Asymmetric palladium-catalyzed annulation of benzene-1,2-diol and racemic secondary propargylic carbonates bearing two different substituents

Article abstract of DOI:10.1016/j.tet.2005.01.084

The palladium-catalyzed cyclization of benzene-1,2-diol with various racemic secondary propargyl carbonates having no acetylenic hydrogen in the presence of (R)-Binap as the chiral ligand afforded the two regioisomers of the corresponding 2,3-dihydro-1,4-

Full text of DOI:10.1016/j.tet.2005.01.084

Tetrahedron 61 (2005) 2589–2599
Asymmetric palladium-catalyzed annulation of benzene-1,2-diol
and racemic secondary propargylic carbonates bearing two
different substituents
a
a
a
a
Norbert Dominczak,a,b Celine Damez, Bouchra Rhers, Jean-Robert Labrosse, Paul Lhoste,
´
Boguslaw Kryczkab and Denis Sinoua,
*
a
` ´ ´ ´
Laboratoire de Synthese Asymetrique, Associe au CNRS, CPE Lyon, Universite Claude Bernard Lyon 1, 43,
´
Boulevard du 11 Novembre 1918, 69622 Villeurbanne cedex, France
bDepartment of Organic and Applied Chemistry, University of Lodz, ul. Narutowicza 68, 90-136 Lodz, Poland
Received 8 November 2004; revised 17 January 2005; accepted 20 January 2005
Abstract—The palladium-catalyzed cyclization of benzene-1,2-diol with various racemic secondary propargyl carbonates having no
acetylenic hydrogen in the presence of (R)-Binap as the chiral ligand afforded the two regioisomers of the corresponding 2,3-dihydro-1,4-
dioxin derivatives in quite good yields, and also in enantioselectivities going from 40 to 97%. The cyclization of benzene-1,2-diol with
methyl (R)-1-methyl-3-phenylpro-2-yn-1-yl carbonate in the presence of dppb as the achiral ligand afforded 2-benzylidene-3-methyl-2,3-
dihydro-1,4-benzodioxine as the major product with 15% ee. The use of (R)-Binap as the chiral ligand afforded the (C) cyclized compound
in 45% ee, when the (K) enantiomer was obtained with 77% ee in the presence of (S)-Binap. All the results suggest that in this case the
enantioselective step is the diastereoselective protonation of the palladium–carbene intermediates.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
structures in quite good yields have been developed. Kundu
and colleagues.33,34 described the palladium(II)–copper
catalyzed condensation of aryl halides and mono-prop-2-
ynilated catechol. We reported also the palladium(0)-
catalyzed condensation of catechol with various propargylic
carbonates leading regio- and stereoselectively to 2,3-
dihydro-2-ylidene-1,4-benzodioxines.35,36 Moreover, per-
forming the condensation in the presence of a chiral
palladium catalyst allowed a very easy access to enantio-
merically enriched derivatives with enantioselectivies up to
97%.37,38 The plausible mechanism for this cyclization
process is shown in Scheme 1. The first step is the anti SN20
attack of the palladium(0) complex on the propargylic
carbonate affording the s-allenyl palladium complex A,39 in
equilibrium with the h3-propargyl palladium complex B.
Selective attack of the monoanion of benzene-1,2-diol to
the central carbon of this h3-propargyl complex gave the
s-alkyl complex C in equilibrium with the carbenic
complex D. This complex D was converted by intra-
molecular proton transfer to the s-alkyl complex E, which
is in equilibrium with the h3-allyl complex F. Internal attack
of the nucleophile on one of the termini of this h3-allylic
complex F afforded the corresponding benzodioxin deriva-
tives G (attack 1) or H (attack 2), respectively. In order to
apply this synthetic route in an asymmetric way, we
The 1,4-benzodioxin and 1,4-benzodioxan subunits are
present in some natural compounds displaying interesting
biological properties.1–5 For example, some 2-substituted
1,4-benzodioxanes exhibit antihyperglycemic properties;6
others act as inhibitors of 5-lipoxygenase,7 or can be used as
a- or b-blocking agents or in antidepression or anti-
hypertension therapy.8–12 Due to these interesting proper-
ties, the synthesis of compounds containing this structure
has been the subject of increasing research during the last
few years. Moreover, these compounds are also interesting
precursors for further synthetic transformations.13–16
If the synthesis of 1,4-benzodioxin structures is now well
documented in the literature,13,17–25 the synthetic routes to
2-alkylidene-2,3-dihydro-1,4-benzodioxines are less
studied, and the published procedures often required a
tedious multistep sequence.26–32
Recently two very facile methods for the synthesis of these
Keywords: Asymmetric catalysis; Palladium; Annulation; 2,3-
Benzodioxin.
* Corresponding author. Tel.: C33 4 72448183; fax: C33 4 78898914;
e-mail: sinou@univ-lyon1.fr
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.084

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N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
Scheme 1.
postulated that the enantioselective step was the attack of
the nucleophile on the h3-allyl intermediate. According to
the results of the literature,40 we expected that this h3-allyl
intermediate E must have two identical substituents at one
of the termini of the h3-allyl complex, allowing an easy
racemization of this complex, or two identical substituents
at the two termini of the h3-allyl complex. We obtained
effectively high enantioselectivities, up to 97%, in our
palladium catalyzed annulation in these two cases.38
methyl chloroformate in CH2Cl2 in the presence of pyridine
and dimethylaminopyridine gave the corresponding carbon-
ates 3a–d in quite good yields. Condensation of the lithium
derivative of hept-1-yne with the corresponding aromatic
aldehyde in THF afforded the propargylic alcohols 5a–g.
Reaction of methyl chloroformate with alcohols 5a, and
5c–e, in CH2Cl2 in the presence of pyridine and dimethyl-
aminopyridine afforded the corresponding propargylic
carbonates 6a, and 6c–e, in moderate chemical yields.
Since the carbonates derived from propargylic alcohols 5b,
5f, and 5g, were unstable, we prepared the corresponding
acetates 7b, 7f, and 7g, together with acetate 7c.
However we have also shown that the benzodioxin
structures were obtained in quite high enantioselectivity
even when the two substituents at the two termini of the h3-
allyl complex were completely different.41 In this paper we
describe in details our results in this field and propose a
mechanism for this enantioselective heteroannulation.
The palladium-catalyzed condensation of carbonates 3a–d
with benzene-1,2-diol was conducted at rt in THF as the
solvent, Pd2(dba)3 associated with dppb as the catalyst
(Scheme 3). The results summarized in Table 1 showed that
the cyclized products 8 and 9 were obtained in high
chemical yields for RZCH3 and CH2CH3 (Table 1, entries 1
and 3), in moderate yield for RZCH(CH3)2 (Table 1, entry
5), when no reaction occurred when the alkyl substituent
was a tert-butyl group. For RZCH3, the major regioisomer
9a (95%)) occurred from the attack of the phenate on the
termini of the h3-allylpalladium complex bearing the alkyl
substituent; this is in quite good agreement with the
2. Results and discussion
In order to study the influence of both the alkyl and the aryl
substituents on the regio-, stereo- and enantioselectivities of
this cyclization, we prepared the corresponding propargylic
carbonates 3a–d, 6a, 6c–e, and acetates 7b, 7c, 7f, and 7g
(Scheme 2). Reaction of propargylic alcohols 2a–d with
Scheme 2.

N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
2591
Scheme 3.
