Rhodium-catalysed asymmetric ring opening of oxabicyclic alkenes with heteroatom nucleophiles

Article abstract of DOI:10.1016/S0022-328X(00)00904-9

We describe a new rhodium catalysed asymmetric ring opening (ARO) reaction of oxabenzonorbornadienes. This reaction produces a new carbon-oxygen bond via an intermolecular allylic displacement of the bridgehead oxygen with a wide variety of alcohols and p

Full text of DOI:10.1016/S0022-328X(00)00904-9

Journal of Organometallic Chemistry 624 (2001) 259–270
www.elsevier.nl/locate/jorganchem
Rhodium-catalysed asymmetric ring opening of oxabicyclic alkenes
with heteroatom nucleophiles
Mark Lautens *, Keith Fagnou, Mark Taylor, Tomislav Rovis
Department of Chemistry, Lash Miller Laboratories, Uni6ersity of Toronto, Toronto, Ontario, Canada M5H 3H6
Received 19 October 2000; accepted 24 November 2000
Abstract
We describe a new rhodium catalysed asymmetric ring opening (ARO) reaction of oxabenzonorbornadienes. This reaction
produces a new carbon–oxygen bond via an intermolecular allylic displacement of the bridgehead oxygen with a wide variety of
alcohols and phenols. This reaction occurs under neutral reaction conditions, and no activation of the alcohol nucleophile is
required. It proceeds with very high regio- and diastereoselectivity (\99:1), and excellent enantioselectivity (up to 99%ee).
Symmetrical substitution patterns on the aromatic ring of the oxabenzonorbornadienes had no effect on the course of the reaction
nor the enantioselectivity. The reaction produces an unusual stereochemical outcome for oxabicyclic ring openings since the trans
rather than the cis product is formed. Very low catalyst loadings can be used, typically 0.25 mol% of the catalytically active
rhodium species. © 2001 Elsevier Science B.V. All rights reserved.
Keywords: Asymmetric ring opening; Rhodium; Oxabenzonorbornadienes; Heteroatom nucleophiles
[3] to produce products complementary to the palla-
dium ‘benchmark.’
1. Introduction
Transition metal catalysed transformations at allylic
positions have come to the forefront of synthetic or-
ganic chemistry. The mildness and selectivity of these
reactions have allowed chemists easy access to struc-
tures, often in enantioenriched form, which were previ-
ously impossible or very difficult to obtain. Methods
have been developed which enable a wide range of
allylic leaving groups to react with a variety of nucle-
ophile classes. Indeed, the application of p-allyl palla-
dium chemistry to organic synthesis has made
significant advancements and remains an area of in-
tense research [1]. In addition to palladium catalysts,
several other transition metals have been found to
catalyse these transformations. By changing the metal,
different, often complementary, selectivities can be ob-
tained. For example, rhodium has recently been shown
to react with allylic carbonates [2] and vinyl epoxides
Among the myriad of molecular architectures present
in pharmacological agents, we have noted that the
hydronaphthalene skeleton is found in a wide range of
compounds possessing diverse biological activities. Ex-
amples include sertraline 2 [4] (an antidepressant), di-
amine 3 [5] (an analgesic), 4 [6] (a dopamine agonist),
homochelidonine 5 (a naturally occurring alkaloid),
dihydrexidine 6 [7] (an antiparkinsonian agent), and
etoposide 7 [8] (used in the treatment of various can-
cers). In addition, CNS agents [9], immunoregulatory
agents [10], antibiotics [11] and antitumor agents [12]
contain variations on this framework [13] (Scheme 1).
We sought to develop a new method which would
permit access to this core structure in enantioenriched
form and with the ability to introduce diversity at every
position. In spite of the recent advances in the field of
asymmetric ring opening (ARO) chemistry, no ARO
reactions with oxabicyclic alkenes have been reported
involving heteroatom nucleophiles. Thus our focus was
to extend the scope of the ARO methodology such that
heteroatoms would be incorporated into the molecule
during the ring-opening step (Scheme 2).
* Corresponding author. Fax: +1-416-9781631.
E-mail address: tstammer@alchemy.chem.utoronto.ca (M. Laut-
ens).
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(00)00904-9

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M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
Scheme 1.
dimethylation with dimethylsulfoxide (DMS). Given
that this stereochemical result is opposite to that pro-
posed for the Hogeveen–Middelkoop substrate we ver-
ified the cis stereochemistry of 9a by X-ray
crystallography. This difference in stereochemical out-
come implies that different mechanisms are operating in
each case. These reaction conditions were found to be
generally applicable for a variety of alcohol nucle-
2. Synthetic precedent and adaptation to
oxabenzonorbornadiene
In 1973, Hogeveen and Middelkoop reported that
[Rh(CO)2Cl]2 catalysed the ring opening reaction of 8a
and 8b with methanol to give methoxycyclohexandienol
products 9a and 9b, respectively [14] (Scheme 3). Ash-
worth and Berchtold later showed that the stereochem-
istry of the incorporated methoxy substituent was cis to
the resulting hydroxyl group by formation of the
Diels–Alder adduct 10 [15]. In chloroform as the sol-
vent, and in the absence of methanol, the oxabicycle
rearranges to give the hydroxyfulvene product 11 [16].
Our initial experiments using the Hogeveen and Mid-
delkoop conditions with oxabenzonorbornadiene 1
failed to induce any ring-opening reaction. Instead a
red precipitate formed after a few minutes which did
not dissolve even with heating. We reasoned that by
using a more highly polarising solvent this problem
could be avoided. Changing the solvent system to a 1:1
mixture of trifluoroethanol (TFE):methanol and in-
creasing the reaction temperature to 60°C gave the
desired product 12 in 70% yield (Scheme 4). To our
surprise, the stereochemistry of 12 was proven to be
trans by comparison to authentic samples of both
stereoisomers of dimethoxytetrahydronaphthalene 13.
The authentic cis isomer of 12 was prepared by reaction
of 1,2-dihydronaphthalene with OsO4 followed by
dimethylation with dimethylsulfate. Trans-12 was pre-
pared by epoxidation of 1,2-dihydronaphthalene fol-
lowed by ring opening with sodium hydroxide and
i
ophiles. EtOH, PrOH, and 2-TMS ethanol can all be
added in moderate yield (Table 1).
3. Development of an asymmetric variant
In order to establish an asymmetric variant of this
ring opening reaction, the effect of added ligands was
studied. Initial experiments using [Rh(CO)2Cl]2 as the
rhodium source with a variety of phosphines1 resulted
in the formation of an insoluble red precipitate, and no
ring opened product. This precipitate could not be
dissolved by further heating nor prolonged stirring.
Scheme 2.
1 Triphenylphosphine, dppe, dppf and dppb all resulted in insoluble
complexes upon addition to a solution of [Rh(CO)2Cl]2.

