, 75 MHz, CDCl3): d =
148.2 (C), 138.3 (C), 132.8 (C), 132.3 (CH), 128.2 (CH), 126.4 (CH),
125.5 (CH), 125.4 (CH), 35.8 (C), 30.5 (3CH3), 25.6 (CH3), 19.3 ppm
(CH3); MS (70 eV, EI): m/z (%): 188 (68, [M]+), 173 (41), 131 (100), 115
(21); HRMS for C14H20 ([M]+) calcd: 188.1565, found: 188.1548.
bined organic phases were dried over MgSO4 and concentrated under re-
duced pressure. The residue was purified by flash chromatography (pen-
tane) to afford styrene derivative 39 (1.08 g, 90% yield). 1H NMR
(300 MHz, CDCl3): d = 7.08 7.02 (m, 4H), 6.19 6.06 (m, 1H), 2.15 (s,
3H), 1.82 (d, J = 1.3 Hz; 3H), 1.62 ppm (d, J = 1.3 Hz, 3H); 13C NMR
(DEPT, 75 MHz, CDCl3): d
= 138.3 (C), 136.7 (C), 135.4 (C), 130.0
(CH), 129.8 (CH), 126.6 (CH), 125.6 (CH), 124.5 (CH), 26.5 (CH3), 20.3
(CH3), 19.6 ppm (CH3); MS (70 eV, EI): m/z (%): 146 (52, [M]+), 131
(100), 115 (16). HRMS for C14H20 ([M]+) calcd: 146.1096, found:
146.1112.
2-Methyl-3-phenylbicyclo[2.2.1]hept-2-ene (43): An LDA solution was
prepared from nBuLi (19.7 mL, 1.44m, 28.4 mmol) and iPr2NH (4.2 mL,
29.6 mmol) in THF (26 mL) at 08C. A solution of bicyclo[2.2.1]heptan-2-
one (2.5 g, 22.7 mmol) in THF (10 mL) was then added dropwise. After
3 h, MeI (4.24 mL, 68.1 mmol) was added dropwise at 08C, and stirring
was maintained for 3 h at room temperature. Aqueous HCl (20 mL, 1m)
was added, and the mixture was extracted with Et2O. The combined or-
ganic layers were dried over anhydrous Na2SO4, filtered, and concentrat-
ed under reduced pressure. Purification of the residue by flash chroma-
tography (pentane/diethyl ether 9.4/6) afforded a mixture of exo- and
endo-3-methylbicyclo[2.2.1]heptan-2-one (2.15 g, 76% yield).
1-(tert-Butyl)-2-(2-methylallyl)benzene (31): tBuLi (5.64 mL, 8.46 mmol,
1.5m) was added to a solution of 1-(tert-butyl)-2-iodobenzene (1.0 g,
3.84 mmol) in THF (6 mL) at À788C. After 30 min at this temperature,
the solution was added to a suspension of CuCN (0.17 g, 1.92 mmol) in
THF (6 mL) at À788C. The reaction mixture was allowed to warm to
room temperature and was stirred for 30 min. The mixture was cooled to
À788C, and a solution of 2-methylallyl bromide (0.52 g, 3.84 mmol) in
THF (2 mL) was added. NH4Cl (10 mL) was added, and the mixture was
extracted with ether (2î10 mL). The combined organic phases were
dried over MgSO4 and concentrated under reduced pressure. The residue
was purified by flash chromatography (pentane) to afford 31 (0.45 g,
63% yield). 1H NMR (300 MHz, CDCl3): d = 7.33 7.04 (m, 4H), 4.82
(m, 1H), 4.43 (m, 1H), 1.68 (s, 2H), 1.32 (s, 9H), 1.25 ppm (s, 3H); 13C
NMR (DEPT, 75 MHz, CDCl3): d = 148.0 (C), 145.9 (C), 137.5 (C),
132.2 (CH), 128.0 (CH), 125.9 (CH), 125.6 (CH), 112.7 (CH2), 42.6
(CH2), 35.6 (C), 31.5 (3CH3), 23.0 ppm (CH3); MS (70 eV, EI): m/z (%):
188 (7, [M]+), 173 (32), 131 (100). HRMS for C14H20 ([M]+) calcd:
188.1565, found: 188.1546.
An LDA solution was prepared from nBuLi (5 mL, 1.58m, 7.9 mmol) and
iPr2NH (1.15 mL, 8.2 mmol) in THF (3 mL) at 08C. A solution of 3-
methylbicyclo[2.2.1]heptan-2-one (0.78 g, 6.3 mmol) in THF (3 mL) was
then added dropwise at À788C. After the mixture had been stirred for
1 h, a solution of PhNTf2 (2.36 g, 6.62 mmol) in THF (4 mL) was added
dropwise at À788C, and stirring was maintained overnight at room tem-
perature. Aqueous HCl (5 mL, 1m) was added, and the mixture was ex-
tracted with Et2O(2î10 mL). The combined organic layers were dried
over anhydrous Na2SO4, filtered, and concentrated under reduced pres-
sure. Purification of the residue by flash chromatography (pentane) af-
forded 3-methylbicyclo[2.2.1]hept-2-en-2-yl trifluoromethanesulfonate
(0.99 g, 61% yield).
1-tert-Butyl-2-(cyclohexylidenemethyl)benzene (33): nBuLi in hexane
(1.6m, 9.4 mL, 15 mmol) was added to a stirred suspension of cyclohexyl-
triphenylphosphonium bromide (6.38 g, 15 mmol) in THF (20 mL) at
08C. The mixture was stirred for 30 min before a solution of 2-tert-butyl-
benzaldehyde (2.43 g, 15 mmol) in THF (10 mL) was added. The mixture
was allowed to warm to room temperature. 1m HCl (30 mL) was added,
and the organic phase was separated. The aqueous phase was extracted
with pentane (20 mL). The combined organic phases were washed
(water, NaHCO3 solution, and brine) and dried over Na2SO4. The solvent
was removed under reduced pressure. The residue was purified by flash
chromatography (silica gel, pentane) to afford 2.94 g (86% yield) of 33
ZnBr2 (15.4 mL, 18.5 mmol, 1.2m in THF) was added dropwise to the so-
lution of PhLi (9.6 mL, 1.76m, 17.0 mmol) in THF (6 mL) at À408C. Stir-
ring was maintained for 30 min at À408C and then 30 min at room tem-
perature. A solution of 3-methylbicyclo[2.2.1]hept-2-en-2-yl trifluorome-
thanesulfonate (0.99 g, 3.86 mmol) and [Pd(PPh3)4] (0.18 g, 0.154 mmol)
in THF (8 mL) were added dropwise. Stirring was maintained for 3 h at
508C. Saturated aqueous NH4Cl (14 mL) was added, and the mixture was
extracted with Et2O. The combined organic layers were dried over anhy-
drous Na2SO4, filtered, and concentrated under reduced pressure. Purifi-
cation of the residue by flash chromatography (pentane) afforded 43
(0.68 g, 96% yield). IR (KBr): n˜ = 2958, 2870, 1682, 1497, 1447, 753,
as a colorless oil. IR (KBr): n˜ = 2954, 2927, 2854, 1479, 759 cmÀ1 1H
;
NMR (CDCl3, 300 MHz): d = 7.42 (dd, J = 7.5 Hz and 1.8 Hz, 1H),
7.23 7.13 (m, 2H), 7.03 (dd, J = 7.1 Hz and 1.8 Hz, 1H), 6.58 (s, 1H),
2.34 2.30 (m, 2H), 2.12 2.07 (m, 2H), 1.73 1.47 (m, 6H), 1.42 ppm (s,
9H); 13C NMR (DEPT, CDCl3, 75 MHz): d = 148.3 (C), 140.2 (C), 137.7
(C), 132.5 (CH), 126.4 (CH), 125.6 (CH), 125.3 (CH), 125.0 (CH), 37.1
(CH2), 36.0 (C), 30.7 (3CH3), 29.9 (CH2), 28.2 (CH2), 27.1 (CH2),
26.7 ppm (CH2); MS (70 eV, EI): m/z (%): 228 (100, [M]+), 213 (24), 171
(67), 131 (66), 41 (61); HRMS for C17H24 ([M]+) calcd: 228.1878, found:
700 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.48 7.41 (m, 4H), 7.30 (m,
;
1H), 3.29 (s, 1H), 2.92 (s, 1H), 2.07 (s, 3H), 1.96 1.86 (m, 2H), 1.68 (d, J
= 8 Hz, 1H), 1.50 (m, 1H), 1.34 1.28 ppm (m, 2H); 13C NMR (DEPT,
75 MHz, CDCl3): d = 139.7, 139.6, 137.6, 128.1, 126.6, 125.5, 49.5, 46.9,
46.4, 27.1, 25.8, 13.7 ppm; MS (70 eV, EI): m/z (%): 184 (29, [M]+), 156
(100); HRMS for C14H16 ([M]+) calcd: 184.1252, found: 184.1243.