Table 1. Palladium-catalyzed condensation of benzene-1,2-diol with propargylic carbonates 3a–ca
Entry
Carbonate 3
Phosphine
Yield (%)
of (8C9)b
% 8/% 9c
ee (%) 8d
ee (%) 9d
1
2
3
4
5
6
3a
3a
3b
3b
3c
3c
dppb
(R)-Binap
dppb
(R)-Binap
dppb
(R)-Binap
90
70
90
95
66
70
5:95
20/80
14/86
32/68
60/40
68/32
nd
nd
93
70
85
83
a Conditions: [benzene-1,2-diol]/[3]/[Pd2(dba)3]/[phosphine]Z48:40:1:4; 25 8C; THF as the solvent.
b After column chromatography.
c Determined by GC.
d Determined by HPLC using a chiral column Chiralpak AD (25 cm!4.6 mm) using hexane/2-propanol as the eluent; nd means that no separation could be
observed whatever the conditions used.
previous published results.36 Increasing the steric bulk of
the substituent R and going from -CH3 or -C2H5 to
–CH(CH3)2 reversed the regioselectivity of the cyclization,
the regioisomer 8c being predominantly obtained in this last
case. The stereochemistry at the double bond for the two
regioisomers was Z, as shown using NOE NMR experi-
ments. Irradiation of the signal of the methyl group for 9a or
of the proton on the carbon near the oxygen for 9b and 9c
showed an enhancement of 6, 8, and 14% of the signal of the
ethylenic proton; for compounds 8b and 8c, irradiation of
the benzylic proton showed an enhancement of the signal of
the ethylenic proton of 2 and 7%, respectively.
amount of carbonate used on the enantioselectivity in the
cyclization of catechol and carbonate 3c; we always
obtained the same results using 1.2 or 2 equiv of carbonate
3c.
Then we turned our attention on the influence of the nature
of the aromatic ring on both the regio- and the enantio-
selectivity of the cyclization (Scheme 4). We have
previously shown that propargylic carbonate 6a and acetate
7b, bearing an electron-donating group on the ring, afforded
a 25:75 and 38:62 mixture of regioisomers 10a/11a and 10b/
11b in 96 and 88% chemical yield, respectively (Table 2,
entries 1 and 3), while carbonate 6c or acetate 7c, bearing an
electron-withdrawing group, gave almost exclusively the
regioisomer 11c in 96 and 56% chemical yield, respectively
(Table 2, entries 5 and 6); in the case of acetate 7c the
chemical yield was increased to 84% when the reaction was
performed at reflux (Table 2, entry 7). Carbonates 6d and
6e, bearing a 2-methylphenyl and a naphthyl substituent,
gave also a mixture of the two regioisomers 10d–e and
11d–e in quite good yields (65 and 93%, respectively), the
last one being the major isomer (94 and 79%, respectively)
(Table 2, entries 9 and 11). The palladium-catalyzed
cyclisation of acetates 7f and 7g gave the corresponding
2-alkylidene-2,3-dihydro-1,4-benzodioxines in moderate
The use of (R)-Binap as the ligand gave quite similar
chemical yields; the observed regioselectivity of the
cyclization was lower using carbonates 3a (Table 1, entry
2) and 3b (Table 1, entry 4), when the reverse selectivity
was also observed for 3c (Table 1, entry 6). The
enantioselectivities of the cyclized products 9a and 9b
were 70 and 85%, respectively (Table 1, entries 2 and 4);
unfortunately, the two enantiomers of the minor regio-
isomers 8a and 8b could not be separated, whatever the
conditions used. The enantiomeric excesses of the two
regioisomers 8c and 9c were 93 and 83% ee, respectively
(Table 1, entry 6). We also studied the influence of the
Scheme 4.

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N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
Table 2. Palladium-catalyzed condensation of benzene-1,2-diol with propargylic carbonates 6 and acetates 7a
Entry
Propargylic
compound
Phosphine
Yield (%)
of 10C11b
% 10/% 11c
ee (%) 10d
ee (%) 11d
1
2
3
4
5
6
7
8
6a
6a
7b
7b
6c
7c
7c
7c
6d
6d
6e
6e
7f
dppb
(R)-Binap
dppb
(R)-Binap
dppb
dppb
dppb/reflux
(R)-Binap
dppb
(R)-Binap
dppb
(R)-Binap
dppb
(R)-Binap
dppb
(R)-Binap
96
84
88
35
96
56
84
49
65
77
93
74
34
30
45
49
25/75
24/76
38/62
39/61
0/100
0/100
0/100
10/90
6/94
63/37
21/79
42/58
4/96
nd
78
86
80
52
40
76
nd
88
85
97
64
85
90
9
10
11
12
13
14
15
16
7f
7g
7g
3/97
7/93
8/92
a Conditions: [benzene-1,2-diol]/[3]/[Pd2(dba)3]/[phosphine]Z48:40:1:4; 25 8C; THF as the solvent.
b After column chromatography.
c Determined by GC.
d Determined by HPLC using a chiral column Chiralpak AD (25 cm!4.6 mm) using hexane/2-propanol as the eluent; nd means that no separation could be
observed whatever the conditions used.
chemical yields (34 and 45%, respectively) (Table 2, entries
13 and 15); the major regioisomer was compound 11 (96%
11f and 93% 11g, respectively). As described previously,
the attack occurred predominantly on the terminus of the
p-allyl bearing the alkyl substituent, the regioisomer 11
being the predominant one; however the ratio of the two
regioisomers depends strongly on the nature of the aryl ring.
The different regioselectivities observed in the cyclization
of carbonates 6a and 6d could be due probably to steric
effects. It is to be noticed that the stereochemistry at the
double bond for the two regioisomers was again Z, as shown
using NOE NMR experiments.
h3-allyl complex, the enantioselective step could not be the
attack of the nucleophile on this h3-allyl intermediate. A
possible mechanism that could be invoked is the epimeriza-
tion of this h3-allyl complex F via a nucleophilic
substitution of PdLn by another PdLn molecule with
inversion of configuration. Although such a mechanism
has been proposed by different groups in the case of
intermolecular palladium-catalyzed alkylation reac-
tions,42–51 we postulated a quite different mechanism in
our case (Scheme 5).
The first step is the formation of the two diastereoisomeric
s-allenyl complexes A and A0 via a SN20 mechanism from
the propargylic carbonate and the palladium(0) complex.
These s-allenyl complexes are in equilibrium with the
corresponding diastereoisomeric h3-propargylic palladium
complexes B and B0 (not shown here). Attack of the
monoanion of benzene-1,2-diol on the central atom of these
s-allenyl complexes gave the diastereoisomeric s-alkyl
complexes C and C0 in equilibrium with the diastereo-
isomeric carbenic complexes D and D0. Since this anion
attacked probably on the less hindered site, the major
diastereoisomers will be isomers C0 and D0. Protonation of
these intermediates C and C0 (or of the corresponding
carbene complexes D and D0) gave four diastereoisomeric
s-alkyl complexes E1–E4, in equilibrium with the corre-
sponding diastereoisomeric h3-allyl complexes F1–F4. If
interconversion occurred readily between complexes F1 and
F2, and complexes F3 and F4, there is no possibility of
interconversion between the diastereoisomeric complexes
F1 and F3 or F4, and F2 and F3 or F4, since the two
substituents at the two termini of the h3-allyl are different.
The attack of the nucleophile on the terminus of
intermediates F1 or F2 bearing the alkyl group afforded
the (R) cyclized product, whereas the (S) enantiomer was
obtained from intermediates F3 and F4. We postulated that
the enantioselection occurred during the step of protonation
of the intermediates C,C0 or D,D0, when the new chiral
center was created. For example, the diastereoisomeric
complexes E1 and E3, and so the h3-allyl intermediates F1
When the cyclization was performed in the presence of (R)-
Binap as the chiral ligand the ratios of the two regioisomers
obtained were generally quite similar, except for carbonate
6d, where a reversal of the regioselectivity was observed,
the regioisomer 10d being now the major one. In each case,
the enantiomeric excess of the regioisomer 11 could be
determined, when the separation of the enantiomers for
regioisomers 10a and 10f was unsuccessful. Enantio-
selectivities in the range 80–90% ee were obtained when
the phenyl ring is para-substituted with a methyl, a
methoxy, or a cyano group, or when this ring was a
heteoatomic one (Table 2, entries 2, 4, 8, 14, and 16); the
presence of a methyl group at the o-position gave a higher ee
(up to 97%) (Table 1, entry 10), whereas the naphtyl group
lowered this enantioselectivity (64% ee) (Table 2, entry 12).
