Asymmetric palladium(0)-mediated synthesis of 2-vinylchroman

Article abstract of DOI:10.1016/S0957-4166(99)00077-4

Optically active 2-vinylchroman was synthesized from the corresponding hydroxy allylic carbonate by palladium-catalyzed cyclization in the presence of various chiral ligands. Enantioselectivity of up to 53% was obtained using NMDPP as the chiral phosphine

Full text of DOI:10.1016/S0957-4166(99)00077-4

Pergamon
Tetrahedron: Asymmetry 10 (1999) 1069–1078
Asymmetric palladium(0)-mediated synthesis of 2-vinylchroman
Jean-Robert Labrosse, Cécilia Poncet, Paul Lhoste and Denis Sinou ∗
Laboratoire de Synthèse Asymétrique, associé au CNRS, CPE Lyon, Université Claude Bernard Lyon 1,
43, boulevard du 11 novembre 1918, 69622 Villeurbanne, Cedex, France
Received 1 February 1999; accepted 1 March 1999
Abstract
Optically active 2-vinylchroman was synthesized from the corresponding hydroxy allylic carbonate by
palladium-catalyzed cyclization in the presence of various chiral ligands. Enantioselectivity of up to 53% was
obtained using NMDPP as the chiral phosphine. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
The 3,4-dihydro-2H-1-benzopyran nucleus is present in many biologically active compounds such as
α-tochopherol or vitamin E. A useful intermediate in the synthesis of such structures is chromanethanol,
3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-ethanol.
Racemic chromanethanol has been prepared using a Friedel–Crafts alkylation between trimethyl-
hydroquinone and an appropriate allylic alcohol,1,2 3,6-dihydro-4-methyl-2H-pyran3 or 3-methylpentan-
1,3,5-triol.4 Since it was shown that the biological activity was strongly influenced by configuration of
the asymmetric center, recent research has focused on the preparation of optically active chromanethanol.
Enantiopure (S)-chromanethanol has been obtained starting with compounds from the chiral pool such as
(R)-mevalonolactone5 or (S)-benzylglycidol.6 The asymmetric Sharpless epoxidation of an intermediate
allowed chromanethanol with 78% ee to be obtained.7 Chemical8 or enzymatic9 resolutions of the final
product, or of an intermediate, have also been used to obtain optically active chromanethanol.
Following our continuing interest in the formation of C–O bonds via palladium(0) alkylation of allylic
substrates by oxygen nucleophiles,10 we expected that 2-vinylchroman 1, a precursor of chromanethanol,
could be obtained by intramolecular palladium(0) nucleophilic substitution of appropriate hydroxy allylic
carbonates 7 or 13. In this paper we describe our results concerning the synthesis of these two hydroxy
allylic carbonates and their asymmetric palladium cyclization.11
∗
Corresponding author. E-mail: sinou@univ-lyon1.fr
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00077-4

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2. Results and discussion
The achiral linear allylic carbonate 7 was prepared as shown in Scheme 1. Reduction of commercial
dihydrocoumarin 2 with diisobutylaluminum hydride (dibal) in toluene followed by a Wittig reaction with
Ph3P_CHCO2C2H5 at room temperature gave hydroxyester 3.12 Protection of the phenolic function of
3 was performed with t-butyldimethylsilyl chloride (TBDMSCl) in the presence of imidazole. Reduction
of the unsaturated ester 4 with dibal at −78°C in toluene afforded (E)-allyl alcohol 5. Esterification
of 5 by treatment with methyl chloroformate followed by deprotection of the phenolic function with
tetrabutylammonium fluoride Bu4NF·3H2O led to the linear hydroxy carbonate 7.
Scheme 1.
The chiral racemic allylic carbonate 13 was prepared as shown in Scheme 2. Iodophenol 8 was
converted to 2-(methoxymethoxy)iodobenzene 9 using chloromethyl methyl ether in the presence of
sodium hydride in tetrahydrofuran (THF). Heck reaction of the protected compound 9 with allylic
alcohol in the presence of Pd(OAc)2 under Jeffery’s conditions,13 gave aldehyde 10 in 20% yield
after column chromatography. Condensation of aldehyde 10 with vinylmagnesium bromide afforded the
secondary allylic alcohol 11 which was esterified to the branched carbonate 12 by reaction with methyl
chloroformate. Finally, the phenolic function of 12 was deprotected using trimethylsilyl bromide to give
the desired chiral racemic hydroxy allylic carbonate 13.
