Mild and stereoselective friedel-crafts alkylation of phenol derivatives with vinyloxiranes: A new access to cycloalkenobenzofurans

Article abstract of DOI:10.1055/s-2007-992353

The ring opening of vinyloxiranes with aryl borates under very mild and neutral conditions affords new hydroxyphenols with interesting levels of regio- and stereoselectivity. The subsequent Mitsunobu-type cyclodehydration proceeds with a good yield giving

Full text of DOI:10.1055/s-2007-992353

LETTER
3011
Mild and Stereoselective Friedel–Crafts Alkylation of Phenol Derivatives with
Vinyloxiranes: A New Access to Cycloalkenobenzofurans
Alkylation of
e
henol
D
er
r
s
with Vin
u
yloxiranes ccio Bertolini, Valeria Di Bussolo, Paolo Crotti, Mauro Pineschi*
Dipartimento di Chimica Bioorganica e Biofarmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy
Fax +39(050)2219660; E-mail: pineschi@farm.unipi.it
Received 5 July 2007
Dedicated to Prof. Franco Macchia on the occasion of his 70th birthday
ed trans-hydroxyphenol 4aa and trans-aryloxy alcohol
Abstract: The ring opening of vinyloxiranes with aryl borates un-
der very mild and neutral conditions affords new hydroxyphenols
with interesting levels of regio- and stereoselectivity. The subse-
quent Mitsunobu-type cyclodehydration proceeds with a good yield
giving a new and easy access to cycloalkenobenzofurans.
5aa, both with a high anti stereoselectivity (>95% de).
The major product 4aa was derived from a regioselective
ring opening at the allylic position of the epoxide (SN2-at-
tack) by the ortho position of the phenol (C-alkylation
pathway) (Scheme 1, equation b). Probably, the dramati-
cally different reaction courses in the different solvents in-
volve different mechanisms in which the nature of the
cationic intermediate and solvation effects may account
for many of the results. In the more solvating THF, the
nucleophilic attack occurs by the internal nucleophile
(i.e., the aryl borate tethered with the oxirane oxygen)
with retention of configuration and with the prevalence of
the ‘harder’ character of the oxygen of the phenol deriva-
tive.8 On the other hand, the lesser solvating ability of the
incipient allylic cationic intermediate by a low-polarity
solvent such as CH2Cl2, may account for the normal ring
opening with inversion of configuration by the highly
nucleophilic arene 1a at its ‘softer’ site (i.e., the ortho ring
carbon of the phenol derivative).
Key words: Friedel–Crafts, vinyloxiranes, regioselectivity, stereo-
selectivity, fused-ring systems
Vinyloxiranes are a particular class of allylic electrophiles
which are valuable building blocks for a variety of syn-
thetic transformations.1 Despite the abundance of studies
on Friedel–Crafts alkylation,2 vinyloxiranes have rarely
been used as the electrophilic partner in intermolecular
processes.3 In these limited examples, strong Lewis acids
were invariably used to promote the reaction and phenols
have never been considered as the electrophilic partner.4–6
We report here a stereoselective intermolecular alkylation
of electron-rich aryl borates with structurally different
vinyloxiranes occurring under very mild reaction condi-
tions. In connection with our recent study,7 we took notice
of the following: tris(3,5-dimethylphenyl)borate (1a) re-
acted readily at room temperature with 1,3-cyclohexadi-
ene monoepoxide (2a) in THF to give cis-aryloxy alcohol
3aa (O-alkylation pathway) as the only product, with high
levels of syn stereoselectivity (>95% de) (Scheme 1,
equation a), whereas upon switching the solvent to
CH2Cl2, the reaction of borate 1a with 2a at –78 °C afford-
Alternative reaction conditions were also considered. For
example, the reactions of vinyloxirane 2a with 4.5 equiv-
alents of 3,5-dimethylphenol in CH2Cl2 at –78 °C in the
presence of stoichiometric amounts of BF3·Et2O or cata-
lytic amounts (5 mol%) of In(OTf)3,9 gave more complex
reaction mixtures, in which trans-hydroxy ether 5aa was
the major reaction product.
Me
O
Me
65% isolated yield
THF, r.t.