The highest enantioselectivity obtained for regioisomer 10
was 88% using heterocyclic acetate 7g (Table 2, entry 16);
acetate 7b and carbonate 6e afforded the corresponding
regioisomers 10b and 10e with 78 and 76% ee, respectively
(Table 2, entries 4 and 12), whereas acetate 7c and
carbonate 6d gave lower enantioselectivities (52 and 40%
ee, respectively) (Table 2, entries 8 and 10).
All these results (one major isomer, high enantioselectivities
for the two regioisomers) could not be explained using the
model shown in Scheme 1. Since the palladium intermediate
F bears two different substituents at the two termini of the

N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
2593
Scheme 5.
and F3, are probably formed in quite different amounts,
affording the corresponding cyclized enantiomers also in
different amounts. It is the same scheme starting from
complexes E2 and E4. The proposed mechanism is different
from that of Yoshida and colleagues.52,53 These authors
observed a cascade chirality transfer process in the
palladium-catalyzed reaction of substituted chiral pro-
pargylic carbonates with phenols, affording chiral cyclic
carbonates in a highly enantiospecific manner. If their
mechanism is a general one, the reaction of a racemic
propargylic carbonate such as 3 or 6 will give the cyclized
product as a racemate, even in the presence of a chiral
ligand, since no racemization of the different intermediates
could occur.
In order to have a deeper insight into our possible

2594
N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
Scheme 6.
mechanism, we performed the palladium-cyclization of
benzene-1,2-diol with two chiral propargylic carbonates
(R)-3a and (R)-12 in the presence of both an achiral ligand
(dppb) and a chiral ligand [(R)- or (S)-Binap] (Scheme 6).
Enantiopure carbonate (R)-3a was obtained from com-
mercial (R)-but-3-yn-2-ol in the presence of methyl
chloroformate, whereas (R)-4-phenylbut-3-yn-2-ol,
obtained from (R)-but-3-yn-2-ol via a Sonogashira
coupling,54 afforded carbonate (R)-12 under the same
conditions. The results are summarized in Table 3. Reaction
of enantiopure propargylic carbonate (R)-12 with benzene-
1,2-diol in the presence of Pd2(dba)3 associated with dppb
afforded the cyclized products 13 and 14 in a 3:97 ratio
(Table 3, entry1); however, compound 14 was obtained as a
racemate. When the same condensation was performed in
the presence of (R)-Binap, compound (K)-14 was obtained
with an enantioselectivity up to 60% (Table 3, entry 2).
Using (S)-Binap as the chiral ligand afforded compound
(C)-14 with 62% ee (Table 3, entry 3). These results could
be explained by a rapid racemization of the intermediate h3-
allyl palladium complex bearing in this case two hydrogens
on one of the termini of the h3-allyl system, the rate of the
racemization being fast compared to the rate of the attack of
the nucleophile.
The use of (S)-Binap afforded the (K) enantiomer with ee
up to 77 and 75% at 25 and 50 8C, respectively (Table 3,
entries 6 and 8). We have previously shown that the
cyclization of racemic propargylic carbonate 3a in the
presence of (R)-Binap gave compound 9a with 70% ee in
the (K) enantiomer (Table 1, entry 2). These results clearly
showed that the cyclization occurred via two different
mechanisms. The first one is similar to the one proposed by
Yoshida and colleagues,52,53 with a transfer of chirality
from the carbonate to the cyclized product; however since
we observed only 15% of transfer of chirality, this
mechanism is not the major one. The other mechanism is
the one proposed in Scheme 5. Using (R)- or (S)-Binap as
the chiral ligand gave, respectively, lower and higher ee in
the cyclized product, indicating that (S)-Binap/(R)-3a is a
match pair, and (R)-Binap/(R)-3a is a mismatch pair. This
quite different behaviour between the two mechanisms
could be due to the presence of a propargylic hydroxy
function in the carbonates used by Yoshida et al,52,53
function which could stabilize the h3-propargylic and h3-
allylic intermediates by complexation, and so allowing the
transfer of chirality.
3. Conclusion
The palladium-condensation of enantiopure propargylic
carbonate (R)-3a with catechol in the presence of dppb
gave the cyclized products 8a/9a in a 4:96 ratio, compound
9a being obtained with an enantioselectivity up to 15% in
the (K) enantiomer (Table 3, entry 4). When the cyclization
was performed in the presence of (R)-Binap, compound 9a
was obtained as the (C) enantiomer with an ee up to 45 and
49%, at 25 and 50 8C, respectively (Table 3, entries 5 and 7).
In conclusion, we have extended the previous asymmetric
palladium-catalyzed annulation of benzene-1,2-diol with
racemic secondary propargylic carbonates and acetates
bearing two different substituents (sH), both on the sp
carbon and on the carbon bearing the carbonate (or acetate)
function. The high enantioselectivities observed could be
explained by a highly stereospecific protonation of the
Table 3. Palladium-catalyzed condensation of benzene-1,2-diol with propargylic carbonates (R)-12 and (R)-3aa
Entry
Propargylic
carbonate
Phosphine
T (8C)
Yield (%) of
cyclized productsb
%14/%13 or
%9a/%8ac
ee (%) 9a or 14d
1
2
3
4
5
6
7
8
(R)-12
(R)-12
(R)-12
(R)-3a
(R)-3a
(R)-3a
(R)-3a
(R)-3a
dppb
25
25
5
25
25
25
50
50
96
80
60
74
32
25
50
50
97/3 (14/13)
82/18 (14/13)
83/17 (14/13)
96/4 (9a/8a)
90/10 (9a/8a)
90/10 (9a/8a)
85/15 (9a/8a)
83/17 (9a/8a)
0
(R)-Binap
(S)-Binap
dppb
(R)-Binap
(S)-Binap
(R)-Binap
(S)-Binap
60 (K)e
62 (C)f
15 (K)g
45 (C)
77 (K)
49 (C)
75 (K)
a Conditions: [benzene-1,2-diol]/[propargylic carbonate]/[Pd2(dba)3]/[phosphine]Z48:40:1:4; THF as the solvent.
b After column chromatography.
c Determined by GC.
d Determined by HPLC using a chiral column Chiralpak AD (25 cm!4.6 mm) using hexane/2-propanol as the eluent; nd means that no separation could be
observed irrespective of the conditions used.
e [a]2D5ZK22.5 (c 1.1, CH2Cl2).
f
[a]2D5ZC19.8 (c 1.1, CH2Cl2).
g [a]2D5ZK3.6 (c 1, diethyl ether).

N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
2595
intermediate palladium–carbene complexes. The results
obtained in the palladium-catalyzed annulation of benzene-
1,2-diol with methyl (R)-1-methyl-3-phenylpro-2-yn-1-yl
carbonate in the presence of an achiral (dppb) or a chiral
ligand [(R)- or (S)-Binap] are in agreement with such a
mechanism. Extension of this work to other bisnucleophiles
is actually in progress.
2.1 Hz, 1H, CHO), 7.46–7.49 (m, 2H, Harom), 7.64 (dd, JZ
8.6, 1.7 Hz, 1H, Harom), 7.81–7.86 (m, 3H, Harom), 7.97 (s,
1H, Harom); 13C NMR (75.5 MHz, CDCl3): d 14.0, 18.8,
22.1, 28.2, 31.1, 64.9, 79.9, 88.0, 124.7, 125.3, 126.2, 127.6,
128.2, 128.3, 133.1, 133.2, 138.6. Anal. Calcd for C18H20O:
C, 85.67; H, 7.99. Found: C, 85.40; H, 8.05.