Scheme 2.
Asymmetric cyclization of allyl carbonates 7 and 13 to give chiral 2-vinylchroman 1 (Scheme 3) was
carried out in the presence of palladium complexes containing various chiral ligands. The enantiomeric
excess of 1 was determined by HPLC analysis with a chiral stationary phase column (Chiralpak
AD). Absolute configuration of product 1 was determined after conversion of a sample exhibiting
[α]D20=−10.3 (c 1.0, CH2Cl2) to chromanethanol 14 (Scheme 4) by treatment with a solution of osmium
tetroxide and sodium periodate followed by reduction with sodium borohydride, and comparison with
the reported sign of rotation [α]D25=−113.4 (c 1.1, CH3OH) for the (R)-enantiomer.14
Representative results concerning this asymmetric cyclization are shown in Table 1. In the case of
BINAP (entry 5) or MeOBIPHEP (entry 7), the product yield in 1, starting from the achiral linear

J.-R. Labrosse et al. / Tetrahedron: Asymmetry 10 (1999) 1069–1078
1071
Scheme 3.
Scheme 4.
allylic carbonate 7, was poor (7% and 19%) with ees of up to 4 and 36%, respectively; performing the
cyclization at 50°C or in CH2Cl2 did not improve these values. In the presence of MeOBIPHEP (entry
8), chiral racemic allylic carbonate 13 gave the cyclized product in higher yield (65%) but with lower ee
(12%) (entry 20). Palladium complexes containing Diop (entry 1), Chiraphos (entry 2) or BDPP (entry
3) as the chiral ligand gave high chemical yield in 1, but low enantioselectivity; in the case of BDPP,
performing the reaction at 0°C decreased both the yield and the ee (entry 4). The P,N-Diop ligand also
gave high yield and low ee (entry 11). The result obtained with Trost’s ligand are also disappointing from
an enantioselectivity point of view (entry 9); however, the same enantioselectivity was obtained starting
from carbonates 7 or 13 (entry 19).
The highest ees were obtained using phosphino-oxazoline or NMDPP as the chiral auxiliary. The
phosphino-oxazoline ligand gave ees of up to 45% in 67% yield (entry 10). Surprisingly, NMDPP, a
chiral monophosphine, gave ees of up to 47% in 92% yield at 25°C (entry 13). Performing the reaction at
0°C or −30°C increased the ees to 50 and 53% (entries 14 and 16), respectively, although a higher reaction
temperature (50°C) gave a lower ee (entry 15). Surprisingly, the catalyst generated in situ from Pd(OAc)2
and NMDPP showed a low activity with no induction (entry 18). These results could be rationalized as
shown in Scheme 3. Absolute configuration of the product is probably determined by the relative stability
of the two intermediates A and B, if the alkylation reaction is slow compared to the equilibrium between
these two η3-allyl complexes, via a η3zσzη3 mechanism. This is probably the case here, and the
nucleophilic addition step determines the asymmetric induction.15,16
With Trost’s ligand, the substrate could not be well accommodated in the chiral pocket, probably
due to steric constraints, and so the enantioselectivity is low. For the phosphino-oxazoline ligand, we
assume that the lesser steric constraint positions the nitrogen atom trans to the less substituted η3-allyl
terminus, the π-allyl intermediate A being the less stable in this case, due to interaction between the
isopropyl group of the phosphino-oxazoline and the two methylene groups of the substrate. The more
stable intermediate B will give the (S)-enantiomer. For the monophosphine NMDPP, the equilibrium
is probably faster, due to easier association and dissociation of the monodentate ligand, and the two

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Table 1
Asymmetric palladium(0)-catalyzed cyclization of carbonates 7 and 13

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Figure 1. Structures of chiral ligands
chiral ligands are more easily sterically accommodated in the π-allyl intermediate than in the case of the
diphosphines.