M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
261
Scheme 3.
Scheme 4.
We next turned to [Rh(COD)Cl]2 and phosphorous
ligands which possess a greater degree of p-acid charac-
ter, so as to mimic the CO ligands of the [Rh(CO)2Cl]2
catalyst. We noted that homogeneous solutions were
produced on mixing the rhodium and phosphite lig-
ands, and modest reactivity was observed (Table 2,
entries 1–3). To determine if phosphine ligands were
compatible, PPh3 was also used and gave similar levels
of reactivity (entry 4).
We next examined bidentate ligands. Indeed, not all
ligands showed the same type or level of reactivity. For
example, dppe did not produce any desired product;
only the dimerisation of the oxabicycle was observed
(entry 5). Dppb, which possesses a larger bite angle
[17], showed improved reactivity (entry 6) and increas-
ing the bite angle further through the use of dppf gave
the best results (entry 7). The yield dropped signifi-
cantly when the reaction was run at room temperature.
Chiral analogues of dppf are known, and of the
ligands studied, PPF–PtBu2 (17) gave the best results,
producing 12 in 84% yield and 86%ee at 60°C (Table 3,
entry 1). We therefore chose to focus our attention on
ligands based on the Josiphos template. Varying the
substituent on the phosphine moieties led to inferior
results (entries 2–4), as did lowering the concentration
of methanol (entry 5). Similarly, running the reaction in
neat methanol also gave lower enantioselectivity. By
increasing the oil bath temperature to 80°C and run-
ning the reaction at reflux, however, the ee was in-
creased to 96% (entry 7). Under these conditions, the
catalysed loading could be decreased to 0.5 mol% with
no reduction in yield or enantioselectivity. A common
by-product in all of these transformations is naphthol
which accounts for the remainder of the mass balance.
Further investigations into the effect of solvent choice
revealed that THF gave similar levels of induction and
quantitative conversion to the desired product by crude
NMR. By allowing the reaction to run overnight, the
catalyst loading could be lowered to 0.25 mol% (entry
11).
Table 1
Rhodium catalysed ring opening with various alcohols

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M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
Table 2
no TFE-induced ring opening was detected when it was
used as the solvent with MeOH as a nucleophile. Even
the very weakly nucleophilic hexafluoroisopropanol
(HFIP) added under these reaction conditions (entry 9).
Once again, we were able to use very low catalyst
loadings and still achieve excellent results.
Effect of ligands on reactivity with [Rh(COD)Cl]2
In order to investigate the effects of substituents on
the aromatic ring of 1, difluoro, methylene dioxy, and
dimethyldibromo substrates were prepared and reacted
under the standard conditions. All gave the correspond-
ing ring opened products 23, 24 and 25 in good yields
and excellent ee’s indicating that this reaction is not
sensitive to electronic effects on the aromatic ring.
We then examined the scope of this ARO reaction
with substituted phenols. While phenol nucleophiles
have been successfully been used in a few transition
metal catalysed systems [18], rhodium had not previ-
ously been used as a catalyst with this class of nucle-
ophile and we had no previous results indicating that
phenols were sufficiently nucleophilic to participate in
oxabicyclic ring opening reactions. Our initial experi-
ments using ten equivalents of phenol gave the desired
product 26 in near quantitative yield and outstanding
Table 3
Ligand and solvent studies
Table 4
Scope of the rhodium catalysed ARO with alcohols
4. Scope of oxygen nucleophiles in the ARO of
oxabenzonorbornadiene
Many different alcohols are compatible with the re-
action conditions providing the products in good yield
and excellent enantioselectivity (Table 4). We were sur-
prised to find that TFE was a good nucleophile for this
transformation when THF was used as the solvent since

M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
263
Table 5
various halo aryl ethers with which further coupling
reactions could be envisaged. An X-ray crystal struc-
ture of 29 confirmed the regiochemistry, the relative
stereochemistry, and provided the absolute configura-
tion of the ring opened products.
Effects of number of equivalents of phenol
We next examined the effect of other substitution
patterns on the reactivity of the phenol. In the case of
a bromo substituent, 3- and 4-bromophenol added in
high yields and excellent enantioselectivity (Table 7,
entries 1, 2), but 2-bromophenol did not give satisfac-
tory results adding in only 17% yield after prolonged
reaction times (entry 3). Despite the low conversion, the
enantioselectivity was still very high, with 37 being
produced in 97%ee. Changing the rhodium source to
[Rh(CO)2Cl]2, increased the yield of the reaction with
2-bromophenol to 92% and had no detrimental effects
on the enantioselectivity (entry 5). It is noteworthy that
[Rh(CO)2Cl]2 forms an insoluble precipitate with dppf
but no precipitate is formed with PPF–PtBu2.
Table 6
Scope of ARO with p-substituted phenols
The enantioselectivity with [Rh(COD)Cl]2/PPF–
PtBu2 with 2-bromophenol is similar to that observed
for 3- and 4-bromophenol which suggests that the
catalytically active complex is the same in each case.
We reasoned that the poor yield with [Rh(COD)Cl]2
might be due to the rhodium being sequestered from
the catalytic cycle by reversible bidentate binding of the
2-halophenol through the oxygen and the bromine
atoms. Such a binding pattern has been invoked by
Noyori [19] for the ruthenium catalysed asymmetric
hydrogenation of o-bromoacetophenone and by Wills
[20] for the rhodium catalysed asymmetric hydrosilya-
tion of o-chloroacetophenone and o-bromoacetophe-
none (Scheme 5).
[Rh(CO)2Cl]2, upon mixing with certain classes of
diphosphines, is known to produce complexes in which
Table 7
Effect of bromophenol substitution and rhodium source on reactivity
enantioselectivity (\99%ee). Subsequent experiments
revealed that the amount of phenol could be lowered to
five equivalents with no deleterious effects (Table 5).
Below five equivalents, however, the reactions did not
go to completion even after prolonged reaction times,
although the enantioselectivity was not adversely
affected.
Various para-substituted phenols were shown to add
in high yields and excellent enantioselectivity (Table 6).
The reaction proceeded well even when aryl bromides
and iodides were used indicating that the rhodium
insertion into the aryl halide bond is slow compared to
ring opening. This selectivity permits the preparation of

264
M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
carbon–oxygen bond via an intermolecular allylic dis-
placement of the bridgehead oxygen with a wide variety
of alcohols and phenols. While the optimal catalyst for
the addition of alcohols and most phenols was deter-
mined to be [Rh(COD)Cl]2/PPF–PtBu2, the addition of
o-halophenols required changing the rhodium source to
[Rh(CO)2Cl]2. These reactions occur under neutral reac-
tion conditions, and no activation of the nucleophile is
required. It proceeds with very high regio- and
diastereoselectivity (\99:1), and excellent enantioselec-
tivity (up to 99%ee). Symmetrical substitution patterns
on the aromatic ring of the oxabenzonorbornadienes
were found to have no influence on the course of the
reaction nor the enantioselectivity. The reaction also
produces an unusual stereochemical outcome for oxabi-
cyclic ring openings since the trans rather than the cis
product is formed. Very low catalyst loadings can be
used, typically 0.25 mol% of the catalytically active
rhodium species. The hydronaphthalene products of
this reaction belong to an important class of compound
possessing a large range of biological activities. Efforts
are underway to apply this methodology in the prepara-
tion of biologically active compounds and to elucidate
the reaction mechanism.
Scheme 5.
Scheme 6.
one of the carbonyls remains bound [21]. As a result,
the [Rh(CO)2Cl]2/PPF–PtBu2 catalyst system might
have one less vacant coordination site compared to the
[Rh(COD)Cl]2 system. This difference could serve to
disfavour bidentate phenol binding that occurs and
thus increase the amount of the catalytically active
species.
6. Experimental
The following general experimental details apply to
all following reactions.
All flasks were flame-dried under a stream of nitro-
gen or argon and cooled before use. Solvents and
solutions were transferred with syringes and cannulae
using standard inert atmosphere techniques.
We observed significant differences in the relative
rates of reaction, with the more acidic alcohols and
phenols adding faster. Similar observations were made
by Sinou of the reactivity of phenols in allylic etherifi-
cation under palladium catalysis [22]. In order to quan-
tify these observations, we conducted competition
experiments using equimolar amounts of sterically simi-
lar nucleophiles possessing different acidities. The rate
difference is best illustrated by the competition experi-
1H-NMR spectra were recorded at 200 MHz using a
Varian Gemini NMR spectrometer or at 400 MHz
using a Varian XL400 spectrometer with CDCl3 as
reference standard (d 7.24 ppm) or some other suitable
solvent. Spectral features are tabulated in the following
order: chemical shift (d, ppm); number of protons;
multiplicity (s — singlet, d — doublet, t — triplet,
q — quartet, m — complex multiplet, br — broad);
coupling constants (J, Hz). 13C-NMR spectra were
recorded at 400 MHz with CDCl3 as reference standard
(d=77.0 ppm) or some other suitable solvent.
IR spectra were obtained using a Nicolet DX FT-JR
spectrometer as a KBr pellet or neat film between KBr
plates. High resolution mass spectra were obtained
from a VG 70-250S (double focusing) mass spectrome-
ter at 70 eV. Combustion analyses were submitted to
Canadian Microanalytical Service Ltd., BC. Optical
rotations were measured on a Perkin Elmer model 243
polarimeter using the sodium D line with spectro-grade
CHCl3 in a 1 dm cell. Melting points were taken on a
Fisher–Johns melting point apparatus and are
uncorrected.
i
ment between PrOH and HFIP. In this case, the only
product detected in the crude NMR was 22. In another
experiment, 4-hydroxyacetophenone and 4-hydroxyan-
isole were mixed. At 68% conversion we observed a
16:1 ratio of 31:35 (Scheme 6) confirming that the
presence of an electron withdrawing group on the aro-
matic ring accelerates the rate of addition.
5. Conclusion
We have described an efficient new rhodium
catalysed asymmetric ring opening (ARO) reaction of
oxabenzonorbornadienes. This reaction produces a new