4.1.3. 1-(2-Furyl)oct-2-yn-1-ol 5f. Yield 69%; oil; Rf 0.30
(petroleum ether/ethyl acetate 10:1); H NMR (300 MHz,
1
4. Experimental
CDCl3): d 0.92 (t, JZ7.1 Hz, 3H, CH3), 1.24–1.44 (m, 4H,
CH2), 1.56 (tt, JZ7.1, 7.1 Hz, 2H, CH2), 2.28 (dt, JZ7.1,
2.1 Hz, 2H, ]C–CH2), 2.38 (bs, 1H, OH), 5.40 (t, JZ
2.1 Hz, 1H, CHO), 6.36 (dd, JZ3.2, 1.9 Hz, 1H, ]CH–),
6.45 (bd, JZ3.2 Hz, 1H, ]CH–), 7.42 (dd, JZ1.9, 1.0 Hz,
1H, ]CH–),); 13C NMR (75.5 MHz, CDCl3): d 14.3, 19.1,
22.6, 28.5, 31.4, 58.7, 87.4, 107.8, 110.7, 115.0, 143.2,
154.1. Anal. Calcd for C12H16O2: C, 74.97; H, 8.39. Found:
C, 74.58; H, 8.42.
General remarks. 1H NMR (300 MHz) and 13C NMR
(75.5 MHz) spectra were obtained using a Bruker AM 300
spectrometer. Chemical shifts are reported with reference to
SiMe4 or CDCl3 as an internal standard. Optical rotations
were determined using a Perkin–Elmer 241 polarimeter. All
reactions were monitored by thin-layer chromatography
carried out on 0.25 mm silica gel plates (60 F-254, Merck).
Compounds were exposed under UV light (254 nm).
Column chromatography was carried out using Merck silica
gel 60 (40–63 mm). HPLC analysis was performed on a
Shimatzu apparatus LC-6A combined with a UV detector
SPD-6A. Reactions involving palladium complexes were
carried out in a Schlenk tube under an argon atmosphere.
Tetrahydrofuran was distilled from sodium/benzophenone
and stored under argon.
4.1.4. 1-(2-Thienyl)oct-2-yn-1-ol 5g. Yield 29%; oil; RfZ
0.50 (petroleum ether/ethyl acetate 8:1); 1H NMR
(300 MHz, CDCl3): d 0.93 (t, JZ7.0 Hz, 3H, CH3), 1.29–
1.44 (m, 4H, CH2), 1.55 (tt, JZ7.0, 7.0 Hz, 2H, CH2), 2.26
(dt, JZ7.0, 1.9 Hz, 2H, ]C–CH2), 2.50 (bs, 1H, OH), 5.63
(t, JZ1.9 Hz, 1H, CHO), 6.95 (dd, JZ5.1, 3.6 Hz, 1H,
]CH–), 7.14 (bd, JZ3.6 Hz, 1H, ]CH–), 7.26 (dd, JZ
5.1, 1.3 Hz, 1H, ]CH–); 13C NMR (75.5 MHz, CDCl3): d
14.4, 19.1, 22.6, 28.5, 31.4, 60.8, 79.6, 87.6, 107.8, 125.7,
126.2, 127.1, 146.0.
Propargylic alcohols 2a, 2b, 2c, 2d, 5a, 5b, 5c, propargylic
carbonates 3a, 6a, 6c, and propargylic acetates 7b and 7c,
have already been described, as well as benzodioxins 10a–c,
and 11a–c.36
4.1.5. Synthesis of (R)-4-phenylbut-3-yn-2-ol. A suspen-
sion of iodobenzene (971 mg, 4.76 mmol), CuI (36.2 mg,
0.2 mmol), Pd(PPh3)2Cl2 (70.2 mg, 0.1 mmol), and Et3N
(1 mL, 7.14 mmol), in THF (7 mL) was stirred for 45 min at
rt. A solution of (R)-but-3-yn-2-ol (350 mg, 5 mmol) in
THF (5 mL) was then added dropwise, and the stirring was
continued for 5 h at rt. After evaporation of the solvent, the
residue was diluted with water (10 mL), and the mixture
was extracted with diethyl ether (3!10 mL). The combined
organic phases were washed with brine (5 mL), and then
dried over Na2SO4. Evaporation of the solvent under
reduced pressure afforded an oil that was purified by
flash-chromatography on silica to give 502 mg (yield 62%)
of (R)-4-phenylbut-3-yn-2-ol. Oil; Rf 0.32 (petroleum
ether/CH2Cl2 1:2); [a]D25ZC43.6 (c 0.8, diethyl ether)
[Ref. 54 (S)-4-phenylbut-3-yn-2-ol: [a]2D5ZK44.8 (c 1.0,
Et2O)]; 1H NMR (300 MHz, CDCl3): d 1.47 (d, JZ6.0 Hz,
3H, CH3), 2.05 (bs, 1H, OH), 4.68 (q, JZ6.0 Hz, 1H,
CHOH), 7.15–7.25 (m, 3H, Harom), 7.33–7.40 (m, 2H,
Harom), in agreement with the literature data.54
4.1. Synthesis of propargylic alcohols
To a solution of hept-1-yne (726 mg, 7.4 mmol) in THF
(10 mL) maintained at K30 8C was added a 2.5 M solution
of n-butyllithium in hexane (3.2 mL, 7.8 mmol) and 1,3-
dimethyltetahydro-2-[1]pyrimidinone (1.36 g, 10.4 mmol).
After being stirred for 2 h at K30 8C, the aromatic aldehyde
(7.4 mmol) was added, and the solution was stirred for 24 h
at K10 8C. A saturated aqueous ammonium chloride
solution (50 mL) was added, and the mixture was extracted
with diethyl ether (3!50 mL). Evaporation of the solvent
under reduced pressure gave a residue which was purified by
flash-chromatography on silica using the appropriate eluent.
4.1.1. 1-(2-Methylphenyl)oct-2-yn-1-ol 5d. Yield 60%;
oil; Rf 0.34 (petroleum ether/ethyl acetate 10:1); H NMR
1
(300 MHz, CDCl3): d 0.89 (t, JZ7.0 Hz, 3H, CH3), 1.24–
1.42 (m, 4H, CH2), 1.48–1.58 (m, 2H, CH2), 2.17 (d, JZ
5.5 Hz, 1H, OH), 2.24 (dt, JZ7.0, 2.0 Hz, 2H, ]C–CH2),
2.43 (s, 3H, CH3), 5.58 (dt, JZ5.5, 2.0 Hz, 1H, CHO), 7.13–
7.25 (m, 3H, Harom), 7.62–7.67 (m, 1H, Harom); 13C NMR
(75.5 MHz, CDCl3): d 14.4, 19.2, 19.3, 22.6, 28.7, 31.5,
63.0, 80.1, 87.9, 126.5, 126.8, 128.6, 131.1, 136.3, 139.4.
Anal. Calcd for C15H20O: C, 83.29; H, 9.32. Found: C,
82.94; H, 9.39.
4.2. Typical procedure for the preparation of
propargylic carbonates
To a solution of propargylic alcohol 2a–d, 6a, or 6c–e
(17.8 mmol), dimethylaminopyridine (436 mg, 3.6 mmol),
pyridine (6.7 mg, 71.4 mmol), in CH2Cl2 (40 mL) cooled at
0 8C wad added methyl chloroformate (5.6 mg, 71.4 mmol).
After stirring for 24 h at rt, the reaction mixture was poured
into a saturated aqueous copper sulfate solution (30 mL),
and the aqueous phase was extracted with diethyl ether (3!
