Rhodium-catalysed asymmetric ring opening reactions with carboxylate nucleophiles

Article abstract of DOI:10.1016/S0040-4020(01)00351-9

We have developed an asymmetric ring opening reaction of oxabenzonorbornadiene with carboxylate nucleophiles to generate enantiomerically enriched hydronaphthalene products containing an allylic carboxylate moiety. These reactions occur in good yield and excellent enantioselectivity (>90% ee). The allylic carboxylate functionality was found to be stable towards reaction with the rhodium catalyst under the reaction conditions. In order to obtain these results, two advancements were required. First, the use of protic additives was necessary for good reactivity. Second, the exchange of the halide ligand on the catalyst from chloride to iodide was required to obtain high ee.

Full text of DOI:10.1016/S0040-4020(01)00351-9

TETRAHEDRON
Pergamon
Tetrahedron 57 /2001) 5067±5072
Rhodium-catalysed asymmetric ring opening reactions with
carboxylate nucleophiles
Mark Lautensp and Keith Fagnou
Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario, M5S 3H6, Canada
Dedicated to Professor Barry M. Trost, in honour of his contributions to research and teachings, on the occasion of his 60th birthday
Received 31 January 2001; revised 15 February 2001; accepted 19 February 2001
AbstractÐWe have developed an asymmetric ring opening reaction of oxabenzonorbornadiene with carboxylate nucleophiles to generate
enantiomerically enriched hydronaphthalene products containing an allylic carboxylate moiety. These reactions occur in good yield and
excellent enantioselectivity /.90% ee). The allylic carboxylate functionality was found to be stable towards reaction with the rhodium
catalyst under the reaction conditions. In order to obtain these results, two advancements were required. First, the use of protic additives was
necessary for good reactivity. Second, the exchange of the halide ligand on the catalyst from chloride to iodide was required to obtain high ee.
q 2001 Elsevier Science Ltd. All rights reserved.
Allylic functionalisation through the intermediacy of
p-allyl transition metal complexes remains an area of
intense study. Palladium catalysts are the most thoroughly
explored,1 but other metals have been shown to exhibit
useful properties.2,3 We4 and others5 have been interested
in exploring the reactivity of rhodium in analogous trans-
formations and complementary reactivities have emerged
when compared to the palladium `benchmark'. While
palladium catalysts will generally react with allylic acetates,
the ability of rhodium catalysts to do so depends heavily on
the nature of the ligands on the metal. It has been
demonstrated that while rhodium±phosphite complexes
will react with allylic acetates, analogous rhodium±
phosphine complexes do not.6 This led us to consider the
use of carboxylate nucleophiles with rhodium catalysis as a
means of generating enantioenriched allylic acetates for use
in subsequent transformations. Herein, we report the
realisation of this goal. Through the combined use of
carboxylate nucleophiles, protic additives, and an intriguing
halide effect on the rhodium catalyst, the asymmetric ring
opening reaction /ARO) of oxabenzonorbornadiene to
produce 1,2-dihydronaphthalenes in good yield and
excellent ee /.90%) has been achieved. The resulting
allylic carboxylate moiety was found to be inert towards
further insertion under the reaction conditions. The utility
of this methodology when coupled with palladium catalysis
has been demonstrated in the preparation of 1,4-dihydro-
naphthalenes /Scheme 1).
Our initial investigations focused on determining whether
carboxylates would be of suf®cient nucleophilicity to
participate in these reactions. We had previously uncovered
a pKa effect with alcohol and phenol nucleophiles where the
more acidic species reacted preferentially in competition
experiments.7 Since carboxylic acids are more acidic than
phenols, we anticipated that this trend would continue.
Unfortunately, reaction of 1 under previously established
conditions in the presence of ®ve equivalents acetic acid
did not give any reaction /Table 1, Entry 1). Increasing
the nucleophilicity by using sodium acetate also did not
produce any reaction, in accord with our earlier ®ndings
with other nucleophiles that a proton source is essential
Scheme 1. Rhodium-catalysed ARO of oxabenzonorbornadiene with carboxylate nucleophiles.
Keywords: asymmetric catalysis; rhodium; carboxylate.
