Palladium-catalyzed synthesis of 2,3-dihydro-2-ylidene-1,4-benzodioxins

Article abstract of DOI:10.1021/jo0103625

Palladium-catalyzed condensation of benzene-1,2-diol with various propargylic carbonates, afforded regio- and stereoselectively 2,3-dihydro-2-ylidene-1,4-benzodioxins. The reaction is suggested to proceed by the formation of a (σ-allenyl)palladium complex, followed by the intermolecular attack of the phenoxide ion on this complex to generate a new (σ-allyl)palladium complex in equilibrium with the corresponding (η³-allyl)palladium complex. Intramolecular attack of the phenoxide ion afforded the corresponding benzodioxan compound. This last attack occurs predominantly at the more electrophilic end of the (η³-allyl)palladium intermediate. The Z- or E-stereochemistry of the products was established by ¹H NMR and proton NOE measurements and also by X-ray analysis on an example. The Z-stereochemistry generally observed is in agreement with the formation of this (η³-allyl)palladium intermediate. However, in the case of tertiary propargylic carbonates, the E-stereochemistry generally observed could be explained by an intramolecular attack of the phenoxide ion on the intermediate (σ-allyl)palladium complex, in slow equilibrium with the (η³allyl)palladium complex.

Full text of DOI:10.1021/jo0103625

6634
J . Org. Chem. 2001, 66, 6634-6642
P a lla d iu m -Ca ta lyzed Syn th esis of
2,3-Dih yd r o-2-ylid en e-1,4-ben zod ioxin s
J ean-Robert Labrosse, Paul Lhoste, and Denis Sinou*
Laboratoire de Synthe`se Asyme´trique, UMR CNRS 5622, CPE Lyon, Universite´ Claude Bernard Lyon 1,
43 boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
sinou@univ-lyon1.fr
Received April 5, 2001
Palladium-catalyzed condensation of benzene-1,2-diol with various propargylic carbonates afforded
regio- and stereoselectively 2,3-dihydro-2-ylidene-1,4-benzodioxins. The reaction is suggested to
proceed by the formation of a (σ-allenyl)palladium complex, followed by the intermolecular attack
of the phenoxide ion on this complex to generate a new (σ-allyl)palladium complex in equilibrium
with the corresponding (η3-allyl)palladium complex. Intramolecular attack of the phenoxide ion
afforded the corresponding benzodioxan compound. This last attack occurs predominantly at the
more electrophilic end of the (η3-allyl)palladium intermediate. The Z- or E-stereochemistry of the
1
products was established by H NMR and proton NOE measurements and also by X-ray analysis
on an example. The Z-stereochemistry generally observed is in agreement with the formation of
this (η3-allyl)palladium intermediate. However, in the case of tertiary propargylic carbonates, the
E-stereochemistry generally observed could be explained by an intramolecular attack of the
phenoxide ion on the intermediate (σ-allyl)palladium complex, in slow equilibrium with the (η3-
allyl)palladium complex.
In tr od u ction
idene-1,4-dihydro-3-substituted-1,4-benzodioxins have been
obtained from the corresponding 2-hydroxymethyl-1,4-
benzodioxin through a zinc salt-mediated Mitsunobu
substitution,7a by an acid-catalyzed ortho ester Claisen
rearrangement or by an Eschenmoser procedure.7b Con-
densation of benzene-1,2-diol and methyl 4-chlorobu-
tynoate in acetone in the presence of potassium carbonate
afforded a mixture of 1,4-benzodioxinic products.7c Pyro-
catechol monoprop-2-ynyl ether and analogues were
cyclized to the corresponding 2,3-dihydro-2-methylene-
1,4-benzodioxins in DMF in the presence of mercuric
Compounds containing 1,4-benzodioxin and 1,4-ben-
zodioxan structures have attracted considerable interest
in recent years, mainly due to their interesting biological
activities. For example, various 2-substituted 1,4-benzo-
dioxans have shown interesting properties as R- or
â-blocking agents and could be used in antidepression
or antihypertension therapy.1 Others exhibit antihyper-
glycemic properties2 or act as inhibitors of 5-lipoxyge-
nase.3 Moreover, the 1,4-benzodioxan structure is found
in a variety of biological active natural products.4 Finally,
these compounds could also be used as intermediates for
very useful synthetic transformations.5
oxide7d or PdCl2(PPh3)2 as the catalyst. Monoprop-2-
7e
ynylated catechol and 2-hydroxy-3-(prop-2-yloxy)naph-
thalene reacted with aryl halides in the presence of
PdCl2(PPh3)2 and CuI in triethylamine to give regio- and
stereoselectively the corresponding 2,3-dihydro-2-ylidene-
1,4-benzo- and naphthodioxins in good yields.7f,g Treat-
ment of 2,3-dibromo-1-propene with the disodium salt of
While there are many approaches for the synthesis of
1,4-benzodioxins,6 the synthetic routes to 2-alkylidene-
2,3-dihydro-1,4-benzodioxins are less common. 2-Alkyl-
(1) (a) Nelson, W. L.; Wennerstrom, J . E.; Dyer, D. C.; Engel, M. J .
Med. Chem. 1977, 20, 880. (b) Marciniak, G.; Delgado, A.; Leclerc, G.;
Velly, J .; Decker, N.; Schwartz, J . J . Med. Chem. 1989, 32, 1402. (c)
Ruffolo J r., R. R.; Boudinell, W.; Hieble, J . P. J . Med. Chem. 1995, 38,
3681. (d) Giardina, D.; Bertini, R.; Brancia, E.; Brasili, L.; Melchiorre,
C. J . Med. Chem. 1985, 28, 1354. (e) Quaglia, W.; Pigini, M.; Tayebati,
S. K.; Piergentili, A.; Gianella, M.; Leonardi, A.; Taddei, C.; Melchiorre,
C. J . Med. Chem. 1996, 39, 2253.
(2) Fagan, G. P.; Chapleo, C. P.; Lane, A. C.; Myers, M.; Roach, C.
F. C.; Stillings, M. R.; Welbourn, A. P. J . Med. Chem. 1988, 31, 944.
(3) Satoh, Y.; Powers, C.; Toledo, L. M.; Kowalski, T. J .; Peters, P.
A.; Kimble, E. F. J . Med. Chem. 1995, 38, 68.
(4) (a) Merlini, L.; Zanarotti, A. Tetrahedron Lett. 1975, 42, 2757.
(b) Merlini, L.; Zanarotti, A. J . Chem. Soc., Chem. Commun. 1979, 695.
(c) Arnone, A.; Merlini, L.; Zanarotti, A. J . Chem. Soc., Chem. Commun.
1979, 696. (d) Bosseray, P.; Guillaumet, G.; Coudert, G.; Wasserman,
H. Tetrahedron Lett. 1989, 30, 1387. (e) Debenedetti, S. L.; Nadinic,
E. L.; Coussio, J . D.; Kimpe, N. De.; Dupont, J . F.; Declercq, J . P.
Phytochemistry 1991, 30, 2757. (f) Tsukamoto, S.; Kato, H.; Hirota,
H.; Fusetani, N. Tetrahedron 1994, 50, 13583.
