Sequential olefin metathesis - Intramolecular asymmetric Heck reactions in the synthesis of polycycles

Article abstract of DOI:10.1139/v03-196

Application of the intramolecular asymmetric Heck reaction in the desymmetrization of a novel class of symmetrical bicyclodienes, synthesized through a diastereoselective double ring-closing metathesis (DSRCM) reaction, was achieved with good yields (appr

Full text of DOI:10.1139/v03-196

399
Sequential olefin metathesis — Intramolecular
asymmetric Heck reactions in the synthesis of
polycycles1
Mark Lautens and Valentin Zunic
Abstract: Application of the intramolecular asymmetric Heck reaction in the desymmetrization of a novel class of
symmetrical bicyclodienes, synthesized through a diastereoselective double ring-closing metathesis (DSRCM) reaction,
was achieved with good yields (approximately 80%) and excellent enantioselectivities (up to 99% ee). Three contiguous
stereocenters are established in a single desymmetrization reaction. The use of thallium carbonate as base in the asym-
metric Heck reaction favours double bond migration in 13. Cationic conditions delivered products with good to excel-
lent enantioselectivities, surpassing the results under neutral conditions.
Key words: asymmetric, Heck, polycycles, metathesis, stereoselective, desymmetrization.
Résumé : L’application de la réaction asymétrique intramoléculaire de Heck pour la désymétrisation d’une nouvelle
classe de bicyclodiènes symétriques, obtenus par une réaction de métathèse à double cyclisation diastéréosélective, a
été réalisée avec de bons rendements (environ 80 %) et d’excellentes énantiosélectivités (jusqu’à 99 % ee). Les trois
stéréocentres contigus ont été établis au cours d’une seule réaction de désymétrisation. L’utilization du carbonate de
thallium comme base dans la réaction asymétrique de Heck favorise la migration de la double liaison dans le composé
13. Les conditions cationiques ont permis de livrer des produits avec des énantiosélectivités allant de bonnes à excel-
lentes qui étaient supérieures à celles obtenues dans des conditions neutres.
Mots clés : asymétrique, Heck, polycycles, métathèse, stéréosélective, désymétrisation.
[Traduit par la Rédaction] Lautens and Zunic 407
Introduction
sized via the intramolecular AHR have been used as build-
ing blocks for complex natural products or as model com-
pounds for pharmaceutically relevant substances (6).
We have reported the formation of cis- and trans-decalin
systems, as well as cis-diquinanes, via a diastereoselective
double ring-closing olefin metathesis reaction (DSRCM) (7)
(see Fig. 1). These symmetrical bicyclodienes are ideal sub-
strates in the area of alkene differentiation reactions. Desym-
Heck reactions are among the most important and widely
used carbopalladation reactions (1, 2). The effect of sub-
strate, catalyst, ligand, and additives has been examined,
resulting in highly selective Heck reactions. The enantio-
selective variant (3) of the Heck reaction has been success-
fully developed to the point where both tertiary and
quaternary centers can be generated in excellent enantio-
selectivity and in good to excellent yields. The application
of the asymmetric Heck reaction (AHR) has been most
widely studied in its intermolecular variant, with ees >96%
having been reported. For the intramolecular Heck reaction,
the ee values are typically around 80%, with notable excep-
tions leading to >90% ee (3).
metrization of
a symmetrical molecule to yield an
enantiomerically enriched product is certainly a topic of
great interest (8).
In this report we describe the intramolecular AHR on the
bicyclodienes generated through the DSRCM methodology
previously reported from our laboratories.
Since the initial reports in 1989 (4), many of the reported
intramolecular AHRs involve the desymmetrization of
prochiral alkene substrates (5).3 This methodology has
proven to be a powerful tool for the rapid construction of
polycyclic compounds. The carbo- and heterocycles synthe-
Results
Substrates used in our studies were conveniently prepared
by appending appropriate aryl-halide tethers to the tertiary
diallylic alcohol 1. Thus, reaction of the tertiary alcohol 1
Received 26 June 2003. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 5 March 2004.
M. Lautens2 and V. Zunic. Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George
Street, Toronto, ON M5H 3H6, Canada.
1This article is part of a Special Issue dedicated to Professor Ed Piers.
2Corresponding author (e-mail: mlautens@alchemy.chem.utoronto.ca).
3A highly enantioselective intramolecular Heck reaction with a monodentate ligand has recently been reported (ref. 5d).
Can. J. Chem. 82: 399–407 (2004)
doi: 10.1139/V03-196
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Can. J. Chem. Vol. 82, 2004
Fig. 1. Strategy for the synthesis of polycycles possessing three contiguous chiral centers.
Scheme 1. DSRCM in the synthesis of diquinane Heck reaction precursors.
with potassium hydride followed by 2-bromobenzyl bromide
or 2-iodobenzyl bromide provided the coupled products 2
and 3 in >80% yield (Scheme 1).
Ring-closing metathesis of the haloaryl tetraenes 2 and 3
with Grubbs catalyst 4 provided the desired cis-fused
bicyclo[3.3.0]octadienes 5 and 6 as the sole bicyclic prod-
ucts in good overall yields.
tertiary amine base, similar levels of enantioselectivity to
those seen under cationic conditions are obtained (Table 1,
entry 2) (12).6 The high enantiomeric excess obtained with
the triflate substrate 77 is the same as when an aryl iodide is
used in the presence of a silver salt (cf. Table 1, entries 4
and 10). Triflate substrates can be used in lieu of the halide
substrates with expensive silver salts.
Recent advances in the AHR have shown that a variety of
other ligands mediate the reaction with equal levels of effi-
ciency (3). A brief survey of other chiral ligands success-
fully used in the AHR is presented in Table 2.
Particularly noteworthy is the fact that the chiral phos-
phinooxazoline (PHOX) (13) ligand (S)-t-Bu-POX (14) does
not efficiently mediate the asymmetric Heck reaction in this
case (Table 2, entry 3). The use of tol-BINAP as ligand pro-
vides 8 with higher levels of enantioselectivity and yield
than with BINAP. The use of cationic conditions with a
more electron-rich bisphosphine will ensure a tighter bind-
ing of the bisphosphine throughout the catalytic cycle of the
reaction.
Having explored the intramolecular AHR in the desym-
metrization of bicyclo[3.3.0]octadienes, we focused our
attention on applying the same transformation to the desym-
metrization of bicyclo[4.4.0]decadienes. The synthesis of the
required aryl-halide-tethered substrates was carried out in a
similar manner to that discussed above for the preparation
of diquinane substrates (Scheme 2). The DSRCM event
With a reliable and efficient route to the desired
bicyclo[3.3.0]octadienes 5 and 6, a detailed investigation
into the AHR was then performed. Since oxidative addition
with aryl iodides is much more facile than the analogous
bromides (1), our initial investigations focused on the iodo-
Heck precursors. Pd2dba3 was used as the palladium(0)
source because of its ease of handling and its reported role
in producing reproducible results (9) in asymmetric Heck re-
actions. The range of substrates that work well with BINAP
(10) in asymmetric Heck reactions led us to initiate our stud-
ies using this ligand. The results from screening a variety of
bases and solvents are shown in Table 1.