Corresponding author. Fax: 11-416-978-1631; e-mail: mlautens@alchemy.chem.utoronto.ca
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020/01)00351-9

5068
M. Lautens, K. Fagnou / Tetrahedron 57 (2001) 5067±5072
Table 1. Development of ring opening reaction with acetate
We have developed an ef®cient asymmetric version of this
reaction through the correct combination of chiral
phosphine ligand and halide ligand. While alcohols and
phenols induce ring opening with ees in excess of 90%
with
a
catalyst generated from PPF-PtBu2 and
[Rh/COD)Cl]2, poor results were obtained with carboxylate
nucleophiles /Table 3, Entries 1 and 5). Ees of 81% could be
obtained by changing the chiral ligand to BPPFA or C2-
Ferriphos /Entries 2, 3and 6, 7), but the best results were
obtained by using PPF-PtBu2 with a rhodium iodide
complex prepared in situ from the rhodium chloride.
Using this protocol, products 2 and 6 were obtained in
.90% yield and 92% ee /Entries 4 and 8). The difference
in the enantioselectivities between the chloro and the iodo
complexes is particularly striking with benzoate as the
nucleophile, where 6 was generated in only 31% ee when
the Rh±Cl complex was used, and in 92% ee when the
halide ligand was changed from Cl to I. These results,
along with our earlier work with nitrogen nucleophiles,8
underlines the importance of considering halide effects in
asymmetric catalysis. Two other examples with methacrylic
acid and propionic acid gave similar yields and ees /Entries 9
and 10).
Entry
Nucleophile
Additive
Yield /%)a
1
AcOH
AcONa
Et
AcOH
AcONH4
None
None
3N´HCl
Et3N
NR
NR
89
89
84
2
3AcONa
4
5
None
Conditions: [Rh/COD)Cl]2 /2.5 mol%), dppf /5 mol%), nucleophile /5 eq.),
additive /5 eq.), and 1 reacted in THF /0.1 M) at re¯ux.
Isolated yield.
a
for the reaction to occur /Entry 2). We thus sought a method
of maintaining both the increased nucleophilicity of an
anionic carboxylate species and the presence of a proton
source. In previous studies, we found that the addition of
ammonium salts as protic additives could be used to
increase the reactivity of aliphatic amines.8 Since proto-
nated amines did not negatively affect the catalyst activity,
we reasoned that the combined use of sodium acetate and an
amine hydrochloride might offer a solution.9 This was
indeed the case, since reaction of 1 in the presence of
equimolar amounts of sodium acetate and triethylamine
hydrochloride generated 2 in 89% yield /Entry 3).10 Other
methods of achieving the same result are through the
combined use of equimolar amounts of acetic acid and
triethylamine or by using ammonium acetate /Entries 4
and 5).
The stability of the allylic carboxylate produced in these
reactions was investigated under the ring opening
conditions. An important question that needed to be
answered was whether the rhodium catalyst was able to
insert into the allylic carboxylate. When benzoate 6 was
subjected to the reaction conditions with ®ve equivalents
of ammonium acetate as the nucleophile no reaction had
The scope of this reaction was found to be general with
respect to the carboxylate nucleophile /Table 2). A variety
of carboxylates effectively induce ring opening, including
formate /Entries 3and 4) and the potassium salt of ethyl
malonate /Entry 7). Benzoate is also compatible despite its
lower nucleophilicity and the higher propensity of the
allylic benzoate moiety to undergo subsequent ionisation
with transition metals /Entries 5 and 6). No appreciable
changes in yields or reaction times were noted for the
different conditions.
1
occurred after 2 h and only 6 was detected in the crude H
NMR. In a second experiment, enantioenriched 2 /92% ee)
was treated with rhodium and BPPFA as the chiral ligand
/which gave 2 in only 78% ee). After 2 h the ee remained
unchanged. This was also the case when enantioenriched 2
/78% ee) was subjected to the reaction conditions with the
[RhI/PPF-PtBu2)] catalyst /which gave 2 in 92% ee). It can
be concluded based on these results that addition of the
carboxylate nucleophile is irreversible and that the high
enantioselectivities obtained with the rhodium iodide PPF-
PtBu2 catalyst are kinetic in origin and not the result of a
reversible thermodynamically controlled process.
Table 2. Scope of ring opening with carboxylate nucleophiles
Preliminary studies of the utility of these ring opened
products have been carried out. An initial goal was the
development of a process which would rely on the differing
chemoselectivities of rhodium and palladium to ®rst create
and then use an allylic carboxylate functionality for
subsequent transformations. This goal has been attained11
as exempli®ed by reaction of 8 with methyldiethyl
malonate and a Pd/0) catalyst to generate 9 as the sole regio-
isomer in good yield [Eq. /1)]. The high regioselectivity is
likely the result of the presence of the OTBS group adjacent
to the p-allyl moiety that directs the nucleophilic attack to
Entry Nucleophile
Additive Product Yield /%)a
1
2
Propionic acid
Methacrylic acid
Et3N
Et3N
3
4
5
5
6
6
7
72
69
69
73
70
81
79
3Sodium formate
Et
3N´HCl
4
5
6
7
Ammonium formate
Benzoic acid
Ammonium benzoate
None
Et3N
None
Ethyl malonate potassium salt Et3N´HCl
Conditions: [Rh/COD)Cl]2 /2.5 mol%), dppf /5 mol%), nucleophile /5 eq.),
additive /5 eq.), and 1 reacted in THF /0.1 M) at re¯ux.