3. Conclusion
In conclusion, 2-vinylchroman could be obtained in quite good yields and with enantioselectivity of up
to 53% by palladium(0)-catalyzed cyclization of the appropriate hydroxy allylic carbonate. The highest
enantioselectivities are obtained using the phosphino-oxazoline ligand or the chiral monophosphine
NMDPP, although Trost’s ligand gives very low enantioselectivities (Fig. 1).
4. Experimental
4.1. General
1H NMR (300 MHz) and 13C NMR (75.5 MHz) spectra were measured on a Bruker AM
300 spectrometer. Chemical shifts are reported in δ ppm referring to tetramethylsilane as an
internal standard. Optical rotations were determined on a Perkin–Elmer 241 polarimeter. Silica gel
column chromatography was carried out using Merck silica gel 60 Gerudan (40–63 µm). Analytical
HPLC was performed on a Shimadsu instrument and with a UV detector. Reactions involving
organometallic catalysis were carried out in Schlenk tubes under an inert atmosphere. Tetrahydrofuran
was distilled from sodium–benzophenone. (2S,3S)-2,3-O-Isopropylidene-2,3-dihydroxy-1,4-bis-
(diphenylphosphanyl)butane (Diop), (2S,4S)-2,4-bis(diphenylphosphanyl) pentane (BDPP), (2S,3S)-
2,3-bis(diphenylphosphanyl)butane (Chiraphos), (R)-2,20-bis(diphenylphosphanyl)-1,10 -binaphthyl
(BINAP), (1S,2S,5R)-5-methyl-1-diphenylphosphanyl)-2-isopropylcyclohexane (NMDPP) were from a
commercial source. (S)-6,60-Dimethoxy-2,20-bis(diphenylphosphanyl)-1,10 -biphenyl (MeOBIPHEP),
1-{(S)-1-[(R)-3,5-dimethyl-2(diphenylphosphanyl)ferrocenyl]ethyl}-1H-pyrazole
and
(S)-2-[2-
diphenylphosphanyl)phenyl]-4-isopropyldihydrooxazole were gifts from Dr. Schmid (Hofmann La
Roche, Basle, Switzerland), Professor Togni (Zürich, Switzerland) and Professor Pfaltz (Mülheim
an der Ruhr, Germany), respectively. (1R,2R)-1,2-Bis-N-[20-(diphenylphosphanyl)benzoyl]-1,2-

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diaminocyclohexane17 and (2R, 3S)-O-isopropylidene-1-diphenylphosphanyl-4-[(N-p-methoxyphenyl)-
N-methylamino]butan-2,3-diol or P,N-Diop18 were prepared according to the literature procedure.
4.2. Ethyl 5-{2-[(tert-butyldimethylsilyl)oxy]phenyl}pent-2-enoate 4
To a solution of imidazole (30.16 g, 0.44 mol) and tert-butyldimethylsilyl chloride (32.05 g, 0.21 mol)
in DMF (50 mL) was added ethyl (5-hydroxyphenyl)pent-2-enoate12 (39.0 g, 0.17 mol) as a mixture of
(E) and (Z) isomers at room temperature. After being stirred for 24 h at room temperature, the solution
was hydrolyzed by water (150 mL). The aqueous solution was extracted with CH2Cl2 (5×75 mL). The
organic phase was washed with a 5% aqueous sodium hydroxide solution (3×100 mL), water (10×50