The results presented in Table 1 show that a variety of
conditions are effective in promoting the asymmetric synthe-
sis of 84 It is generally accepted that cationic conditions,
e.g., use of silver(I) salts to sequester a halide from palla-
dium after the oxidative addition of the aryl halide, will gen-
erally lead to chiral products with higher enantiomeric ratios
than those realized under neutral conditions (3, 9, 11).5
However, under neutral conditions and in the presence of a
4 The relative stereochemistry of 8 was proven by careful analysis of various 2D NMR experiments (COSY, ROESY, HMQC). The absolute
stereochemistry of 8 has yet to be determined.
5 Cationic conditions facilitate the binding of the chiral bidentate ligand, olefin, and aryl group in the square planar Pd(II) intermediate in the
enantiodescriminating carbopalladation step.
6 Overman (see ref. 12) in his studies in the use of asymmetric Heck reactions in the synthesis of chiral oxindoles noted a similar phenome-
non. No conclusive argument was put forth in his studies, and results in our studies do not help to explain the highly effective role of ter-
tiary amine bases in asymmetric Heck reactions. See ref. 9, as well as ref. 12.
7 Substrate 7 was prepared in four steps, starting from 1 and 2-(tert-butyldimethylsilyloxy)benzylbromide. See experimental section for
details.
© 2004 NRC Canada

Lautens and Zunic
Table 1. Effects of solvents and bases on the asymmetric synthesis of 8.
401
Entry
Substrate
Pd source
Solvent
Base (2 equiv.)
Yield (%)
Enantiomeric excess (%)
1
2
5
6
6
6
6
6
6
6
6
7
Pd(OAc)2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
Et3N
43
52
60
80
37
73
77
57
60
53
93
98
83
97
97
94
99
91
63
97
Pd2dba3-CHCl3
Pd2dba3-CHCl3
Pd2dba3-CHCl3
Pd2dba3-CHCl3
Pd2dba3-CHCl3
Pd2dba3-CHCl3
Pd2dba3-CHCl3
Pd2dba3-CHCl3
Pd2dba3-CHCl3
Et3N
3
K2CO3
Ag2CO3
Ag3PO4
Ag3PO4
Ag3PO4
Ag3PO4
Ag3PO4
K2CO3
4
5
6
7
Toluene
DMA
8
9
NMP
10
CH3CN
was carried out in a highly efficient process with the
Grubbs second generation catalyst (4,5-dihydroIMES)
(PCy3)Cl2Ru=CHPh (9). The reaction was efficient with cat-
alyst loadings as low as 2 mol% (cf. 12 mol% of
[Cl2(Cy3P)2Ru=CHPh] (4)) (7) and was complete in 30 min
in refluxing dichloromethane. A 4.5:1 mixture of diastere-
omeric bicyclo[4.4.0]decadienes was obtained, favouring the
cis-fused decalin. The minor diastereomer was removed by
stirring the reaction mixture with silica gel for ~15 min at
room temperature followed by flash chromatography on sil-
ica gel.8
Application of the AHR to aryl iodide cis-12 provided
regioisomeric alkene products9 in a 1:1 ratio and a combined
60% yield (Scheme 3). This system is more complex, since
olefin isomerization is now a significant process. A β-hy-
dride addition – elimination step involving 13 with a chiral
hydridopalladium species, formed from the Heck reaction of
cis-12, leads to the formation of 14. Of note, the two regio-
isomeric products have different ee values (15).
Table 2. Effect of ligand in the asymmetric synthesis of 8.
Entry
Ligand
Yield (%)
ee (%)
1
2
3
(S)-BINAP
(S)-p-tol-BINAP
57
87
18
91
99
29
(S)-t-Bu-Pox
Studies on the bicyclo[3.3.0]octadiene series revealed p-
tol-BINAP to be the ligand that delivered products with the
highest enantiomeric excess. Having obtained alkenes 13
and 14 in modest enantioselectivity, a brief study of chiral
ligands was carried out to determine whether the alkene
isomerization process could be controlled (Table 3).
Enantiomeric excesses in this series are lower, perhaps be-
cause of the elevated temperature used (100 °C versus 80 °C)
for the desymmetrization of the bicyclo[4.4.0]decadiene 12.
The higher temperatures were required because of the slug-
gish nature of the Pd-PHOX catalysts with this substrate.10
p-tol-BINAP is clearly the ligand that affords products with
the highest enantiomeric ratios. Unlike palladium catalysts
derived from BINAP, virtually no C=C double bond migra-
tion has been reported for Pd-PHOX catalysts. Yet, in the
present system, the use of the (S)-t-Bu-POX and (S)-i-Pr-(S)-
DIPOF (16) ligands resulted in a 1:2 ratio of the
regioisomers 13 and 14, respectively, with lower levels of
enantioselectivity than seen with the BINAP catalysts (Ta-
ble 3, entries 3 and 4).
The use of silver salts in the reactions of 12 did not seem
to lead to any bias in the formation of the regioisomeric
alkene products. However, the utilization of Tl2CO3 as base
provided a 1:5.6 ratio of 13:14 (Scheme 4) with similar
yields and levels of enantiomeric excesses as those seen with
silver salts.
8 Generally, the isolation of the bicyclodienes mentioned in this report required triethylamine-neutralized silica gel in the purification step.
9 The relative stereochemistry of 13 and 14 are assumed to be as depicted, since 2D-NMR experiments (ROESY, NOESY) were unsuccessful
at elucidating the relative stereochemistry assignment of 13 and 14. To our knowledge, the intramolecular Heck reaction is a facile means to
access cis-fused bicycles (see refs. 1–3). The absolute stereochemistry of 13 and 14 have yet to be determined.
10For the sake of consistency, the same temperature was used throughout the series in this ligand survey.
© 2004 NRC Canada

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Can. J. Chem. Vol. 82, 2004
Scheme 2. Synthesis of bicyclo[4.4.0]decadienes for intramolecular Heck reactions. Conditions: (a) KH, 2-iodobenzyl bromide, THF,
23 °C, 12 h, 85%; (b) (4,5-dihydroIMES) (PCy3)Cl2Ru=CHPh (9) (2 mol%), CH2Cl2, reflux, 30 min, 4.5:1 (cis-12:trans-12), 100%.