228.1866.
[29]
1-(tert-Butyl)-2-vinylbenzene (36):
To a suspension of methyltriphe-
2-Ethyl-3-phenylbicyclo[2.2.1]hept-2-ene (46): An analogous procedure
was used as described for 43 starting from 3-ethylbicyclo[2.2.1]hept-2-en-
2-yl trifluoromethanesulfonate (0.42 g, 1.54 mmol), ZnBr2 (6.2 mL, 1.2m,
7.4 mmol), PhLi (3.9 mL, 1.76m, 6.8 mmol), [Pd(PPh3)4] (4 mol%, 0.07 g,
0.062 mmol) that afforded 46 (0.26 g, 86% yield). IR (KBr): n˜ = 2961,
nylphosphonium iodide (0.96 g, 2.7 mmol) in THF (5 mL) at 08C was
added nBuLi (1.08 mL, 2.7 mmol, 2.5m). After 30 min, 2-(tert-butyl)ben-
zaldehyde (0.44 g, 2.7 mmol) in THF (5 mL) was added, and the reaction
mixture was allowed to warm to room temperature. Water (25 mL) was
added, and the mixture was extracted with ether (2î10 mL). The com-
bined organic phases were dried over MgSO4 and concentrated under
reduce pressure. The residue was purified by flash chromatography (pen-
tane/diethyl ether 9:1) to afford styrene 36 (0.30 g, 70% yield). 1H NMR
(300 MHz, CDCl3): d = 7.36 7.27 (m, 3H), 7.16 7.07 (m, 2H), 5.36 (dd,
J = 17.0 Hz and 1.5 Hz, 1H), 5.16 (dd, J = 10.8 Hz and 1.5 Hz, 1H),
1.34 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 147.1 (C),
139.2 (CH), 138.0 (C), 129.2 (CH), 127.5 (CH), 126.1 (CH), 125.6 (CH),
115.0 (CH2), 35.7 (C), 31.3 ppm (3CH3); MS (70 eV, EI): m/z (%): 160
(34, [M]+), 145 (100), 128 (20), 117 (31).
2869, 1496, 698 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.19 7.10 (m,
;
4H), 7.02 (m, 1H), 2.99 (s, 1H), 2.78 (s, 1H), 2.25 [sextet (coalescence of
dq), J = 15 Hz and 7.5 Hz, 1H], 2.06 [sextet (coalescence of dq), J = 15
and 7.5 Hz, 1H], 1.68 1.59 (m, 2H), 1.37 (m, 1H), 1.21 (m, 1H), 1.06
1.03 (m, 2H), 1.01 ppm (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d = 145.6, 139.1, 137.7, 128.1, 126.7, 125.6, 47.2, 47.0, 46.5, 26.8, 26.3,
20.9, 13.2 ppm; MS (70 eV, EI): m/z (%): 198 (34, [M]+), 170 (90), 155
(100); HRMS for C15H18 ([M]+) calcd: 198.1409, found: 198.1390.
15-Ethyl-16-phenyltetracyclo[6.6.2.02,7.09,14]hexadeca-2(7),3,5,9(14),10,12,
15-heptene (49): To a solution of ethyl iodide (0.37 g, 2.4 mmol) in di-
ethyl ether (4 mL) at À788C was added a solution of nBuLi (3.36 mL,
1.5m). After 0.5 h at À788C, the solution was warmed to room tempera-
ture and kept at this temperature for 0.5 h. The solution was then cooled
to 08C, and 15-phenyl-16-(phenylsulfonyl)tetracyclo[6.6.2.02,7.09,14]hexa-
deca-2(7),3,5,9(14),10,12,15-heptene[30] (0.84 g, 2 mmol) was added. The
1-Methyl-2-(2-methyl-1-propenyl)benzene (39): To a suspension of iso-
propyltriphenylphosphonium iodide (3.6 g, 8.3 mmol) in THF (10 mL) at
08C was added nBuLi (5.55 mL, 1.5m, 8.3 mmol). After 30 min, 2-methyl-
benzaldehyde (1.0 g, 8.3 mmol) in THF (10 mL) was added, and the mix-
ture was allowed to warm to room temperature. Water (25 mL) was
added, and the mixture was extracted with ether (2î10 mL). The com-
4260
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 4252 4264

À
Diastereoselective Remote C H Activation
4252 4264
mixture was refluxed for 6 h. The reaction mixture was diluted with
CH2Cl2 and washed with a saturated solution of NH4Cl. The combined
organic layers were dried over MgSO4 and concentrated under vacuum.
Purification by flash chromatography (pentane/CH2Cl2 9:1) afforded 49
(0.17 g, 27% yield) and the starting material (0.47 g). 1H NMR
(300 MHz, CDCl3): d = 7.33 6.87 (m, 12H), 5.16 (s, 1H), 4.97 (s, 1H),
142.3 (C), 132.8 (CH), 128.6 (CH), 128.4 (2CH), 128.1 (2CH), 126.3 (C),
126.1 (CH), 120.0 (CH), 117.6 (CH), 83.4 (CH), 53.4 (CH), 35.9 (C),
26.3 ppm (3CH3); MS (70 eV, EI): m/z (%): 270 (1, [M]+), 184 (100), 165
(20), 106 (13); HRMS for C18H22O2 ([M]+) calcd: 270.1620; found:
270.1611.