M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
265
Gas chromatography was performed on a Hewlett
Packard 5890 gas chromatograph using an Advanced
Separation Technologies G-TA or B-TA chiral
columns. HPLC analysis was performed on a Waters
600E with Chiralcel OD or OJ columns. Analytical
TLC was performed using EM Separations precoated
silica gel 0.2 mm layer UV 254 fluorescent sheets.
Column chromatography was performed as ‘flash chro-
matography’ as reported by Still [23] using (200–400
mesh) Merck grade silica gel.
Diethyl ether, THF, benzene and toluene were dis-
tilled from sodium benzophenone ketyl immediately
prior to use. CH2Cl2 was distilled from calcium hy-
dride. DME was distilled from sodium benzophenone
ketyl and stored. DMF was dried and stored over
activated molecular sieves. Furan was distilled prior to
use. 4,5-dibromobenzodioxole was prepared by bromi-
nation of benzodioxole in acetic acid in the presence of
NaOAc. Mosher’s acid chloride was prepared by reflux-
ing Mosher’s acid (MTPA, obtained from Aldrich) in
thionyl chloride in the presence of a catalytic amount of
NaCl for 60 h and purified by bulb to bulb distillation.
The PPF–PtBu2 ligand was donated by Solvias. The
oxabenzonorbornadienes were prepared according to
literature procedure [24]. All other reagents were ob-
tained from Aldrich and used as received unless other-
wise stated.
J=12.8 Hz); 13C-NMR (400 MHz, acetone-d) l 138.5,
133.2, 129.1, 128.4, 128.3, 128.2, 126.8, 126.3, 83.1,
73.0, 57.1. HRMS Calc. for C11H12O2 [M+]: 176.0837.
Found: 176.0835.
6.1.2. (1S,2S)-2-(Ethoxy)-1,2-dihydro-naphthalen-1-ol
(14)
Following the general procedure, 14 was obtained as
a white crystalline solid (553 mg, 84%). The ee was
determined to be 97% using HPLC analysis on a Chi-
ralcel OD column, u=254 nm. Retention times in 1.5%
isopropanol in hexanes were 13.6 min and 14.2 min
(major). Rf=0.26 on silica gel (20% ethyl ace-
tate:hexanes); m.p. 33°C (Et2O); [h]2D5=185.9 (c=9.6,
CHCl3); IR (KBr, cm−1) 3601 (br), 3040 (m), 2977 (s),
1
1454 (s), 1396 (m), 1185 (s), 1104 (s); H-NMR (400
MHz, CDCl3) l 7.59–7.57 (1H, m), 7.27–7.20 (2H, m),
7.07–7.05 (1H, m), 6.43 (1H, dd, J=9.9, 2.2 Hz), 6.01
(1H, dd, J=9.9, 2.2 Hz), 4.90 (1H, d, J=10.6 Hz),
4.18 (1H, ddd, J=10.6, 2.2, 2.2 Hz), 3.79 (1H, AB, dq,
J=9.4, 6.9 Hz),), 3.58 (1H, AB, dq, J=9.4, 6.9 Hz),
2.65 (1H, s), 1.27 (3H, t, J=6.9 Hz); 13C-NMR (400
MHz, CDCl3) l 135.9, 131.9, 128.0, 127.8, 127.8, 126.1,
124.9, 80.7, 72.5, 64.6, 15.5. HRMS Calc. for C12H14O2
[M+]: 190.0994. Found: 190.0993.
6.1.3. (1S,2S)-2-(Isopropoxy)-1,2-dihydro-
naphthalen-1-ol (15)
6.1. General procedure for the ARO reactions with alco-
hol nucleophiles
Following the general procedure, 15 was obtained as
a colourless oil (666 mg, 94%). The ee was determined
to be 92% using HPLC analysis on a Chiralcel OD
column, u=486 nm. Retention times in 1.5% iso-
propanol in hexanes were 9.7 min (major) and 10.7
min. Rf=0.42 on silica gel (10% ethyl acetate:hexanes);
[Rh(COD)Cl]2 (1) was added to a flame dried round
bottom flask, (S,R)-PPF–PtBu2 (unless otherwise indi-
cated) followed by addition of THF and nucleophile
(THF:nucleophile 1:1) The mixture was heated until the
reaction was complete as judged by thin layer chro-
matography. The solvents were removed in vacuo and
the crude mixture was purified by flash chromato-
graphy.
[h]2D5= +154.0 (c=12.6, CHCl3); IR (KBr, cm−1
)
3435 (br), 3038 (w), 2952 (s), 1454 (m), 1249 (s), 1087
1
(s); H-NMR (400 MHz, CDCl3) l 7.61–7.58 (1H, m),
7.27–7.19 (2H, m), 7.06–7.04 (1H, m), 6.40 (1H, dd,
J=9.9, 2.0 Hz), 5.95 (1H, dd, J=9.9, 2.2 Hz), 4.87 (1
H, d, J=10.8 Hz), 4.24 (1H, ddd, J=10.8, 2.2, 2.2
Hz), 3.85 (1H, h, J=6.2 Hz), 2.98 (1H, s), 1.25 (6H,
dd, J=8.8, 6.2 Hz); 13C-NMR (400 MHz, CDCl3) l
136.2, 132.3, 129.6, 128.0, 127.9, 127.8, 126.3, 125.0,
78.9, 73.0, 71.1, 23.5, 22.4. HRMS Calc. for C13H16O2
[M+]: 204.1150. Found: 204.1150.
6.1.1. (1R,2R)-2-Methoxy-1,2-dihydro-naphthalen-1-ol
(12)
Following the general procedure using (R,S)-PPF-
PtBu2, 12 was obtained as a white crystalline solid (586
mg, 96%). The ee was determined to be 97% using
HPLC analysis on a Chiralcel OD column, u=486 nm.
Retention times in 4% isopropanol in hexanes were 10.1
min (major) and 11.1 min. Rf=0.29 on silica gel (10%
ethyl acetate:hexanes); m.p. 86–87°C (Et2O); [h]2D5= −
208 (c=10.1, CHCl3); Rf=0.39 on silica (20% ethyl
acetate:hexanes). IR (KBr, cm−1) 3277 (br), 2971 (m),
1466 (m), 1285 (m), 1114 (s), 1048 (m), 979 (m), 775 (s);
1H-NMR (400 MHz, CDCl3) l 7.60–7.62 (1H, m),
7.30–7.21 (2H, m), 7.13–7.11 (1H, m), 6.50 (1H, dd,
J=9.9,1.8 Hz), 6.04 (1H, dd, J=9.9, 2.2 Hz), 4.85
(1H, dd, J=9.9, 6.2 Hz), 3.50 (3H, s), 2.89 (1H, d,
6.1.4. (1S,2S)-3-(1-propenyloxy)-1,2-dihydro-
naphthalen-1-ol (18)
Following the general procedure, 18 was obtained as
a colourless oil (898 mg, 60%) which solidified on
sitting. The ee was determined to be \99% using
HPLC analysis on a Chiralcel OD column, u=486 nm.
Retention times in 1.5% isopropanol in hexanes were
15.2 and 16.3 min (major). Rf=0.17 on silica gel (10%
ethyl acetate:hexanes); m.p. 25–26°C (Et2O); [h]2D5= +
195.1° (c=11.5, CHCl3); IR (KBr, cm−1) 3435 (br),