Scheme 3. Desymmetrization of bicyclo[4.4.0]decadienes.
The exploration of the analogous aryl triflate substrate
same spectrometer with CDCl3 as reference standard (δ =
tethered to the bicyclo[4.4.0]decadienes was also undertaken
77.16 ppm). IR spectra were obtained using a Nicolet DX
in attempts to increase the enantiomeric excesses of the
FT-IR spectrometer as a neat film between KBr plates. High
resolution mass spectra were obtained from a VG 70-250S
(double focusing) mass spectrometer at 70 eV.
High performance liquid chromatography (HPLC) was
polycyclic products.11 Subjecting triflate cis-15 under AHR
conditions provided the polycyclic products 13 and 14 in
~1:1 ratio but with significantly higher levels of asymmetric
induction (Scheme 5). Attempts are now being directed at
performed on an Agilent 1100 Series HPLC using a
expanding the scope of this sequential olefin metathesis –
CHIRACEL OD column. Column chromatography was per-
intramolecular AHR sequence and highlighting the useful-
formed as flash chromatography, as reported by Still et al.
ness of the polycycles through further chemical transforma-
(17), using (200–400 mesh) Merck grade silica gel.
tions.
Toluene and THF were distilled from sodium–benzophe-
none. DMF was dried by prolonged standing over molecular
sieves. CH2Cl2 was distilled from CaH2.
Summary
Grubbs catalyst (4) was prepared according to the litera-
ture procedure (18) and triturated for 12–18 h in a 1:1
mixture of acetone and methanol. The absence of free tri-
cyclohexyl phosphine and tricyclohexyl phosphine oxide
was confirmed by 31P NMR and was crucial for the double
metathesis reactions to proceed. (DihydroIMES)(PCy3)-
Cl2Ru=CHPh (9) was used as received from Strem. The
following compounds were prepared as reported in the
literature: 4-Allyl-3-vinyl-hepta-1,5-dien-3-ol (1) (7), 3-
cyclohept-4-enyl-penta-1,4-dien-3-ol (10) (7), and 2-(tert-
butyldimethylsilyloxy)benzyl bromide (19).
The stereoselective synthesis of tetracycles is made possi-
ble using a DSRCM and asymmetric Heck strategy. Cationic
conditions in the asymmetric Heck reaction gave high
enantioselectivities in the desymmetrization process in
which three contiguous chiral centers are established with
high enantioselectivities in a single step.
Experimental
The following experimental details apply to all subsequent
experiments.
All reactions were carried out under an atmosphere of dry
argon or nitrogen in oven- (overnight at 90 °C and then
cooled under a stream of Ar or N2) or flame-dried glassware.
Solvents and solutions were transferred with syringes and
cannulae, using standard inert atmosphere techniques.
1H NMR spectra were recorded at 400 MHz, using a
Varian XL400 spectrometer with CDCl3 and TMS as refer-
ence standards (δ = 0.00 parts per million (ppm) or
7.26 ppm). 13C NMR were recorded at 100 MHz using the
1-(2-Allyl-1,1-divinyl-pent-4-enyloxymethyl)-2-bromo-
benzene (2)
KH (35% dispersion in mineral oil, 1.0 g, 4 equiv.) was
washed three times with pentane, dried under a stream of ar-
gon, and suspended in THF (10 mL). A solution of alcohol 1
in THF (5 mL) was added dropwise via cannula. After
15 min at room temperature, 2-bromobenzyl bromide was
added all at once, and the resulting solution was stirred at
11Substrate cis-15 was prepared in four steps, starting from 10 and 2-(tert-butyldimethylsilyloxy)benzylbromide. See experimental section for
details.
© 2004 NRC Canada

Lautens and Zunic
Table 3. Effect of ligands in the asymmetric synthesis of 13 and 14.
403
Entry
Ligand
13:14a
13 ee (%)
14 ee (%)
Combined yield (%)b
1
2
3
(S)-BINAP
(S)-p-tol-BINAP
1:1.1
1:1.5
~1:2
11
50
37
30
35
—
50
44
40
c
(S)-t-Bu-POX
4
1:2.4
19
1.6
53
(S)-i-Pr-(S)-DIPOF
1
aRatio was determined by integration of the singlet at 3.30 ppm (13) and the triplet at 2.83 ppm (14) in the H NMR of
the crude reaction mixture.
bCombined isolated yield.
cUndetermined.
room temperature for 2 h. The mixture was quenched by
dropwise addition of water (25 mL) and then extracted with
ether (3 × 30 mL). The organic layers were dried over
Na2SO4, filtered, and concentrated. Flash chromatography
(100% hexanes) on triethylamine-washed silica gel provided
the product as a colourless oil (740 mg, 95%). IR (neat):
3074(m), 2978(m), 2922(m), 1914(w), 1869(w), 1831(w),
1638(m), 1439(m), 1269(w), 1091(s), 931(s), 910(s), 748(s),
65.13, 43.10, 40.79. HR-MS calcd. for C15H15OBr ([M]+):
290.0306; found: 290.0301.
1-(2-Allyl-1,1-divinyl-pent-4-enyloxymethyl)-2-iodobenzene
(3)
Following the the benzylation procedure to make 2, alco-
hol 1 (1.15 g, 6.4 mmol) was reacted with 2-iodobenzyl-
bromide (2.09 g, 7.06 mmol) to yield the product (2.08 g,
83%) as a colourless oil. IR (neat): 3073(m), 2911(m),
1952(w), 1908(w), 1864(w), 1627(s), 1440(s), 1085(s),
1
667(w). H NMR (400 MHz, CDCl3) δ: 7.62 (1H, d, J =
8 Hz), 7.48 (1H, d, J = 8 Hz), 7.31 (1H, t, J = 7.6 Hz), 7.12–
7.08 (1H, m), 5.93–5.86 (2H, m), 5.88–5.80 (2H, m), 5.38
(2H, dd, J = 11.2 Hz, 0.8 Hz), 5.31 (2H, dd, J = 17.6 Hz,
0.8 Hz), 5.01–4.93 (4H, m), 4.40 (2H, s), 2.48–2.42 (2H, m),
2.02–1.94 (2H, m), 1.84–1.90 (1H, m). 13C NMR (100 MHz,
CDCl3) δ: 139.22, 138.78, 137.67, 132.22, 128.44, 128.27,
127.39, 121.89, 118.04, 115.41, 83.98, 64.97, 48.28, 34.56.
HR-MS calcd. for C19H23OBr ([M]+): 345.2788; found:
345.2791.