1-(2-Hydroxy-4-methylphenyl)-3,3-dimethyl-1-phenyl-2-butanol
(14a):
2.25 (q, J
= 7.5 Hz, 2H), 1.02 ppm (t, J =
7.5 Hz, 3H); 13C NMR
Reaction of (E)-13 (0.75 g, 3 mmol) and a solution of BH3¥THF (9 mL,
9 mmol, 3 equiv) in THF (25 mL) at 508C for 17 h according to the gen-
(DEPT, 75 MHz, CDCl3): d = 147.5 (C), 146.4 (C), 145.9 (C), 142.8 (C),
139.0 (C), 128.1 (2CH), 127.3 (2CH), 126.5 (CH), 124.6 (2CH), 124.5
(2CH), 122.6 (2CH), 122.5 ppm (2CH); MS (70 eV, EI): m/z (%): 308
(38, [M]+), 279 (33), 178 (100); anal. calcd. for C24H20: C 93.46, H 6.54;
found: C 93.27, H 6.61.
eral procedure afforded diol 14a (0.56 g, 66% yield). IR (KBr): n˜
=
3389, 2870, 1447, 1270, 718 cmÀ1; H NMR (300 MHz, CDCl3): d = 7.21
6.49 (m, 8H), 4.18 (d, J = 3.1 Hz, 1H), 3.88 (d, J = 3.1 Hz, 1H), 2.17 (s,
3H), 0.82 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 155.2
(C), 142.6 (C), 138.7 (C), 132.7 (CH), 128.5 (2CH), 128.1 (2CH), 126.2
(CH), 123.1 (C), 120.9 (CH), 118.4 (CH), 83.7 (CH), 53.3 (CH), 35.9 (C),
26.3 (3CH3), 20.9 ppm (CH3); MS (70 eV, EI): m/z (%): 284 (1, [M]+),
198 (100), 183 (33), 165 (13), 120 (15); HRMS for C15H16O2 ([M]+) calcd:
284.1776; found: 284.1796.
1
Products of the hydroboration oxidation procedure: General procedure
for the reactions of hydroboration oxidation:
Preparation of 1-(2-hydroxyphenyl)-3,3-dimethyl-1-phenyl-2-butanol
(12): A solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) was added to a sol-
ution of 3,3-dimethyl-1,1-diphenyl-1-butene (11) (0.71 g, 3 mmol) in THF
(25 mL) at room temperature under an argon atmosphere. After stirring
at 508C for 24 h, the mixture was quenched by addition of 2m NaOH
(12 mL) and 30% H2O2 (12 mL). The resulting mixture was stirred at
room temperature for 30 min and was then extracted with diethyl ether
(10 mL). The combined organic layers were dried over MgSO4, filtered,
and concentrated under reduced pressure. Purification of the residue by
flash chromatography (pentane/ether 7:3) afforded the product 12 in
60% yield.
1-(2-Hydroxyphenyl)-3,3-dimethyl-1-(4-methylphenyl)-2-butanol (14b):
Reaction of (Z)-13 (0.75 g, 3 mmol) and a solution of BH3¥THF (9 mL,
9 mmol, 3 equiv) in THF (25 mL) at 508C for 17 h according to the gen-
eral procedure afforded diol 14b (0.48 g, 56% yield). IR (KBr): n˜
=
3412, 2957, 1488, 1250, 753 cmÀ1; H NMR (300 MHz, CDCl3): d = 7.24
6.51 (m, 8H), 4.20 (d, J = 3.1 Hz, 1H), 3.91 (d, J = 3.1 Hz, 1H), 2.19 (s,
3H), 0.83 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 155.5
(C), 139.2 (C), 135.8 (C), 132.8 (CH), 129.2 (2CH), 128.6 (CH), 128.0
(2CH), 126.4 (C), 120.0 (CH), 117.7 (CH), 83.8 (CH), 53.4 (CH), 35.9
(C), 26.3 (3CH3), 20.8 ppm (CH3); MS (70 eV, EI): m/z (%): 284 (1, [M]+
), 198 (100), 183 (39), 165 (13); HRMS for C19H24O2 ([M]+) calcd:
284.1776; found: 284.1761.
1
2-[(2-Hydroxyphenyl)(phenyl)methyl]-3,3-dimethyl-1-butanol (3): Reac-
tion of 1 (0.75 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol,
3 equiv) in THF (25 mL) at 508C for 12 h according to the general proce-
dure afforded diol 3 (0.68 g, 80% yield). IR (KBr): n˜ = 3400, 3306, 2962,
1455, 1368, 1232, 752, 704 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.22
;
2’-(1-Hydroxy-2-methyl-propyl)-biphenyl-2-ol (16a, R = H): Reaction of
15a (0.62 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv)
in THF (25 mL) at 908C for 12 h according to the general procedure af-
forded diol 16a (0.58 g, 80% yield). IR (KBr): n˜ = 3300, 2958, 1520,
7.01 (m, 7H), 6.77 6.73 (m, 2H), 4.29 (d, J = 5.3 Hz, 1H), 3.73 (dd, J =
11 and 3.3 Hz, 1H), 3.52 (dd, J = 11 and 9.9 Hz, 1H), 2.30 (ddd, J =
9.9 Hz, 5.3 Hz and 3.3 Hz, 1H), 0.91 ppm (s, 9H); 13C NMR (DEPT,
75 MHz, CDCl3): d = 154 (C), 142.1 (C), 131.1 (C), 130.9 (CH), 129.3
(2CH), 128.3 (2CH), 127.8 (CH), 126.1 (CH), 120.1 (CH), 117.2 (CH),
62.2 (CH2), 53.9 (CH), 46.5 (CH), 34.4 (C), 28.7 ppm (3CH3); MS (70 eV,
EI): m/z (%): 284 (29, [M]+), 183 (100); HRMS for C19H24O2 ([M]+)
calcd: 284.1776; found: 284.1756; an X-ray analysis of compound 3 has
been carried out (see Figure 1).[31]
1315, 1110, 905 cmÀ1 1H NMR (400 MHz, [D6]DMSO, 908C): d = 8.78
;
(brs, 1H), 7.53 (dd, J = 7.7 and 1.3 Hz, 1H), 7.30 (dt, J = 7.7 and
1.3 Hz, 1H), 7.22 (dt, J = 7.3 and 1.3 Hz), 7.16 (dt, J = 8.2 and 1.8 Hz,
1H), 7.06 7.02 (m, 2H), 6.91 (dd, J = 8.2 and 1.8 Hz, 1H), 6.83 (dt, J =
7.3 and 1.2 Hz, 1H), 4.28 (d, J = 6.4 Hz, 1H), 3.01 (brs, 1H), 1.71 (sex,
J = 6.7 Hz, 1H), 0.76 (d, J = 6.7 Hz, 3H), 0.56 ppm (d, J = 6.7 Hz,
3H); 13C NMR (DEPT, 75 MHz, [D6]DMSO): d? = 153.6 (C), 142.9 (C),
136.9 (C), 130.6 (CH), 129.5 (CH), 127.8 (CH), 127.6 (C), 126.0 (CH),
125.7 (CH), 125.3 (CH), 118.2 (CH), 115.2 (CH), 73.8 (CH), 33.3 (CH),
18.9 (CH3), 19.9 ppm (CH3); MS (70 eV, EI): m/z (%): 242 (20, [M]+),
224 (100); HRMS for C16H18O2 ([M]+) calcd: 242.1307; found: 242.1310.