mL) and then dried with sodium sulfate. Evaporation of the solvent gave a residue which was purified by
flash chromatography, using petroleum ether:ethyl acetate (25:1) as the eluent, to give compound 4 (E:Z
mixture, 90:10) as an oil (45.5 g, 77%). Isomer 4, E: Rf=0.42; 1H NMR (300 MHz): δ (CDCl3) 0.24 (s,
6H, SiCH3), 1.05 (s, 9H, t-Bu), 1.29 (t, 3H, J=7.1 Hz, CH3), 2.48 (td, 2H, J=7.9, 7.0 Hz, CH2CH_),
2.75 (t, 2H, J=7.9 Hz, CH2), 4.18 (q, 2H, J=7.1 Hz, CH2CH3), 5.85 (d, 1H, J=15.8 Hz, _CH–CO),
6.75–7.15 (m, 5H, _CH–, Harom); 13C NMR (75.5 MHz): δ (CDCl3) −4.1 (SiCH3), 14.3 (CH3), 18.3
(CMe3), 25.8 (CMe3), 29.3 (CH2), 32.8 (CH2), 60.2 (OCH2), 118.4, 121.2, 121.6, 127.3, 130.2, 131.5,
1
148.6 and 153.6 (–CH_, Carom), 166.7 (CO). Isomer 4, Z: Rf=0.48; H NMR (300 MHz): δ (CDCl3)
0.27 (s, 6H, SiCH3), 1.05 (s, 9H, t-Bu), 1.30 (t, 3H, J=7.2 Hz, CH3), 2.77 (t, 2H, J=7.6 Hz, CH2), 2.98
(tdd, 2H, J=7.6, 7.4, 1.5 Hz, CH2CH_), 4.18 (q, 2H, J=7.2 Hz, CH2CH3), 5.78 (dt, 1H, J=11.4, 1.5, Hz,
_CH–CO), 6.25 (dt, 1H, J=11.4, 7.4 Hz, –CH_), 6.75–7.25 (m, 4H, Harom); 13C NMR (75.5 MHz): δ
(CDCl3) −4.1 (SiCH3), 14.4 (CH3), 18.3 (CMe3), 25.9 (CMe3), 29.3 (CH2), 29.7 (CH2), 59.8 (OCH2),
118.4, 121.1, 120.1, 127.1, 130.3, 131.8, 149.6 and 153.6 (–CH_, Carom), 166.4 (CO). Anal. calcd for
C19H30O3Si: C, 68.22; H, 9.04. Found: C, 68.45; H, 8.89.
4.3. (E)-5-{2-[(tert-Butyldimethylsilyl)oxy]phenyl}pent-2-en-1-ol 5
To a solution of compound 4 (62 g, 0.185 mol) in toluene (600 mL) maintained at −78°C was added
slowly a 1.5 M solution of dibal (310 mL) in toluene. After being stirred for 2 h at −78°C, the solution
was treated at room temperature with methanol (400 mL), acidified by 1 N hydrochloric acid (500 mL),
and filtered on Celite. The aqueous solution was extracted with CH2Cl2 (5×75 mL). The organic phase
was dried with sodium sulfate, and evaporated in vacuo to give an oil which was purified by flash
chromatography, using petroleum ether:ethyl acetate (4:1) as the eluent, to give compound 5 (50.1 g,
1
93%). Oil; Rf=0.27; H NMR (300 MHz): δ (CDCl3) 0.25 (s, 6H, SiCH3), 1.05 (s, 9H, t-Bu), 1.48 (s,
1H, OH), 2.34 (dtd, 2H, J=9.2, 6.9, 2.1 Hz, CH2CH_), 2.68 (td, 2H, J=6.9, 2.2 Hz, CH2), 4.08 (d, 2H,
J=5.5 Hz, CH2OH), 5.56–5.82 (m, 2H, –CH_), 6.78 (dd, 1H, J=8.1, 1.1 Hz, Harom), 6.88 (ddd, 1H,
J=7.3, 7.3, 1.1 Hz, Carom), 7.02–7.16 (m, 2H, Harom); 13C NMR (75.5 MHz): δ (CDCl3) −4.1 (SiCH3),
18.3 (CMe3), 25.9 (CMe3), 30.4 (CH2), 32.7 (CH2), 63.8 (CH2OH), 118.4, 121.0, 127.0, 129.4, 130.3,
132.3, 132.9 and 153.6 (–CH_, Carom). Anal. calcd for C17H28O2Si: C, 69.81; H, 9.65. Found: C, 69.74;
H, 9.95.