(5) (a) Lee, T. V.; Leigh, A. J .; Chapleo, C. B. Tetrahedron 1990, 46,
921. (b) Lee, T. V.; Leigh, A. J .; Chapleo, C. B. Synlett 1989, 30. (c)
Moreau, P.; Guillaumet, G.; Coudert, G. Synth. Commun. 1994, 24,
1781. (d) Mata, E. G.; Suarez, A. G. Synth. Commun. 1997, 27, 1291.
(6) (a) Katritzky, A. R.; Sewell, M. J .; Topsom, R. D.; Monro, A. M.;
Potter, G. W. H. Tetrahedron 1966, 22, 931. (b) Farina, G.; Zecchi, G.
Synthesis 1977, 755. (c) Guillaumet, G.; Coudert, G.; Loubinoux, B.
Tetrahedron Lett. 1979, 4379. (d) Ruiz, N.; Pujol, M. D.; Guillaumet,
G.; Coudert, G. Tetrahedron Lett. 1992, 33, 2965. (e) Adam, W.;
Schmidt, E.; Takayama, K. Synthesis 1982, 322. (f) Chapleo, C. B..
Davis, J . A.; Myers, P. L.; Readhead, M. J .; Stillings, M. R.; Welbourn,
A. P.; Hampton, F. C.; Sugden, K. J . Heterocycl. Chem. 1984, 21, 77.
(g) Lee, T. V.; Leigh, A. J .; Chapleo, C. B. Synthesis 1989, 208. (h)
Lee, H. H.; Denny, W. A. J . Chem. Soc., Perkin Trans. 1 1990, 1071.
(i) Massacret, M.. Goux, C.; Lhoste, P.; Sinou, D. Tetrahedron Lett.
1994, 35, 6093. (j) Massacret, M.; Lhoste, P.; Lakhmiri, R.; Parella, T.
Sinou, D. Eur. J . Org. Chem. 1999, 2665.
(7) (a) Ruiz, N.; Rollin, P. Tetrahedron Lett. 1989, 30, 1637. (b)
Moreau, P.; Al Neirabeyeh, M.; Guillaumet, G.; Coudert, G. Tetrahe-
dron Lett. 1991, 32, 5525. (c) Cabiddu, S.; Floria, C.; Melis, S.; Sotgiu,
F.; Cerioni, G. J . Heterocycl. Chem. 1986, 23, 1815. (d) Yamamoto, M.
J . Chem. Soc., Perkin Trans. 1 1979, 3161. (e) Basak, A., Bhattacharya,
G., Mallik, U. K.; Khamrai, U. K. Synth. Commun. 1997, 27, 367. (f)
Chowdhury, C.; Kundu, N. G. Chem. Commun. 1996, 1067. (g)
Chowdhury, C.; Chaudhury, G.; Guha, S.; Mukherjee, A. K.; Kundu,
N. G. J . Org. Chem. 1998, 63, 1863. (h) Organ, M. G.; Miller, M.;
Konstantinou, Z. J . Am. Chem. Soc. 1998, 120, 9283.
10.1021/jo0103625 CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/01/2001

Synthesis of 2,3-Dihydro-2-ylidene-1,4-benzodioxins
J . Org. Chem., Vol. 66, No. 20, 2001 6635
Sch em e 1
dppb or 1,4-bis(diphenylphosphino)butane, THF, room
temperature]. A wide variety of propargylic carbonates
were used successfully in this cyclization reaction (Table
1).
Propargyl carbonate 1a underwent annulation to give
2,3-dihydro-2-methylene-1,4-benzodioxin (2) in 81% yield
(Table 1, entry 1). The methyl-substituted alkynyl car-
bonate 1b gave the corresponding 2,3-dihydro-3-methyl-
2-methylene-1,4-benzodioxin (3) in 95% yield (Table 1,
entry 2). However, substitution of the methyl group by
an ethyl, a tert-butyldimethylsilyloxymethyl, or a tert-
butyl group gave a mixture of the two annulated regio-
isomers, in lower yield in the latter case: carbonate 1c
afforded a 90/10 mixture of compounds 4 and 5, and
carbonates 1d ,e gave compounds 6/7 and 8/9 in a 31/69,
and 25/75 ratio, respectively (Table 1, entries 4 and 5).
It is to be noticed that the cyclization leading to benzo-
dioxans 5 and 9 was totally stereoselective, only the
Z-isomer being obtained, whereas a 90/10 mixture of
Z/ E-isomers was obtained in the case of compound 7.
We then turned our attention to the cyclization reac-
tion using unsubstituted secondary carbonates 1f-i. As
expected, carbonate 1f led to the totally regioselective
formation of 2,3-dihydro-3-methyl-2-methylene-1,4-ben-
zodioxin (3) (Table 1, entry 6), while carbonates 1g-i
gave a mixture of 2,3-dihydro-3-alkyl-2-methylene- and
2,3-dihydro-2-alkylidene-1,4-benzodioxins, the former be-
ing predominant (Table 1, entries 7-9). However increas-
ing the steric bulk of the R2 group favored the cyclization
to the alkylidene product, the formation of this compound
being highly stereoselective.
Substituted secondary carbonates 1j,k , having two
identical substituents, gave 2,3-dihydro-2-ylidene-1,4-
benzodioxins 16 and 17 in quite good yields and with total
stereoselectivity, only the Z-isomer being formed (Table
1, entries 10 and 11). However no cyclization product was
observed using carbonate 1l bearing two very bulky
substituents (Table 1, entry 12).
Propargylic carbonate 1m , having an n-pentyl and a
phenyl group as substituents, afforded a mixture of the
two regioisomers 18 and 19 (Table 1, entry 13), while the
propargylic carbonate 1n , bearing an n-hexyl and a
trifluoromethyl group, cyclized regio- and stereospecifi-
cally to 2,3-dihydro-2-n-hexyl-3-trifluoroethylidene-1,4-
benzodioxin (20) (Table 1, entry 14).
Condensation of propargylic tertiary carbonates 1o,p
with benzene-1,2-diol afforded regiospecifically the cor-
responding 2,3-dihydro-3-alkylidene-1,4-benzodioxins 21
and 22 (Table 1, entries 15 and 16). Carbonates 1q,r ,
bearing a methyl and an isopropyl group and a methyl
and a benzyl group, respectively, afforded a mixture of
two regioisomers 23/24 and 25/26 in a 66/34 and 32/68
ratio, respectively (Table 1, entries 17 and 18); for
compounds 24 and 26, the major stereoisomer had the
E-stereochemistry. Finally, reaction of benzene-1,2-diol
with substituted tertiary carbonates 1s,t led regio- and
stereoselectively to the formation of heterocycles 27 and
28, having the Z-stereochemistry (Table 1, entries 19 and
20).