1
1012(s), 906(s), 752(s). H NMR (400 MHz, CDCl3) δ: 7.77
(1H, d, J = 7.6 Hz), 7.57 (1H, d, J = 7.6 Hz), 7.36 (1H, t, J =
8 Hz), 6.96 (1H, t, J = 8 Hz), 5.90 (2H, dd, J = 17.6 Hz,
10.8 Hz), 5.89–5.80 (2H, m), 5.39 (2H, dd, J = 11.2 Hz,
1.6 Hz), 5.31 (2H, dd, J = 17.6 Hz, 1.6 Hz), 5.02–4.94
(4H, m), 4.29 (2H, s), 2.49–2.43 (2H, m), 2.02–1.94
(2H, m), 1.90–1.84 (1H, m). 13C NMR (100 MHz, CDCl3) δ:
141.95, 138.84, 138.78, 137.63, 128.61, 128.23, 118.08,
115.43, 96.91, 83.99, 69.69, 48.26, 34.56. HR-MS calcd. for
C19H23OI ([M]+): 393.0715; found: 393.0703.
3a-(2-Bromobenzyloxy)-1,3a,6,6a-tetrahydropentalene (5)
To a solution of 2 (930 mg, 2.67 mmol) in 50 mL of di-
chloromethane was added Grubbs catalyst 4 all at once.
The reaction was stirred under a closed system for 20 h at
room temperature. The solvent was removed in vacuo, and
the residue was purified by flash chromatography (100%
hexanes → 5% Et2O–hexanes) on triethylamine-washed sil-
ica gel to provide the product (530 mg, 70%) as a colourless
oil. IR (neat): 3047(s), 2918(s), 2851(s), 1619(w), 1467(m),
1350(s), 1218(m), 1097(m), 1070(m), 989(m), 750(s). 1H
NMR (400 MHz, CDCl3) δ: 7.47–7.53 (2H, m), 7.30–7.24
(1H, m), 7.11–7.07 (1H, m), 5.94–5.91 (2H, m), 5.84–5.82
(2H, m), 4.46 (2H, s), 2.90–2.84 (3H, m), 2.14–2.08
(2H, m). 13C NMR (100 MHz, CDCl3) δ: 138.97, 134.67,
132.38, 132.35, 129.28, 128.58, 127.43, 122.52, 106.00,
3a-(2-Iodobenzyloxy)-1,3a,6,6a-tetrahydro-pentalene (6)
Following the procedure for RCM of tetraene 2,
iodobenzyl ether 3 (2.00 g, 5.08 mmol) was reacted with
Grubbs catalyst 4 (250 mg, 6 mol%) in CH2Cl2 (50 mL) to
provide the product (1.18 g, 70%) as a colourless oil after
flash chromatography (5% Et2O–hexanes) on triethylamine-
washed silica gel. IR (neat): 3060(s), 2912(s), 1444(m),
1350(s), 1215(m), 1097(m), 1077(s), 1009(s), 942(w),
1
747(s). H NMR (400 MHz, CDCl3) δ: 7.87–7.76 (1H, m),
7.49–7.47 (1H, m), 7.34–7.30 (1H, m), 6.96–6.92 (1H, m),
5.94–5.92 (2H, m), 5.84 (2H, dt, J = 6 Hz, 1.6 Hz), 4.38
(2H, s), 2.91–2.84 (3H, m), 2.07–2.15 (2H, m). 13C NMR
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Can. J. Chem. Vol. 82, 2004
Scheme 4. Regiocontrol in the asymmetric Heck reaction using Tl salts.
Scheme 5. Asymmetric synthesis of 13 and 14 under cationic conditions.
(100 MHz, CDCl3) δ: 141.80, 139.01, 134.71, 132.41,
128.99, 128.90, 128.30, 106.00, 97.70, 69.81, 43.21, 40.80.
HR-MS calcd. for C15H13OI ([M]+): 338.0149; found:
338.0167.
room temperature, and the reaction mixture was stirred at
room temperature for 30 min. The reaction was diluted with
water (10 mL) and extracted with ether (3 × 10 mL). The
combined organic layers were dried over Na2SO4, filtered,
and concentrated. The residue (2-(2-allyl-1,1-divinyl-pent-4-
enyloxymethyl)-phenol) was then used in the next reaction
without further purification. IR (neat): 3386(s), 3075(m),
2923(m), 1826(w), 1638(m), 1491(m), 1241(s), 1026(m),
Preparation of trifluoromethanesulfonic acid 2-(6,6a-
dihydro-1H-pentalen-3a-yloxymethyl)-phenyl ester (7)
KH (35% dispersion in mineral oil, 1.0 g, 3 equiv.) was
washed three times with pentane, dried under a stream of ar-
gon, and suspended in 10 mL of THF. Alcohol 1 in 5 mL of
THF was added via cannula. The solution was heated to re-
flux for 10 min, cooled to room temperature, and a solution
of 2-(tert-butyldimethylsilyloxy)benzyl bromide (19) in
5 mL of THF was added via cannula. The solution was
stirred at reflux for 3 h, cooled to room temperature,
quenched by dropwise addition of water (25 mL), extracted
with ether (3 × 30 mL), dried over Na2SO4, filtered, and
concentrated. Flash chromatography (100% hexanes) on
triethylamine-washed silica gel provided 1-(2-allyl-1,1-
divinyl-pent-4-enyloxymethyl)-2-(tert-butyldimethylsiloxy)-
benzene (939 mg, 85%) as a colourless oil. IR (neat):
3088(s), 2919(s), 2855(s), 1634(m), 1579(m), 1491(s),
1250(s), 1070(m), 913(s), 832(s), 730(m). 1H NMR
(400 MHz, CDCl3) δ: 7.57–7.55 (1H, m), 7.11 (1H, td, J =
7.6 Hz, 0.8 Hz), 6.98 (1H, td, J = 7.6 Hz, 0.8 Hz), 6.74 (1H,
dd, J = 8 Hz, 0.8 Hz), 5.92–5.82 (4H, m), 5.35 (2H, dd, J =
10.8 Hz, 1.6 Hz), 5.29 (2H, dd, J = 17.8 Hz, 1.6 Hz), 5.02–
4.94 (4H, m), 4.40 (2H, s), 2.51–2.44 (2H, m), 2.01–1.93
(2H, m), 0.97 (9H, s), 0.18 (6H, s). 13C NMR (100 MHz,
CDCl3) δ: 152.21, 138.96, 137.91, 131.09, 131.46, 127.46,
127.25, 121.20, 118.03, 117.72, 115.28, 83.69, 61.07, 48.21,
34.57, 18.30, –4.11. HR-MS calcd. for C21H30O2Si ([M –
C4H9]+): 341.1936; found: 341.1934.