4.4. (E)-5-{2-[(tert-Butyldimethylsilyl)oxy]phenyl}pent-2-enyl methyl carbonate 6
To a solution of alcohol 5 (52 g, 0.18 mol), 4-dimethylaminopyridine (4.34 g, 35 mmol) and pyridine
(37.3 mL, 0.71 mol) in CH2Cl2 (510 mL) maintained at 0°C, was slowly added methyl chloroformate
(55 mL, 0.71 mol). After being stirred at room temperature for 24 h, the solution was hydrolyzed by

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a saturated aqueous solution of copper sulfate (250 mL), and the aqueous phase was extracted with
diethyl ether (4×100 mL). Evaporation of the solvent in vacuo gave a residue which was purified by
flash chromatography, using petroleum ether:ethyl acetate (3:1) as the eluent, to give carbonate 6 (57.3
1
g, 92%). Oil; Rf=0.45; H NMR (300 MHz): δ (CDCl3) 0.21 (s, 6H, SiCH3), 1.10 (s, 9H, t-Bu), 2.34
(td, 2H, J=7.9, 6.6 Hz, CH2CH_), 2.67 (t, 2H, J=7.9 Hz, CH2), 3.78 (s, 3H, CH3), 4.57 (d, 2H, J=6.6
Hz, CH2OCO), 5.62 (dt, 1H, J=15.4, 6.6 Hz, –CH_), 5.87 (dt, 1H, J=15.4, 6.6 Hz, –CH_), 6.75 (dd,
1H, J=6.9, 6.9 Hz, Harom), 6.78 (d, 1H, J=8.1 Hz, Harom), 7.10 (m, 2H, Harom); 13C NMR (75.5 MHz):
δ (CDCl3) −4.1 (SiCH3), 18.3 (CMe3), 25.8 (CMe3), 30.4 (CH2), 32.7 (CH2), 54.7 (CH3), 68.7 (CH2O),
118.4, 121.0, 123.6, 127.0, 130.3, 132.1, 136.8 and 153.6 (–CH_, Carom), 155.7 (CO). Anal. calcd for
C19H30O4Si: C, 65.10; H, 8.63. Found: C, 64.73; H, 8.64.
4.5. (E)-5-(2-Hydroxyphenyl)pent-2-enyl methyl carbonate 7
A solution of compound 6 (13.1 g, 37 mmol) and tetrabutylammonium fluoride trihydrate (19.6 g, 74
mmol) in THF (200 mL) was stirred at room temperature for 1 h. After evaporation of the solvent, the
residue was treated with diethyl ether (100 mL) and water (50 mL). After usual workup, evaporation
of the solvent in vacuo gave a residue which was purified by flash chromatography, using petroleum
ether:ethyl acetate (8:3) as the eluent, to give hydroxy carbonate 7 (7.4 g, 84%). Oil; Rf=0.49; 1H NMR
(300 MHz): δ (CDCl3) 2.38 (td, 2H, J=7.4, 6.9 Hz, CH2CH_), 2.72 (t, 2H, J=7.4 Hz, CH2), 3.78 (s, 3H,
CH3), 4.57 (d, 2H, J=6.7 Hz, CH2OCO), 5.61 (dt, 1H, J=15.4, 6.9 Hz, –CH_), 5.88 (dt, 1H, J=15.4, 6.7
Hz, –CH_), 6.74 (d, 1H, J=7.8 Hz, Harom), 6.87 (ddd, 1H, J=8.3, 8.3, 1.1 Hz, Harom), 7.08 (m, 2H, Harom);
13C NMR (75.5 MHz): δ (CDCl3) 29.5 (CH2), 32.4 (CH2), 54.9 (CH3), 68.7 (CH2O), 115.4, 120.8, 123.7,
127.3, 127.5, 130.3, 136.7 and 153.6 (–CH_, Carom), 155.9 (CO). Anal. calcd for C13H15O4: C, 66.09;
H, 6.83. Found: C, 65.84; H, 6.56.