Since the condensation of carbonate 1d and benzene-
1,2-diol gave a mixture of two functionalized regioisomers
6 and 7 in a 31/69 ratio, we expected that modification
of the structure of the palladium catalyst could change
this ratio and afford regioselectively one of the regioiso-
mers. Table 2 summarizes the results obtained by
modifying the ligand. Among the diphosphines used, the
catechol in the presence of Pd(PPh3)4 afforded 2,3-
dihydro-2-methylene-1,4-benzodioxin in 67% yield.7h
Recently, Tsuji et al. have shown that propargylic
carbonates reacted with soft carbon nucleophiles and oxo
nucleophiles.8 The formation of furans was observed
using soft carbon nucleophiles such as alkyl acetoacetate
or acetylacetone via a double alkylation process, with the
alkyl acetoacetate or the acetylacetone behaving as a
bisnucleophile.9 As part of our ongoing interest in devel-
oping methods for the preparation of benzodioxan deriva-
tives via organometallic catalysis,6i,j we expected that
benzene-1,2-diol could react as a bisnucleophile with
propargyl carbonates under palladium catalysis to give
the expected 2-alkylidene-2,3-dihydro-1,4-benzodioxins
according to Scheme 1. We described previously some
preliminary results concerning this heteroannulation
reaction,10 and we wish to report in greater detail the
results of our investigation, as well as the scope and
limitations of this methodology.
Resu lts a n d Discu ssion
The conditions described previously for the heteroan-
nulation of benzene-1,2-diol using the bis(carbonate) of
2-buten-1,4-diol were used as our standard reaction
conditions [1 equiv of benzene-1,2-diol, 1.2 equiv of
propargylic carbonate, 2.5 mol % Pd2(dba)3, 10 mol %
(8) Tsuji, J .; Mandai, T. Angew. Chem., Int. Ed. Engl. 1995, 34, 2589.
(9) (a) Tsuji, J .; Watanabe, H.; Minami, I.; Shimizu, I. J . Am. Chem.
Soc. 1985, 107, 2196. (b) Minami, I.; Yuhara, M.; Watanabe, H.; Tsuji,
J . J . Organomet. Chem. 1987, 334, 225.
(10) Labrosse, J .-R.; Lhoste, P.; Sinou, D. Tetrahedron Lett. 1999,
40, 9025.

6636 J . Org. Chem., Vol. 66, No. 20, 2001
Labrosse et al.
Ta ble 1. Rea ction of P r op a r gylic Ca r bon a tes 1a -t w ith Ben zen e-1,2-d iol in th e P r esen ce of P a lla d iu m Ca ta lysta

Synthesis of 2,3-Dihydro-2-ylidene-1,4-benzodioxins
J . Org. Chem., Vol. 66, No. 20, 2001 6637
Ta ble 1 (Con tin u ed )
a
Reactions were carried out at room teperature for 24 h using the following ratios: [1]:[benzene-1,2-diol]:[Pd2(dba)3]:[dppb] ) 48:40:
1:4. Yields refer to chromatographically isolated pure products. c Determined by GC and 1H NMR. e Less than 4% of another product,
b
probably 2,3-dihydro-2-propylidene-1,4-benzodioxin, was also formed.
Ta ble 2. Rea ction of P r op a r gylic Ca r bon a tes 1d w ith
Ben zen e-1,2-d iol in th e P r esen ce of P a lla d iu m Ca ta lysta
2, entries 1 and 2). The very large difference between
dppe and dppp, on one hand, and dppb, dpppe, dpph, and
dppf, on the other hand, could be related to the larger
cone angle of the later diphoshines. Monophosphines such
as triphenylphosphine, tris(p-tolyl)phosphine), tris(o-
tolyl)phosphine, and tris(furyl)phosphine also gave good
yields of cyclized products (Table 2, entries 7-10).
However comparison of entries 8-10 showed that the
regioselectivity is probably under steric control; P(C6H4-
2-Me)3 having a larger cone angle than PPh3 and P(C6H4-
4-Me)3 (145 vs 194°, respectively), gave predominantly
the regioisomer 7, although the two former gave a 50/50
mixture of the two regioisomers 6 and 7. The more basic
tris(o-methoxyphenyl)phosphine gave no reaction at all.
products
entry
phosphine
dppe
dppp
dppb
dpppe
dpph
dppf
PPh3
P(C6H4-2-Me)3
P(C6H4-4Me)3
P(2-furyl)3
P(C6H4-2-OMe)3
6 (%) 7 (%) (Z/ E ratio) yield (%)
1
2
3
4
5
6
7
8
9
41
22
31
48
42
42
52
17
50
21
59 (93/7)
78 (92/8)
69 (89/11)
52 (88/12)
58 (93/7)
58 (85/15)
48 (88/12)
83 (94/6)
50 (86/14)
79 (93/7)
15
11
97
60
98
92
86
88
89
74
0
10
11
a
Reactions were carried out at room teperature for 24 h using
Id en tifica tion of Str u ctu r es. The structure of these
heterocyclic compounds could be assigned from 1H and
13C NMR spectra and elemental analysis. The heteroan-
nulation was found to be highly stereoselective, the
Z-isomer being exclusively or almost exclusively obtained.
This Z-stereochemistry was assigned on the basis of
several pieces of evidence. For compound 7 for example,
the olefinic proton signal of the major isomer appears at
higher field (δ 4.91 ppm) than the minor one (δ 5.45 ppm),
due to the deshielding effect of the oxygen of the 1,4-
benzodioxane ring system. We can therefore attribute the
Z-configuration to the major isomer according to the
litterature references.11 However, to confirm this attribu-
tion, compound 7 was desilylated and then acetylated to
the following ratios: [1]:[benzene-1,2-diol]:[Pd2(dba)3]:[-PPh2] ) 48:
b
40:1:4. Yields refer to chromatographically isolated pure prod-
ucts. c Determined by GC and 1H NMR.
highest yields were obtained using dppb, dppf [or 1,1′-
bis(diphenylphosphino)ferrocene], and dpph [or 1,6-bis-
(diphenylphosphino)hexane], 97, 92, and 98% yield,
respectively (Table 2, entries 3, 5, and 6), while dpppe
[or 1,5-bis(diphenylphosphino)pentane] gave lower yield
(60%, Table 1, entry 4). Practically the same selectivity
was observed using these ligands. Conversely dppe [or
1,2-bis(diphenylphosphino)ethane] and dppp [or 1,3-bis-
(diphenylphosphino)propane] gave very low yields (Table

6638 J . Org. Chem., Vol. 66, No. 20, 2001
Labrosse et al.
Sch em e 2
signal of the minor isomer at δ 4.68 ppm. Finally, the
X-ray diffraction study of 2-benzylidene-2,3-dihydro-3-
phenyl-1,4-benzodioxin (17) was also performed and
confirmed the Z-stereochemistry of this compound.
Mech a n ism . The reaction is believed to proceed ac-
cording to Scheme 3. Propargylic carbonate 1 reacts with
palladium(0) to generate an allenylpalladium intermedi-
ate A and methanoate anion. Attack of the monoanion
of benzene-1,2-diol on the central sp carbon of this
intermediate A gives a new intermediate B. Abstraction
of the proton from the secondary hydroxyl function forms
a new (σ-allyl)palladium complex which equilibrates to
(syn- and (anti-η3-allyl)palladium intermediates D. In-
tramolecular nucleophilic displacement by the phenoxide
provides the observed products and regenerates the
palladium(0) catalyst. According to this mechanism, the
regio- and stereoselectivity of this process arises from the
(η3-allyl)palladium displacement step.