1
912(s), 753(s). H NMR (400 MHz, CDCl3) δ: 7.75 (1H,
br s), 7.18–7.14 (1H, m), 6.93–6.78 (3H, m), 5.91–5.75
(4H, m), 5.44–5.31 (4H, m), 5.02–4.95 (4H, m), 4.55
(2H, s), 2.39–2.32 (2H, m), 1.99–1.91 (2H, m), 1.87–1.82
(1H, m). 13C NMR (100 MHz, CDCl3) δ: 156.33, 138.01,
136.83, 128.98, 127.70, 123.56, 119.82, 118.77, 116.68,
115.92, 85.33, 65.69, 47.79, 34.42. HR-MS calcd. for
C19H24O2 ([M]+): 284.1776; found: 284.1780.
In a 10 mL round-bottom flask was added 2-(2-allyl-1,1-
divinyl-pent-4-enyloxymethyl)-phenol (215 mg, 0.75 mmol),
CH2Cl2 (5 mL), and Et3N (440 µL, 4 equiv.). The solution
was then cooled to –78 °C and Tf2O (254 µL, 2 equiv.) was
added dropwise via syringe. The reaction mixture was
stirred at –78 °C for 15 min, at which point water (5 mL)
was added. The flask was warmed to room temperature and
extracted with ether (3 × 15 mL), and the organic extracts
were dried over Na2SO4, filtered, and concentrated. Flash
chromatography (2% Et2O–hexanes) on triethylamine-
washed silica gel provided trifluoromethanesulfonic acid 2-
(2-allyl-1,1-divinyl-pent-4-enyloxy methyl)-phenyl ester as a
colourless oil (240 mg, 81%). IR (neat): 3074(s), 2903(m),
1918(w), 1863(w), 1634(m), 1487(m), 1413(s), 1210(s),
1
1099(s), 1066(s), 996(s), 896(s), 764(s), 605(m). H NMR
(400 MHz, CDCl3) δ: 7.68 (1H, dd, J = 7.6 Hz, 0.8 Hz), 7.38
(1H, td, J = 7.6 Hz, 1.2 Hz), 7.32 (1H, td, J = 8.2 Hz, 2 Hz),
7.25–7.23 (1H, m), 5.87 (2H, dd, J = 17.6 Hz, 11.2 Hz),
5.86–5.78 (2H, m), 5.40 (2H, dd, J = 11.2 Hz, 1.2 Hz), 5.30
(2H, dd, J = 17.6 Hz, 1.6 Hz), 5.00–4.93 (4H, m), 4.46
(2H, s), 2.45–2.39 (2H, m), 1.99–1.92 (2H, m), 1.89–183
In a 10 mL round-bottom flask was added 1-(2-allyl-1,1-
divinyl-pent-4-enyloxymethyl)-2-(tert-butyldimethylsiloxy)-
benzene (300 mg, 0.75 mmol) and 3 mL of THF. To this so-
lution was added TBAF (235 mg, 0.90 mmol) all at once at
© 2004 NRC Canada

Lautens and Zunic
405
(1H, m). 13C NMR (100 MHz, CDCl3) δ: 146.89, 138.66,
137.32, 132.97, 129.77, 128.70, 128.47, 121.00, 120.31,
118.72 (q, J = 319.2 Hz), 118.33, 115.43, 84.27, 59.77,
48.24, 34.48. HR-MS calcd. for C18H20O4SF3 ([M –
C2H3]+): 389.1023; found: 389.1034.
520 mg (65%) of the cis-bicyclo[4.4.0]decadiene as a clear
oil. IR (neat): 3011(m), 2922(s), 1952(w), 1911(w),
1826(w), 1871(w), 1650(w), 1562(m), 1434(s), 1371(m),
1265(m), 1202(m), 1110(m), 1066(s), 945(m), 747(s),
1
647(m). H NMR (400 MHz, CDCl3) δ: 7.76 (1H, d, J =
8 Hz), 7.52 (1H, d, J = 8 Hz), 7.32 (1H, t, J = 7.6 Hz), 6.93
(1H, t, J = 7.6 Hz), 5.89 (2H, dt, J = 9,9 Hz, 3.6 Hz), 5.63
(2H, dt, J = 9.9 Hz, 2.1 Hz), 4.42 (2H, s), 2.23–2.17
(1H, m), 2.14–2.01 (4H, m), 1.90–1.83 (2H, m), 1.51–1.59
(2H, m). 13C NMR (100 MHz, CDCl3) δ: 142.09, 138.92,
130.29, 129.93, 129.07, 128.81, 128.31, 97.70, 74.68, 68.79,
34.58, 24.51, 23.46. HR-MS calcd. for C17H19OI ([M]+):
366.0480; found: 366.0483.
In a 25 mL round-bottom flask was added trifluoro-
methanesulfonic acid 2-(2-allyl-1,1-divinyl-pent-4-enyloxy
methyl)-phenyl ester (230 mg, 0.58 mmol) and 10 mL of
CH2Cl2. Catalyst 4 (24 mg, 5 mol%) was added, and the so-
lution was stirred under a closed atmosphere at room tem-
perature for 12 h. The solvent was removed on the rotary
evaporator to provide the crude product, which was purified
by flash chromatography (100% hexanes → 5% Et2O–hex-
anes) on triethylamine-washed silica gel. The yield of the ti-
tle compound was 150 mg (75%). IR (neat): 3053(m),
2923(m), 2849(m), 1968(w), 1487(m), 1419(s), 1350(m),
1214(s), 1142(s), 1059(m), 992(m), 895(s), 764(m), 707(m),
Preparation of triflouromethanesulfonic acid 2-(1,7,8,8a-
tetrahydro-2H-naphthalen-4a-yloxymethyl)-phenol ester
(15)
1
597(m). H NMR (400 MHz, CDCl3) δ: 7.61–7.58 (m, 1H),
KH (35% dispersion in mineral oil, 1.0 g, 3 equiv.) was
washed three times with pentane, dried under a stream of ar-
gon, and suspended in 10 mL of THF. Alcohol 10 in 5 mL
of THF was added via cannula. The solution was heated to
reflux for 10 min, cooled to room temperature, and a solu-
tion of 2-(tert-butyldimethylsilyloxy)benzyl bromide (19) in
5 mL of THF was added via cannula. The solution was
stirred at reflux for 3 h, cooled to room temperature,
quenched by dropwise addition of water (25 mL), extracted
with ether (3 × 30 mL), dried over Na2SO4, filtered, and
concentrated. Flash chromatography (100% hexanes) on
triethylamine-washed silica gel provided tert-butyl[2-(1-
cyclohept-4-enyl-1-vinyl-allyloxymethyl)-phenoxy]-
dimethylsilane (939 mg, 85%) as a colourless oil. IR (neat):
2929(s), 1858(w), 1602(m), 1584(m), 1489(s), 1378(m),
7.38–7.31 (m, 2H), 7.25–7.23 (m, 1H), 5.93 (2H, dt, J =
5.6 Hz, 2 Hz), 5.81 (2H, dt, J = 5.6 Hz, 2 Hz), 4.50 (2H, s),
2.92–2.83 (3H, m), 2.15–2.08 (2H, m). 13C NMR (100 MHz,
CDCl3) δ: 147.37, 134.92, 132.74, 132.13, 130.13, 130.60,
129.10, 128.49, 121.11, 118.72 (J = 318.4 Hz), 106.30,
59.98, 42.99, 40.84. HR-MS calcd. for C16H15O4SF3 ([M]+):
360.3530; found: 360.3538.