Isolated yield.
a

M. Lautens, K. Fagnou / Tetrahedron 57 (2001) 5067±5072
5069
Table 3. ARO with carboxylate nucleophiles
Entry
X liganda
Chiral ligand
Nucleophile/additive
Product
Yield /%)b
Ee /%)c
1
2
3Cl
4
5
6
7
8
9
10
Cl
Cl
C
l
Cl
Cl
Cl
l
PPF-PtBu2
BPPFA
2-Ferriphos
PPF-PtBu2
PPF-PtBu2
BPPFA
C2-Ferriphos
PPF-PtBu2
PPF-PtBu2
PPF-PtBu2
Ammonium acetate
Ammonium acetate
Ammonium acetate
Ammonium acetate
Ammonium benzoate
Ammonium benzoate
Ammonium benzoate
Ammonium benzoate
Propionic acid/Et3N
Methacrylic acid/Et3N
2
2
2
2
6
6
6
6
3
4
81
86
89
93d
72
75
74
91d
75
71
61
78
78
92
31
81
81
92
91
91
l
l
a
Conditions /X ligandˆCl): [Rh/COD)Cl]2 /0.5 mol%), ligand /1.5 mol%), nucleophile /5 eq.), additive /5 eq.), and 1 reacted in THF /0.1 M) at re¯ux.
Conditions /X ligandˆI): [Rh/COD)Cl]2 /0.5 mol%), ligand /1.5 mol%) added to ¯ask followed by addition of AgOTf /2 mol%) then Bu4NI /4 mol%). To
this was added 1. The nucleophile /5 eq.) and additive /5 eq.) were added to this solution in THF /0.1 M) at re¯ux.
Isolated yield.
Ee determined by CSP HPLC with a Chiralcel OD collumn.
These reactions were run on a 1 g scale.
b
c
d
the distal position.12 The intramolecular process was also
goal, two changes to our earlier protocols were made.
First, the combined use of a carboxylate nucleophile with
a protic additive is vital to induce reaction. If the carboxylic
acid is not deprotonated or if a proton source is not avail-
able, no reaction occurs. Second, an intriguing halide effect
on the rhodium catalyst must be utilised to obtain high
enantioselectivity.
examined. Treatment of 10 with base and catalytic
Pd/PPh3)4 causes rearrangement to 11 and subsequent
decarboxylation to give 12 in 61% yield [Eq. /2)]. This
rearrangement does not occur after 2 h in the absence of
the palladium catalyst. The 1,4-dihydronaphthalene
products obtained through the sequential application of
rhodium and palladium catalysis are synthetically
interesting and belong to a biologically important class of
compounds.13
It was established that no reaction of the allyl carboxylate
occurred with the rhodium catalyst under the reaction
conditions and that the high enantioselectivities are not
the result of a reversible addition/insertion process. The
utility of these products has been demonstrated through
their application in the preparation of 1,4-dihydronaphtha-
lenes. The hydronaphthalene products of these reactions
constitute an important molecular scaffold in medicinal
chemistry and can be found in a wide range of natural and
synthetic compounds possessing a large diversity of
biological activities. We are currently exploring the
application of this methodology to other ring systems.
ꢀ1†
1. Experimental
1.1. General
/2)
All ¯asks were ¯ame-dried under a stream of nitrogen or
argon and cooled before use. Solvents and solutions were
transferred with syringes and cannulae using standard inert
1
atmosphere techniques. H NMR spectra were recorded 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; multi-
plicity /s-singlet, d-doublet, t-triplet, q-quartet, m-complex
multiplet); coupling constants /J, Hz). 13C NMR spectra
were recorded at 100 MHz with CDCl3 as reference
standard /dˆ77.0 ppm) or some other suitable solvent. IR
spectra were obtained using a Nicolet DX FT-JR spectro-
In conclusion, we have shown that carboxylate nucleophiles
can be effectively used to induce ring opening reactions of
oxabenzonorbornadiene in good yield and excellent
enantioselectivity /.90% ee). In order to achieve this

5070
M. Lautens, K. Fagnou / Tetrahedron 57 (2001) 5067±5072
meter as a KBr pellet or neat ®lm between KBr plates. High
resolution mass spectra were obtained from a VG 70-250S
/double focusing) mass spectrometer at 70 eV. Melting
points were taken on a Fisher±Johns melting point
apparatus and are uncorrected. 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
¯uorescent sheets. Column chromatography was performed
as `Flash Chromatography' as reported by Still14 using
/200±400 mesh) Merck grade silica gel. THF was distilled
from sodium benzophenone ketyl immediately prior to use.