Concerning the regioselectivity of the process, carbon-
ates 1b,c,f,g,o-q,s,t led to differently substituted (η3-
allyl)palladium intermediates D (monosubstituted, di-
substituted on the same end ofthe π-allyl, or trisubstituted),
and we observed that the ring formation by oxygen
displacement occurred preferentially, almost exclusively,
at the more substituted end of the allylic system (Table
1, entries 2, 3, 6, 7, 15, 16, 19, and 20). Carbonates
1e,h ,i,q,r gave also unsymmetrical η3-allyl intermediates;
however, 1e led to the formation of the regioisomer 9 only
(Table 1, entry 5), arising from the attack on the less
hindered end of the η3-allyl intermediate, while a mixture
of regioisomers was obtained in the other cases (Table 1,
entries 8, 9, 17 and 18). This regioselectivity could be
explained in the following way. The (η3-allyl)palladium
intermediate D is a cationic species, with the charge lying
preferentially at the more substituted carbon for elec-
tronic reasons. Allylic substitution at this more electro-
philic carbon gives the observed products. The opposite
regioselectivity observed concerning the attack for entry
5, and even for entries 17 and 18, could be attributed to
steric hindrance, the more substituted and electrophilic
end being now too crowded. This is in agreement with
results observed by Larock et al. in the palladium-
catalyzed annulation of 1,2-dienes.12
Introduction of an electron-withdrawing group such as
CF3 on one termini of the η3-allyl intermediate affords
exclusively regioisomer 20, resulting from the attack of
the nucleophile on the effectively more electrophilic
carbon of the η3-allyl intermediate (Table 1, entry 14).
Introduction of a phenyl (Table 1, entries 9 and 13) or a
benzyl group (Table 1, entries 8 and 18) on one end of
the η3-allyl system modifies also the relative electrophi-
licity of the two termini of the η3-allyl intermediate and
affords a mixture of the two regioisomers.
To confirm this hypothesis, we condensed benzene-1,2-
diol with carbonates 1m ,u ,w and acetates 31a ,b, bearing
various substituents on the phenyl ring, in the presence
of palladium(0). We assumed that the intermediate η3-
allyl complex with a positive charge on the carbon
bearing the aryl group will be destabilized in the case of
an electron-withdrawing group and stabilized in the case
of an electron-donating group; so the presence of an
electron-donating group would increase the amount of
give acetate 30 (Scheme 2). We noticed again that the
chemical shift of the vinylic proton in the E-isomer was
further downfield (δ 5.47 ppm) than the corresponding
one in the Z-isomer (δ 4.95 ppm). Moreover, this assign-
ment was confirmed by the proton NOE measurement:
when the methylene protons of the ring of the major
isomer of compound 30 (δ 4.50 ppm) were irradiated, the
vinylic proton signal of the major isomer at δ 4.95 ppm
showed a strong enhancement (5.8%). This experiment
confirmed the Z/E-stereochemistry of the double bond for
compound 7. For compound 13, which is also a mixture
of two stereoisomers, we observed again for the vinylic
proton of the major isomer a signal at higher field (δ 4.95
ppm) than for the minor isomer (δ 5.43 ppm), in agree-
ment with a Z-stereochemistry for the major isomer.
Moreover, irradiation of the OCH2 signal of the major
isomer at δ 4.47 ppm led to a 7.4% enhancement of the
vinylic proton signal at δ 4.95 ppm.
For compounds 5, 9, 11, 16, 18, 20, and 27, which are
obtained as a single stereoisomer, we noticed that the
signal of the vinylic proton was at δ 4.55-4.96 ppm, very
close to the values observed for the vinylic proton anti to
the oxygen ring (δ 4.75 ppm). Moreover, irradiation of
the proton R to the oxygen for compounds 9, 16, and 20
afforded an enhancement of the signal of the vinylic
proton of 5.9, 2.1, and 9.2%, respectively, in agreement
with a Z-configuration. When the vinylic proton of
compound 18 or the methyl group of compound 27 was
irradiated, an enhancement of the olefinic proton signal
of 6.3 and 2.9%, respectively, was observed, confirming
the Z-configuration. For compounds 15, 17, 19, and 28,
bearing a phenethylydene substituent, irradiation of the
allylic proton of the ring (compounds 15 and 17), the
vinylic proton (compound 19), or the methyl group
(compound 26) showed an enhancement of respectively
the vinylic proton signal (9.8 and 9.0%), the allylic proton
signal (11.3%), and the vinylic proton signal (3.9%). These
results allowed the unambiguous attribution of the
Z-stereochemistry for all these compounds.
Concerning compound 24, irradiation of the signal of
the OCH2 group of the major isomer at δ 4.70 ppm
showed an enhancement of 10.9% of the signal of the
methyl of the isopropylidene group at δ 1.10 ppm, and
conversely irradiation the signal at δ 1.10 ppm showed
an enhancement of 17% of the signal of the OCH2 group.
Irradiation of the signal of the methyl group of the same
isomer at δ 1.75 showed no enhancement. For heterocycle
26, an enhancement of 7.7% of the OCH2 signal of the
major isomer was observed by irradiation of the ben-
zylidene signal of the major isomer at δ 4.76 ppm, while
no effect was observed by irradiation of the benzylidene
(11) (a) J ager, V.; Gunther, H. J . Tetrahedron Lett. 1977, 2543. (b)
Yamamoto, M. J . Chem. Soc., Chem. Commun. 1978, 649. (c) Arcadi,
A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.; Pietroni, B. R.
J . Org. Chem. 1992, 57, 976.
(12) (a) Larock, R. C.; He, Y.; Leong, W. W.; Han, X.; Refvik, M. D.;
Zenner, J . M. J . Org. Chem. 1998, 63, 2154. (b) Larock, R. C.; Tu, C.;
Pace, P. J . Org. Chem. 1998, 63, 6859.

Synthesis of 2,3-Dihydro-2-ylidene-1,4-benzodioxins
J . Org. Chem., Vol. 66, No. 20, 2001 6639
Sch em e 3
Ta ble 3. Rea ction of P r op a r gylic Ca r bon a tes 1m ,u -w a n d Aceta tes 31a ,b w ith Ben zen e-1,2-d iol in th e P r esen ce of
P a lla d iu m Ca ta lysta
a
Reactions were carried out at room teperature for 24 h using the following ratios: [1 or 31]:[benzene-1,2-diol]:[Pd2(dba)3]:[dppb] )
0.48:40:1:4. Yields refer to chromatographically isolated pure products. c Determined by GC and 1H NMR.
b
Sch em e 4
2-aryl-2,3-dihydro-3-hexylidene-1,4-benzodioxine, and re-
versely an electron-withdrawing group would increase
the amount of 2-benzylidene-2,3-dihydro-3-pentyl-1,4-
benzodioxine. The results summarized in Table 3 are in
quite good agreement with this hypothesis. Carbonate
1u gave a mixture of two regioisomers 32 and 33 (Table
3, entry 2), in a 25/75 ratio, quite closed to that obtained
using carbonate 1m . Carbonate 1w , or acetate 31a in the
presence of NEt3, having an electron-withdrawing group,
afforded only the cyclized regioisomer 35. Conversely
acetate 31b bearing an electron-donating group gave the
two regioisomers 36 and 37 in a 38/62 ratio. Carbonate
1v afforded also regiospecifically the cyclized product 34
only, but this is probably due to steric reason. It is to be
noticed that NOE experiments showed that all stereo-
isomers have the Z-configuration; for example, irradiation
of the signal of the vinylic proton of 36 at δ 4.45-4.60
ppm showed an enhancement of 3.8% of the signal of the
benzylic proton at δ 5.40 ppm, although irradiation of
the signal of the benzylic proton of 37 at δ 5.55 ppm
showed an enhancement of 7.8% of the signal of the
vinylic proton at δ 4.45-4.60 ppm.