30 mL). Evaporation of the solvent under reduced pressure
4.1.2. 1-(2-Naphtyl)oct-2-yn-1-ol 5e. Yield 72%; oil; Rf
0.24 (petroleum ether/ethyl acetate 10:1); 1H NMR
(300 MHz, CDCl3): d 0.90 (t, JZ7.0 Hz, 3H, CH3), 1.24–
1.40 (m, 4H, CH2), 1.51–1.61 (m, 2H, CH2), 2.10 (s, 1H,
OH), 2.25 (dt, JZ7.2, 2.1 Hz, 2H, ]C–CH2), 5.50 (t, JZ

2596
N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
afforded an oil that was purified by flash-chromatography on
silica to give the corresponding propargylic carbonate.
7.42–7.50 (m, 2H, Harom), in agreement with the literature
data.36
4.2.1. 1-Ethyl-3-phenylprop-2-yn-1-yl methyl carbonate
3b. Yield 77%; oil; Rf 0.64 (petroleum ether/ethyl acetate
7:1); 1H NMR (300 MHz, CDCl3): d 1.08 (t, JZ7.4 Hz, 3H,
CH3), 1.91 (dq, JZ7.4, 6.4 Hz, 2H, CH2), 3.75 (s, 3H,
OCH3), 5.42 (t, JZ6.4 Hz, 1H, CHO), 7.24–7.29 (m, 3H,
Harom), 7.39–7.45 (m, 2H, Harom); 13C NMR (75.5 MHz,
CDCl3): d 9.6, 28.6, 55.1, 69.9, 86.2, 86.5, 122.6, 128.7,
132.2, 129.1, 155.4. Anal. Calcd for C13H14O3: C, 71.53; H,
6.47. Found: C, 71.29; H, 6.61.
4.2.7. Methyl (R)-1-methyl-3-phenylprop-2-yn-1-yl car-
bonate. Yield 91%; oil; Rf 0.56 (petroleum ether/ethyl
1
acetate 6:1); [a]2D5ZC167.4 (c 1, diethyl ether); H NMR
(300 MHz, CDCl3): d 1.65 (d, JZ6.7 Hz, 3H, CH3), 3.83 (s,
3H, CH3), 5.57 (q, JZ6.7 Hz, 1H, CHO), 7.26–7.36 (m, 3H,
Harom), 7.42–7.50 (m, 2H, Harom), in agreement with the
literature data.36
4.3. Typical procedure for the preparation of
propargylic acetates
4.2.2. 1-Isopropyl-3-phenylprop-2-yn-1-yl methyl car-
bonate 3c. Yield 84%; oil; Rf 0.73 (petroleum ether/ethyl
acetate 7:1); H NMR (300 MHz, CDCl3): d 1.07 (d, JZ
6.8 Hz, 3H, CH3), 1.15 (d, JZ6.6 Hz, 3H, CH3), 2.25 (m,
1H, CHMe2), 3.82 (s, 3H, OCH3), 5.30 (d, JZ5.7 Hz, 1H,
CHO), 7.22–7.29 (m, 3H, Harom), 7.39–7.47 (m, 2H, Harom);
13C NMR (75.5 MHz, CDCl3): d 17.9, 18.6, 33.2, 55.3, 74.1,
84.9, 87.3, 122.7, 128.6, 129.0, 132.3, 155.6. Anal. Calcd
for C14H16O3: C, 72.39; H, 6.94. Found: C, 72.22; H, 6.98.
To a solution of propargylic alcohol (1.6 mmol), and
pyridine (514 mg, 6.5 mmol), in CH2Cl2 (10 mL) cooled
at 0 8C wad added acetyl chloride (521 mg, 6.5 mmol).
After stirring for 24 h at rt, the mixture was poured into a
saturated aqueous copper sulfate solution (10 mL), and the
aqueous phase was extracted with diethyl ether (3!10 mL).
Evaporation of the solvent under reduced pressure afforded
an oil that was purified by flash-chromatography on silica to
give the corresponding propargylic acetate.
1
4.2.3. 1-ter-Butyl-3-phenylprop-2-yn-1-yl methyl car-
bonate 3d. Yield 86%; mp 71 8C; Rf 0.65 (petroleum
ether/ethyl acetate 10:1); H NMR (300 MHz, CDCl3): d
1.10 (s, 9H, CH3), 3.83 (s, 3H, OCH3), 5.18 (s, 1H, CHO),
7.27–7.35 (m, 3H, Harom), 7.41–7.49 (m, 2H, Harom); 13C
NMR (75.5 MHz, CDCl3): d 30.8, 35.4, 55.2, 70.4, 85.6,
89.5, 122.5, 128.6, 129.2, 132.4, 155.6. Anal. Calcd for
C15H18O3: C, 73.15; H, 7.37. Found: C, 73.35; H, 7.08.
4.3.1. 1-(2-Furyl)oct-2-yn-1-yl acetate 7f. Yield 93%; oil;
Rf 0.56 (petroleum ether/ethyl acetate 10:1); 1H NMR
(300 MHz, CDCl3): d 0.90 (t, JZ7.2 Hz, 3H, CH3), 1.31–
1.38 (m, 4H, CH2), 1.55 (m, 2H, CH2), 2.10 (s, 3H,
COCH3), 2.26 (dt, JZ7.2, 2.1 Hz, 2H, ]C–CH2), 6.36 (dd,
JZ3.2, 1.7 Hz, 1H, ]CH–), 6.49–6.52 (m, 2H, ]CH-,
CHO), 7.41 (m, 1H, ]CH–). 13C NMR (75.5 MHz,
CDCl3): d 14.3, 19.1, 21.3, 22.5, 28.3, 31.4, 59.3, 74.6,
88.0, 110.2, 110.8, 143.7, 150.6, 170.0. Anal. Calcd for
C14H19O3 [MCH]C 235.1334. Found: 235.1335.
1
4.2.4. Methyl 1-(2-methylphenyl)oct-2-yn-1-yl carbonate
6d. Yield 56%; oil; Rf 0.73 (petroleum ether/ethyl acetate
1
10:1); H NMR (300 MHz, CDCl3): d 0.88 (t, JZ7.0 Hz,
3H, CH3), 1.27–1.37 (m, 4H, CH2), 1.50–1.55 (m, 2H,
CH2), 2.35 (dt, JZ7.1, 2.0 Hz, 2H, ]C–CH2), 2.43 (s, 3H,
CH3), 3.80 (s, 3H, OCH3), 6.42 (t, JZ2.0 Hz, 1H, CHO),
7.16–7.26 (m, 3H, Harom), 7.58–7.62 (m, 2H, Harom); 13C
NMR (75.5 MHz, CDCl3): d 14.3, 19.2, 19.4, 22.5, 28.4,
31.4, 55.4, 68.7, 78.7, 89.8, 126.6, 128.4, 129.3, 131.1,
135.6, 136.6, 155.4. Anal. Calcd for C17H22O3: C, 74.42; H,
8.08. Found: C, 74.52; H, 8.18.
4.3.2. 1-(2-Thienyl)oct-2-yn-1-yl acetate 7g. Yield 82%;
oil; Rf 0.50 (petroleum ether/ethyl acetate 10:1); H NMR
1
(300 MHz, CDCl3): d 0.89 (t, JZ7.0 Hz, 3H, CH3), 1.30–
1.40 (m, 4H, CH2), 1.53 (tt, JZ7.1, 7.1 Hz, 2H, CH2), 2.03
(s, 3H, COCH3), 2.25 (dt, JZ7.1, 1.9 Hz, 2H, ]C–CH2),
6.67 (t, JZ1.9 Hz, 1H, CHO), 6.93 (dd, JZ5.1, 3.6 Hz, 1H,
]CH–), 7.19 (bd, JZ3.6 Hz, 1H, ]CH–), 7.27 (dd, JZ
5.1, 1.1 Hz, 1H, ]CH–). 13C NMR (75.5 MHz, CDCl3): d
14.3, 19.1, 21.3, 22.5, 28.4, 31.4, 61.4, 76.8, 88.2, 127.0,
127.1, 127.8, 141.3, 169.9. Anal. Calcd for C14H18O2S: C,
67.17; H, 7.25. Found: C, 67.44; H, 7.18.