The PPF-PtBu2 ligand was donated by Solvias.
Oxabenzonorbornadiene 1,15 BPPFA, and C2-Ferriphos
were prepared according to literature procedure. All other
reagents were obtained from Aldrich and used as received
unless otherwise stated.
4.92 /1H, d, Jˆ9.0 Hz), 2.64 /1H, s), 2.12 /3H, s); 13C NMR
/100 MHz, CDCl3) d 171.3, 135.2, 131.5, 129.5, 128.3,
126.7, 126.0, 125.4, 75.3, 71.7, 21.2. HRMS calcd for
C12H12O3 /M1): 204.0786. Found: 204.0791.
1.3.2. )1S,2S)-Propionic acid 1-hydroxy-1,2-dihydro-
naphthalen-2-yl-ester )3). Following the general proce-
dure, 3 was obtained as a white crystalline solid /75%).
The ee was determined to be 91% using HPLC analysis
on a Chiralcel OD column, 10% isopropanol in hexanes,
lˆ254 nm. Retention times were 6.7 min and 11.0 min
25
D
/major). ‰aŠ ˆ1124 /cˆ20.1, CHCl3); Rfˆ0.24 on silica
gel /20% ethyl acetate:hexanes); mp 55±568 /Et2O); IR
/KBr, cm21) 3 491 /br), 3 048 /w), 2984 /w), 173 9 /s), 1454
/m), 1363 /w), 1182 /s), 1083 /m). H NMR /400 MHz,
1
CDCl3) d 7.55±7.52 /1H, m), 7.29±7.24 /2H, m), 7.11±
7.08 /1H, m), 6.50 /1H, dd, Jˆ10.0, 2.0 Hz), 5.85 /1H, dd,
Jˆ12.8, 2.8 Hz), 5.61 /1H, ddd, Jˆ9.2, 2.8, 2.0 Hz), 4.93
/1H, d, Jˆ9.2 Hz), 2.40 /2H, qd, Jˆ7.6, 1.2 Hz), 1.16 /3H,
t, Jˆ7.6 Hz); 13C NMR /100 MHz, CDCl3) d 174.8, 135.3,
131.5, 129.4, 128.3, 128.3, 126.7, 125.9, 125.5, 75.2, 71.9,
27.7, 9.0. HRMS calcd C13H14O3 /M1): 218.0943. Found:
218.0938.
1.2. Representative procedure for the in situ exchange of
chloride to iodide ligands
To a ¯ame-dried round bottomed ¯ask under inert
atmosphere was added [Rh/COD)Cl]2 /5 mg, 0.01 mmol)
and /S,R)-PPF-PtBu2 /12 mg, 0.022 mmol), which was
dissolved in 2 mL THF and stirred at room temperature
for 5 min to produce a dark red solution. In a separate
¯ame-dried round bottomed ¯ask was added AgOTf
/11 mg, 0.04 mmol). The rhodium±phosphine solution
was transferred to the ¯ask containing the AgOTF via
cannula resulting in the formation of a white precipitate.
This heterogeneous mixture was stirred at room temperature
for 5 min prior to its transfer to a ¯ame-dried ¯ask contain-
ing TBAI /22 mg, 0.06 mmol). After stirring for 5 additional
minutes, this red±brown solution was ready for use.