OH
3aa
Me
O
(equation a)
Me
1a
(1/3)B
+
Me
Me
O
Me
(equation b)
+
O
CH2Cl2, –78 °C
OH
OH
OH
2a
Me
5aa
4aa
14% isolated yield,
>95% de
40% isolated yield,
>95% de
Scheme 1 Product distribution in the reaction of aryl borate 1a with vinyloxirane 2a using different reaction conditions
SYNLETT 2007, No. 19, pp 3011–3015
x
x
.x
x
.2
0
0
7
Advanced online publication: 08.11.2007
DOI: 10.1055/s-2007-992353; Art ID: D20207ST
© Georg Thieme Verlag Stuttgart · New York

3012
F. Bertolini et al.
LETTER
Table 1 Results of the Alkylation of Aromatic Borates 1a and 1b with Vinyloxiranesa
Entry Vinyloxirane
Borate, conditions
Ratio
Ratio
Main product (Yield%)c
deb
C-/O-alkylationb SN2/SN2¢
Me
Me
O
Me
6a
1
>95:<5
>95:<5
75:25d
n.a.
n.a.
OH
OH
Me
O
(1/3)B
6aa (54)
1a, –78 °C, 2 h
O
MeO
OMe
OMe
2
82:18d
6a
OH
MeO
O
OH
(1/3)B
6ab (75)
1b, –78 °C, 2 h
1b, –78 °C, 2 h
O
O
MeO
OMe
OH
3
4
6b
6c
>90:<10
>95:<5
<5:>95
>95:<5
n.d.
OH
6bb (65)
Me
Me
COOEt
EtOOC
1b, –30 °C, 18 h
>95
n.a.
OH
OH
6cb (40)
88:12
15:85d
O
Me
Me
5
6
1a, –78 °C, 18 h
1b, –78 °C, 1 h
HO
6d
OH
6da (E/Z = 78:22) (48)
O
Complex mixture
6e
2a
>95:<5
>95:<5
MeO
OMe
O
7
1b, –78 °C, 18 h
1b, –78 °C, 18 h
>95
85
OH
OH
4ab (65)
MeO
OMe
O
8
9
>95:<5
>95:<5
>95:<5
70:30
2b
2c
OH
OH
4bb (58)
MeO
OMe
O
1b, –78 °C, 18 h
>95
OH
O
H
4cb (35)e
a All reactions were performed in accordance with the typical procedure.
b Diastereoisomeric excess was determined by 1H and 13C NMR analysis of the crude reaction mixture; n.d = not determined; n.a. = not applicable.
c Isolated yield of the pure product after chromatographic purification on silica gel, unless otherwise stated.
d The SN2¢-adducts were contaminated by substantial amounts (ca. 35% of the original crude mixture) of the corresponding para-alkylated
SN2 products.
e Obtained as an inseparable mixture with the corresponding SN2¢-adduct.
Synlett 2007, No. 19, 3011–3015 © Thieme Stuttgart · New York

LETTER
Alkylation of Phenol Derivatives with Vinyloxiranes
3013
In order to verify the generality of the Friedel–Crafts-type The application of a Mitsunobu-type cyclodehydration to
ring opening of vinyloxiranes, the reactions of aryl borate compounds 4aa and 4ba,12 readily gave cis-3,4,4a,9b-tet-
1a and of tris(3,5-dimethoxyphenyl)borate (1b) with a rahydrodibenzofurans 7aa and 7ba (>95% de). Likewise,
series of aliphatic and cyclic vinyloxiranes in CH2Cl2 at a the cyclodehydration of hydroxyphenols 4bb and 4cb al-
low temperature were examined (Table 1). Butadiene lowed a simple preparation of the corresponding new cis-
monoxide reacted readily with borates 1a and 1b to give benzofurans 7bb and 7cb, respectively, incorporating a
fair isolated yields of the corresponding hydroxyphenols seven- or an eight-membered ring bearing the double
6aa and 6ab, deriving from an SN2 attack by the ortho po- bond adjacent to the ring fusion and in the b-position with
sition of the phenol derivative at the allylic position of the respect to the aromatic ring. The stereochemistry of the
epoxide (entries 1 and 2, Table 1). A remarkable reversal ring fusion was established by 1D NOESY experiments,
of the regiocontrol of the ring opening was found in the re- thus unequivocally establishing the relative trans config-
action of (Z)-vinyloxirane 6b with borate 1b, affording uration of the starting cyclic hydroxyphenols of type 4
the corresponding (E)-hydroxy phenol 6bb deriving from (Scheme 2).