266
M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
3037 (m), 2857 (s), 1454 (s), 1165 (s), 1083 (s); 1H-
NMR (400 MHz, CDCl3) l 7.61–7.58 (1H, m), 7.27–
7.20 (2H, m), 7.08–7.05 (1H, m), 6.44 (1H, dd,
J=9.9, 2.0 Hz), 6.00 (1H, dd, J=9.9, 2.4 Hz), 6.00–
5.92 (1H,m), 5.32 (1 H, ddd, J=17.2, 3.3, 1.6 Hz),
5.21 (1H, ddd, J=10.4, 2.9, 1.3 Hz), 4.94 (1H, d,
J=10.2 Hz), 4.27 (1H, ddd, J=10.3, 2.2, 2.2 Hz),),
4.23 (1H, dddd, J=12.8, 5.5, 1.5, 1.5 Hz), 4.12 (1H,
dddd, J=12.8, 5.9, 1.5, 1.5 Hz), 3.09 (1H, s); 13C-
NMR (400 MHz, CDCl3) l135.8, 134.5, 131.8, 128.1,
127.7, 127.6, 127.4, 126.1, 125.0, 117.5, 80.1, 76.7,
72.4, 70.2. HRMS Calc. for C14H14O2 [M+]: 202.0994.
Found: 202.0994.
6.1.7. (1S,2S)-2-(4-methoxybenzyloxy-1,2-dihydro-
naphthalen-1-ol (20)
Following the general procedure, 20 was obtained
as a crystalline solid (1.18 g, 87%). The ee was deter-
mined to be 97% using HPLC analysis on a Chiralcel
OD column, u=486 nm. Retention times in 1.5%
isopropanol in hexanes were 37.1 and 42.1 min (ma-
jor). Rf=0.53 on silica gel (30% ethyl ace-
tate:hexanes); m.p. 63–64°C (Et2O); [h]2D5= +138.5
(c=10.5, CHCl3); IR (KBr, cm−1) 3435 (br), 3035
(m), 2836 (s), 1612 (s), 1513 (s), 1454 (m), 1249 (s),
1082 (s); 1H-NMR (400 MHz, CDCl3) l 7.59–7.57
(1H, m), 7.32 (2H, ddd, J=8.7, 2.8, 1.9 Hz), 7.28–
7.22 (1H, m), 6.90 (2H, ddd, J=8.7, 2.8, 1.9 Hz), 6.46
(1H, dd, J=9.9, 2.1 Hz), 6.04 (1H, dd, J=9.9, 2.4
Hz), 4.96 (1H, d, J=10.1 Hz), 4.64 (1H, dd, J=57.1,
11.4 Hz), 4.32 (1H, ddd, J=10.2, 2.2, 2.2 Hz), 3.80
(1H, s), 2.96 (1H, s); 13C-NMR (400 MHz, CDCl3) l
159.2, 135.9, 131.9, 129.9, 129.5, 128.1, 127.8, 127.6,
127.5, 126.1, 125.0, 113.8, 80.0, 72.5, 70.9, 55.1.
HRMS Calc. for C17H16O2 [M+]: 252.1150. Found:
252.1148.
6.1.5. (1S,2S)-2-(2-Trimethylsilyl-ethoxy)-
1,2-dihydro-naphthalen-1-ol (16)
Following the general procedure, 16 was obtained as
a colourless oil (482 mg, 53%). The ee was determined
to be 95% using HPLC analysis on a Chiralcel OD
column, u=486 nm. Retention times in 0.5% iso-
propanol in hexanes were 17.9 and 18.5 min (major).
Rf=0.25 on silica gel (10% ethyl acetate:hexanes);
[h]2D5= +119.2 (c=13.0, CHCl3); IR (KBr, cm−1)
3447 (br), 3037 (m), 2972 (s), 1454 (m), 1381 (m), 1118
6.1.8. (1S,2S)-2-(2,2,2-Trifluoro-ethoxy)-
1,2-dihydro-naphthalen-1-ol (21)
1
(s), 1078 (s); H-NMR (400 MHz, CDCl3) l 7.59–7.57
(1H, m), 7.28–7.21 (2H, m), 7.08–7.06 (1H, m), 6.43
(1H, dd, J=9.9, 2.0 Hz), 6.03 (1H, dd, J=9.9, 2.2
Hz), 4.89 (1 H, d, J=10.6 Hz), 4.18 (1H, ddd, J=
10.6, 2.2, 2.2 Hz), 3.85–3.78 (2H, m), 3.63–3.56 (2H,
m), 2.79 (1H, s), 1.05–0.97 (2H, m), 0.36 (9H, m);
13C-NMR (400 MHz, CDCl3) l. 135.9, 132.0, 127.9,
127.9, 127.8, 127.6, 126.1, 124.9, 80.4, 72.6, 66.5, 18.6,
−1.4. HRMS Calc. for C15H22O2Si [M+]: 262.1389.
Found: 262.1388.
Following the general procedure, 21 was obtained as
a white crystalline solid (594 mg, 70%). The ee was
determined to be 98% using HPLC analysis on a Chi-
ralcel OD column, u=254 nm. Retention times in 4%
isopropanol in hexanes were 11.3 (major) and 13.3
min. Rf=0.41 on silica gel (20% ethyl ace-
tate:hexanes); m.p. 79–80°C (Et2O); [h]2D5=145.4 (c=
12.6, CHCl3); IR (KBr, cm−1) 3354 (br), 3036 (w),
2939 (w), 1455 (w), 1275 (s), 1169 (s), 1050(m), 977
(m); 1H-NMR (400 MHz, CDCl3) l 7.57–7.55 (1H,
m), 7.30–7.23 (2H, m), 7.10–7.08 (1H, m), 6.48 (1H,
dd, J=9.9, 2.0 Hz), 5.94 (1H, dd, J=9.9, 2.4 Hz),
4.96 (1 H, d, J=2.2 Hz), 4.38 (1H, ddd, J=9.9, 2.4,
2.2 Hz), 4.03 (2H, q, JH–F=8.6 Hz), 2.55 (1H, s);
13C-NMR (400 MHz, CDCl3) l 135.5, 131.7, 129.2,
128.3, 128.1, 126.6, 125.9, 125.2, 122.4, 83.0, 72.8, 67.0
(q, JC–F=34.4 Hz). HRMS Calc. for C12H11O2F3
[M+]: 244.0711. Found: 244.0720.
6.1.6. (1S,2S)-2-Benzyloxy-1,2-dihydro-naphthalen-1-ol
(19)
Following the general procedure, 19 was obtained as
a crystalline solid (1.22 g, 70%). The ee was deter-
mined to be \98% using HPLC analysis on a Chiral-
cel OD column, u=486 nm. Retention times in 1.5%
isopropanol in hexanes were 29.0 and 32.5 min (ma-
jor). Rf=0.34 on silica gel (20% ethyl ace-
tate:hexanes); m.p. 52–54°C (Et2O); [h]2D5= +167.3
(c=10.0, CHCl3); IR (KBr, cm−1) 3305 (br), 3020
(w), 2876 (w), 1496 (m), 1352 (m), 1281 (m), 1169 (m),
6.1.9. (1S,2S)-2-(2,2,2-Trifluoro-1-trifluoromethyl-
ethoxy)-1,2-dihydro-naphthalen-1-ol (22)
1
1050 (s), 777 (s); H-NMR (400 MHz, CDCl3) l 7.58–
Following the general procedure, 22 was obtained as
a white solid (974 mg, 90%). The ee was determined to
be 93% using HPLC analysis on a Chiralcel OD
column, u=486 nm. Retention times in 1.5% iso-
propanol in hexanes were 11.3 and 17.6 min (major);
Rf=0.28 on silica gel (10% ethyl acetate:hexanes);
m.p. 88.5–90°C (Et2O); [h]2D5= +101.8 (c=10.9,
CHCl3); IR (KBr, cm−1) 3191 (br), 2937 (m), 1379 (s),
1280 (s), 1247 (s), 1194 (s), 1100 (s), 954 (s), 753 (m);
1H-NMR (400 MHz, CDCl3) l 7.55–7.53 (1H, m),
7.56 (1H, m), 7.41–7.22 (7H, m), 7.22–7.07 (1H, m),
6.46 (1H, dd, J=9.9, 2.1 Hz), 6.05 (1H, dd, J=9.9,
2.1 Hz), 4.98 (1H, d, J=10.4 Hz), 4.78 (1H, d, J=
11.7 Hz), 4.63 (1H, d, J=11.7 Hz), 4.33 (1H, ddd,
J=10.4, 2.2, 2.2 Hz), 2.61 (1H, s); 13C-NMR (400
MHz, CDCl3) l 138.0, 135.9, 131.9, 128.5, 128.3,
128.1, 127.9, 127.9, 127.8, 127.4, 126.2, 125.1, 80.4,
72.6, 71.3. HRMS Calc. for C17H16O2 [M+]: 252.1150.
Found: 252.1148.