2-Benzhydryl-3,3-dimethyl-1-butanol (9): Reaction of 8 (0.75 g, 3 mmol)
and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in THF (25 mL) at
508C for 24 h according to the general procedure afforded alcohol 9
(0.51 g, 63% yield). 1H NMR (300 MHz, CDCl3): d
= 7.39 7.10 (m,
10H), 4.20 (d, J = 8.2 Hz, 1H), 3.74 3.61 (m, 2H), 2.34 (ddd, J = 8 Hz,
5.3 Hz and 3.3 Hz, 1H), 0.91 ppm (s, 9H); 13C NMR (DEPT, 75 MHz,
2’-(1-Hydroxy-2-methyl-propyl)-4-methoxy-biphenyl-2-ol (16b,
R
=
CDCl3): d
= 146.1 (C), 144.0 (C), 129.1 (2CH), 128.7 (2CH), 128.6
OMe): Reaction of 15b (0.71 g, 3 mmol) and a solution of BH3¥THF
(9 mL, 9 mmol, 3 equiv) in THF (25 mL) at 908C for 12 h according to
the general procedure afforded diol 16b (0.66 g, 81% yield).
(2CH), 128.4 (2CH), 126.3 (CH), 125.9 (CH), 62.6 (CH2), 54.2 (CH),
52.1 (CH), 34.5 (C), 29.3 ppm (3CH3); MS (70 eV, EI): m/z (%): 268 (17,
[M]+), 167 (100); elemental analysis calcd (%) for C19H24O: C 85.03, H
9.01; found: C 84.85, H 9.11.
We observed two rotamers at room temperature as in 16a (R = H). IR
(KBr): n˜ = 3306, 2959, 1620, 1520, 1468, 1314, 1164, 1003, 763 cmÀ1
;
1-(2-Hydroxyphenyl)-2,3,3-trimethyl-1-phenyl-2-butanol (10): Reaction of
1 (0.75 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in
THF (25 mL) at 508C for 1 h according to the general procedure afford-
ed diol 10 (0.26 g, 30% yield). IR (KBr): n˜ = 3370, 2955, 1580, 1488,
1H NMR spectra of the two rotamers (300 MHz, CDCl3): d = 7.44 7.42
(m, 1H), 7.31 7.17 (m, 2H), 7.14 7.06 (m, 1H), 6.90 6.87 (m, 1H), 6.47
6.39 (m, 2H), 4.1 (d, J = 8.8 Hz, 1H), 3.71 (s, 3H), 1.94 1.82 (m, 1H),
0.86 (d, J
= 6.6 Hz, 3H), 0.45 ppm (d, J =
7.1 Hz, 3H); 1H NMR
1253, 752 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.46 7.43 (m, 2H),
;
(300 MHz, CDCl3): d = 7.44 7.42 (m, 1H), 7.31 7.17 (m, 2H), 7.14 7.06
(m, 1H), 6.90 6.87 (m, 1H), 6.47 6.39 (m, 2H), 4.22 (d, J = 7.9 Hz, 1H),
3.72 (s, 3H), 1.79 1.70 (m, 1H), 0.81 (d, J = 6.6 Hz, 3H), 0.51 ppm (d, J
= 7.1 Hz, 3H); 13C NMR spectra of the two rotamers (DEPT, 75 MHz,
CDCl3): d = 160.3 (C), 153.6 (C), 142.3 (C), 136.3 (C), 131.5 (CH), 131.1
(CH), 128.4 (CH), 127.8 (CH), 126.1 (CH), 120.5 (CH), 106.6 (CH),
101.4 (CH), 76.8 (CH), 55.3 (CH3), 34.4 (CH), 19.1 (CH3),18.9 ppm
(CH3); 13C NMR (DEPT, 75 MHz, CDCl3): d = 160.4 (C), 153.7 (C),
142.7 (C), 135.2 (C), 131.2 (CH), 130.8 (CH), 128.5 (CH), 128.1 (CH),
127.8 (CH), 120.0 (CH), 112.5 (CH), 101.6 (CH), 77.7 (CH), 55.3 (CH3),
33.5 (CH), 19.2 (CH3), 18.4 ppm (CH3); MS (70 eV, EI): m/z (%): 272 (1,
[M]+), 211 (100), 168 (10); HRMS for C17H20O3 ([M]+) calcd: 272.1412;
found: 272.1419.
7.20 6.93 (m, 5H), 6.77 6.74 (m, 1H), 6.66 6.61 (m, 1H), 4.07 (s, 1H),
1.11 (s, 3H), 0.90 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d =
154.6 (C), 143.4 (C), 132.2 (CH), 130.2 (C), 129.3 (2CH), 128.5 (2CH),
128.1 (CH), 126.5 (CH), 120.0 (CH), 118.2 (CH), 81.3 (C), 59.5 (CH),
39.5 (C), 26.4 (3CH3), 24.3 ppm (CH3); MS (70 eV, EI): m/z (%): 284 (1,
[M]+), 209 (22), 184 (100), 165 (23), 101 (79), 83 (28); HRMS for
C19H24O2 ([M]+) calcd: 284.1776; found: 284.1750; an X-ray analysis of
compound 10 has been carried out (see Figure 1).[32]
1-(2-Hydroxyphenyl)-3,3-dimethyl-1-phenyl-2-butanol (12): Reaction of
11 (0.71 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv)
in THF (25 mL) at 508C for 24 h according to the general procedure af-
forded diol 12 (0.48 g, 60% yield). IR (KBr): n˜ = 3428, 2959, 1583, 1495,
1254, 751 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.18 6.89 (m, 7H),
;
6.73 6.23 (m, 2H), 4.19 (d, J = 2.9 Hz, 1H), 3.85 (d, J = 2.9 Hz, 1H),
2’-(1-Hydroxy-2-methyl-propyl)-4-trifluoromethyl-biphenyl-2-ol (16c, R
= CF3): Reaction of 15c (0.83 g, 3 mmol) and a solution of BH3¥THF
0.78 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 155.3 (C),
Chem. Eur. J. 2004, 10, 4252 4264
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4261

J. A. Varela, P. Knochel et al.
FULL PAPER
(9 mL, 9 mmol, 3 equiv) in THF (25 mL) at 908C for 12 h according to
the general procedure afforded diol 16c (0.76 g, 82% yield).