an allylic transposition of the original double bond (SN2¢-
To sum up, a mild ring opening of cyclic and aliphatic
attack) (entry 3). The substitution of the allylic residue
vinyloxiranes with representative electron-rich aryl bo-
with a carbomethoxy group, as present in compound 6c,
gave a diminished reactivity (75% conversion after 18 h at
–30 °C), and restored the SN2-type attack (entry 4). The
reaction of a tertiary vinyloxirane, such as isoprene
monoxide 6d, with aryl borates 1a,b proved to be less
straightforward. For example, the reaction with borate 1a
gave low yields of diastereoisomeric hydroxyphenols de-
riving mainly from an SN2¢-attack (entry 5). Phenyl vinyl-
oxirane 6e invariably gave a complicated mixture of
products (entry 6). To our delight, the reaction of borate
1b with cyclic vinyloxiranes 2a–c occurred exclusively
rates afforded hydroxyphenols,13 which are very difficult
to access by other routes, with interesting levels of regio-
and stereoselectivity. The subsequent cyclodehydration is
of particular interest when cyclic hydroxyphenols are
considered, because it gives a new and easy access to
cycloalkenobenzofurans.
Acknowledgment
This work was supported by the Ministero dell’Università e della
Ricerca (PRIN 2004, PRIN 2006) and by the University of Pisa. We
with the C-alkylation manifold with complete regioselec- are also grateful to Merck (2005 ADP Chemistry Award).
tivity at the allylic position of the epoxide and at the ortho
position of the phenol derivative (entries 7 and 8). Only in
the case of the eight-membered vinyloxirane 2c substan-
tial amounts (ca 30%) of the SN2¢-type-attack product
were recovered as an inseparable mixture with the main
product 4cb (entry 9). Importantly, the stereoselectivity
associated with the ring opening was uniformly high in all
cases (entries 7–9, Table 1).
References and Notes
(1) For recent examples, see: (a) Kimura, M.; Mukai, R.;
Tamaki, T.; Horino, Y.; Tamaru, Y. J. Am. Chem. Soc. 2007,
129, 4122. (b) Brunner, B.; Stogaitis, N.; Lautens, M. Org.
Lett. 2006, 8, 3473. (c) Charrier, N.; Gravestock, D.; Zard,
S. Z. Angew. Chem. Int. Ed. 2006, 45, 6520. (d) Restorp, P.;
Somfai, P. Eur. J. Org. Chem. 2005, 3946; and references
cited therein.
Several different methods are available for the obtainment
of partially and fully hydrogenated dibenzofuran moi-
eties, which are frequently found in biologically interest-
ing molecules.10 We envisioned that hydroxyphenols
obtained from cyclic vinyloxiranes, could be suitable
precursors to prepare cycloalkenobenzofurans of type 7
(Scheme 2). It should be noted that this class of com-
pounds, bearing the double bond adjacent to the ring
fusion and in b position with respect to the aromatic ring,
is not easy to prepare by current methods.11
(2) For a review, see: (a) Olah, G. A.; Krishnamurti, R.;
Prakash, S. G. K. In Comprehensive Organic Synthesis, Vol.
3; Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford,
1991, 293. For recent examples, see: (b) Bertolini, F.;
Crotti, P.; Macchia, F.; Pineschi, M. Tetrahedron Lett. 2006,
47, 61. (c) Prakash, S. G. K.; Linares-Palomino, P. J.;
Glinton, K.; Chacko, S.; Rasul, G.; Mathew, T.; Olah, G. A.
Synlett 2007, 1158.
(3) Vinyloxiranes have been used in an intramolecular process
to control a 7-endo-selective Friedel–Crafts-type
cyclization. See: Nagumo, S.; Miyoshi, I.; Akita, H.;
Kawahara, N. Tetrahedron Lett. 2002, 43, 2223.