5). Effectively attack of the phenoxide on the σ-allenyl
complex A afforded, after hydrogen exchange, two dia-
stereoisomeric (σ-allyl)palladium complexes C1 and C2
that are in equilibrium with the corresponding η3-allyl
complexes D1 and D2 (R3 ) H). In this case the stereo-
selectivity depends on the relative abundance of the
different (syn- and (anti-η3-allyl)palladium intermediates
D1 and D2. The controlling factor seems to be the steric
hindrance in the (η3-allyl)palladium intermediates. In the
(anti-η3-allyl)palladium complex D1, the steric hindrance
2,3-Dihydro-2-ylidene-1,4-benzodioxins bearing only
one substituent on the double bond had mainly, if not
exclusively, the Z-stereochemistry. This could be ex-
plained on the basis of the π-allyl mechanism (Scheme

6640 J . Org. Chem., Vol. 66, No. 20, 2001
Labrosse et al.
Sch em e 5
is higher than in the (syn-η3-allyl)palladium complex D2;
attack of the phenoxide gives predominantly the Z-
stereoisomer.
process is often quite regio- and stereoselective, the major
regioisomer being formed by the intramolecular attack
of the phenoxide ion on the more electrophilic termini of
the (η3-allyl)palladium intermediate. The stereochemistry
of the double bond in the resulting heterocycle depends
on substitution pattern of the propargylic carbonate:
primary and secondary carbonates afforded mainly, if not
at all, the Z alkene, although tertiary carbonates gave
predominantly the E-isomer.
However 2,3-dihydro-2-ylidene-1,4-benzodioxins 24 and
26 bearing two substituents on the double bond exhibited
mainly the E-stereochemistry. To explain this quite
different behavior, we postulated that, due to steric
hindrance on the double bond, the σ h η3 h σ equilibrium
leading to the formation of the (η3-allyl)pallladium in-
termediates D is slower in these two examples. There is
therefore a competition between the attack of the phe-
noxide on the (η3-allyl)palladium and on the (σ-allyl)-
palladium intermediates. It was shown previously that
the attack on the (η3-allyl)palladium intermediate oc-
curred predominantly, if not entirely, at the more sub-
stituted termini of the η3-allyl system affording in these
cases the two compounds 23 and 25. Comparison of
entries 15-18 in Table 1 shows that the substitution of
a methyl group by an isopropyl or a benzyl group favors
the formation of compounds 24 and 26. The major
E-stereochemistry observed for these compounds could
be explained by assuming that they are formed mainly
by the second attack of the phenoxide on the (σ-allyl)-
palladium complexes C. Attack of the phenoxide on the
(σ-allenyl)palladium complex A gives two diastereoiso-
meric (σ-allyl)palladium complexes C1 and C2. We could
expected this attack to occur from the less sterically
hindered side, affording in this case predominantly the
stereoisomer C1 (R2 ) CH3), which will give the E-isomer.
Exp er im en ta l Section
Reactions involving palladium catalysis were performed in
Schlenk tubes under a nitrogen atmosphere. Solvents and
reagents were purified by conventional methods. Thin-layer
chromatography was performed on precoated sheets 60F254
,
and silica gel chromatography was done using Merck SiO2
(Gerudan SI 60, 0.040-0.063 mm). Melting points are uncor-
1
rected. H NMR solutions were recorded at 200 or 300 MHz,
and 13C NMR spectra at 75 MHz; NMR chemical shifts are
reported in ppm downfield from TMS, and J values are given
in hertz. Pd2(dba)3, triphenylphosphine, tris(2-methylphenyl)-
phosphine, tris(4-methylphenyl)phosphine, tris(2-furyl)phos-
phine, tris(2-methoxyphenyl)phosphine, 1,2-bis(diphenylphos-
phino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(di-
phenylphosphino)butane, 1,5-bis(diphenylphosphino)pentane,
1,6-bis(diphenylphosphino)hexane, and benzene-1,2-diol were
purchased from a commercial source.
Alcohols used as starting materials for the synthesis of
carbonates 1d ,13 1e,14 1h ,15 1k ,16 1l,17 1m ,18 1n ,19 1r ,20 1s,21
(13) Naidi, S. D.; Olmstead, M. M.; Schore, N. E. J . Organomet.
Chem. 1992, 431, 335.
(14) MacInnes, I.; Walton, J . C. J . Chem. Soc., Perkin Trans. 2 1987,
1077.
Con clu sion
The palladium-catalyzed condensation of benzene-1,2-
diol with various propargylic carbonates provides a
versatile and easy access to a wide variety of 2,3-dihydro-
2-ylidene-1,4-benzodioxins with quite good yields. The
(15) Burger, J . Med. Chem. 1966, 9, 469.
(16) Pilcher, A. S.; de Shong, P. J . Org. Chem. 1996, 61, 6901.
(17) Brown, H. C.; Molander, G. A.; Singh, S. M.; Racherla, U. S. J .
Org. Chem. 1985, 50, 1577.
(18) Han Y.; Huang Y.-Z. Tetrahedron Lett. 1995, 36, 7277.

Synthesis of 2,3-Dihydro-2-ylidene-1,4-benzodioxins
J . Org. Chem., Vol. 66, No. 20, 2001 6641
and 1t,22 as well as carbonates 1a ,23 1b,9b 1c,9b 1d ,24 1g,25 1i,26
1j,9b and 1o,9b were prepared according to known procedures.
Dihydrobenzodioxins 2,7g 15,7g and 2127 have already been
described.
dCH), 5.45 (t, J ) 7.0 H, 0.1H, dCH), 6.80-7.10 (m, 4H,
Harom); 13C NMR (CDCl3) δ -5.1, 18.4, 26.0 (E), 26.1 (Z), 56.6
(Z), 57.8 (E), 60.6 (E), 65.1 (Z), 107.0 (E), 107.7 (Z), 116.5 (E),
116.6 (Z), 117.2 (E), 117.4 (Z), 122.0 (E), 122.2 (Z), 122.3, 142.6,
143.2, 144.0. Anal. Calcd for C16H24O3Si: C, 65.72; H, 8.28.
Found: C, 65.39; H, 8.61.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed An -
n u la tion Rea ction s. A mixture of Pd2(dba)3 (20.8 mg, 2.2 ×
10-2 mmol) and diphosphine (9.1 × 10-2 mmol) or monophos-
phine (18.2 × 10-2 mmol), in THF (7 mL), was stirred under
a nitrogen atmosphere at room temperature for 30 min. This
catalyst solution was added to a mixture of benzene-1,2-diol
(100 mg, 0.9 mmol) and the corresponding propargylic carbon-
ate (1.1 mmol) or the corresponding acetate (1.1 mmol) in the
presence of triethylamine (267 mg, 2.6 mmol). The resulting
solution was stirred at room temperature for 24 h. The solvent
was evaporated and the residue chromatographed over silica
eluting with petroleum ether/ethyl acetate to afford the
corresponding 2,3-dihydro-1,4-benzodioxin. The yields of the
products from the reactions are listed in Tables 1-3. The
spectral data of some of the compounds are listed below, and
others have been incorporated in the Supporting Information.