4.2.5. Methyl 1-(2-naphtyl)oct-2-yn-1-yl carbonate 6e.
Yield 46%; oil; Rf 0.56 (petroleum ether/ethyl acetate 10:1);
1H NMR (300 MHz, CDCl3): d 0.97 (t, JZ7.0 Hz, 3H,
CH3), 1.31–1.49 (m, 4H, CH2), 1.56–1.65 (m, 2H, CH2),
2.35 (dt, JZ7.0, 2.0 Hz, 2H, ]C–CH2), 3.83 (s, 3H, CH3),
6.63 (t, JZ2.0 Hz, 1H, CHO), 7.84–7.92 (m, 3H, Harom),
7.77 (dd, JZ8.7, 2.0 Hz, 1H, Harom), 7.49–7.55 (m, 2H,
Harom), 8.12 (s, 1H, Harom); 13C NMR (75.5 MHz, CDCl3): d
14.4, 19.3, 22.6, 28.5, 31.5, 55.3, 70.9, 78.2, 90.2, 125.5,
126.8, 127.1, 127.6, 128.1, 128.8, 129.0, 133.5, 134.0,
135.0, 155.5. HRMS (EI) calcd for C20H23O3 [MCH]C:
311.1647. Found: 311.1646.
4.4. Typical procedure for the palladium-catalyzed
annulation reaction
A mixture of Pd2(dba)3 (20.8 mg, 2.2!10K2 mmol), and
diphosphine (9.1!10K2 mmol) in THF (7 mL) was stirred
under a nitrogen atmosphere at rt 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
carbonate (1.1 mmol), or propargylic acetate (1.1 mmol) in
the presence of triethylamine (269 mg, 2.6 mmol). The
resulting solution was stirred at rt for 24 h. The solvent
was evaporated and the residue was chromatographed
over silica with petroleum ether/ethyl acetate as the
eluent to afford the corresponding 2,3-dihydro-1,4-
benzodioxine.
4.2.6. Methyl (R)-1-methylprop-2-yn-1-yl carbonate.
Yield 82%; oil; Rf 0.72 (petroleum ether/ethyl acetate
5:1); [a]2D5ZC109 (c 1, diethyl ether); 1H NMR (300 MHz,
CDCl3): d 1.65 (d, JZ6.7 Hz, 3H, CH3), 3.83 (s, 3H, CH3),
5.57 (q, JZ6.7 Hz, 1H, CHO), 7.26–7.36 (m, 3H, Harom),

N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
2597
4.4.1. (3Z)-2-Ethylidene-3-phenyl-2,3-dihydro-1,4-
benzodioxine (8a) and (2Z)-2-benzylidene-3-methyl-2,3-
dihydro-1,4-benzodioxine (9a). Rf 0.63 (petroleum ether/
ethyl acetate 40:1).
For 10d. 1H NMR (300 MHz, CDCl3): d 0.78 (t, JZ6.8 Hz,
3H, CH3), 1.19–1.31 (m, 6H, CH2), 2.08–2.12 (m, 2H,
CH2), 2.28 (s, 3H, CH3), 4.16 (t, JZ7.3 Hz, 1H, ]CH–),
5.45 (s, 1H, OCH), 6.77–7.22 (m, 7H, Harom), 7.37–7.40 (m,
1H, Harom); 13C NMR (75.5 MHz, CDCl3): d 14.4, 20.7,
23.0, 25.6, 31.8, 31.9, 75.4, 104.3, 116.8, 118.0, 122.3,
122.9, 126.2, 127.3, 129.9, 130.4, 133.1, 136.3, 142.5,
142.6, 142.9.
For 8a. 1H NMR (300 MHz, CDCl3): d 1.71 (d, JZ6.8 Hz,
3H, CH3), 4.54 (q, JZ6.8 Hz, 1H, ]CH–), 5.50 (s, 1H,
OCH), 6.89–7.86 (m, 9H, Harom); 13C NMR (75.5 MHz,
CDCl3): d 20.0, 76.4, 105.4, 120.8, 122.0, 126.4, 127.1,
131.3, 132.9, 133.5, 138.9, 146.7, 147.5, 151.6.
For 11d. 1H NMR (300 MHz, CDCl3): d 0.82 (t, JZ6.8 Hz,
3H, CH3), 1.19–1.31 (m, 6H, CH2), 1.66–1.81 (m, 2H,
CH2), 2.26 (s, 3H, CH3), 4.50 (t, JZ7.3 Hz, 1H, OCH), 5.63
(s, 1H, ]CH–), 6.77–7.22 (m, 7H, Harom), 7.79 (d, JZ
7.6 Hz, 1H, Harom); 13C NMR (75.5 MHz, CDCl3): d 14.5,
19.7, 22.8, 24.5, 29.3, 74.0, 110.4, 116.7, 117.9, 122.2,
122.4, 126.7, 128.0, 128.9, 130.8, 135.2, 136.7, 143.4,
144.5, 145.5. Anal. Calcd for C21H24O2: C, 81.78; H, 7.84.
Found: C, 81.56; H, 8.02.
For 9a. 1H NMR (300 MHz, CDCl3): d 1.65 (d, JZ6.5 Hz,
3H, CH3), 4.72 (q, JZ6.5 Hz, 1H, OCH), 5.72 (s, 1H,
]CH–), 6.89–7.86 (m, 9H, Harom); 13C NMR (75.5 MHz,
CDCl3): d 22.2, 74.9, 109.7, 120.8, 122.0, 126.4, 127.1,
131.3, 132.9, 133.5, 138.9, 146.7, 147.5, 151.6. Anal. Calcd
for C16H14O2: C, 80.65; H, 5.92. Found: C, 80.61; H, 5.99.
4.4.2. (2Z)-2-Phenyl-3-propylidene-2,3-dihydro-1,4-
benzodioxine (8b) and (2Z)-2-benzylidene-3-ethyl-2,3-
dihydro-1,4-benzodioxine (9b). Rf 0.68 (petroleum ether/
ethyl acetate 40:1).
4.4.5. (2Z)-2-Hexylidene-3-(2-naphthyl)-2,3-dihydro-1,4-
benzodioxine (10e) and (2Z)-2-(2-naphthylmethylene)-3-
pentyl-2,3-dihydro-1,4-benzodioxine (11e). Rf 0.74
(petroleum ether/ethyl acetate 40:1).
For 8b. 1H NMR (300 MHz, CDCl3): d 1.04 (d, JZ7.5 Hz,
3H, CH3), 2.32 (m, 2H, CH2), 4.50 (m, 1H, ]CH–), 5.49 (s,
1H, OCH), 6.90–7.90 (m, 9H, Harom); 13C NMR (75.5 MHz,
CDCl3): d 14.4, 18.0, 76.4, 112.7, 117.9, 122.3, 122.4,
128.0, 128.7, 128.8, 129.3, 137.2, 143.8, 145.3, 146.0.