M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
267
7.31–7.26 (2H, m), 7.11–7.09 (1H, m), 6.49 (1H, dd,
J=9.9, 2.1 Hz), 5.92 (1H, dd, J=9.9, 2.4 Hz), 5.07
(1H, dd, J=9.7, 5.0 Hz), 4.63 (1H, ddd, J=9.9, 1.5,
1.5 Hz), 4.58 (1H, h, JH–F=6.1 Hz), 2.50 (1H, d,
J=4.2 Hz); 13C-NMR (400 MHz, CDCl3) l 135.2,
131.5, 129.7, 128.5, 128.3, 126.7, 125.2, 122.9, 120.1,
85.4, 75.4 (h, JC–F=32.2 Hz), 73.5. HRMS Calc. for
C13H10O2F6 [M+]: 312.0585 Found: 312.0574.
determined to be 97% using HPLC analysis on a Chi-
ralcel OD column, u=486 nm. Retention times in 4%
isopropanol in hexanes were 16.8 (major) and 19.3 min.
Rf=0.39 on silica gel (50% ethyl acetate:hexanes); m.p.
114–116°C (Et2O); [h]2D5= −197.1 (c=10.0, CHCl3);
IR (KBr, cm−1) 3349 (s), 2901 (m), 1700 (w), 1532 (w),
1
1404 (m), 1258 (m), 1081 (s), 936 (s); H-NMR (400
MHz, CDCl3) l 6.96–6.93 (1H, m), 6.23–6.19 (1H, m),
4.89 (1H, s), 3.96–3.90 (1H, m), 3.38–3.35 (3H, m),
2.61–2.57 (3H, m), 2.54 (3H, s), 1.82–1.54 (1H, m);
13C-NMR (400 MHz, CDCl3) l 137.3, 134.4, 133.2,
129.7, 129.5, 129.0, 128.1, 125.3, 75.3, 66.6, 56.6, 21.0,
20.6. HRMS Calc. for C13H16O2Br2 [M+]: 361.9518.
Found: 361.9335.
6.1.10. (1S,2S)-6,7-Difluoro-2-methoxy-1,2-dihydro-
naphthalen-1-ol (23)
Following the general procedure, 23 was obtained as
a white crystalline solid (74.9 mg, 88%). The ee was
determined to be 96.4% using HPLC analysis on a
Chiralcel OD column, u=486 nm. Retention times in
4% isopropanol in hexanes were 8.9 and 10.1 min
(major). Rf=0.27 on silica gel (30% ethyl ace-
tate:hexanes); m.p. 129–131°C (Et2O); [h]2D5= +134.4
(c=9.3, CHCl3); IR (KBr, cm−1) 3269 (br), 2937 (w),
6.2. General procedure for the ARO reactions with
phenol nucleophiles
To a flame dried round bottom flask, [Rh(COD)Cl]2,
(S,R)-PPF–PtBu2 (unless otherwise indicated) and 1
were added. THF (2 ml) and the phenol nucleophile
were then added followed by heating to 80°C for 1.5 h.
The reaction mixture was then poured in to ether and
washed three times with 5% aqueous NaOH. The
aqueous layers were combined and back extracted three
times with ether. The organic layers were combined,
washed with brine, dried over Na2SO4, and concen-
trated in vacuo. The resulting crude product was
purified by flash chromatography.
1
1597 (m), 1503 (s), 1306 (s), 1103 (s), 893 (s); H-NMR
(400 MHz, CDCl3) l 7.40 (1H, ddd, JH–F=10.8, 7.8
Hz, JH–H=0.6 Hz), 6.85 (1H, dd, JH–F=10.9, 7.8 Hz),
6.31 (1H, dd, J=10.0, 2.0 Hz), 6.05 (1H, dd, J=10.0,
2.0 Hz), 4.79 (1H, d, J=11.0 Hz), 4.05 (1H, ddd,
J=11.0, 2.0, 2.0 Hz), 3.49 (3H, s), 2.94 (1H, d, J=2.2
Hz); 13C-NMR (400 MHz, CDCl3) l 151.0 (d, JH–F
=
12.5 Hz), 148.5 (dd, JH–F=12.5,2.9 Hz), 133.2 (dd,
J
H–F=5.2, 3.6 Hz), 128.9 (dd, JH–F=6.6, 4.4 Hz),
128.0 (d, JH–F=2.2 Hz), 126.5 (dd, JH–F=2.2, 1.5
Hz), 115.1 (d, JH–F=18.3 Hz), 114.8 (d, JH–F=19.8
Hz), 82.3, 72.0, 57.0. HRMS Calc. for C11H10O2F2
[M+]: 212.0649. Found: 212.0658.
6.2.1. (1S,2S)-2-Phenoxy-1,2-dihydro-naphthalen-1-ol
(26)
Following the general procedure, 26 was obtained as
a white crystalline solid (130.7 mg, 83%). The ee was
determined to be 99.2% using HPLC analysis on a
Chiralcel OD column, u=486 nm. Retention times in
4% isopropanol in hexanes were 15.2 (major) and 17.8
min. Rf=0.26 on silica gel (10% ethyl acetate:hexanes);
m.p. 109–110°C (Et2O); [h]2D5= +204.7 (c=10.1,
CHCl3); IR (KBr, cm−1) 3337 (br), 3029 (w), 2866 (w),
6.1.11. (1S,2S)-6-Methoxy-5,6-dihydro-naphtho-
[2,3-d][1,3]dioxol-5-ol (24)
Following the general procedure, 24 was obtained as
a white crystalline solid (127.5 mg, 90%). The ee was
determined to be 95% using HPLC analysis on a Chi-
ralcel OD column, u=486 nm. Retention times in 4%
isopropanol in hexanes were 19.2 min (major) and 22.6
min. Rf=0.24 on silica (30% ethyl acetate:hexanes);
m.p. 117–119°C (Et2O); [h]2D5= +298.7 (c=11.1,
CHCl3); IR (KBr, cm−1) 3248 (br), 2926 (s), 1600 (m),
1
1600 (m), 1496 (s), 1249 (s), 1062 (s); H-NMR (400
MHz, CDCl3) l 7.65–7.63 (1H, m), 7.33–7.25 (4H, m),
7.13–7.11 (1H, m), 7.01–6.95 (3H, m), 6.51 (1H, dd,
J=9.9, 1.6 Hz), 6.02 (1H, dd, J=9.9, 2.2 Hz), 5.19
(1H, d, J=10.4 Hz), 5.11 (1H, ddd, J=10.4, 2.0, 2.0
Hz), 2.66 (1H, s); 13C-NMR (400 MHz, CDCl3) l
157.4, 135.5, 131.9, 129.7, 129.0, 128.2, 128.0, 126.4,
126.1, 125.2, 121.5, 115.9, 79.1, 72.4. HRMS Calc. for
C16H14O2 [M+]: 238.0994. Found: 238.0984.
1
1483 (s), 1260 (s), 1113 (s), 941 (s), 876 (s); H-NMR
(400 MHz, CDCl3) l 7.10 (1H, s), 6.59 (1H, s), 6.34
(1H, d, J=9.9 Hz), 5.92–5.99 (3H, m), 4.77 (1H, d,
J=9.9 Hz), 4.04 (1H, d, J=10.1 Hz), 3.49 (3H, s), 2.2
(1Hs); 13C-NMR (400 MHz, CDCl3) l 147.2, 146.9,
130.4, 128.1, 126.0, 124.8, 107.1, 106.7, 101.0, 82.0,
72.3, 56.7. HRMS Calc. for C12H12O4 [M+]: 220.0736.
Found: 220.0684.
6.2.2. (1S,2S)-2-(4-Fluorophenoxy)-1,2,-dihydro-
naphthalen-1-ol (27)
Following the general procedure, 27 was obtained as
a white crystalline solid (163 mg, 92%). The ee was
determined to be 97% by HPLC analysis on a Chiralcel
OD column, u=486 nm). Retention times in 1.5%
isopropanol in hexanes were 28.1 (major) and 29.5 min.
6.1.12. (1S,2S)-6,7-Dibromo-2-methoxy-5,8-dimethyl-
1,2-dihydro-naphthalen-1-ol (25)
Following the general procedure, 25 was obtained as
a white crystalline solid (171.6 mg, 79%). The ee was