4.6. 2-(Methoxymethoxy)iodobenzene 9
A solution of iodophenol 8 (20.0 g, 91 mmol) in THF (90 mL) was added to a mixture of 60% NaH
(4.45 g, 0.11 mol) in THF (60 mL). After 20 min, chloromethyl methyl ether (8.3 g, 0.1 mol) was added
slowly at room temperature. The solution was refluxed for 2 h, then hydrolyzed by cold water (900 mL),
and extracted with diethyl ether (5×180 mL). Evaporation of the solvent in vacuo gave a residue which
was purified by flash chromatography, using petroleum ether:ethyl acetate (50:1) as the eluent, to give
1
compound 9 (21.5 g, 90%). Oil; Rf=0.36; H NMR (300 MHz): δ (CDCl3) 3.51 (s, 3H, CH3), 5.24 (s,
2H, OCH2O), 6.77 (ddd, 1H, J=7.9, 7.4, 1.5 Hz, Harom), 7.08 (dd, 1H, J=8.1, 1.5 Hz, Harom), 7.29 (ddd,
1H, J=8.1, 7.4, 1.5 Hz, Harom), 7.78 (dd, 1H, J=7.9, 1.5 Hz, Harom); 13C NMR (75.5 MHz): δ (CDCl3)
56.4 (CH3), 94.9 (CH2), 87.2, 114.9, 123.6, 129.4, 139.5 and 156.0 (Carom). These spectral data are in
agreement with the literature.19
4.7. 3-[2-(Methoxymethoxy)phenyl]propanal 10
A solution of 2-(methoxymethoxy)iodobenzene 9 (2.5 g, 9.5 mmol) and allylic alcohol (1.37 g, 23.5
mmol) in DMF (40 mL) was added to a stirred solution of Pd(OAc)2 (72.3 mg, 0.32 mmol), NaHCO3 (2.0
g, 23 mmol), and benzyltriethylammonium chloride (2.16 g, 9.5 mmol), in DMF (15 mL). The mixture
was heated at 70°C for 36 h, then cooled to 25°C, and hydrolyzed by a saturated aqueous ammonium
chloride solution (250 mL). The aqueous phase was extracted with diethyl ether (7×25 mL). The organic
phase was washed with saturated aqueous sodium chloride (4×30 mL) and dried with sodium sulfate.

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The solvent was removed in vacuo to afford an oil which was purified by flash chromatography, using
petroleum ether:ethyl acetate (6:1) as the eluent, to give compound 10 (363 mg, 20%). Oil; Rf=0.54; 1H
NMR (300 MHz): δ (CDCl3) 2.75 (dt, 2H, J=7.5, 1.4 Hz, CH2CHO), 2.95 (t, 2H, J=7.5 Hz, CH2), 3.47
(s, 3H, CH3), 5.21 (s, 2H, OCH2O), 6.90–7.20 (m, 4H, Harom), 9.83 (t, 1H, J=1.4 Hz, CHO); 13C NMR
(75.5 MHz): δ (CDCl3) 23.5 (CH2), 44.0 (CH2CHO), 56.1 (CH3), 94.3 (OCH2O), 113.9, 121.8, 127.8,
129.3, 130.1 and 155.1 (Carom), 202.3 (CHO); m/z (EIMS, 70 eV) 194 (M+, 2%), 132 (17) and 45 (100).
4.8. 5-[2-(Methoxymethoxy)phenyl]pent-1-en-3-ol 11
A 1 M solution of vinylmagnesium bromide in THF (29.4 mL, 30 mmol) was added very slowly to
a stirred solution of aldehyde 10 (1.94 g, 10 mmol) in THF (30 mL) and cooled to −30°C. After being
stirred at room temperature for 3 h, the solution was hydrolyzed by a saturated aqueous ammonium
chloride solution (50 mL), and the aqueous phase was extracted with CH2Cl2 (5×25 mL). The organic
solution was washed with a saturated solution of sodium chloride (3×80 mL) and dried with sodium
sulfate. The solvent was removed in vacuo to afford an oil which was purified by flash chromatography,
using petroleum ether:ethyl acetate (4:1) as the eluent, to give compound 11 (1.18 g, 54%). Oil; Rf=0.42;
1H NMR (300 MHz): δ (CDCl3) 1.58 (s, 1H, OH), 1.84 (m, 2H, CH2CHOH), 2.76 (t, 2H, J=7.7 Hz,
CH2), 3.49 (s, 3H, CH3), 4.15 (bdt, 1H, J=6.3, 6.3 Hz, CHOH), 5.13 (ddd, 1H, J=10.3, 1.4, 1.4 Hz,
_CH2), 5.22 (s, 2H, OCH2O), 5.25 (ddd, 1H, J=17.1, 1.4, 1.4 Hz, _CH2), 5.91 (ddd, 1H, J=17.1, 10.3,
6.3 Hz, –CH_), 6.95 (ddd, 1H, J=7.3, 7.3, 1.1 Hz, Harom), 7.07 (dd, 1H, J=9.0, 1.1 Hz, Harom), 7.13–7.21
(m, 2H, Harom); 13C NMR (75.5 MHz): δ (CDCl3) 26.2 (CH2CHOH), 37.4 (CH2), 56.2 (CH3), 72.3
(CHOH), 94.5 (OCH2O), 114.0, 114.6, 121.9, 127.3, 130.8, 141.1 and 155.1 (Carom, –CH_, _CH2).