For 10e. 1H NMR (300 MHz, CDCl3): d 0.90 (t, JZ6.8 Hz,
3H, CH3), 1.46–1.65 (m, 6H, CH2), 2.28 (dt, JZ7.2, 7.2 Hz,
2H, CH2), 4.53 (t, JZ7.2 Hz, 1H, ]CH–), 5.64 (s, 1H,
OCH), 6.85–8.13 (m, 11H, Harom); 13C NMR (75.5 MHz,
CDCl3): d 14.1, 22.5, 22.6, 24.2, 29.0, 76.1, 111.1, 116.4,
117.6, 122.0, 122.1, 125.3, 126.3, 126.4, 127.1, 127.7,
128.3, 133.1, 133.2, 134.4, 143.0, 143.4, 145.2.
For 9b. 1H NMR (300 MHz, CDCl3): d 1.13 (t, JZ7.3 Hz,
3H, CH3), 1.91 (m, 2H, CH2), 4.50 (m, 1H, OCH), 5.64 (s,
1H, ]CH–), 6.90–7.90 (m, 9H, Harom); 13C NMR
(75.5 MHz, CDCl3): d 10.4, 25.0, 76.6, 106.8, 116.6,
118.1, 122.2, 123.1, 127.2, 128.7, 129.3, 134.8, 142.5,
142.6, 146.0. Anal. Calcd for C17H16O2: C, 80.93; H, 6.39.
Found: C, 81.13; H, 6.34.
For 11e. 1H NMR (300 MHz, CDCl3): d 0.90 (t, JZ6.8 Hz,
3H, CH3), 1.25–1.44 (m, 6H, CH2), 1.75–1.95 (m, 2H,
CH2), 4.61 (dd, JZ7.9, 6.2 Hz, 1H, OCH), 5.77 (s, 1H,
]CH–), 6.85–8.13 (m, 11H, Harom); 13C NMR (75.5 MHz,
CDCl3): d 14.1, 22.6, 25.2, 31.5, 31.6, 74.9, 106.4, 116.3,
117.8, 121.9, 122.8, 125.8, 126.1, 127.2, 127.6, 127.8,
127.9, 128.1, 132.1, 132.4, 133.6, 142.2, 142.3, 146.3. Anal.
Calcd for C24H24O2: C, 83.69; H, 7.02. Found: C, 83.29; H,
6.98.
4.4.3. (2Z)-2-(2-Methylpropylidene)-3-phenyl-2,3-di-
hydro-1,4-benzodioxine (8c) and (2Z)-2-benzylidene-3-
isopropyl-2,3-dihydro-1,4-benzodioxine (9c). RfZ0.80
(petroleum ether/ethyl acetate 40:1).
For 8c. 1H NMR (300 MHz, CDCl3): d 0.90 (d, JZ4.9 Hz,
6H, CH3), 2.91 (m, 1H, CHMe2), 4.27 (d, JZ9.0 Hz, 1H,
4.4.6. (3Z)-2-(2-Furyl)-3-hexylidene-2,3-dihydro-1,4-
benzodioxine (10f) and (2Z)-2-(2-furylmethylene)-3-pen-
tyl-2,3-dihydro-1,4-benzodioxine (11f). Rf 0.5 (petroleum
ether/ethyl acetate 60:1C0.5% Et3N).
]CH–), 5.33 (s, 1H, OCH), 6.72–7.65 (m, 9H, Harom); 13
C
NMR (75.5 MHz, CDCl3): d 23.2, 23.4, 24.6, 76.3, 118.4,
116.7, 118.0, 118.4, 122.3, 122.4, 128.0, 128.8, 134.8,
137.3, 143.7, 143.9.
For 10f. 1H NMR (300 MHz, CDCl3): d 0.86 (t, JZ6.8 Hz,
3H, CH3), 1.27–1.36 (m, 4H, CH2), 1.41–1.58 (m, 2H,
CH2), 1.69–1.86 (m, 2H, CH2), 4.74 (t, JZ7.5 Hz, 1H,
]CH–), 5.54 (s, 1H, OCH), 6.45–6.47 (m, 1H, Harom), 6.85
(d, JZ3.2 Hz, 1H, Harom), 6.92–7.12 (m, 4H, Harom), 7.35–
7.36 (m, 1H, Harom).
For 9c. 1H NMR (300 MHz, CDCl3): d 1.00 (d, JZ6.6 Hz,
6H, CH3), 1.95 (m, 1H, CH2), 4.04 (d, JZ9.8 Hz, 1H,
OCH), 5.46 (s, 1H, ]CH–), 6.72–7.65 (m, 9H, Harom); 13
C
NMR (75.5 MHz, CDCl3): d 18.9, 19.0, 29.2, 81.6, 108.4,
116.6, 118.1, 122.1, 123.2, 127.2, 128.7, 129.3, 142.2,
142.8, 143.3, 144.7. Anal. Calcd for C18H18O2: C, 81.17; H,
6.81. Found: C, 81.06; H, 6.78.
For 11f. 1H NMR (300 MHz, CDCl3): d 0.86 (t, JZ6.8 Hz,
3H, CH3), 1.27–1.36 (m, 4H, CH2), 1.41–1.58 (m, 2H,
CH2), 1.69–1.86 (m, 2H, CH2), 4.49 (dd, JZ8.1, 6.0 Hz,
1H, OCH), 5.68 (s, 1H, ]CH–), 6.45–6.47 (m, 1H, Harom),
6.85 (d, JZ3.2 Hz, 1H, Harom), 6.92–7.12 (m, 4H, Harom),
7.35–7.36 (m, 1H, Harom); 13C NMR (75.5 MHz, CDCl3): d
14.4, 22.9, 25.4, 31.7, 31.8, 74.3, 96.8, 109.9, 112.1, 116.6,
118.1, 122.3, 123.2, 141.2, 142.5, 142.7, 145.1, 150.0.
4.4.4. (2Z)-2-Hexylidene-3-(2-methylphenyl)-2,3-di-
hydro-1,4-benzodioxine (10d) and (2Z)-2-(2-methyl-
benzylidene)-3-pentyl-2,3-dihydro-1,4-benzodioxine
(11d). Rf, 0.46 for 10d and 0.38 for 11d (petroleum ether/
ethyl acetate 60:1).

2598
N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
HRMS (EI) calcd for C18H21O3 [MCH]C: 285.1491.
Found: 285.1493.
Acknowledgements
J.-R. L. and N. D. thank the French Ministery of Education
for a fellowship.
4.4.7. (2Z)-2-Hexylidene-3-(2-thienyl)-2,3-dihydro-1,4-
benzodioxine (10g) and (3Z)-2-pentyl-3-(2-thienyl-
methylene)-2,3-dihydro-1,4-benzodioxine (11g). Rf 0.46
(petroleum ether/ethyl acetate 60:1C0.5% Et3N).
For 10g. 1H NMR (300 MHz, CDCl3): d 0.82 (t, JZ6.8 Hz,
3H, CH3), 1.10–1.18 (m, 4H, CH2), 1.32–1.55 (m, 2H,
CH2), 1.63–1.85 (m, 2H, CH2), 4.70 (t, JZ7.4 Hz, 1H,
]CH–), 5.66 (s, 1H, OCH), 6.84–6.93 (m, 4H, Harom), 7.03
(d, JZ3.6 Hz, 1H, Harom), 7.05–7.10 (m, 1H, Harom), 7.18–
7.21 (m, 1H, Harom).
References and notes
1. Merlini, L.; Zanarotti, A.; Pelter, A.; Rochefort, M. P.;
Haensel, R. J. Chem. Soc., Chem. Commun. 1979, 695.
2. Arnone, A.; Merlini, L.; Zanarotti, A. J. Chem. Soc., Chem.
Commun. 1979, 696–697.
3. Bosseray, P.; Guillaumet, G.; Coudert, G.; Wasserman, H.
Tetrahedron Lett. 1989, 30, 1387–1390.