5-[1-(2-Iodobenzyloxy)-1-vinyl-allyl]-cycloheptene (11)
Following the benzylation procedure for 2 and 3, alcohol
10 (1.15 g, 6.4 mmol) was reacted with 2-iodobenzyl bro-
mide (2.09 g, 7.06 mmol) to yield the product (2.08 g, 83%)
as a colourless oil. IR (neat): 3014(m), 2919(s), 1948(w),
1912(w), 1864(w), 1791(w), 1641(w), 1436(s), 1202(m),
1
1
1107(s), 928(s), 748(s), 748(s), 690(s). H NMR (400 MHz,
1252(s), 1114(m), 924(s), 838(s), 758(m), 692(m). H NMR
CDCl3) δ: 7.78–7.76 (1H, m), 7.58–7.56 (1H, m), 7.38–7.32
(1H, m), 6.97–6.93 (1H, m), 5.87 (2H, dd, J = 17.6 Hz,
11.2 Hz), 5.79–5.77 (2H, m), 5.36 (2H, dd, J = 11.2 Hz,
1.6 Hz), 5.82 (2H, dd, J = 17.8 Hz, 1.6 Hz), 4.29 (2H, s),
2.32–2.25 (2H, m), 2.07–1.98 (4H, m), 1.82 (1H, tt, J =
10.8 Hz, 2.4 Hz), 1.71–1.04 (2H, m). 13C NMR (100 MHz,
CDCl3) δ: 142.09, 138.83, 137.88, 132.04, 128.59, 128.23,
128.18, 117.74, 96.97, 83.95, 69.56, 28.18, 28.15. HR-MS
calcd. for C19H23OI ([M]+): 394.0792; found: 394.0793.
(400 MHz, CDCl3) δ: 7.56–7.54 (1H, m), 7.13–7.09 (1H, m),
7.00–6.96 (1H, m), 6.75–6.73 (1H, m), 5.84 (2H, dd, J =
17.6 Hz, 11.2 Hz), 5.79–5.77 (2H, m), 5.33 (2H, dd, J =
10.8 Hz, 1.6 Hz), 5.26 (2H, dd, J = 17.6 Hz, 1.6 Hz), 4.39
(2H, s), 2.32–2.27 (2H, m), 2.08–1.97 (4H, m), 1.80 (1H, tt,
J = 10.8 Hz, 2.4 Hz), 1.12–1.04 (2H, m), 0.97 (9H, s), 0.18
(6H, s). 13C NMR (100 MHz, CDCl3) δ: 152.29, 138.18,
132.12, 131.23, 127.48, 127.27, 121.23, 118.09, 117.41,
83.65, 60.92, 52.99, 28.19, 25.85, 18.31, –4.10. HR-MS
calcd. for C25H38O2Si ([M]+): 396.6448; found: 396.6451.
In a 10 mL round-bottom flask was added tert-butyl[2-(1-
cyclohept-4-enyl-1-vinyl-allyloxymethyl)-phenoxy]-dimethyl-
silane (300 mg, 0.75 mmol) and 3 mL of THF. To this solu-
tion was added TBAF all at once at room temperature, and
the reaction mixture was stirred at room temperature for
10 min. The reaction was diluted with water (10 mL) and
extracted with ether (3 × 10 mL). The combined organic lay-
ers were dried over Na2SO4, filtered, and concentrated. The
residue [2-(1-cyclohept-4-enyl-1-vinyl-allyloxymethyl)phe-
nol] was then used in the next reaction without further purifi-
cation. IR (neat): 3362(s), 3017(m), 2930(m), 1930(w),
1861(w), 1590(m), 1244(s), 1024(s), 845(w), 754(s),
4a-(2-Iodobenzyloxy)-1,2,4a,7,8,8a-hexahydro-napthalene
(12)
In a 100 mL round-bottom flask was added 5-[1-(2-
iodobenzyloxy)-1-vinyl-allyl]-cycloheptene
2.15 mmol) and 50 mL of CH2Cl2 under nitrogen. To this
solution was added ruthenium catalyst (35 mg,
(850
mg,
9
0.04 mmol), and the solution was refluxed for 1 h, at which
time all of the starting material had been consumed. 1H
NMR analysis showed a 4.5:1 mixture of diastereomers (in-
tegration of signals at 5.89 ppm (multiplet corresponding to
all of the olefinic protons of the trans decalin plus half of
the olefin protons of the cis decalin product) and 5.63 ppm
(half of the olefin protons of the cis decalin)). Silica gel
(~200 mg) was added, and the mixture was stirred at room
temperature for 15 min. The solution was filtered, and the
silica gel was washed with a copious amount of CH2Cl2. The
solvent was removed in vacuo, and the residue was purified
by flash chromatography (2% Et2O–hexanes) to provide
1
692(w). H NMR (400 MHz, CDCl3) δ: 8.01 (1H, br s),
7.20–7.16 (1H, m), 6.95–6.80 (3H, m), 5.85 (2H, dd, J =
17.8 Hz, 11.2 Hz), 5.77–5.75 (2H, m), 5.42 (2H, d, J =
10.8 Hz), 5.32 (2H, d, J = 17.6 Hz), 4.59 (2H, s), 2.32–2.26
(2H, m), 2.03–1.92 (4H, m), 1.82 (1H, tt, J = 10.4 Hz,
2.4 Hz), 1.15–1.06 (2H, m). 13C NMR (100 MHz, CDCl3) δ:
© 2004 NRC Canada

406
Can. J. Chem. Vol. 82, 2004
156.37, 136.92, 131.74, 128.92, 127.60, 123.37, 119.80,
118.60, 116.64, 85.16, 65.74, 52.11, 28.07, 27.98. HR-MS
calcd. for C19H24O2 ([M]+): 284.1776; found: 284.1778.