R1
H
R1
R1
R1
(4) (a) Taylor, S. K.; Clark, D. L.; Heinz, K. L.; Schramm, S. B.;
Westermann, C. D.; Barnell, K. K. J. Org. Chem. 1983, 48,
592. (b) The drastic reaction conditions used in this work,
allowed direct ring opening of the oxirane ring by the Lewis
acid promoter and caused the resulting alcohols to undergo a
further Friedel–Crafts alkylation to give diarylated products.
(5) For Friedel–Crafts reactions of a sulfonyl-substituted vinylic
epoxide with various aromatics promoted by BF3·Et2O, see:
Brandänge, S.; Bäckvall, J.-E.; Leijonmarck, H. J. Chem.
Soc., Perkin Trans. 1 2001, 2051.
DEAD, PPh3
THF, r.t., 2 h
O
OH
OH
H
n
n
4aa,
4ab,
4bb,
4cb,
R1 = Me, n = 1
R1 = OMe, n = 1
R1 = OMe, n = 2
R1 = OMe, n = 3
7aa (83%)
7ab (81%)
7bb (80%)
7cb (70%)
(6) For the reactions of methyl 4,5-epoxypentenoate with aryl
ethers, see: Ono, M.; Tanikawa, S.; Suzuki, K.; Akita, H.
Tetrahedron 2004, 60, 10187; and references cited therein.
Scheme 2 Mitsunobu-type cyclodehydration of cyclic hydroxy-
phenols to cycloalkenobenzofurans
Synlett 2007, No. 19, 3011–3015 © Thieme Stuttgart · New York

3014
F. Bertolini et al.
LETTER
(7) Pineschi, M.; Bertolini, F.; Haak, R. M.; Crotti, P.; Macchia,
F. Chem. Commun. 2005, 1426.
(8) Tsuji, Y.; Toteva Garth, H. A.; Richard, J. P. J. Am. Chem.
Soc. 2003, 125, 15455.
(9) For the use of indium salts in Friedel–Crafts-type reactions
of heteroarenes with epoxides, see: (a) Yadav, J. S.; Reddy,
B. V. S.; Parimala, G. Synlett 2002, 1143. (b) Bandini, M.;
Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. J. Org.
Chem. 2002, 67, 5386.
(10) For the synthesis of tetrahydrobenzofurans, see:
(a) Hosokawa, T.; Miyagi, S.; Murahashi, S.-I.; Sonoda, A.
J. Org. Chem. 1978, 43, 2752. (b) Guzzo, P. R.; Buckle, R.
N.; Chou, M.; Dinn, S. R.; Flaugh, M. E.; Kiefer, A. D. Jr.;
Ryter, K. T.; Sampognaro, A. J.; Tregay, S. W.; Xu, Y.-C.
J. Org. Chem. 2003, 68, 770. (c) Yamashita, M.; Inaba, T.;
Nagahama, M.; Shimizu, T.; Kosaka, S.; Kawasaki, I.; Ohta,
S. Org. Biomol. Chem. 2005, 3, 2296. (d) Crich, D.;
Sannigrahi, M. Tetrahedron 2002, 58, 3319. For the
obtainment of hexahydrodibenzofurans, see: (e) Liu, Q.;
Han, B.; Zhang, W.; Yang, L.; Liu, Z.-L.; Yu, W. Synlett
2005, 2248. (f) Kurono, N.; Honda, E.; Komatsu, F.; Orito,
K.; Tokuda, M. Tetrahedron 2004, 60, 1791. (g) Nguyen,
R.-V.; Yao, X.; Li, C.-J. Org. Lett. 2006, 8, 2397.
(11) (a) Clive, D. L. J.; Daigneault, S. J. Org. Chem. 1991, 56,
5285. (b) Trost, B. M.; Tang, W.; Toste, F. D. J. Am. Chem.
Soc. 2005, 127, 14785.