268
M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
Rf=0.39 on silica (20% ethyl acetate in hexanes); m.p.
127–129°C (Et2O); [h]2D5= +216 (c=9.5, CHCl3). IR
(KBr, cm−1) 3309 (b), 3071 (w), 2864 (w), 1504 (s),
1284 (m), 1052 (s), 781 (s), 692 (m); 1H-NMR (400
MHz, CDCl3): l 7.63–7.61 (1H, m), 7.31–7.26 (2H,
m), 7.12–7.10 (1H, m), 7.00–6.95 (2H, m), 6.92–6.88
(2H, m), 6.51 (1H, dd, J=2.1, 9.9 Hz), 5.98 (1H, dd,
J=2.2, 9.9 Hz), 5.15 (1H, dd, J=3.6, 10.0 Hz), 5.01
(1H, ddd, J=2.1, 2.1, 10.1 Hz), 2.54 (1H, d, J=3.8
Hz); 13C-NMR (400 MHz, CDCl3): l 157.6 (d, JC–
F=239 Hz), 156.4, 153.4, 135.4, 131.8, 129.1, 128.2,
126.5, 125.7, 125.2, 117.5 (d, JC–F=8 Hz), 116.1 (d,
dd, J=10.0, 2.0 Hz), 6.00 (1H, dd, J=9.7, 2.2 Hz),
5.20 (1H, dd, J=9.7, 3.6 Hz), 5.09 (1H, ddd, J=10.0,
2.0, 2.0 Hz), 2.70 (1H, d, J=3.9 Hz); 13C-NMR (400
MHz, CDCl3) l 156.5, 135.3, 132.5, 131.7, 129.3,
128.3, 128.1, 126.5, 125.3, 117.6, 113.7, 79.4, 72.2.
HRMS Calc. for C16H11OBr [M−H2O]+ 297.9994.
Found: 297.9995.
6.2.5. (1S,2S)-2-(4-Iodophenoxy)-1,2,-dihydro-
naphthalen-1-ol (30)
Following the general procedure, 30 was obtained as
a white crystalline solid (193 mg, 73%). The ee was
determined by deiodinating 30 (40 mg, 0.11 mmol) by
reaction with t-BuLi (0.32 ml, 1.7M) in diethyl ether
(2 ml) at −78°C followed by quenching with iso-
propanol. Extraction with ether from water, washing
with brine, drying over anhydrous sodium sulfate and
removal of the solvents in vacuo gave a white crys-
talline solid 26 (24 mg, 92%). The ee was determined
to be 98% by HPLC analysis on a Chiralcel OD
column, u=256 nm. Retention times in 4% iso-
propanol in hexanes were 15.2 (major) and 17.9 min;
Rf=0.44 on silica (20% ethyl acetate in hexanes); m.p.
160–162°C (Et2O); [h]2D5= +107 (c=9.7, CHCl3). IR
(KBr, cm−1) 3264 (br), 3050 (w), 2926 (w), 2843 (w),
1581 (m), 1485 (s), 1388 (w), 1279 (m), 1246 (s), 1046
J
C–F=23.5 Hz);. HRMS Calc. for [M+] (C16H13O2F):
256.0810. Found: 256.0911.
6.2.3. (1S,2S)-2-(4-Chlorophenoxy)-1,2,-dihydro-
naphthalen-1-ol (28)
Following the general procedure, 28 was obtained as
a white crystalline solid (169 mg, 89%). The ee was
determined to be 92% by formation of Mosher’s ester.
Rf=0.47 on silica (20% ethyl acetate in hexanes); m.p.
125–125.5°C (Et2O); [h]2D5= +150 (c=10.6, CHCl3).
IR (KBr, cm−1) 3302 (br), 3064 (w), 2874 (w), 1590
(m), 1489 (s), 1362 (w), 1230 (s), 1052 (m), 890 (w),
846 (m), 778 (s), 663 (m); 1H-NMR (400 MHz,
CDCl3): l 7.65–7.64 (1H, m), 7.33–7.26 (4H, m),
7.16–7.13 (1H, m), 6.91(1H, ddd, J=2.0, 2.0, 8.9 Hz),
6.55 (1H, dd, J=1.8, 9.9 Hz), 5.99 (1H, dd, J=2.2,
9.9 Hz), 5.19 (1H, dd, J=3.8, 10.0 Hz), 5.07 (1H,
ddd, J=2.0, 2.0, 10.1 Hz), 2.56 (1H, d, J=4.0 Hz);
13C-NMR (400 MHz, CDCl3): l 155.8, 135.2, 131.7,
129.5, 129.3, 128.2, 128.1, 126.5, 126.2, 125.3, 125.2,
116.9, 79.2, 72.1. HRMS Calc. for [M−H2O]+
(C16H11OCl): 254.0498. Found: 254.0499.
1
(m), 824 (m), 780 (m), 571 (w); H-NMR (400 MHz,
CDCl3): l 7.63–7.61 (1H, m), 7.58–7.55 (2H, m),
7.30–7.27 (2H, m), 7.13–7.11 (1H, m), 6.73 (2H, ddd,
J=2.2, 2.2, 9.0 Hz), 6.52 (1H, dd, J=1.8, 9.8 Hz),
5.96 (1H, dd, J=2.2, 9.8 Hz), 5.16 (1H, d, J=10.0
Hz), 5.05 (1H, ddd, J=2.0, 2.0, 10.0 Hz), 2.54 (1H,
s); 13C-NMR (400 MHz, CDCl3): l 157.3, 138.5,
135.3, 131.7, 129.4, 128.3, 128.1, 126.6, 125.3, 125.3,
118.1, 83.6, 79.2, 72.2. HRMS Calc. for [M−H2O]+
(C16H11OI): 345.9855. Found: 345.9849.
6.2.4. (1R,2R)-2-(4-Bromophenoxy)-1,2-dihydro-
naphthalen-1-ol (29)
Following the general procedure using (R,S)-PPF-
PtBu2, 29 was obtained as a white crystalline solid
(239.7 mg, 90%). The ee was determined by debromi-
6.2.6. (1S,2S)-2-(4-Acylphenoxy)-1,2,-dihydro-
naphthalen-1-ol (31)
t
nating 29 (40 mg, 0.11 mmol) by reaction with BuLi
Following the general procedure, 31 was obtained as
a white crystalline solid (177 mg, 91%). The ee was
determined to be\99% by formation of Mosher’s es-
ter; Rf=0.28 on silica (30% ethyl acetate in hexanes);
m.p. 124–126°C (Et2O); [h]2D5= +153 (c=9.8,
CHCl3). IR (KBr, cm−1) 3367 (b), 3069 (w), 2916 (w),
1668 (s), 1601 (s), 1265 (s), 1053 (m), 835 (m), 779
(m); 1H-NMR (400 MHz, CDCl3): l 7.94 (2H, d,
J=8.8 Hz), 7.66–7.64 (1H, m), 7.34–7.27 (2H, m),
7.16–7.14 (1H, m), 6.98 (2H, d, J=8.8 Hz), 6.57 (1H,
d, J=9.9 Hz), 5.99 (1H, d, J=9.9 Hz), 5.21 (2H, s),
2.85 (1H, s), 2.56 (3H, s); 13C-NMR (400 MHz,
CDCl3): l 196.8, 161.4, 135.3, 131.7, 130.7, 130.6,
129.6, 128.3, 128.1, 126.6, 125.4, 125.0, 115.2, 79.0,
72.0, 26.3. HRMS Calc. for [M−H2O]+ (C18H14O2):
262.0994. Found: 262.0989.
(0.32 ml, 1.7 M) in diethyl ether (2 ml) at −78°C
followed by quenching with isopropanol. Extraction
with ether from water, washing with brine, drying over
anhydrous sodium sulfate and removal of the solvents
in vacuo gave a white crystalline solid 26 (24 mg,
92%). The ee was determined to be 96.8% by HPLC
analysis on a Chiralcel OD column, u=486 nm. Re-
tention times in 4% isopropanol in hexanes were 15.2
and 17.5 min (major). Rf=0.26 on silica gel (10%
ethyl acetate:hexanes); m.p. 145–146°C (Et2O); [h]2D5=
−135.7 (c=10.2, CHCl3); IR (KBr, cm−1) 3290 (br),
3060 (m), 2870 (w), 1583 (m), 1484 (s), 1227 (s), 1052
1
(m), 980 (s), 776 (s); H-NMR (400 MHz, CDCl3) l
7.70–7.65 (1H, m), 7.44–7.42 (2H, m), 7.35–7.32 (2H,
m), 7.18−7.16 (1H, m), 6.88–6.86 (2H, m), 6.56 (1H,