2,3-Dih yd r o-2-m eth yl-3-m eth ylen e-1,4-ben zod ioxin (3):
oil; Rf 0.3 (petroleum ether/ethyl acetate 100/1); 1H NMR
(CDCl3) δ 1.55 (d, J ) 6.6 Hz, 3H, CH3), 4.41 (d, J ) 1.5 Hz,
1H, dCH2), 4.54 (q, J ) 6.6 Hz, 1H, CHCH3), 4.74 (d, J ) 1.5
Hz, 1H, dCH2), 6.80-7.00 (m, 4H, Harom); 13C NMR (CDCl3) δ
17.4, 69.2, 89.7, 116.1, 117.3, 122.0, 122.2, 142.5, 143.1, 154.2.
Anal. Calcd for C10H10O2: C, 74.04; H, 6.22. Found: C, 73.84;
H, 6.37.
(Z)-2,3-Dih yd r o-2-eth ylid en e-3-m eth yl-1,4-ben zod iox-
1
in (16): oil; Rf 0.24 (petroleum ether/ethyl acetate 100/1); H
NMR (CDCl3) δ 1.50 (d, J ) 6.4 Hz, 3H, CH3), 1.76 (d, J ) 7.0
Hz, 3H, CH3), 4.51 (q, J ) 6.4 Hz, 1H, OCH), 4.84 (q, J ) 7.0
Hz, 1H, dCH), 6.80-7.00 (m, 4H, Harom); 13C NMR (CDCl3) δ
9.4, 17.4, 69.7, 100.7, 116.2, 117.3, 121.8, 121.9, 142.8, 143.2,
147.2. Anal. Calcd for C11H12O2: C, 74.96; H, 6.87. Found: C,
74.61; H, 6.68.
(Z)-2-Ben zylid en e-2,3-d ih yd r o-3-p h en yl-1,4-ben zod iox-
in (17): white solid; mp 68-70 °C; Rf 0.52 (petroleum ether/
ethyl acetate 100/1); 1H NMR (CDCl3) δ 5.45 (s, 1H, OCH),
5.70 (s, 1H, dCH), 7.00-7.80 (m, 14H, Harom); 13C NMR (CDCl3)
δ 76.7, 109.3, 116.6, 117.9, 122.9, 127.2, 127.9, 128.6, 128.8,
129.3, 134.4, 136.7, 142.5, 143.6, 146.2. Anal. Calcd for
C
21H16O2: C, 83.97; H, 5.37. Found: C, 83.91; H, 5.50.
(Z)-2,3-Dih ydr o-2-n -h exyliden e-3-ph en yl-1,4-ben zodiox-
in (18): obtained as an inseparable mixture of the two
regioisomers 18 and 19; oily mixture; Rf 0.36 (petroleum ether/
ethyl acetate 10/1); 1H NMR (CDCl3) δ 0.95-1.10 (m, 3H, CH3),
1.32-1.52 (m, 6H, CH2), 2.39 (bs, 2H, CH2), 4.55-4.70 (m, 1H,
dCH), 5.68 (s, 1H, OCH), 6.80-7.90 (m, 9H, Harom); 13C NMR
(CDCl3) δ 14.2, 22.6, 24.3, 29.1, 76.1, 110.1, 117.7, 122.1, 122.2,
128.6, 127.8, 137.0, 143.1, 143.6, 145.5. Anal. Calcd for
2,3-Dih yd r o-2-eth yl-3-m eth ylen e-1,4-ben zod ioxin (4):
obtained as an inseparable mixture of the two regioisomers 4
and 5; oily mixture; Rf 0.54 (petroleum ether/ethyl acetate 100/
1); 1H NMR (CDCl3) δ 1.10 (t, J ) 7.3 Hz, 3H, CH3), 1.75-
1.95 (m, 2H, CH2), 4.32-4.44 (m, 2H, OCH, dCH2), 4.78 (d, J
) 2.0 Hz, 1H, dCH2), 6.80-7.10 (m, 4H, Harom); 13C NMR
(CDCl3) δ 9.9, 24.6, 74.8, 90.7, 116.1, 117.5, 121.9, 122.3, 142.4,
142.5, 152.6. Anal. Calcd for C11H12O2: C, 74.96; H, 6.87.
Found: C, 74.76; H, 6.92.
C
20H22O2: C, 81.59; H, 7.54. Found: C, 81.61; H, 7.66.
(Z)-2-Ben zylid en e-2,3-d ih yd r o-3-n -p en t yl-1,4-b en zo-
d ioxin (19): obtained as an inseparable mixture of the two
regioisomers 18 and 19; oily mixture; Rf 0.49 (petroleum ether/
ethyl acetate 100/1); 1H NMR (CDCl3) δ 0.95-1.10 (m, 3H,
CH3), 1.32-1.52 (m, 6H, CH2), 1.90 (m, 2H, CH2), 4.55-4.70
(m, 1H, dCH), 5.56 (s, 1H, OCH), 6.80-7.90 (m, 9H, Harom);
13C NMR (CDCl3) δ 14.2, 22.7, 25.3, 31.6, 31.7, 75.0, 106.5,
116.4, 117.9, 122.0, 122.9, 127.0, 128.5, 129.1, 133.5, 142.3,
142.4, 146.0.
(Z)-2,3-Dih yd r o-2-n -h exyl-2-(2,2,2-tr iflu or oeth ylid en e)-
1,4-ben zod ioxin (20): oil; Rf 0.5 (petroleum ether/ethyl
acetate 150/1); 1H NMR (CDCl3) δ 0.90 (d, J ) 6.6 Hz, 3H,
CH3), 1.25-1.90 (m, 10H, CH2), 4.45 (t, J ) 7.5 Hz, 1H, OCH),
4.96 (q, J ) 6.8 Hz, 1H, dCH), 6.92-7.10 (m, 4H, Harom); 13C
NMR (CDCl3) δ 14.0, 22.5, 25.0, 28.8, 30.9, 31.6, 73.0, 95.0 (q,
J ) 35.6 Hz), 116.6, 117.7, 122.5, 123.7, 124.8 (q, J ) 269.6
Hz), 141.2, 141.8, 154.1 (q, J ) 5.1 Hz); 19F δ -57.7. Anal.
Calcd for C16H19F3O2: C, 63.97; H, 6.38. Found: C, 64.09; H,
6.20.