1077, 1011, 755 cmÀ1
;
1H NMR (CDCl3, 300 MHz): d = 7.95 (m, 1H),
7.84 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.39 7.32 (m, 2H),
7.13 7.10 (m, 1H), 4.26 4.15 (m, 8H), 2.26 (brs, 1H), 1.90 1.80 (m, 1H),
1.56 (brs, 1H), 1.03 (d, J = 6.6 Hz, 3H), 0.98 ppm (d, J = 6.6 Hz, 3H);
We observed two rotamers at room temperature as in 16a (R = H). IR
(KBr): n˜ = 3413, 2964, 1422, 1331, 1168, 1126, 912, 515 cmÀ1 1H NMR
;
13C NMR (DEPT, CDCl3, 75 MHz): d
= 164.2 (C), 149.6 (C), 134.1
(300 MHz, CDCl3): d = 7.46 7.43 (m, 1H), 7.36 7.23 (m, 2H), 7.17 7.03
(m, 4H), 3.97 (d, J = 8.8 Hz, 1H), 1.97 1.82 (m, 1H), 0.85 (d, J =
(CH), 131.8 (2CH), 131.5 (2CH), 130.5 (C), 128.7 (C), 128.3 (CH), 128.2
(C), 125.9 (CH), 121.8 (CH), 92.5 (C), 83.4 (C), 74.3 (CH), 70.2 (5CH),
69.8 (CH), 68.5 (CH), 67.2 (CH), 33.1 (CH), 21.0 (CH3), 18.9 ppm (CH3);
elemental analysis calcd for C27H25BrFeO3: C 60.82, H 4.73; found: C
60.72, H 4.77; an X-Ray analysis of compound 23 has been carried out
(see Figure 2).[34]
1
6.2 Hz, 3H), 0.43 ppm (d, J = 7.1 Hz, 3H); H NMR (300 MHz, CDCl3):
d = 7.46 7.43 (m, 1H), 7.36 7.23 (m, 2H), 7.17 7.03 (m, 4H), 4.13 (d,
J = 8.4 Hz, 1H), 1.74 1.65 (m, 1H), 0.81 (d, J = 6.2 Hz, 3H), 0.51 ppm
(d, J
= = 153.1, 141.8,
6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
141.5, 135.4, 134.2, 131.6, 131.0, 130.7, 130.4, 129.1, 128.5, 128.2, 126.2,
125.6, 122.0, 117.3, 113.6, 113.1, 78.3, 77.0, 34.5, 33.5, 19.2, 18.9, 18.5 ppm;
MS (70 eV, EI): m/z (%): 310 (1, [M]+), 292 (100); HRMS for
C17H17F3O3 ([M]+) calcd: 310.1181; found: 310.1190.
3-tert-Butyl-2-(3-hydroxy-2-methyl-propyl)phenol (28): Reaction of 24
(0.56 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in
THF (25 mL) at 908C for 36 h according to the general procedure afford-
ed diol 28 (0.41 g, 61% yield). IR (KBr): n˜ = 3433, 3116, 2956, 1579,
2’-Hydroxymethyl-biphenyl-2-ol (19):[33] To
a solution of 18 (0.13 g,
1473, 1269, 982 cmÀ1 1H NMR (300 MHz, CDCl3): d = 8.28 (brs, 1H),
;
0.45 mmol) in pentane (1 mL) was added dropwise LAH (0.45 mL,
0.45 mmol, 1m in diethyl ether). After 1 h, the reaction mixture was fil-
tered into a sealed tube and the solvent was pumped off. THF (4 mL)
and BH3¥THF (2 mL, 1m) were added, and the mixture was heated to
908C for 12 h. The reaction mixture was quenched by adding NaOH
(4 mL, 2m) and H2O2 (4 mL). The mixture was extracted with ether (2î
5mL). The combined organic phases were dried over MgSO4 and concen-
trated under reduced pressure. Purification by flash chromatography
(pentane/diethyl ether 1:1) afforded 19 (0.02 g, 16% yield). 1H NMR
(300 MHz, CDCl3): d = 7.49 7.46 (m, 1H), 7.39 7.31 (m, 2H), 7.24 7.18
(m, 2H), 7.06 7.03 (m, 1H), 6.94 6.89 (m, 2H), 4.43 ppm (s, 2H);
13C NMR (DEPT, 75 MHz, CDCl3): d = 152.8 (C), 138.9 (C), 136.3 (C),
130.9 (CH), 130.6 (CH), 129.4 (CH), 129.2 (CH), 128.7 (CH), 128.5
(CH), 127.6 (C), 120.8 (CH), 116.4 (CH), 63.7 ppm (CH2).
6.93 6.90 (m, 2H), 6.68 6.65 (m, 1H), 3.95 (brs, 1H), 3.57 3.37 (m, 2H),
2.90 2.74 (m, 2H), 1.88 1.81 (m, 1H), 1.33 (s, 9H), 1.05 ppm (d, J =
6.6 Hz, 3H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 155.6 (C), 149.8
(C), 126.5 (CH), 125.9 (C), 119.1 (CH), 113.7 (CH), 65.17 (CH2), 36.9
(CH), 36.5 (C), 32.3 (3CH3), 29.4 (CH2), 18.5 ppm (CH3); MS (70 eV,
EI): m/z (%): 222 (91, [M]+), 204 (19), 189 (53), 163 (83), 121 (100);
HRMS for C14H22O2 ([M]+) calcd: 222.1620; found: 222.1618.
3-tert-Butyl-2-(1-hydroxy-2-methyl-propyl)phenol (29): Reaction of 24
(0.56 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in
THF (25 mL) at 908C for 45 min according to the general procedure af-
forded alcohol 29 (0.29 g, 47% yield). IR (KBr): n˜ = 3436, 2959, 1469,
1365, 1106, 1007, 757 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.45 7.42
;
(m, 1H), 7.32 7.29 (m, 1H), 7.19 7.08 (m, 2H), 4.92 (dd, J = 8.8 and
3.7 Hz, 1H), 2.17 2.05 (m, 1H), 1.62 (d, J = 3.7 Hz, 1H), 1.37 (s, 9H),
(Rp*)-1-(2-Hydroxyphenyl)-2-[(a)-(R*)-1-hydroxy-2-methylpropyl]ferro-
cene (22a): Reaction of 20a (0.632 g, 2 mmol) with BH3¥THF (6 mL,
6 mmol) in THF (15 mL) at 658C for 12 h followed by oxidation with 2m
NaOH (8 mL) and 30% H2O2 (8 mL), and purification of the product by
flash chromatography (silica gel, pentane/diethyl ether = 3:1) according
to the general procedure gave 0.315 g (45% yield) of 22a as an orange
1.14 (d, J
= 6.6 Hz, 3H), 0.63 ppm (d, J =
7.1 Hz, 3H); 13C NMR
(DEPT, 75 MHz, CDCl3): d = 147.5 (C), 142.7 (C), 127.7 (CH), 127.3
(CH), 126.6 (CH), 125.9 (CH), 75.5 (CH), 35.7 (C), 35.1 (CH), 32.6
(3CH3), 19.9 (CH3), 19.8 ppm (CH3); MS (70 eV, EI): m/z (%): 206 (3,
[M]+), 163 (100), 145 (11), 129 (14), 117 (11), 57 (21); HRMS for
C14H22O([ M]+) calcd: 206.1671; found: 206.1659.
1
oil. IR (KBr): n˜ = 3349, 3093, 2960, 2928, 2871, 1498, 755 cmÀ1; H NMR
(CDCl3, 300 MHz): d = 8.07 (brs, 1H), 7.35 7.32 (m, 1H), 7.27 7.21 (m,
1H), 6.97 6.94 (m, 1H), 6.90 6.84 (m, 1H), 4.38 4.31 (m, 8H), 4.00 (d,
J = 8.0 Hz, 1H), 2.41 (brs, 1H), 1.78 1.66 (m, 1H), 0.98 (d, J = 6.6 Hz,
3H), 0.71 ppm (d, J = 7.1 Hz, 3H); 13C NMR (DEPT, CDCl3, 75 MHz):
d = 153.8 (C), 132.8 (CH), 128.9 (CH), 123.0 (C), 119.8 (CH), 116.7
(CH), 90.4 (C), 81.9 (C), 76.2 (CH), 71.0 (CH), 70.9 (CH), 69.7 (5CH),
67.3 (CH), 33.4 (CH), 20.0 (CH3), 19.2 ppm (CH3); MS (70 eV, EI): m/z
(%): 332 (25, [MÀH2O]+), 289 (100); HRMS for C20H20FeO([ MÀH2O]+
) calcd: 332.0864, found: 332.0850.