M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
269
6.2.7. (1S,2S)-2-(h,h,h)-Trifluoro-4-methylphenoxy)-
1,2,-dihydro-naphthalen-1-ol (32)
Hz), 5.93 (1H, dd, J=1.4, 9.7 Hz), 5.20–5.13 (2H, m),
2.25 (1H, s). 13C-NMR (400 MHz, CDCl3): l 160.8,
135.0, 134.2, 131.5, 130.0, 128.5, 128.3, 126.7, 125.4,
124.4, 119.0, 116.2, 104.6, 79.2, 72.0. HRMS Calc. for
[M−H2O]+ (C17H11ON): 245.0841. Found: 245.0845.
Following the general procedure, 32 was obtained as
a white crystalline solid (184 mg, 87%). The ee was
determined to be 95% by HPLC analysis on a Chiralcel
OD column, u=486 nm. Retention times in 4% iso-
propanol in hexanes were 14.8 and 17.3 min (major).
Rf=0.46 on silica (20% ethyl acetate in hexanes); m.p.
118–119°C (Et2O); [h]2D5= +178 (c=9.6, CHCl3). IR
(KBr, cm−1) 3360 (br), 3061 (w), 2874 (w), 1617 (m),
1518 (m), 1326 (s), 1103 (s), 1051 (m), 839 (m), 782 (m),
745 (w); 1H-NMR (400 MHz, CDCl3): l 7.63–7.54
(1H, m), 7.55 (2H, d, J=8.6 Hz), 7.33–7.24 (2H, m),
7.14–7.12 (1H, m), 7.01 (2H, d, J=8.6 Hz), 6.55 (1H,
dd, J=1.6, 9.9 Hz), 5.97 (1H, dd, J=2.0, 9.9 Hz),
5.21–5.13 (2H, m), 2.47 (1H, d, J=3.6 Hz); 13C-NMR
(400 MHz, CDCl3): l 159.9, 135.2, 131.7, 129.6, 128.4,
128.2, 127.1 (q, JC–F=3.6 Hz), 126.6, 125.4, 124.9,
123.4 (d, JC–F=33.0 Hz), 122.9 (d, JC–F=271.6 Hz),
115.6, 79.1, 72.1; HRMS Calc. for [M+] (C17H13O2F3):
306.0868. Found: 306.0852.
6.2.10. (1S,2S)-2-(4-Methoxyphenoxy)-1,2,-
dihydro-naphthalen-1-ol (35)
Following the general procedure, 35 was obtained as
a white crystalline solid (159 mg, 85%). The ee was
determined to be 95% by HPLC analysis on a Chiralcel
OD column, u=256 nm. Retention times in 4% iso-
propanol in hexanes were 22.1 (major) and 25.9 min.
Rf=0.33 on silica (20% ethyl acetate in hexanes); m.p.
91–92°C (Et2O); [h]2D5= +129 (c=9.9, CHCl3); IR
(KBr, cm−1) 3349 (br), 3050 (w), 2822 (w), 1508 (s),
1
1233 (s), 1046 (m), 825 (m), 751 (m), 695 (w); H-NMR
(400 MHz, CDCl3): l 7.66–7.64 (1H, m), 7.30–7.27
(2H, m), 7.12–7.10 (1H, m), 6.91 (2H, ddd, J=2.3, 2.3,
9.1 Hz), 6.84 (2H, ddd, J=2.4, 2.4, 9.2 Hz), 6.49 (1H,
dd, J=2.0, 9.9 Hz), 6.02 (1H, dd, J=2.4, 9.9 Hz), 5.17
(1H, dd, J=3.3, 10.1 Hz), 5.02 (1H, ddd, J=2.0, 2.0,
10.3 Hz), 3.77 (3H, s), 3.12 (1H, d, J=3.4 Hz). 13C-
NMR (400 MHz, CDCl3): l 154.3, 151.2,135.5, 131.9,
128.7, 128.1, 127.9, 126.4, 126.3, 125.2, 117.2, 114.8,
80.0, 72.4, 55.7. HRMS Calc. for [M+] (C17H14O2):
250.0994. Found: 250.1006.
6.2.8. (1S,2S)-2-(4-Methylphenoxy)-
1,2,-dihydro-naphthalen-1-ol (33)
Following the general procedure, 33 was obtained as
a white crystalline solid (57 mg, 65%). The ee was
determined to be 91% by HPLC analysis on a Chiralcel
OD column, u=256 nm. Retention times in 1% iso-
propanol in hexanes were 33.8 (major) and 37.1 min.
Rf=0.49 on silica (20% ethyl acetate in hexanes); m.p.
80–81°C (Et2O); [h]2D5= +145 (c=12.1, CHCl3). IR
(KBr, cm−1) 3303 (br), 3050 (w), 2210 (m), 1598 (s),
6.2.11. (1S,2S)-2-(3-Bromophenoxy)-1,2,-
dihydro-naphthalen-1-ol (36)
Following the general procedure, 36 was obtained as
a white crystalline solid (200 mg, 92%). The ee was
determined to be 96% by HPLC analysis on a Chiralcel
OD column, u=486 nm. Retention times in 1.5%
isopropanol in hexanes were 22.8 and 32.1 min (major).
Rf=0.44 on silica (20% ethyl acetate in hexanes); m.p.
120–122°C (Et2O); [h]2D5= +254° (c=9.2, CHCl3). IR
(KBr, cm−1) 3341 (br), 3071 (w), 2884 (w), 1581 (m),
1472 (s), 1358 (m), 1237 (s), 1028 (s), 987 (s), 780 (s),
689 (m), 569 (m); 1H-NMR (400 MHz, CDCl3): l
7.57–7.62 (1H, m), 7.22–7.30 (2H, m), 7.14–7.08 (4H,
m), 6.82–6.88 (1H, m), 6.49 (1H, dd, J=1.4, 9.9 Hz),
5.94 (1H, dd, J=2.1, 9.9 Hz), 5.13 (1H, dd, J=2.9, 9.9
Hz), 5.03 (1H, ddd, J=1.9, 1.9, 9.9 Hz), 2.76 (1H, d,
J=3.6 Hz). 13C-NMR (400 MHz, CDCl3): l 158.1,
135.3, 131.7, 130.7, 129.6, 128.3, 128.1, 126.5, 125.3,
125.3, 124.5, 122.9, 119.2, 114.5, 79.3, 72.1. HRMS
calculated for [M−H2O]+ (C16H11OBr): 297.9993.
Found: 297.9976.
1
1503 (s), 1238 (s), 1025 (m), 859 (m), 778 (m); H-NMR
(400 MHz, CDCl3): l 7.67–7.65 (1H, m), 7.33–7.28
(2H, m), 7.14–7.11 (3H, m), 6.88 (2H, d, J=8.4 Hz),
6.51 (1H, dd, J=1.8, 9.9 Hz), 6.04 (1H, dd, J=2.0, 9.9
Hz), 5.20 (1H, dd, J=1.6, 10.2 Hz), 5.09 (1H, ddd,
J=1.8, 1.8, 10.2 Hz), 2.87 (1H, d, J=2.7 Hz), 2.33
(3H, s). 13C-NMR (400 MHz, CDCl3): l 155.0, 135.4,
131.8, 130.7, 130.1, 128.8, 128.1, 127.9, 126.4, 126.2,
125.1, 115.6, 79.0, 72.3, 20.5. HRMS Calc. for [M+]
(C17H16O2): 252.1150. Found: 252.1140.
6.2.9. (1S,2S)-2-(4-Cyanophenoxy)-1,2,-
dihydro-naphthalen-1-ol (34)
Following the general procedure, 34 was obtained as
a white crystalline solid (160 mg, 88%). The ee was
determined to be 97% by HPLC analysis on a Chiralcel
OD column, u=256 nm. Retention times in 3% iso-
propanol in hexanes were 35.3 and 37.7 min (major).
Rf=0.40 on silica (30% ethyl acetate in hexanes); m.p.
140–141°C (Et2O); [h]2D5= +182.3 (c=11.2, CHCl3)
IR (KBr, cm−1) 3303 (b) 3050 (w) 2210 (m) 1598 (s)
6.2.12. (1S,2S)–2-(2-Bromophenoxy)-1,2,-
dihydro-naphthalen-1-ol (37)
Following the general procedure, 37 was obtained as
a white crystalline solid (206 mg, 94%). The ee was
determined to be 97% by HPLC analysis on a Chiralcel
OD column, u=486 nm. Retention times in 1.5%
1
1503 (s) 1238 (s) 1025 (m) 859 (m) 778 (m); H-NMR
(400 MHz, CDCl3): l 7.62–7.57 (3H, m), 7.33–7.27
(3H, m), 7.14–7.12 (1H, m), 6.56 (1H, dd, J=1.4, 9.7