2-(1-Hydroxybut-3-en-2-yl)-3,5-dimethoxyphenol (6ab):
yield: 75%; colorless oil; TLC (hexanes–EtOAc, 8:2): Rf
0.13. 1H NMR (200 MHz, CDCl3): d = 3.73 (s, 6 H), 3.89
(dd, J1 = 10.2 Hz, J1 = 3.2 Hz, 1 H), 4.02–4.15 (m, 1 H),
4.16–4.28 (m, 1 H), 5.00–5.19 (m, 2 H), 6.03–6.12 (m, 2 H),
6.13–6.23 (m, 1 H). 13C NMR (500 MHz, CDCl3): d = 40.0,
54.5, 55.7, 65.7, 91.2, 94.7, 108.0, 116.1, 136.7, 156.6,
158.6, 159.8.
(E)-2-(6-Hydroxynon-4-en-3-yl)-3,5-dimethoxyphenol
(6bb): yield: 65%; colorless oil; TLC (hexanes–EtOAc,
7:3): Rf 0.27. 1H NMR (250 MHz, CDCl3): d = 0.79 (t, 3 H),
0.86 (t, J = 7.1 Hz, 3 H), 1.19–1.52 (m, 4 H), 1.62–1.82 (m,
2 H), 2.20 (br s, 1 H, CHOH), 3.69 (s, 3 H), 3.71 (s, 3 H),
3.74–3.89 (m, 1 H), 4.06–4.13 (m, 1 H), 5.55 (dd, J1 = 16.3
Hz, J2 = 6.7 Hz, 1 H), 5.98–6.18 (m, 3 H). 13C NMR (62.5
MHz, CDCl3): d = 12.3, 13.9, 18.61, 25.49, 38.27, 39.31,
55.1, 55.6, 72.7, 91.4, 94.4, 110.2, 132.6, 134.4, 158.8,
159.1.
(4S*,5S*,E)-Ethyl 5-Hydroxy-4-(2-hydroxy-4,6-
dimethylphenyl)oct-2-enoate (6cb): yield: 40%; colorless
oil; TLC (hexanes–EtOAc, 7:3): Rf 0.19. 1H NMR (200
MHz, CDCl3): d = 0. 93 (t, J = 7.1 Hz, 3 H), 1.25 (t, J = 5.7
Hz, 3 H), 1.33–1.74 (m, 4 H), 3.52 (br s, 1 H, CHOH), 3.74
(s, 6 H), 3.95–4.30 (m, 4 H), 5.78 (d, J = 15.8 Hz, 1 H), 6.04
(s, 1 H), 6.11 (s, 1 H), 7.38 (dd, J1 = 15.8 Hz, J2 = 7.2 Hz, 1
H), 9.22 (br s, 1 H). 13C NMR (50 MHz, CDCl3): d = 13.7,
14.1, 19.0, 38.1, 42.3, 55.1, 55.7, 60.3, 75.4, 91.0, 94.8,
108.0, 123.1, 145.2, 156.8, 158.2, 160.1, 167.0.
(12) Aristoff, P. A.; Harrison, A. W.; Huber, A. M. Tetrahedron
Lett. 1984, 25, 3955.
(13) Aryl borates 1a,b were prepared from the corresponding
commercially available phenols with BH3·SMe2,14 and were
used immediately after their preparation.
(1S*,2R*)-2-(2-Hydroxy-4,6-dimethoxyphenyl)cyclo-
hept-3-enol (4bb): yield: 58% [obtained as an inseparable
mixture with 7% of the corresponding (1S*,2S*)-
Typical Procedure for the Preparation of Hydroxy-
phenols (Entry 7, Table 1): Under an argon atmosphere, a
solution of aryl borate 1b (705 mg, 1.5 mmol) in CH2Cl2 (1.0
mL) was added at –78 °C to a stirred solution of vinyloxirane
2a (96 mg, 1.0 mmol) in CH2Cl2 (0.5 mL). The mixture was
allowed to react for 18 h at –78 °C, then quenched with brine
(2.0 mL) and diluted with Et2O or CH2Cl2 (20 mL).