1.3.3. )1S,2S)-2-Methyl acrylic acid 1-hydroxy-1,2-dihy-
dronaphthalen-2-yl-ester )4). Following the general
procedure, 4 was obtained as a white crystalline solid
/71%). The ee was determined to be 91% using HPLC
analysis on a Chiralcel OD column, 10% isopropanol in
hexanes, lˆ254 nm. Retention times were 6.4 min and
25
D
9.6 min /major). ‰aŠ ˆ1141 /cˆ8.7, CHCl3); Rfˆ0.32 on
silica gel /20% ethyl acetate:hexanes); mp 80±828 /Et2O);
IR /KBr, cm21) 3450 /br), 3030 /w), 2928 /w), 1722 /s),
1637 /m), 1454 /m), 1289 /m), 1163 /s); 1H NMR
/400 MHz, CDCl3) d 7.56±7.55 /1H, m), 7.29±7.24 /2H,
m), 7.10±7.09 /1H, m), 6.51 /1H, dd, Jˆ9.9, 1.9 Hz), 6.15
/1H, s), 5.87 /1H, dd, Jˆ9.9, 3.0 Hz), 5.67 /1H, ddd, Jˆ9.3,
2.1, 2.1 Hz), 5.61 /1H, s), 5.01 /1H, dd, Jˆ9.0, 5.7 Hz),
2.74 /1H, d, Jˆ6.1 Hz), 1.96 /3H, s); 13C NMR
/100 MHz, CDCl3) d 167.6, 135.9, 135.3, 131.5, 129.4,
128.3, 128.2, 126.6, 126.4, 125.8, 125.5, 75.9, 71.9, 18.3.
HRMS calcd C14H12O2 /M1±H2O): 212.0837. Found:
212.0831.
1.3. Representative procedure for the asymmetric ring
opening reaction with carboxylate nucleophiles
To a round bottom ¯ask containing the rhodium iodide
/S,R)-PPF-PtBu2 complex /1 mol% to 1) was added 1
/100 mg, 0.694 mmol). The red±brown solution was then
heated to re¯ux followed by addition of ammonium acetate
/267 mg, 3.47 mmol). The reaction was allowed to stir at
re¯ux until 1 was consumed as determined by TLC analysis.
Upon completion, the crude mixture was poured into a
saturated aqueous solution of NaHCO3 and extracted three
times with ethyl acetate. The organic layers were combined,
dried over Na2SO4 and concentrated. The resulting solid
was puri®ed by ¯ash chromatography.
1.3.4. )1S*,2S*)-Formic acid 1-hydroxy-1,2-dihydro-
naphthalen-2-yl-ester )5). Following the general proce-
dure, 5 was obtained as a white crystalline solid /73%).
Rfˆ0.25 on silica gel /30% ethyl acetate:hexanes); mp
133±1358 /Et2O); IR /KBr, cm21) 3146 /br), 2935 /w),
1
1720 /s), 1482 /w), 1186 /s), 1049 /m), 968 /m); H NMR
/400 MHz, CDCl3) d 8.17 /1H, d, Jˆ0.8 Hz), 7.52±7.50
/1H, m), 7.29±7.27 /2H, m), 7.13±7.11 /1H, m), 6.54
/1H, dd, Jˆ9.6, 1.6 Hz), 5.88 /1H, dd, Jˆ9.6, 2.8 Hz),
5.71±5.68 /1H, m), 4.96 /1H, d, Jˆ8.8 Hz), 2.8 /1H, s);
13C NMR /100 MHz, CDCl3) d 160.9, 134.8, 131.4,
130.0, 128.5, 126.9, 126.1, 124.6, 74.8, 71.4. HRMS calcd
for C11H10O3 /M1): 190.0630. Found: 190.0625.
1.3.1. )1S,2S)-Acetic acid 1-hydroxy-1,2-dihydro-
naphthalen-2-yl-ester )2). Following the general proce-
dure, 2 was obtained as a crystalline solid /93% yield).
The ee was determined to be 92% using HPLC analysis
on a Chiralcel OD column, 10% isopropanol in hexanes,
lˆ254 nm. Retention times were 8.0 min and 11.3min
25
D
/major). ‰aŠ ˆ11.2 /cˆ11.3, CHCl3); Rfˆ0.26 on silica
gel /20% ethyl acetate:hexanes); mp 67±688 /Et2O); IR
/KBr, cm21): 3620 /br), 3048 /w), 2977 /w), 1744 /s),
1454 /m), 1370 /s), 1235 /s), 1057 /m); 1H NMR
/400 MHz, CDCl3) d 7.54±7.53/1H, m), 7.29±7.24 /2H,
m), 7.10±7.08 /1H, m), 6.50 /1H, dd, Jˆ3.9, 1.3 Hz), 5.85
/1H, dd, Jˆ9.9, 3.1 Hz), 5.59 /1H, ddd, Jˆ9.0, 2.8, 1.9 Hz),
1.3.5. )1S,2S)-Benzoic acid 1-hydroxy-1,2-dihydro-
naphthalen-2-yl-ester )6). Following the general proce-
dure, 6 was obtained as a white crystalline solid /91%).