3-tert-Butyl-2-(2-hydroxy-2-methyl-propyl)phenol (30): Reaction of 24
(0.56 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in
THF (25 mL) at 908C for 45 min according to the general procedure af-
forded diol 30 (0.19 g, 30% yield). IR (KBr): n˜ = 3233, 2971, 1576, 1447,
1366, 1263, 1112, 981 cmÀ1 1H NMR (300 MHz, CDCl3): d = 9.70 (brs,
;
1H), 6.98 (t, J = 7.9 Hz, 1H), 6.88 (dd, J = 7.9 and 1.3 Hz, 1H), 6.74
(dd, J = 7.9 and 1.3 Hz, 1H), 3.18 (s, 2H), 1.30 (s, 9H), 1.24 ppm (s,
6H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 157.3 (C), 149.4 (C), 127.1
(CH), 123.6 (C), 118.2 (CH), 115.5 (C), 74.0 (C), 40.8 (CH2), 35.9 (C),
32.4 (3CH3), 29.2 ppm (2CH3); MS (70 eV, EI): m/z (%): 222 (25, [M]+),
204 (27), 189 (45), 164 (82), 149 (100), 121 (21), 59 (34); HRMS for
C14H22O2 ([M]+) calcd: 222.1620; found: 222.1616.
(Rp*)-1-(2-Hydroxy-4-methylphenyl)-2-[(a)-(R*)-1-hydroxy-2-methylpro-
pyl]ferrocene (22b): Reaction of 20b (0.330 g, 1 mmol) with BH3¥THF
(3 mL, 3 mmol) in THF (8 mL) at 658C for 12 h, followed by oxidation
with 2m NaOH (4 mL) and 30% H2O2 (4 mL), and purification of the
product by flash chromatography (silica gel, pentane/diethyl ether = 3:1)
according to the general procedure gave 0.171 g (47% yield) of 22b as
an orange oil. IR (KBr): n˜ = 3361, 3095, 2959, 2922, 2870, 1622, 1468,
3-(2-tert-Butyl-phenyl)-2-methylpropan-1-ol (32): Reaction of 31 (0.56 g,
3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in THF
(25 mL) at 908C for 7 d according to the general procedure afforded al-
cohol 32 (0.30 g, 49% yield). IR (KBr): n˜ = 338, 2872, 1483, 1108, 1034,
1
1
1453, 811 cmÀ1; H NMR (CDCl3, 300 MHz): d = 7.94 (brs, 1H), 7.21 (d,
759 cmÀ1; H NMR (300 MHz, CDCl3): d = 7.33 7.30 (m, 1H), 7.17 7.14
J = 8.0 Hz, 1H), 6.78 (s, 1H), 6.70 6.67 (m, 1H), 4.36 4.30 (m, 8H), 3.99
(d, J = 7.5 Hz, 1H), 2.33 (s, 3H), 1.80 1.68 (m, 1H), 0.98 (d, J = 6.6 Hz,
3H), 1.43 ppm (d, J = 6.6 Hz, 3H); 13C NMR (DEPT, CDCl3, 75 MHz):
d = 153.5 (C), 139.1 (C), 132.5 (CH), 120.8 (CH), 119.8 (C), 117.3 (CH),
90.3 (C), 82.0 (C), 76.2 (CH), 71.0 (CH), 71.0 (CH), 69.7 (5CH), 67.2
(CH), 33.4 (CH), 21.1 CH3), 20.0 (CH3), 19.3 ppm (CH3); MS (70 eV,
EI): m/z (%): 346 (44, [MÀH2O]+), 303 (100); HRMS for C21H22FeO
([MÀH2O]+) calcd: 346.1020, found: 346.1014.
1-[2-(4-Bromobenzoyloxy)phenyl]-2-(1-hydroxy-2-methylpropyl)ferro-
cene (23): 4-Dimethylaminopyridine (146 mg, 1.2 mmol) and 4-bromo-
benzoyl chloride (263 mg, 1.2 mmol) were added to a solution of 5
(140 mg, 0.5 mmol) in dry CH2Cl2 (10 mL), and the mixture was stirred
at room temperature for 12 h. The solution was washed with water, dried
over Na2SO4, and the solvent was removed under reduced pressure. The
product was purified by flash chromatography (silica gel, CH2Cl2) to
afford 23 (193 mg; 91% yield) as an orange solid, which was recrystal-
lized from methanol. M.p. 1478C; IR (KBr): n˜ = 3528, 1720, 1588, 1268,
(m, 1H), 7.07 7.05 (m, 3H), 3.58 3.54 (m, 2H), 2.91 (dd, J = 14.6 and
6.8 Hz, 1H), 2.68 (dd, J = 14.6 and 7.9 Hz, 1H), 2.15 1.93 (m, 1H), 1.35
(s, 3H), 0.91 ppm (d, J
CDCl3): d = 148.0 (C), 138.9 (C), 131.2 (CH), 126.3 (CH), 125.7 (CH),
125.6 (CH), 67.9 (CH2), 37.4 (CH), 37.3 (CH2), 35.9 (C), 31.8 (3CH3),
16.8 ppm (CH3); MS (70 eV, EI): m/z (%): 206 (37, [M]+), 131 (100), 105
(100), 91 (47); HRMS for C14H22O([ M]+) calcd: 206.1671; found:
206.1674.
=
6.6 Hz, 3H); 13C NMR (DEPT, 75 MHz,
3-tert-Butyl-2-{[(1S*,2R*)-2-hydroxycyclohexyl]methyl}phenol (34): Re-
action of 33 (0.684 g, 3 mmol) with BH3¥THF (9 mL, 9 mmol) in THF
(25 mL) at 908C for 36 h, followed by oxidation with 2m NaOH (12 mL)
and 30% H2O2 (12 mL), and purification of the product by flash chroma-
tography (pentane:ether = 1:1) according to the general procedure gave
0.479 g (61% yield) of 34 as a white solid. M.p. 1618C; IR (KBr): n˜ =
3523, 3239, 2936, 2854, 1580, 1467, 1019 cmÀ1 1H NMR ([D6]DMSO,
;
400 MHz): d = 8.92 (s, 1H), 6.88 6.85 (m, 1H), 6.79 6.77 (m, 1H), 6.64
6.62 (m, 1H), 4.61 4.60 (m, 1H), 3.35 (s, 1H), 3.29 3.24 (m, 1H), 3.22
4262
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 4252 4264

À
Diastereoselective Remote C H Activation
4252 4264
3.15 (m, 1H), 2.73 2.67 (m, 1H), 1.84 1.75 (m, 2H), 1.60 1.59 (m, 1H),
1.51 1.24 (m, 10H), 1.19 1.14 (m, 2H), 1.02 0.86 ppm (m, 2H); 13C
NMR (DEPT, [D6]DMSO, 100 MHz): d = 156.6 (C), 148.9 (C), 126.0
(C), 125.3 (CH), 116.9 (CH), 112.7 (CH), 74.4 (CH), 44.5 (CH), 35.8 (C),
35.7 (CH2), 32.2 (3CH3), 29.8 (CH2), 29.0 (CH2), 25.6 (CH2), 24.6 ppm
(CH2); MS (70 eV, EI): m/z (%): 262 (25, [M]+), 244 (82), 229 (100);
HRMS for C17H26O2 ([M]+) calcd: 262.1933, found: 262.1914.