Evaporation of the dried (MgSO4) organic solution afforded
a crude reaction mixture which was purified by silica gel
column chromatography eluting with hexanes–EtOAc (7:3),
to give pure 2-[(1R*,6S*)-6-hydroxycyclohexen-2-yl]-3,5-
dimethoxyphenol (4ab; 162 mg, 65%), as a light yellow oil;
TLC (hexanes–EtOAc, 1:1): Rf 0.36. 1H NMR (250 MHz,
CDCl3): d = 1.70–1.90 (m, 1 H), 2.05–2.18 (m, 1 H), 2.30–
2.43 (m, 2 H), 2.50–2.67 (br s, 1 H, CHOH), 3.82 (s, 3 H),
3.83 (s, 3 H), 3.95–4.10 (m, 2 H), 5.67–5.83 (m, 2 H), 5.93–
6.05 (m, 1 H), 6.10–6.25 (m, 1 H), 6.50–6.70 (br s, 1 H,
ArOH). 13C NMR (62.5 MHz, CDCl3): d = 24.6, 30.7, 40.6,
55.1, 55.6, 71.2, 91.5, 94.5, 106.1, 107.7, 128.8, 156.9,
159.2, 159.9.
2-[(1R*,6S*)-6-Hydroxycyclohexen-2-yl]-3,5-dimethyl-
phenol (4aa): yield: 40%; solid; mp 119–122 °C; TLC
(hexanes–EtOAc, 7:3): Rf 0.20. 1H NMR (200 MHz,
MeOD): d = 1.56–1.86 (m, 2 H), 1.93–2.12 (m, 2 H), 2.17 (s,
3 H), 2.27 (s, 3 H), 3.62–3.89 (m, 1 H), 4.12–4.33 (m, 1 H),
5.45 (d, J = 9.8 Hz, 1 H), 5.56–5.71 (m, 1 H), 6.46 (s, 2 H).
13C NMR (50 MHz, MeOD): d = 21.0, 21.2, 26.4, 33.4, 45.3,
71.1, 115.3, 124.2, 125.4, 126.0, 131.7, 137.6, 139.5, 157.1.
2-(1-Hydroxybut-3-en-2-yl)-3,5-dimethylphenol (6aa):
yield: 54%; colorless oil; TLC (hexanes–EtOAc, 6:4): Rf
0.31. 1H NMR (200 MHz, CDCl3): d = 2.24 (s, 3 H), 2.28 (s,
3 H), 3.63 (br s, 1 H), 3.81–4.19 (m, 3 H), 5.04–5.24 (m, 2
H), 6.22 (ddd, J1 = 16.6 Hz, J2 = 10.4 Hz, J3 = 5.3 Hz, 1 H),
6.58 (s, 1 H), 6.60 (s, 1 H), 8.26 (br s, 1 H). 13C NMR (50
MHz, CDCl3): d = 20.7, 44.8, 65.1, 116.1, 116.5, 122.4,
123.6, 136.0, 137.6, 154.7.
stereoisomer]; TLC (hexanes–EtOAc, 7:3): Rf 0.16. 1H
NMR (200 MHz, CDCl3): d = 1.40–2.42 (m, 6 H), 3.70 (s, 3
H), 3.74 (s, 3 H), 3.93–4.17 (m, 2 H), 5.50–5.61 (m, 1 H),
5.77–5.95 (m, 1 H), 6.01 (d, J = 2.3 Hz, 1 H), (6.06 d, J = 2.3
Hz, 1 H), 6.94–7.03 (br s, 1 H, ArOH). 13C NMR (50 MHz,
CDCl3): d = 24.7, 27.8, 39.8, 43.3, 55.1, 55.6, 71.1, 91.2,
94.4, 109.0, 132.1, 133.0, 156.3, 159.5, 159.7.