Anal. calcd for C13H18O3: C, 70.04; H, 8.09. Found: C, 70.24; H, 8.16.
4.9. 3-[2-(Methoxymethoxy)phenyl]-1-vinylpropyl methyl carbonate 12
A solution of methyl chloroformate (1.7 mL, 25 mmol) in CH2Cl2 (5 mL) was added slowly to a
solution of alcohol 11 (1.18 g, 5.3 mmol), 4-dimethylaminopyridine (0.13 g, 1.0 mmol), and pyridine
(1.2 mL, 20 mmol), in CH2Cl2 (10 mL) at 0°C. After being stirred for 24 h, the solution was hydrolyzed
by a saturated copper sulfate aqueous solution (10 mL), and extracted with diethyl ether (4×10 mL). The
organic phase was washed with water (4×10 mL) and dried with sodium sulfate. Removal of the solvent
in vacuo afforded an oil which was purified by flash chromatography, using petroleum ether:ethyl acetate
1
(6:1) as the eluent, to give compound 12 (1.1 g, 74%). Oil; Rf=0.62; H NMR (300 MHz): δ (CDCl3)
1.84–2.10 (m, 2H, CH2CHOH), 2.71 (t, 2H, J=7.0 Hz, CH2), 3.48 (s, 3H, CH3), 3.79 (s, 3H, CH3), 5.10
(bdt, 1H, J=6.6, 6.6 Hz, CHO), 5.19 (s, 2H, OCH2O), 5.23 (ddd, 1H, J=10.3, 1.3, 1.3 Hz, _CH2), 5.34
(ddd, 1H, J=17.2, 1.3, 1.3 Hz, _CH2), 5.85 (ddd, 1H, J=17.2, 10.3, 6.6 Hz, –CH_), 6.93 (ddd, 1H, J=7.3,
7.3, 1.5 Hz, Harom), 7.05 (dd, 1H, J=8.1, 1.5 Hz, Harom), 7.10–7.20 (m, 2H, Harom); 13C NMR (75.5 MHz):
δ (CDCl3) 26.1 (CH2CHO), 34.4 (CH2), 54.7 (CH3), 56.1 (CH3), 78.8 (CHOCO), 94.4 (OCH2O), 113.9,
117.2, 121.7, 127.4, 130.1, 130.2, 136.0 and 155.2 (Carom, –CH_, _CH2), 155.3 (CO2). Anal. calcd for
C15H20O5: C, 64.27; H, 7.19. Found: C, 64.87; H, 7.09.
4.10. 3-(2-Hydroxyphenyl)-1-vinylpropyl methyl carbonate 13
To a solution of carbonate 12 (1.10 g, 3.9 mmol) in CH2Cl2 (25 mL) at −30°C containing molecular
sieves, trimethylsilyl bromide (2.41 g, 15.7 mmol) was added slowly. After being stirred for 20 h at 0°C,
the solution was hydrolyzed by a saturated aqueous solution of NaHCO3 (100 mL). The solution was

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then stirred in the presence of Amberlyst 15 (20 g) for 20 min. After filtration, the organic layer was
separated and washed with a saturated aqueous sodium chloride solution (3×50 mL). The organic phase
was dried with sodium sulfate, evaporated to give an oil which was purified by flash chromatography,
using petroleum ether:ethyl acetate (5:1) as the eluent, to give compound 13 (154 mg, 17%). Oil; Rf=0.44;
1H NMR (300 MHz): δ (CDCl3) 2.00 (m, 2H, CH2CHOH), 2.68 (t, 2H, J=7.9 Hz, CH2), 3.80 (s, 3H,
CH3), 5.10 (m, 1H, CHO), 5.23 (ddd, 1H, J=10.5, 1.1, 1.1 Hz, _CH2), 5.33 (ddd, 1H, J=17.3, 1.1, 1.1 Hz,
_CH2), 5.85 (ddd, 1H, J=17.3, 10.5, 6.6 Hz, –CH_), 6.75 (d, 1H, J=7.5 Hz, Harom), 6.87 (ddd, 1H, J=7.5,
7.5, 1.1 Hz, Harom), 7.10 (m, 2H, Harom); 13C NMR (75.5 MHz): δ (CDCl3) 25.8 (CH2CHOCO), 34.2
(CH2), 54.9 (CH3), 79.1 (CHOCO), 115.4, 117.8, 120.7, 127.3, 127.5, 130.3, 135.8 and 153.9 (Carom
,
–CH_, _CH2), 155.6 (CO2); m/z (EIMS, 70 eV) 160 (M+−CH3OH−CO2, 60%), 145 (75), 131 (40), 107
(75) and 77 (100); m/z (CIMS, NH3) 254 (MH++NH3, 30), 161 (MH+−CH3CO2H, 100), 159 (82), 145
(20), 131 (15), 107 (32) and 94 (42).