(Z)-2,3-Dih yd r o-2-p r op ylid en e-1,4-ben zod ioxin (5): ob-
tained as an inseparable mixture of the two regioisomers 4
and 5; oily mixture; Rf 0.8 (petroleum ether/ethyl acetate 10/
1
1); H NMR (CDCl3) δ 1.10 (m, 3H, CH3), 2.25-2.40 (m, 2H,
CH2CH3), 4.46 (s, 2H, OCH2), 4.74 (t, J ) 7.3 Hz, 1H, dCH),
6.80-7.10 (m, 4H, Harom); 13C NMR (CDCl3) δ 14.1, 17.5, 65.5,
110.2, 116.6, 117.4, 121.9, 122.1, 143.1, 144.2, 152.6.
ter t-Bu tyld im eth yl[(2,3-d ih yd r o-3-m eth ylen e-1,4-ben -
zod ioxin -2-yl)m eth ox y]sila n e (6): oil; Rf 0.2 (petroleum
ether/ethyl acetate 80/1); 1H NMR (CDCl3) δ 0.05 (s, 3H,
SiCH3), 0.07 (s, 3H, SiCH3), 0.88 (s, 9H, CH3), 3.85 (dd, J )
10.9, 5.9 Hz, 1H, CH2), 3.85 (dd, J ) 10.9, 6.3 Hz, 1H, CH2),
4.45 (d, J ) 1.8 H, 1H, dCH2), 4.56 (dd, J ) 6.3, 5.9 Hz, 1H,
CHO), 4.80 (d, J ) 1.8 H, 1H, dCH2), 6.80-7.00 (m, 4H, Harom);
13C NMR (CDCl3) δ -5.4, 18.3, 25.8, 62.9, 74.2, 92.2, 116.1,
117.4, 121.9, 122.3, 142.0, 142.1, 150.3. Anal. Calcd for
2,3-Dih yd r o-2-et h yl-2-m et h yl-3-m et h ylen e-1,4-b en zo-
d ioxin (22): oil; Rf 0.31 (petroleum ether); 1H NMR (CDCl3) δ
0.98 (t, J ) 7.4 Hz, 3H, CH3), 1.52 (s, 3H, CH3), 1.65-1.75 (m,
2H, CH2), 4.43 (s, 1H, dCH2), 4.72 (s, 1H, dCH2), 6.80-7.00
(m, 4H, Harom); 13C NMR (CDCl3) δ 8.1, 22.3, 29.4, 75.6, 90.1,
115.6, 117.5, 121.5, 122.3, 141.6, 142.3, 155.7. Anal. Calcd for
C
16H24O3Si: C, 65.72; H, 8.28. Found: C, 65.39; H, 8.61.
t er t -Bu t yld im e t h yl[(2,3-d ih yd r o-1,4-b e n zod ioxin -2-
ylid en e)eth oxy]sila n e (7): obtained as an inseparable mix-
ture of the Z- and E-isomers (Z/ E 90/10); oily mixture; Rf 0.24
(petroleum ether/ethyl acetate 100/1); 1H NMR (CDCl3) δ 0.12
(s, 6H, SiCH3), 0.88 (s, 9H, CH3), 4.27 (d, J ) 7.0 Hz, 0.2H,
dCHCH2O), 4.47 (d, J ) 6.3 Hz, 1.8H, dCHCH2O), 4.47 (s,
1.8H, OCH2), 4.69 (s, 0.2H, OCH2), 4.91 (t, J ) 6.3 H, 0.9H,
C
12H14O2: C, 75.75; H, 7.42. Found: C, 75.75; H, 7.65.
2,3-Dih ydr o-2-isopr opyl-2-m eth yl-3-m eth ylen e-1,4-ben -
zod ioxin (23): obtained as an inseparable mixture of the two
regioisomers 23 and 24; oily mixture; Rf 0.50 (petroleum ether/
ethyl acetate 15/1); 1H NMR (CDCl3) δ 0.92 (d, J ) 6.8 Hz,
3H, CH3), 0.94 (d, J ) 6.8 Hz, 3H, CH3), 1.41 (s, 3H, CH3),
1.88 (hept, J ) 6.8 Hz, 1H, CHMe2), 4.44 (d, J ) 1.9 Hz, 1H,
dCH2), 4.80 (d, J ) 1.9 Hz, 1H, dCH2), 6.88 (bs, 4H, Harom);
13C NMR (CDCl3) δ 15.8, 17.4, 18.5, 30.3, 78.7, 91.3, 115.8,
117.7, 121.8, 122.6, 141.5, 143.0, 155.5. Anal. Calcd for
(19) Ishihara, T.; Yamasaki, Y.; Ando, T. Tetrahedron Lett. 1985,
26, 79.
(20) O’Hagan, D.; Zaidi, N. A. Tetrahedron: Asymmetry 1994, 5,
1111.
(21) Grible, G. W.; J oyner, H. H.; Switzer, F. L. Synth. Commun.
1992, 22, 2997.
C
13H16O2: C, 76.43; H, 7.90. Found: C, 76.62; H, 8.02.
2,3-Dih yd r o-2-(1,2-d im et h ylb u t -1-en ylid en e)-1,4-b en -
zod ioxin (24): obtained as an inseparable mixture of the two
regioisomers 23 and 24; oily mixture; Rf 0.50 (petroleum ether/
ethyl acetate 15/1); 1H NMR (CDCl3) δ 1.00 (d, J ) 7.0 Hz, 1.2
H, CH3 (Z)), δ 1.10 (d, J ) 6.8 Hz, 4.8 H, CH3 (E)), 1.59 (s,
0.6H, CH3 (Z)), 1.75 (s, 2.4H, CH3 (E)), 2.70 (hept, J ) 6.8 Hz,
0.8 H, CHMe2 (E)), 3.38 (hept, J ) 7.0 Hz, 0.8 H, CHMe2 (Z)),
4.60 (s, 0.4 H, CH2 (Z)), 4.70 (s, 1.6 H, CH2 (E)), 6.80-7.00 (m,
4H, Harom); 13C NMR (CDCl3) δ 9.0 (E), 10.7 (Z), 20.6 (Z), 21.6
(22) Yu, W.-Y.; Alper, H. J . Org. Chem. 1997, 62, 5684.
(23) Allcock, S. J .; Gilchrist, T. L.; Shuttleworth, S. I.; King, F. D.
Tetrahedron 1991, 47, 10053.
(24) Hagashi, M.; Saigo, K. Tetrahedron Lett. 1997, 38, 6241.
(25) Hori, Y.; Mitsudo, T.-A.; Watanabe, Y. Tetrahedron Lett. 1986,
27, 5389.
(26) Tsuji, J .; Suguria, T.; Minami, I. Synthesis 1989, 603.
(27) Dzvinchuk, I. B.; Lozinski, M. O. J . Org. Chem. USSR 1989,
25, 1142.

6642 J . Org. Chem., Vol. 66, No. 20, 2001
Labrosse et al.