270
M. Lautens et al. / Journal of Organometallic Chemistry 624 (2001) 259–270
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(KBr, cm−1) 3341 (br), 3071 (w), 2884 (w), 1581 (m),
1472 (s), 1358 (m), 1237 (s), 1028 (s), 987 (s), 780 (s),
1
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7.33–7.23 (3H, m), 7.14–7.12 (1H, m), 6.95(1H, dd,
J=1.1, 8.2 Hz), 6.92–6.87 (1H, m), 6.52 (1H, dd,
J=2.0, 9.9 Hz), 6.06 (1H, dd, J=1.8, 9.9 Hz), 5.32
(1H, d, J=11.0 Hz), 5.10 (1H, ddd, J=2.0, 2.0, 11.0
Hz), 2.85 (1H, d, J=3.2 Hz). 13C-NMR (400 MHz,
CDCl3): l 154.3, 135.4, 133.6, 131.8, 129.1, 128.6,
128.3, 128.0, 126.4, 126.0, 124.9, 122.9, 115.6, 113.5,
82.2, 72.5. HRMS Calc. for [M−H2O]+ (C16H11OBr):
297.9993. Found: 297.9976.
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We would like to thank NSERC, the ORDCF, As-
traZeneca Research Center Montreal, and the Univer-
sity of Toronto for valuable support of our
programmes and Solvias AG and A. Togni for provid-
ing the Josiphos ligands used in this study. K.F. also
thanks NSERC and AstraZeneca for an Industrial
Postgraduate Scholarship and NSERC for a postgradu-
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