4.11. General procedure for the cyclization reaction
A solution of tris(dibenzylideneacetone)dipalladium (22.9 mg, 0.025 mmol) and the ligand (0.1 mmol
for a bidendante ligand or 0.2 mmol for a monophosphine) in 5 mL of THF was stirred at room
temperature for 30 min. To the solution was added the hydroxy carbonate (23.6 mg, 0.1 mmol) dissolved
in 4 mL of THF. The mixture was stirred at the desired temperature for 24 h and then the solvent was
removed in vacuo. The residue was purified by silica gel chromatography, using petroleum ether:ethyl
1
acetate (10:1) as the eluent, to give 2-vinylchromane 1. Oil; Rf=0.72; H NMR (300 MHz): δ (CDCl3)
1.86 (dddd, 1H, J=13.6, 9.9, 9.3, 5.5 Hz, H-3ax), 2.08 (dddd, 1H, J=13.6, 5.9, 4.4, 2.6 Hz, H-3eq), 2.78
(ddd, 1H, J=16.5, 5.5, 4.4 Hz, H-4eq), 2.88 (ddd, 1H, J=16.5, 9.3, 5.9 Hz, H-4ax), 4.56 (bddd, 1H, J=9.9,
5.5, 2.6 Hz, H-2), 5.24 (ddd, 1H, J=10.7, 1.5, 1.5 Hz, _CH2), 5.39 (ddd, 1H, J=17.3, 1.5, 1.5 Hz, _CH2),
6.00 (ddd, 1H, J=17.3, 10.7, 5.5 Hz, –CH_), 6.85 (m, 2H, Harom), 7.09 (m, 2H, Harom); 13C NMR (75.5
MHz): δ (CDCl3) 24.2 (CH2), 27.5 (CH2), 76.2 (CHO), 116.3, 116.9, 120.2, 121.8, 127.3, 129.5, 137.6
and 154.3 (–CH_, _CH2, Carom). These data are in agreement with the literature.20
The enantiomeric excess of 2-vinylchroman 1 was determined by HPLC analysis with a chiral
stationary phase column (Chiralpak AD, eluent: n-hexane, rate 0.5 mL min−1), the enantiomer (S) being
eluted first.
4.12. Determination of the configuration of compound 1
A solution of 1 (100 mg, 0.63 mmol), exhibiting [α]D20=−10.3 (c 1.0, CH2Cl2), in 7 mL of ace-
tone:water (3:1) and cooled to 0°C was treated by a 2.5% solution of osmium tetroxide (128 mg, 0.013
mmol) in t-butanol, then by sodium periodate (403 mg, 1.88 mmol). The mixture was stirred for 6 h at
room temperature, then diluted with 40 mL water, and extracted with 3×35 mL ethyl acetate. Evaporation
of the solvent in vacuo gave an oil which was diluted in ethanol (10 mL). NaBH4 (170 mg, 4.5 mmol)
was added and the solution was stirred at 0°C for 30 min. After hydrolysis with a 10% HCl solution (53
mL), the chromanethanol was extracted with ethyl acetate (4×30 mL). Evaporation of the solvent gave
a residue which was purified by flash chromatography, using petroleum ether:ethyl acetate (2:1) as the
20
eluent, to give 75.2 mg of chromanethanol 14 (73%) having [α]D −13.6 (c 1.2, CH3OH), and so the
(R) configuration was assigned.14

1078
J.-R. Labrosse et al. / Tetrahedron: Asymmetry 10 (1999) 1069–1078
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