(E), 26.7 (Z), 29.0 (E), 61.3 (E), 62.0 (Z), 116.8 (E), 117.4 (E),
120.8 (Z), 121.3 (Z), 121.7 (E), 122.2, 136.7 (Z), 137.3 (E), 144.0,
144.3, 144.4.
mixture of the Z- and E-isomers (Z/ E 90/10): Rf 0.45 (petro-
leum ether/ethyl acetate 4/3); 1H NMR (CDCl3) δ 2.65 (bs, 1H,
OH), 4.17 (d, J ) 7.7 Hz, 0.2H, dCHCH2O), 4.38 (d, J ) 7.0
Hz, 1.8H, dCHCH2O), 4.44 (s, 1.8H, OCH2), 4.64 (s, 0.2H,
OCH2), 4.93 (t, J ) 7.0 H, 0.9H, dCH), 5.53 (t, J ) 7.7 H,
0.1H, dCH), 6.80-7.10 (m, 4H, Harom); 13C NMR (CDCl3) δ 55.8
(Z), 56.8 (E), 65.0 (E), 65.9 (Z), 106.5 (E), 106.7 (Z), 116.5 (E),
116.6 (Z), 117.2 (E), 117.4 (Z), 122.2 (E), 122.4 (E and Z), 122.5
(Z), 142.4, 143.9, 144.5. These data are in agreement with
those published in the literature.7e
2-Ben zyl-2,3-d ih yd r o-2-m eth yl-3-m eth ylen e-1,4-ben zo-
d ioxin (25): obtained as an inseparable mixture of the two
regioisomers 25 and 26; oily mixture; Rf 0.36 (petroleum ether/
ethyl acetate 100/1); 1H NMR (CDCl3) δ 1.43 (s, 3H, CH3), 2.90
(d, J ) 13.6 Hz, 1H, CH2), 3.05 (d, J ) 13.6 Hz, 1H, CH2),
4.31 (d, J ) 2.0 Hz, 1H, dCH2), 4.74 (d, J ) 2.0 Hz, 1H, d
CH2), 6.80-7.35 (m, 9H, Harom); 13C NMR (CDCl3) δ 22.6, 42.6,
75.5, 91.3, 115.9-130.7, 139.2, 136.0-144.0, 155.1. Anal. Calcd
for C17H16O2: C, 80.92; H, 6.40. Found: C, 80.86; H, 6.44.
2,3-Dih yd r o-2-(1-m eth yl-2-p h en yleth ylid en e)-1,4-ben -
zod ioxin (26): obtained as an inseparable mixture of the two
regioisomers 25 and 26; oily mixture; Rf 0.45 (petroleum ether/
ethyl acetate 100/1); 1H NMR (CDCl3) δ 1.66 (s, 0.9H, CH3 (Z)),
1.72 (s, 2.1H, CH3 (E)), 3.41 (s, 1.4H, OCH2 (E)), 3.62 (s, 0.6H,
OCH2 (Z)), 4.68 (s, 0.6H, CH2 (Z)), 4.76 (s, 1.4H, CH2 (E)),
6.80-7.35 (m, 9H, Harom); 13C NMR (CDCl3) δ 14.6 (E), 15.6
(Z), 36.4 (E), 37.9 (Z), 61.4, 114.2 (E), 114.3 (Z), 115.9-130.7,
136.0 (E), 138.3 (Z),136.0-144.0, 144.1.
Acetic Acid 2,3-Dih ydr o-1,4-ben zodioxin -2-yliden e Eth -
yl Ester (30). To a solution of the alcohol 29 (60 mg, 0.34
mmol) and pyridine (107 mg, 1.35 mmol) in CH2Cl2 (10 mL)
at 0 °C was added acetyl chloride (107.5 mg, 1.35 mmol). After
the mixture was stirred for 24 h at room temperature, a
saturated aqueous solution of copper sulfate (10 mL) was
added, and the mixture was extracted with diethyl ether (3 ×
10 mL). Evaporation of the solvent gave an oil that was
purified on silica gel eluting with ethyl acetate/petroleum ether
(1/4) to give 73.5 mg of the ester 30 (99% yield) as an
inseparable mixture of the Z- and E-isomers (Z/ E 90/10): Rf
0.54; 1H NMR (CDCl3) δ 2.90 (s, 3H, CH3), 4.50 (s, 1.8H, OCH2),
4.65 (d, J ) 8.4 Hz, 0.2H, dCHCH2O), 4.73 (s, 0.2H, OCH2),
4.85 (d, J ) 7.1 Hz, 1.8H, dCHCH2O), 4.95 (t, J ) 7.1 H, 0.9H,
dCH), 5.47 (t, J ) 8.4 H, 0.1H, dCH), 6.80-7.10 (m, 4H,
(Z)-2,3-Dih yd r o-2,2-d im et h yl-3-et h ylid en e-1,4-b en zo-
d ioxin (27): oil; Rf 0.50 (petroleum ether/ethyl acetate 100/
1
1); H NMR (CDCl3) δ 1.52 (s, 6H, CH3), 1.78 (d, J ) 6.8 Hz,
3H, CH3), 4.92 (q, J ) 6.8 Hz, 1H, dCH), 6.75-7.10 (m, 4H,
H
arom); 13C NMR (CDCl3) δ 9.6, 25.2, 73.0, 99.6, 115.8, 117.5,
H
arom). Anal. Calcd for C12H12O4: C, 65.43; H, 5.50. Found: C,
121.3, 122.0, 141.8, 142.4, 149.6. Anal. Calcd for C12H14O2: C,
75.75; H, 7.42. Found: C, 76.05; H, 7.44.
65.95; H, 5.39.
(Z)-3-Ben zylid en e-2,3-d ih yd r o-2,2-d im eth yl-1,4-ben zo-
d ioxin (28): white solid; mp 54-57 °C; Rf 0.22 (petroleum
ether/ethyl acetate 100/1); 1H NMR (CDCl3) δ 1.61 (s, 6H, CH3),
5.73 (s, 1H, dCH), 6.90-7.00 (m, 3H, Harom), 7.10-7.15 (m,
1H, Harom), 7.23-7.30 (m, 1H, Harom), 7.38 (t, J ) 7.3 Hz, 2H,
Ack n ow led gm en t. We grateful acknowledge the
French MENRT for a grant (J .-R. L.). We are indebted
to Dr. A. Thozet, Centre de Diffractome´trie H. Long-
chambon, Universite´ Claude Bernard Lyon 1, for pro-
viding X-ray diffraction data for compound 17.
H
arom), 7.72 (d, J ) 7.3 Hz, 2H, Harom); 13C NMR (CDCl3) δ 25.4,
73.5, 104.1, 115.9, 117.7, 121.6, 122.7, 126.9, 129.1, 134.6,
134.6, 141.9, 149.8. Anal. Calcd for C17H16O2: C, 80.92; H, 6.40.
Found: C, 80.82; H, 6.37.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the preparation of the unknown propargylic
alcohols, propargylic carbonates 1a -n and 1u -w , and ace-
tates 31a ,b and spectral data listings for these compounds,
analytical and spectral data for compounds 8-14 and 32-37,
and the X-ray diffraction study data for compound 17 with
ORTEP diagram. This material is available free of charge via
the Internet at http://pubs.acs.org.
2,3-Dih yd r o-1,4-ben zod ioxin -2-ylid en eeth a n ol (29). A
solution of compound 7 (2.6 g, 9 mmol) and Bu4NF‚3H2O (4.6
g, 18 mmol) in THF (80 mL) was stirred at room temperature
for 1 h. After evaporation of the solvent, the residue was
diluted with diethyl ether (100 mL), and the etheral solution
washed with water (3 × 40 mL). Evaporation of the solvent
gave a residue that was purified by column chromatography
to give 1.5 g of compound 29 (95% yield), as an inseparable
J O0103625