CDCl3): d = 136.4 (C), 136.4 (C), 130.3 (CH), 129.5 (CH), 126.5 (CH),
126.0 (CH), 62.5 (CH2), 36.3 (CH2), 19.4 ppm (CH3); MS (70 eV, EI): m/z
(%): 136 (39, [M]+), 105 (100), 91 (26), 77 (18).
(3-Phenylbicyclo[2.2.1]hept-2-yl)methanol (44): Reaction of 43 (0.55 g,
3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in THF
(25 mL) at 508C for 36 h according to the general procedure afforded al-
cohol 44 (0.39 g, 64% yield). IR (KBr): n˜ = 3338, 2961, 2879, 1494, 1446,
1023, 756, 704 cmÀ1 1H NMR (300 MHz, CDCl3): d
; = 7.22 7.08 (m,
Bis-4-bromobenzoylester of 3-tert-butyl-2-{[(1S*,2R*)-2-hydroxycyclo-
hexyl]methyl}phenol (35): 4-Dimethylaminopyridine (183 mg, 1.5 mmol)
and 4-bromobenzoyl chloride (329 mg, 1.5 mmol) were added to a solu-
tion of 34 (131 mg, 0.5 mmol) in dry CH2Cl2 (10 mL), and the mixture
was stirred at room temperature for 12 h. The solution was washed with
water, dried over Na2SO4, and the solvent was removed under reduced
pressure. The product was purified by flash chromatography (CH2Cl2) to
afford 301 mg (96% yield) of 34 as a white solid, which was recrystallized
from acetonitrile. M.p. 918C; IR (KBr): n˜ = 2932, 2862, 1734, 1716, 1590,
5H), 3.59 (dd, J = 11.1 and 5.8 Hz, 1H), 3.40 (dd, J = 11.1 Hz and
8.9 Hz, 1H), 3.21 (dd, J = 11.7 Hz and 2.8 Hz, 1H), 2.42 2.37 (m, 3H),
1.74 (dt, J = 8.4 Hz and 2.7 Hz, 1H), 1.60 1.53 (m, 2H), 1.46 1.37 (m,
3H), 1.21 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d = 140.5, 129.6,
127.9, 125.8, 62.4, 47.4, 43.8, 42.6, 40.5, 39.5, 23.0, 22.7 ppm; MS (70 eV,
EI): m/z (%): 202 (16, [M]+), 184 (54), 91 (100); HRMS for C14H18O
([M]+) calcd: 202.1357; found: 202.1343.
[3-(2-Hydroxyphenyl)bicyclo[2.2.1]hept-2-yl]methanol (45): Reaction of
43 (0.55 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv)
in THF (25 mL) at 908C for 24 h according to the general procedure af-
1270 cmÀ1 1H NMR (CDCl3, 300 MHz): d = 8.13 8.10 (m, 2H), 7.74
;
7.71 (m, 2H), 7.54 7.51 (m, 2H), 7.45 7.42 (m, 2H), 7.31 (dd, J = 8.0 Hz
and 1.3 Hz, 1H), 7.17 (t, J = 8.0 Hz), 6.96 (dd, J = 8.0 Hz and 0.9 Hz,
1H), 4.86 4.78 (m, 1H), 3.15 3.08 (m, 1H), 2.83 2.75 8m, 1H), 2.36 2.23
(m, 1H), 2.14 2.11 (m, 1H), 1.77 1.74 (m, 1H), 1.66 1.63 (m, 1H), 1.57
1.53 (m, 1H), 1.48 1.38 (m, 10H), 1.34 1.05 ppm (m, 3H); 13C NMR
(DEPT, CDCl3, 75 MHz): d = 165.4 (C), 164.2 (C) , 150.8 (C), 150.5 (C),
132.1 (2CH), 131.6 (2CH), 131.4 (2CH), 131.3 (C), 130.9 (2CH), 129.3
(C), 128.9 (C), 128.7 (C), 127.7 (C), 126.3 (CH), 124.6 (CH), 120.3 (CH),
79.1 (CH), 43.0 (CH), 36.5 (C), 32.5 (CH2), 32.4 (3CH3), 31.3 (CH2), 30.2
(CH2), 25.8 (CH2), 24.7 ppm (CH2); elemental analysis calcd (%) for
C31H32Br2O4: C 59.25, H 5.13; found: C 59.53, H 5.33; an X-ray analysis
of compound 35 has been carried out (see Figure 3).[35]
forded diol 45 (0.30 g, 46% yield). IR (KBr): n˜ = 3536, 2954, 1630 cmÀ1
;
1H NMR (300 MHz, CDCl3): d = 7.32 (d, J = 7.6 Hz, 1H), 7.08 (t, J =
7.8 Hz, 1H), 6.89 (t, J = 6.8 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 3.51 3.39
(m, 2H), 3.28 (d, J = 11.1 Hz, 1H), 2.62 2.55 (m, 2H), 2.49 (s, 1H), 1.94
(m, 1H), 1.70 1.62 (m, 2H), 1.49 1.34 ppm (m, 3H); 13C NMR (75 MHz,
CDCl3): d = 154.4, 129.4, 129.0, 127.1, 120.5, 116.6, 63.9, 43.4, 42.9, 41.1,
40.5, 24.1, 22.7 ppm; HRMS for C14H18O2 ([M]+) calcd: 218.1307; found:
218.1294.
1-[3-(2-Hydroxyphenyl)bicyclo[2.2.1]hept-2-yl]-1-ethanol (47). Reaction
of 46 (0.59 g, 3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol,
3 equiv) in THF (25 mL) at 508C for 18 h according to the general proce-
dure afforded diol 47 as a colorless solid (0.51 g, 74% yield). M.p. =
2-(2-tert-Butyl-phenyl)ethanol (37): Reaction of 36 (0.48 g, 3 mmol) and
a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in THF (25 mL) at 908C
for 3.5 days according to the general procedure afforded alcohol 37
(0.21 g, 40% yield). IR (KBr): n˜ = 3325, 2876, 1486, 1365, 1251, 1110,
1738C; IR (KBr): n˜ = 3546, 3286, 2963, 2938, 1728, 1454 cmÀ1 1H NMR
;
(300 MHz, CDCl3:CD3OD, 4:1): d = 7.34 (dd, J = 8.1 Hz and 1.5 Hz,
1H), 7.00 (td, J = 8.1 Hz and 1.5 Hz, 1H), 6.81 6.74 (m, 2H), 3.81 (dc, J
= 10.3 Hz and 5.9 Hz, 1H), 3.56 (dd, J = 11.8 Hz and 3.7 Hz, 1H), 2.34
(s, 1H), 2.27 (s, 1H) 2.06 (m, 1H), 1.92 (m, 1H), 1.58 (d, J = 8.8 Hz,
1042, 748 cmÀ1 1H NMR (400 MHz, CDCl3): d = 7.42 7.40 (m, 1H),
;
7.25 7.16 (m, 3H), 3.88 (t, J = 7.5 Hz, 2H), 3.19 (t, J = 7.5 Hz, 2H),
1.45 ppm (s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 148.1 (C),
136.3 (C), 131.6 (CH), 126.3 (CH), 126.2 (CH), 125.8 (CH), 64.3 (CH2),
37.4 (CH2), 35.7 (C), 31.6 ppm (3CH3); MS (70 eV, EI): m/z (%): 178
(49, [M]+), 145 (37), 121 (100), 105 (58), 91 (28); HRMS for C12H18O
([M]+) calcd: 178.1358; found: 178.1354.