The ee was determined to be 92% using HPLC analysis
on a Chiralcel OD column, 10% isopropanol in hexanes,

M. Lautens, K. Fagnou / Tetrahedron 57 (2001) 5067±5072
5071
lˆ254 nm. Retention times were 9.0 min and 11.1 min
/major). Rfˆ0.3on silica gel /10% ethyl acetate:hexanes);
methyl diethyl malonate solution was then transferred to
the ®rst ¯ask via cannula. The combined solution was
heated at re¯ux for 2 h then poured into water and extracted
with ethyl acetate. The combined extracts were dried over
Na2SO4 and concentrated. The resulting crude oil was
puri®ed by ¯ash chromatography /5% ethyl acetate in
hexanes) to give a colourless oil 9 /51 mg, 91%). Rfˆ0.27
25
D
mp 107±1098 /Et2O); ‰aŠ ˆ1299 /cˆ11.3, CHCl3); IR
/KBr, cm21) 3619 /br), 3071 /w), 2977 /w), 1724 /s),
1451 /m), 1324 /m), 1265 /s), 1110 /s). 1H NMR
/400 MHz, CDCl3) d 8.10 /2H, d, Jˆ7.6 Hz), 7.64±7.59
/2H, m), 7.48±7.45 /2H, m), 7.34±7.32 /2H, m), 7.13±
7.11 /1H, m), 6.55 /1H, d, Jˆ10.0 Hz), 5.97 /1H, dd,
Jˆ9.8, 2.9 Hz), 5.86 /1H, ddd, Jˆ9.8, 2.0, 2.0 Hz), 5.11
/1H, d, Jˆ9.0 Hz), 2.84 /1H, s); 13C NMR /100 MHz,
CDCl3) d 166.9, 135.3, 133.3, 131.6, 129.9, 129.8, 129.7,
128.4, 128.4, 128.4, 126.8, 126.1, 125.5, 76.1, 71.9. HRMS
calcd for C17H14O3 /M1): 266.0943. Found: 266.0938.
on silica gel /5% ethyl acetate:hexanes); IR /KBr, cm21
)
3036 /w), 2956 /s), 1735 /s), 1472 /m), 1257 /s), 1077 /s);
1H NMR /400 MHz, CDCl3) d 7.55 /2H, d, Jˆ8.1 Hz),
7.32±7.24 /1H, m), 7.20±7.12 /2H, m), 6.19±6.10 /2H,
m), 5.18±5.13/1H, m), 4.50±4.45 /1H, m), 4.28±4.10
/4H, m), 1.30±1.24 /6H, m), 1.10 /3H, s), 0.98 /9H, s),
0.22 /3H, s), 0.16 /3H, s); 13C NMR /100 MHz, CDCl3) d
170.8, 170.7, 140.9, 135.9, 127.8, 127.0, 126.7, 126.3,
125.8, 77.2, 65.7, 61.5, 60.9, 44.5, 25.9, 18.2, 15.1, 14.0,
13.9, ±4.2, 24.6. HRMS calcd C20H27O5Si /M1±C4H9):
375.1628. Found: 375.1626.
1.3.6. )1S*,2S*)-Malonic acid ethyl ester )1-hydroxy-1,2-
dihydronaphthalen-2-yl) ester )7). Following the general
procedure, 7 was obtained as a colourless oil /79%).
Rfˆ0.29 on silica gel /30% ethyl acetate:hexanes); IR
/KBr, cm21) 3470 /br), 2983 /w), 1731 /s), 1453 /w),
1370 /m), 1150 /s), 1031 /m); 1H NMR /400 MHz,
CDCl3) d 7.56±7.54 /1H, m), 7.27±7.21 /2H, m), 7.08±
7.06 /1H, m), 6.48 /1H, dd, Jˆ9.9, 2.1 Hz), 5.83/1H, dd,
Jˆ9.7, 2.8 Hz), 5.70 /1H, ddd, Jˆ9.7, 2.5, 2.2 Hz), 4.97
/1H, d, Jˆ9.5 Hz), 4.18 /2H, q, Jˆ7.2 Hz), 3.43 /2H, dd,
Jˆ23.6, 15.9 Hz), 3.21 /1H, s), 1.25 /3H, t, Jˆ7.1 Hz); 13C
NMR /100 MHz, CDCl3) d 167.1, 166.5, 135.0, 131.5,
129.6, 128.3, 128.1, 126.6, 125.6, 125.1, 77.0, 71.6, 61.9,
41.6, 14.0. HRMS calcd for C15H14O4 /M1±H2O):