In a 10 mL round-bottom flask was added 2-(1-cyclohept-
4-enyl-1-vinyl-allyloxymethyl)-phenol (215 mg, 0.75 mmol),
CH2Cl2 (5 mL), and Et3N (440 µL, 4 equiv.). The solution
was then cooled to –78 °C and Tf2O (254 µL, 2 equiv.) was
added dropwise via syringe. The reaction mixture was
stirred at –78 °C for 15 min, at which point water (5 mL)
was added. The flask was warmed to room temperature and
extracted with ether (3 × 15 mL), and the organic extracts
were dried over Na2SO4, filtered, and concentrated. Flash
chromatography (2% Et2O–hexanes) on treithylamine-
washed silica gel provided triflouromethanesulfonic acid 2-
(1-cyclohept-4-enyl-1-vinyl-allyloxymethyl)-phenyl ester as
a colourless oil (240 mg, 81%). IR (neat): 3018(w),
2928(w), 1866(w), 1422(s), 1214(s), 1143(s), 1093(m),
1003(w), 894(m), 767(m), 628(w). 1H NMR (400 MHz,
CDCl3) δ: 7.68–7.66 (1H, m), 7.39–7.36 (1H, m), 7.33–7.29
(1H, m), 7.24–7.22 (1H, m), 5.83 (2H, dd, J = 17.8 Hz,
10.8 Hz), 5.87–5.75 (2H, m), 5.36–5.39 (2H, m), 5.29–5.24
(2H, m), 4.46 (2H, s), 2.30–2.23 (2H, m), 2.03–1.96
(4H, m), 1.83–1.77 (1H, m), 1.10–1.02 (2H, m). 13C NMR
(100 MHz, CDCl3) δ: 147.00, 137.60, 133.10, 131.98,
131.98, 129.78, 128.69, 128.47, 120.99, 118.72 (q, J =
319.2 Hz), 117.96, 84.22, 59.71, 52.86, 28.11. HR-MS
calcd. for C20H23O4SF3 ([M]+): 416.1269; found: 416.1280.
In a 100 mL round-bottom flask was added triflourometh-
anesulfonic acid 2-(1-cyclohept-4-enyl-1-vinyl-allyloxymethyl)-
phenyl ester (850 mg, 2.15 mmol) and 50 mL of CH2Cl2 un-
der nitrogen. To this solution was added ruthenium catalyst
9 (35 mg, 0.04 mmol), and the solution was refluxed for 1 h,
at which time all of the starting material had been con-
sumed. 1H NMR analysis showed a 4.5:1 mixture of
diastereomers (integration of signals at 5.90 ppm (multiplet
corresponding to all of the olefinic protons of the trans
decalin plus half of the olefin protons of the cis decalin
product) and 5.59 ppm (half of the olefin protons of the cis
decalin)). Silica gel (~200 mg) was added, and the mixture
was stirred at room temperature for 15 min. The solution
was filtered, and the silica gel was washed with a copious
amount of CH2Cl2. The solvent was removed in vacuo, and
the residue was purified by flash chromatography (2% Et2O–
hexanes) to provide 520 mg (65%) of the cis-bicyclo-
[4.4.0]decadiene (15) as a clear oil. IR (neat): 3029(m),
2941(s), 1487(m), 1454(m), 1418(s), 1330(w), 1209(s),
1143(s), 1056(m), 895(s), 763(m), 734(m), 602(m). 1H
NMR (400 MHz, CDCl3) δ: 7.65–7.63 (1H, m), 7.37–7.22
(3H, m), 5.90 (2H, dt, J = 10.4 Hz, 3.6 Hz), 5.59 (2H, dt, J =
9.6 Hz, 2 Hz), 4.56 (2H, s), 2.20–2.00 (5H, m), 1.87–1.79
(2H, m), 1.50–1.59 (2H, m). 13C NMR (100 MHz, CDCl3) δ:
147.13, 133.09, 130.60, 130.50, 129.59, 128.86, 128.48,
120.95, 118.72 (q, J = 319.2 Hz), 74.97, 58.62, 34.44, 24.39,
23.40. HR-MS calcd. for C18H19O4SF3 ([M]+): 388.0956;
found: 388.0962.
(74 µL, 0.513 mmol), and 2 mL of CH3CN under an argon
flush. The mixture was heated to 70 °C for 3 h and then the
aryl halide (0.342 mmol) in 1 mL of CH3CN was added via
cannula. The reaction was stirred at 70 °C for 16 h. The re-
action was cooled to room temperature, diluted with water
(5 mL), and extracted with ether (3 × 10 mL). The organic
layers were combined, dried over Na2SO4, filtered, and con-
centrated. Flash chromatography (2.5% Et2O–hexanes → 5%
Et2O–hexanes) provided the product as an oil.
General procedure for the asymmetric Heck reaction
using Pd2dba3
In a 10 mL round-bottom flask equipped with a stir bar
and reflux condenser was added Pd2dba3 (8.15 mg,
0.0089 mmol), (R)-tol-BINAP (12.19 mg, 0.01958 mmol),
and base (0.356 mmol) in solvent (1 mL) under an argon at-
mosphere. The solution was stirred at room temperature for
40 min, and then a solution of the aryl halide (0.178 mmol)
in 1.5 mL of solvent was added via cannula under argon.
The reaction was heated to 80 °C and stirred at this tempera-
ture for 36 h. The flask was cooled to room temperature, di-
luted with ether (20 mL), and washed with saturated
aqueous NaHCO3 (7 mL). The aqueous layer was further ex-
tracted with Et2O (2 × 10 mL), and the combined organic
extracts were washed with brine (7 mL) and dried over
Na2SO4. Removal of the organic solvent followed by flash
chromatography (5%–10% Et2O–hexanes) provided the
product as a colourless oil.
4b,6a,7,11-Tetrahydro-10-oxa-pentaleno[1,6a-a]naphthalene
(8)
Following the general procedure for the asymmetric Heck
reaction, the title compound was obtained as a colorless oil,
which darkens upon storage at room temperature for pro-
longed time. The enantiomeric excess of the cyclized prod-
uct was determined by HPLC analysis, as follows:
CHIRACEL OD, 10% i-PrOH–hexanes, retention times for
the enantiomers = 10.9 min, 11.5 min. (VO = 0.5 ml/min,
23 °C, UV monitor: 254 nm.) [α]2D5 = +124.7 (c = 1.0,
1
CHCl3) (99% ee). H NMR (400 MHz, CDCl3) δ: 7.23 (1H,
d, J = 7.2 Hz), 7.18 (1H, d, J = 7.2 Hz), 7.13 (1H, d, J =
7.2 Hz), 7.08 (1H, d, J = 7.2 Hz), 5.96 (1H, dt, J = 5.6 Hz,
2 Hz), 5.83 (1H, dt, J = 5.6 Hz, 2.8 Hz), 5.72 (1H, dt, J =
6.4 Hz, 2 Hz), 5.66 (1H, dt, J = 6 Hz, 1.6 Hz), 4.70 (1H, d,
J = 14 Hz), 4.60 (1H, d, J = 14 Hz), 3.83 (1H, d, J = 2 Hz),
3.48 (1H, dt, J = 8.8 Hz, 2 Hz), 2.83 (1H, ddt, J = 17.2 Hz,
8.8 Hz, 2 Hz), 2.16 (1H, dd, J = 17.2 Hz, 2 Hz). 13C NMR
(100 MHz, CDCl3) δ: 136.10, 135.13, 134.36, 134.14,
133.50, 132.65, 128.06, 127.58, 125.77, 125.13, 97.42,
64.18, 50.46, 50.31, 36.99. HR-MS calcd. for C15H13O
([M]+): 210.1042; found: 210.1044.