Typical Procedure for the Preparation of 2,3-Dihydro-
benzofuranes via Mitsunobu Cyclodehydration (Scheme
2): Triphenylphosphine (262.3 mg, 1.0 mmol) and diethyl-
azodicarboxylate (118 mL, 0.75 mmol) were added to a
stirred solution of hydroxyphenol 4ab (125 mg, 0.5 mmol)
in anhyd THF (2.0 mL) under argon. The reaction was
followed by TLC up to complete consumption of the starting
hydroxyphenol and the solvent was removed in vacuo. The
crude reaction mixture was purified by silica gel column
chromatography to give pure (4aR*,9bR*)-7,9-dimethoxy-
3,4,4a,9b-tetrahydrodibenzo[b,d]furan (7ab; 94 mg, 81%) as
a light yellow oil. 1H NMR (200 MHz, CDCl3): d = 1.75–
2.31 (m, 4 H), 3.75 (s, 3 H), 3.79 (s, 3 H), 3.81–3.88 (m, 1
H), 4.93–5.05 (m, 1 H), 5.73–5.95 (m, 2 H), 6.00 (d, J = 2.0
Hz, 1 H), 6.05 (d, J = 2.0 Hz, 1 H). 13C NMR (50 MHz,
CDCl3): d = 19.2, 25.1, 39.0, 55.1, 55.4, 82.3, 88.7, 91.0,
110.1, 126.0, 126.7, 156.7, 161.1, 161.5.
(4aR*,9bR*)-7,9-Dimethyl-3,4,4a,9b-tetrahydro-
dibenzo[b,d]furan (7aa): yield: 83%; colorless oil; TLC
(hexanes–Et2O, 9:1): Rf 0.51. 1H NMR (200 MHz, CDCl3):
d = 1.75–2.12 (m, 2 H), 2.19–2.30 (m, 2 H), 2.27 (s, 3 H),
2.30 (s, 3 H), 3.77 (br d, J = 6.9 Hz, 1 H), 4.94–5.00 (m, 1
H), 5.68–5.95 (m, 2 H), 6.48 (s, 1 H), 6.50 (s, 1 H). 13C NMR
(50 MHz, CDCl3): d = 18.3, 19.0, 21.4, 24.9, 40.1, 81.3,
108.0, 122.6, 125.1, 126.9, 127.8, 134.0, 138.2.
(5aR*,10aR*)-1,3-Dimethoxy-6,7,8,10a-tetrahydro-5aH-
benzo[d]cyclohepta[b]furan (7bb): yield: 80% (obtained
as an inseparable mixture with 10% of the corresponding
trans stereoisomer); light yellow oil; TLC (hexanes–EtOAc,
Synlett 2007, No. 19, 3011–3015 © Thieme Stuttgart · New York

LETTER
9:1): Rf 0.38. 1H NMR (200 MHz, CDCl3): d = 1.55–1.75 (m,
Alkylation of Phenol Derivatives with Vinyloxiranes
3015
yellow oil; TLC (hexanes–EtOAc, 9:1): Rf 0.45. 1H NMR
(200 MHz, CDCl3): d = 0.95–2.25 (m, 8 H), 3.72 (s, 3 H),
3.76 (s, 3 H), 4.10–4.26 (m, 1 H), 4.50–4.67 (m, 1 H), 5.11
(dd, J1 = 10.6 Hz, J2 = 7.0 Hz, 1 H), 5.68–5.88 (m, 1 H), 6.00
(s, 2 H). 13C NMR (50 MHz, CDCl3): d = 26.6, 26.7, 28.2,
29.2, 40.4, 55.5 (2 × C), 88.3, 91.3, 91.5, 11.8, 130.5, 133.3,
156.7, 160.5, 161.6.
2 H), 1.92–2.07 (m, 2 H), 2.09–2.22 (m, 2 H), 3.76 (s, 3 H),
3.80 (s, 3 H), 4.25 (d, J = 9.8 Hz, 1 H), 4.88 (ddd, J1 = 4.5
Hz, J2 = 9.8 Hz, 1 H), 5.62–5.68 (m, 2 H), 6.00–6.05 (m, 2
H). 13C NMR (50 MHz, CDCl3): d = 19.4, 26.7, 28.7, 42.4,
55.3, 55.5, 85.5, 88.1, 91.1, 127.6, 129.7, 159.0, 160.3,
160.7.
(5aS*,11aS*,Z)-1,3-Dimethoxy-5a,6,7,8,11a-hexa-
hydrobenzo[b]cycloocta[d]furan (7cb): yield: (70%); light
(14) Brown, C. A.; Krishnamurthy, S. J. Org. Chem. 1978, 43,
2731.
Synlett 2007, No. 19, 3011–3015 © Thieme Stuttgart · New York

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