1H), 1.52 1.39 (m, 4H), 1.07 ppm (d,
J =
5.9 Hz, 3H); 13C NMR
(75 MHz, CD3OD): d = 156.8, 131.1, 129.5, 127.8, 120.2, 116.6, 67.7, 52.6,
44.3, 42.4, 42.1, 39.4, 24.6, 23.6, 23.5 ppm; MS (70 eV, EI): m/z (%): 232
(22, [M]+), 214 (40), 186 (75), 107 (100); HRMS for C15H20O2 ([M]+)
calcd: 232.1464; found: 232.1449; an X-ray analysis of compound 47 has
been carried out (see Figure 4).[37]
3-tert-Butyl-2-(2-hydroxy-ethyl)phenol (38): Reaction of 36 (0.48 g,
3 mmol) and a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in THF
(25 mL) at 908C for 3.5 days according to the general procedure afforded
diol 38 (0.10 g, 17% yield). IR (KBr): n˜ = 3516, 3400, 2959, 1579, 1462,
2-[16-(1-Hydroxyethyl)tetracyclo[6.6.2.02,7.09,14]hexadeca-2(7),3,5,9(14),
10,12-hexaen-15-yl]phenol (50): Reaction of 49 (0.92 g, 3 mmol) and a
solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in THF (25 mL) at 508C
for 24 h according to the general procedure afforded diol 50 (0.58 g, 57%
yield). 1H NMR (300 MHz, CDCl3): d = 7.33 6.41 (m, 8H), 4.23 (d, J =
2.6 Hz, 1H), 4.22 (d, J = 1.3 Hz, 1H), 3.73 (dd, J = 9.9 Hz and 1.3 Hz,
1H), 2.90 (dc, J = 9.9 and 6.2 Hz, 1H), 2.26 (td, J = 9.9 and 2.6 Hz,
1H), 1.24 ppm (d, J = 6.2 Hz, 3H); 13C NMR (DEPT, 75 MHz, CDCl3):
d = 153.9 (C), 146.0 (C), 143.1 (C), 142.5 (C), 141.9 (C), 129.6 (C), 128.4
(CH), 127.7 (CH), 126.4 (CH), 125.9 (CH), 125.9 (CH), 125.7 (CH),
125.6 (CH), 124.6 (CH), 123.8 (CH), 122.7 (CH), 120.5 (CH), 115.8
(CH), 69.3 (CH), 50.3 (2CH), 47.5 (CH), 38.7 (CH), 21.0 ppm (CH3); ele-
mental analysis calcd (%) for C24H22O2: C 84.18, H 6.48; found: C 83.99,
H 6.55.
1365, 1265, 1039 cmÀ1 1H NMR (300 MHz, CDCl3): d = 7.05 (t, J =
;
7.9 Hz, 1H), 7.00 (dd, J = 7.9 and 1.3 Hz, 1H), 6.80 (dd, J = 7.9 and
1.3 Hz, 1H), 4.00 (t, J = 5.5 Hz, 2H), 3.20 (t, J = 5.5 Hz, 2H), 1.38 ppm
(s, 9H); 13C NMR (DEPT, 75 MHz, CDCl3): d = 156.3 (C), 149.4 (C),
127.1 (CH), 125.9 (C), 118.7 (CH), 115.3 (CH), 64.7 (CH2), 35.9 (C), 31.9
(3CH3), 30.4 ppm (CH2); MS (70 eV, EI): m/z (%): 194 (88, [M]+), 161
(90), 121 (100), 107 (17), 91 (16), 55 (18); HRMS for C12H18O2 ([M]+)
calcd: 194.1307; found: 194.1295.
2-Methyl-3-o-tolyl-propan-1-ol (40): Reaction of 39 (0.44 g, 3 mmol) and
a solution of BH3¥THF (9 mL, 9 mmol, 3 equiv) in THF (25 mL) at 908C
for 2 d according to the general procedure afforded alcohol 40 (0.40 g,
81% yield). IR (KBr): n˜ = 3350, 2871, 2927, 1493, 1460, 1032, 741 cmÀ1
;
1H NMR (300 MHz, CDCl3): d = 6.94 6.91 (m, 4H), 3.37 3.24 (m, 2H),
2.56 (dd, J = 13.7 and 6.4 Hz, 1H), 2.20 (dd, J = 13.7 and 7.9 Hz, 1H),
2.11 (s, 3H), 1.78 1.67 (m, 1H), 0.74 ppm (d, J = 6.6 Hz, 3H); 13C NMR
(DEPT, 75 MHz, CDCl3): d = 138.9 (C), 136.2 (C), 130.2 (CH), 129.8
(CH), 125.9 (CH), 125.6 (CH), 67.8 (CH2), 36.9 (CH2), 36.6 (CH3), 19.4
(CH), 16.6 ppm (CH3); MS (70 eV, EI): m/z (%): 164 (9, [M]+), 121
(100), 93 (42), 77 (18); HRMS for C11H16O([ M]+) calcd: 164.1201;
found: 164.1211.
Acknowledgement
We thank the DFG (SFB260, Leibniz-Programm). J.A.V. thanks the
Alexander-von-Humboldt Stiftung and the European Community (Marie
Curie Fellowship of the program ™Improving Human Research Potential
and the Socio-economic Knowledge Base∫ contract number HPMFCT-
2000 00451) for both fellowships. We thank Chemetall GmbH (Frank-
furt) and Degussa-H¸ls AG (Hanau) for generous gifts of chemicals.
2-(o-Tolyl)ethanol (42): [36] Reaction of 41 (0.35 g, 3 mmol) and a solution
of BH3¥THF (9 mL, 9 mmol, 3 equiv) in THF (25 mL) at 908C for
3.5 days according to the general procedure afforded alcohol 42 (0.26 g,
64% yield). IR (KBr): n˜ = 3339, 2948, 2876, 1493, 1455, 1044, 744 cmÀ1
;
1H NMR (300 MHz, CDCl3): d = 7.19 (m, 4H), 3.85 (t, J = 6.8 Hz, 2H),
3.92 (t, J = 6.8 Hz, 2H), 2.73 ppm (s, 3H); 13C NMR (DEPT, 75 MHz,
[1] J. C. W. Lohrenz, H. Jacobsen, Angew. Chem. 1996, 108, 1403;
Angew. Chem. Int. Ed. Engl. 1996, 35, 1305, and references therein.
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À
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Received: January 9, 2004
Published online: July 7, 2004
4264
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www.chemeurj.org
Chem. Eur. J. 2004, 10, 4252 4264