4b,7,7a,8,9,13-Hexahydrodibenzo[c,i]chromene (13) and
4b,5,7a,8,9,13-hexahydrodibenzo[c,i]chromene (14)
Following the general procedure for the asymmetric Heck
reaction, the title compounds were obtained as colorless oils
after flash chromatography (2% Et2O–hexanes → 5% Et2O–
hexanes). Enantiomeric excesses of the cyclized products
were determined by HPLC analysis, as follows: CHIRACEL
OD, 10% i-PrOH–hexanes, retention times for the enantio-
mers: 13 = 4.02 min, 4.55 min; 14 = 4.43 min, 5.60 min.
General procedure for the asymmetric Heck reaction
using Pd(OAc)2
In a 10 mL round-bottom flask equipped with a stir bar
and reflux condenser was added Pd(OAc)2 (11.5 mg,
0.0513 mmol), (R)-BINAP (63.88 mg, 0.1025 mmol), Et3N
© 2004 NRC Canada

Lautens and Zunic
407
(VO = 1 ml/min, 23 °C, UV monitor: 220 nm.) 13 = [α]D25
=
Edited by L.S. Liebeskind. JAI, Greenwich. 1996. pp. 119–
151; (c) M. Shibasaki, C.J.D. Boden, and A. Kojima. Tetrahe-
dron, 53, 7371 (1997).
–101.2 (c = 0.90, CHCl3) (82% ee, using (S)-tol-BINAP);
14 = [α]2D5 = –88.9 (c = 0.85, CHCl3) (66% ee, using (S)-tol-
BINAP).
4. (a) Y. Sato, M. Sodeoka, and M. Shibasaki. J. Org. Chem. 54,
4738 (1989); (b) N.E. Carpenter, D.J. Kucera, and L.E. Over-
man. J. Org. Chem. 54, 5846 (1989).
5. For example, see: (a) K. Kondo, M. Sodeoka, M. Mori, and M.
Shibasaki. Tetrahedron Lett. 34, 4219 (1993); (b) Y. Sato, S.
Watanabe, and M. Shibasaki. Tetrahedron Lett. 35, 2589
(1992); (c) Y. Sato, T. Honda, and M. Shibisaki. Tetrahedron
Lett. 33, 2593 (1992); (d) R. Imbos, A. Minnaard, and B.L.
Feringa. J. Am. Chem. Soc. 124, 184 (2002).
6. (a) Y. Sato, M. Mori, and M. Shibasaki. Tetrahedron Asymme-
try, 6, 757 (1995); (b) K. Kagechika and M. Shibisaki. J. Org.
Chem. 56, 4093 (1991); (c) S. Nukui, M. Sodeoka, H. Sasai,
and M. Shibisaki. J.Org. Chem. 60, 398 (1995); (d) T.
Takemoto, M. Sodeoka, H. Sasai, and M. Shibisaki. J. Am.
Chem. Soc. 115, 8477 (1993); (e) A.B. Dounay, K. Hatanaka,
J.J. Kodanko, M. Oestreich, L.E. Overman, L.A. Pfeifer, and
M.W. Weiss. J. Am. Chem. Soc. 125, 6261 (2003).
7. (a) M. Lautens and G. Hughes. Angew. Chem. Int. Ed. 38, 129
(1999); (b) M. Lautens, G. Hughes, and V. Zunic. Can. J.
Chem. 78, 868 (2000).
4b,7,7a,8,9,13-Hexahydrodibenzo[c,i]chromene (13)
IR (neat): 3405(m), 2927(s), 1717(s), 1603(w), 1457(m),
1
1271(m), 1082(m), 1032(w), 747(m). H NMR (400 MHz,
CDCl3) δ: 7.22–7.15 (3H, m), 7.01 (1H, d, J = 7.6 Hz),
5.93–5.90 (1H, m), 5.70–5.66 (2H, m), 5.54–5.50 (1H, m),
4.98 (1H, d, J = 15.6 Hz), 4.83 (1H, d, J = 15.6 Hz), 3.30
(1H, s), 2.63–2.56 (1H, m), 2.65–2.08 (3H, m), 1.64–1.87
(3H, m). 13C NMR (100 MHz, CDCl3) δ: 136.01, 133.9,
129.42, 129.18, 129.18, 128.92, 127.48, 127.02, 126.16,
124.63, 124.12, 72.09, 62.37, 42.07, 36.59, 28.59, 26.16,
25.48. HR-MS calcd. for C16H18O ([M]+): 238.1357; found:
238.1359.
4b,5,7a,8,9,13-Hexahydrodibenzo[c,i]chromene (14)
IR (neat): 3419(m), 2924(m), 1713(s), 1603(m), 1458(w),
1299(m), 1278(m), 1108(w), 1072(w), 1018(w), 755(w),
1
734(m). H NMR (400 MHz, CDCl3) δ: 7.21–7.13 (3H, m),
7.04–7.02 (1H, m), 5.85 (1H, dt, J = 10.4 Hz, 3.6 Hz), 5.70–
5.65 (2H, m), 5.55–5.52 (1H, m), 5.00 (1H, s), 2.83 (1H, t,
J = 6.4 Hz), 2.41–2.26 (3H, m), 2.10–2.03 (2H, m), 1.96–
1.89 (1H, m), 1.51–1.41 (1H, m). 13C NMR (100 MHz,
CDCl3) δ: 138.00, 133.91, 131.28, 129.64, 128.63, 127.33,
126.60, 126.20, 124.40, 124.20, 71.89, 63.93, 39.15, 38.92,
30.78, 27.41, 24.48. HR-MS calcd. for C16H18O ([M]+):
238.1357; found: 238.1359.
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Acknowledgment
We thank the University of Toronto, the Natural Sciences
and Engineering Research Council of Canada (NSERC), and
the Merck Frosst Centre for Therapeutic Research for finan-
cial support. V.Z. would like to thank NSERC and the
Ontario Graduate Scholarship (OGS) for postgraduate schol-
arships.
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© 2004 NRC Canada