258.0892. Found: 258.0899.
1.3.9. )1S*,2S*)-Malonic acid )1-tert-butyldimethyl-
siloxy-1,2-dihydronaphthalen-2-yl) ester ethyl ester
)10). To
a dried round bottom ¯ask, 7 /270 mg,
0.98 mmol), imidazole /134 mg, 1.96 mmol), and dimethyl-
aminopyridine /6 mg, 0.05 mmol) were dissolved in
dichloromethane /4 mL). Tert-butyldimethylsilyl chloride
/222 mg, 1.47 mmol) was then added portionwise and
allowed to react for 24 h. The reaction was then quenched
with water, extracted with dichloromethane, dried over
Na2SO4 and concentrated in vacuo. Flash chromatography
/10% ethyl acetate in hexanes) gave a colourless oil 10
/343 mg, 90%). Rfˆ0.34 on silica gel /10% ethyl acetate:
hexanes). IR /KBr, cm21) 2983/w), 1731 /s), 1453/w),
1370 /m), 1150 /s), 1031 /m); 1H NMR /400 MHz,
CDCl3) d 7.41±7.39 /1H, m), 7.24±7.22 /2H, m), 7.07±
7.05 /1H, m), 6.47 /1H, dd, Jˆ9.9, 1.8 Hz), 5.83/1H, dd,
Jˆ9.7, 2.7 Hz), 5.60 /1H, ddd, Jˆ9.3, 2.9, 2.0 Hz), 5.00
/1H, dd, Jˆ9.3, 0.5 Hz), 4.22±4.15 /2H, m), 3.40 /2H, dd,
Jˆ19.6, 16.0 Hz), 1.57 /1H, s), 1.25 /3H, t, Jˆ7.1 Hz), 0.92
/9H, s), 0.13 /3H, s), 0.09 /3H, s); 13C NMR /100 MHz,
CDCl3) d 166.3, 166.2, 136.2, 132.1, 129.4, 128.0, 127.9,
126.5, 125.9, 125.7, 76.4, 71.6, 61.6, 41.7, 25.8, 18.1, 14.0,
24.3, 24.5. HRMS calcd for C17H21O5Si /M1±C4H9):
333.1158. Found: 333.1149.
1.3.7. )1S,2S)-Benzoic acid 1-)tert-butyl-dimethyl-silany-
loxy)-1,2-dihydronaphthalen-2-yl ester )8). In a dried
round bottom ¯ask, 6 /266 mg, 1.0 mmol), imidazole
/134 mg, 1.96 mmol), and dimethylaminopyridine /6 mg,
0.05 mmol) were dissolved in dichloromethane /4 mL).
Tert-butyldimethylsilyl chloride /222 mg, 1.47 mmol) was
then added portionwise and allowed to react for 24 h. The
reaction was then quenched with water, extracted with
dichloromethane, dried over Na2SO4 and concentrated in
vacuo. Flash chromatography /10% ethyl acetate in
hexanes) gave a colourless oil 8 /365 mg, 96%). Rfˆ0.48
25
D
on silica gel /10% ethyl acetate:hexanes). ‰aŠ ˆ1314
/cˆ19.9, CHCl3); IR /KBr, cm21) 2983/w), 1713 /s),
1453 /w), 1370 /m), 1150 /s), 1031 /m); 1H NMR
/400 MHz, CDCl3) d 8.06 /2H, d, Jˆ7.8 Hz), 7.60±7.52
/1H, m), 7.50±7.40 /3H, m), 7.30±7.22 /2H, m), 7.14±
7.06 /1H, m), 6.53/1H, d, Jˆ8.2 Hz), 5.96±5.86 /2H, m),
5.19 /1H, d, Jˆ9.4 Hz), 0.88 /9H, s), 0.11 /3H, s), 0.05 /3H,
s); 13C NMR /100 MHz, CDCl3) d 166.1, 136.5, 133.0,
132.3, 130.3, 129.8, 129.2, 127.9, 127.8, 126.5, 126.5,
126.0, 75.7, 72.1, 25.8, 18.1, 24.3, 24.4. HRMS calcd
C19H19O3Si /M1±C4H9): 323.1103. Found: 323.1100.
1.3.10. [4-)tert-Butyl-dimethyl-silanyloxy)-1,4-dihydro-
naphthalen-1-yl]-acetic acid ethyl ester )12). To a dried
round bottom ¯ask, 10 /100 mg, 0.256 mmol) was dissolved
in THF /4 mL). Potassium hydride /11.3mg, 0.28 mmol)
was then added portionwise and allowed to react for ®ve
minutes at room temperature. Triphenylphosphine
/34.1 mg, 0.13 mmol) was then added followed by
Pd/PPh3)4 /14.8 mg, 0.013mmol). The reaction was then
heated to re¯ux for 2 h. The solvent was then removed in
vacuo and the resulting oil puri®ed by ¯ash chromatography
/5% ethyl acetate in hexanes) giving 12, a colourless oil
/54 mg, 61%). Rfˆ0.27 on silica gel /5% ethyl
acetate:hexanes); IR /KBr, cm21) 3036 /w), 2956 /s),
1735 /s), 1472 /m), 1257 /s), 1077 /s); 1H NMR
/400 MHz, CDCl3) d 7.54±7.52 /1H, m), 7.30±7.23 /3H,
m), 6.09 /1H, ddd, Jˆ2.4, 4.6, 10.2 Hz), 6.02 /1H, ddd,
Jˆ10.2, 2.0, 0.5 Hz), 5.22±5.21 /1H, m), 4.15 /2H, q,
Jˆ7.2 Hz), 3.92±3.87 /1H, m), 2.62 /1H, dd, Jˆ15.7,
5.7 Hz), 2.39 /1H, dd, Jˆ15.2, 9.0 Hz), 1.25 /3H, t,
1.3.8. 2-[4-)tert-Butyl-dimethyl-silanyloxy)-1,4-dihydro-
naphthalen-1-yl]-2-methyl-malonic acid diethyl ester
)9). To a ¯ame-dried round bottomed ¯ask was added
Pd2/dba)3 /2.3mg, 0.002 mmol) and triphenylphosphine
/2.6 mg, 0.01 mmol) followed by the addition of THF
/2 mL). The solution was stirred at room temperature for
5 min then 8 /50 mg, 0.13mmol) was added. In a separate
¯ask, methyl diethylmalonate /35 mg, 0.2 mmol) was
dissolved in THF /1 mL) followed by the addition of NaH
/5 mg, 0.2 mmol) and stirring for 5 min. This sodium

5072
M. Lautens, K. Fagnou / Tetrahedron 57 (2001) 5067±5072
Jˆ7.2 Hz), 0.98 /9H, s), 0.21 /3H, s), 0.15 /3H, s); 13C NMR
/100 MHz, CDCl3) d 171.7, 138.3, 136.1, 131.8, 128.2,
127.2, 127.0, 126.9, 126.6, 65.3, 60.5, 42.7, 36.5, 25.9,
18.2, 14.2, 24.2, 24.5. HRMS calcd C17H21O5Si /M1±
C4H9): 289.1260. Found: 289.1257.
isopropanol and hexa¯uoroisopropanol /HFIP), only HFIP
was incorporated in the product. Analogously, reaction in
the presence of both 4-methoxyphenol and 4-hydroxyaceto-
phenone resulted in a 16:1 product mixture with addition of
4-hydroxyacetophenone constituting the major product. See
Refs. 4b and 4c.
8. Lautens, M.; Fagnou, K. Submitted for publication.
9. Since the pKa of acetic acid is lower than that of the conjugate
acid of aliphatic amines, sodium acetate will remain deproto-
nated even when 1 equivalent Et3N´HCl is added.
Acknowledgements
We would like to thank AstraZeneca /Montreal), NSERC,
the ORDCF and the University of Toronto for valuable
support of this research program. We thank Solvias AG
for generously supplying us with the PPF-PtBu2 ligand
used in these studies. K. F. would like to thank AstraZeneca
and NSERC for an industrial postgraduate scholarship /IPS)
and an NSERC PGS.
10. The relative stereochemistry for the acetate adduct was proven
by deprotection of the acetate moiety, and dimethylation with
iodomethane. This dimethoxy-1,2-dihydronaphthalene was
identical to authentic trans-dimethoxy-1,2-dihydronaphtha-
lene prepared via an alternative method.
11. A full account of this work will be reported elsewhere in due
course.
12. The directing effect of an oxygen functionality adjacent to the
p-allyl palladium moiety has been found in other systems.
See: /a) Genet, J. P.; Piau, F.; Ficini, J. Tetrahedron Lett.
1980, 21, 3183. /b) Genet, J. P.; Balabane, M.; Charbonnier,
F. Tetrahedron Lett. 1982, 23, 5027. /c) Akermark, B.;
Ljungqvist, A.; Panunzio, M. Tetrahedron Lett. 1981, 22,
1055. /d) Trost, B. M.; Molander, G. A. J. Am. Chem. Soc.
1981, 103, 5969. /e) Tsuji, J.; Kataoka, H.; Kobayashi, Y.
Tetrahedron Lett. 1981, 22, 2575.
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7. For example, when a competition experiment was run with