For 11g. 1H NMR (300 MHz, CDCl3): d 0.82 (t, JZ6.8 Hz,
3H, CH3), 1.24–1.26 (m, 4H, CH2), 1.32–1.55 (m, 2H,
CH2), 1.63–1.85 (m, 2H, CH2), 4.45 (dd, JZ7.9, 6.2 Hz,
1H, OCH), 5.87 (s, 1H, ]CH–), 6.84–6.93 (m, 4H, Harom),
7.03 (d, JZ3.6 Hz, 1H, Harom), 7.05–7.10 (m, 1H, Harom),
7.18–7.21 (m, 1H, Harom); 13C NMR (75.5 MHz, CDCl3): d
16.8, 25.3, 27.8, 34.2, 34.3, 76.8, 103.7, 119.2, 120.5, 124.7,
125.6, 128.5, 129.2, 129.3, 139.6, 144.9, 145.1, 146.8. Anal.
Calcd for C18H20O2S: C, 71.97; H, 6.71. Found: C, 71.81;
H, 6.58.
4. Debenedetti, S. L.; Nadinic, E. L.; Coussio, J. D.; De Kimpe,
N.; Feneau-Dupont, J.; Declercq, J. P. Phytochemistry 1991,
30, 2757–2758.
5. Tsukamoto, S.; Kato, H.; Hirota, H.; Fusetani, N. Tetrahedron
1994, 50, 13583–13592.
6. Fagan, G. P.; Chapleo, C. B.; Lane, A. C.; Myers, M.; Roach,
A. G.; Smith, C. F. C.; Stillings, M. R.; Welbourn, A. P.
J. Med. Chem. 1988, 31, 944–948.
7. Satoh, Y.; Powers, C.; Toledo, L. M.; Kowalski, T. J.; Peters,
P. A.; Kimble, E. F. J. Med. Chem. 1995, 38, 68–75.
8. Nelson, W. L.; Wennerstrom, J. E.; Dyer, D. C.; Engel, M.
J. Med. Chem. 1977, 20, 880–885.
4.5. Separation of the enantiomers
9. Marciniak, G.; Delgado, A.; Leclerc, G.; Velly, J.; Decker, N.;
Schwartz, J. J. Med. Chem. 1989, 32, 1402–1407.
10. Ruffolo, R. R., Jr.; Bondinell, W.; Hieble, J. P. J. Med. Chem.
1995, 38, 3681–3716.
The enantiomeric excesses of the obtained compounds were
determined by HPLC on a chiral column Chiralpak AD
(25 cm!4.6 mm).
11. Giardina, D.; Bertini, R.; Brancia, E.; Brasili, L.; Melchiorre,
C. J. Med. Chem. 1985, 28, 1354–1357.
8a/9a (hexane/2-propanol 98:2): 8a: non-separated; 9a:
RtZ14.5 min for the (K) enantiomer and 16.2 min for the
(C) enantiomer.
12. Quaglia, W.; Pigini, M.; Tayebati, S. K.; Piergentili, A.;
Giannella, M.; Leornadi, A.; Taddei, C.; Melchiorre, C.
J. Med. Chem. 1996, 39, 2253–2258.
8b/9b (hexane/2-propanol 98:2): 8b: non-separated; 9b:
RtZ15.3 and 17.8 min.
13. Lee, T. V.; Leigh, A. J.; Chapleo, C. B. Synlett 1989, 30–32.
14. Lee, T. V.; Leigh, A. J.; Chapleo, C. B. Tetrahedron 1990, 46,
921–934.
8c/9c (hexane/2-propanol 99:1): 8c: RtZ10.2 and 20.9 min;
9c: RtZ32.4 and 35.0 min.
15. Moreau, P.; Guillaumet, G.; Coudert, G. Synth. Commun.
1994, 24, 1781–1787.
16. Mata, E. G.; Suarez, A. G. Synth. Commun. 1997, 27,
1291–1300.
10a/11a (hexane/2-propanol 96:4): 10a: non-separated;
11a: RtZ44.8 and 51.7 min.
17. Katritzky, A. R.; Sewell, M. J.; Topsom, R. D.; Monro, A. M.;
Potter, G. W. H. Tetrahedron 1966, 22, 931–939.
18. Farina, G.; Zecchi, G. Synthesis 1977, 755.
19. Guillaumet, G.; Coudert, G.; Loubinoux, B. Tetrahedron Lett.
1979, 20, 4375–4378.
10b/11b (hexane/2-propanol 96:4): 10b: RtZ15.6 and
19.8 min; 11b: RtZ11.8 and 12.3 min.
10c/11c (hexane/2-propanol 96:4): 10c: RtZ27.7 and
32.6 min; 11c: RtZ15.8 and 17.4 min.
20. Adam, W.; Schmidt, E.; Takayama, K. Synthesis 1982,
322–324.
21. Chapleo, C. B.; Davis, J. A.; Myers, P. L.; Readhead, M. J.;
Stillings, M. R.; Welbourn, A. P.; Hampson, F. C.; Sugden,
K. J. J. Heterocycl. Chem. 1984, 21, 77–80.
10d/11d (hexane): 10d: RtZ24.9 and 32.1 min; 11d: RtZ
13.8 and 14.8 min.
22. Lee, H. H.; Denny, W. A. J. Chem. Soc., Perkin Trans. 1 1990,
1071–1074.
10e/11e (hexane/2-propanol, 150:1): 10e: RtZ32.0 and
42.9 min; 11e: RtZ19.7 and 20.4 min.
23. Ruiz, N.; Pujol, M. D.; Guillaumet, G.; Coudert, G.
Tetrahedron Lett. 1992, 33, 2965–2968.
10f/11f (hexane/2-propanol 98:2) 10f: non-separated; 11g:
RtZ13.4 and 14.6 min.
24. Massacret, M.; Goux, C.; Lhoste, P.; Sinou, D. Tetrahedron
Lett. 1994, 35, 6093–6096.
25. Massacret, M.; Lhoste, P.; Lakhmiri, R.; Parella, T.; Sinou, D.
Eur. J. Org. Chem. 1999, 2665–2673.
10g/11g (hexane): 10g: RtZ15.3 and 16.2 min; 11g: RtZ
29.4 and 38.7 min.

N. Dominczak et al. / Tetrahedron 61 (2005) 2589–2599
2599
26. Yamamoto, M. J. Chem. Soc., Perkin Trans. 1 1979,
3161–3165.
42. Trost, B. M.; Strege, P. E. J. Am. Chem. Soc. 1977, 99,
1649–1651.
27. Cabiddu, S.; Floris, C.; Melis, S.; Sotgiu, F.; Cerioni, G.
J. Heterocycl. Chem. 1986, 23, 1815–1820.
28. Rosnati, V.; Salimbeni, A. Tetrahedron 1986, 42, 4541–4548.
29. Ruiz, N.; Rollin, P. Tetrahedron Lett. 1989, 30, 1637–1640.
30. Moreau, P.; Al Neirabeyeh, M.; Guillaumet, G.; Coudert, G.
Tetrahedron Lett. 1991, 32, 5525–5528.
43. Takahashi, T.; Jinbo, Y.; Kitamura, K.; Tsuji, J. Tetrahedron
Lett. 1984, 25, 5921–5924.
44. Mackenzie, P. B.; Whelan, J.; Bosnich, B. J. Am. Chem. Soc.
1985, 107, 2046–2054.
45. Moreno-Man˜as, M.; Ribas, J.; Virgili, A. J. Org. Chem. 1988,
53, 5328–5335.
31. Basak, A.; Bhattacharya, G.; Mallik, U. K.; Khamrai, U. K.
Synth. Commun. 1997, 27, 367–373.
46. Murahashi, S.-I.; Taniguchi, Y.; Imada, Y.; Tanigawa, Y.
J. Org. Chem. 1989, 54, 3292–3303.
¨
47. Backwall, J.-E.; Granberg, K. L.; Heuman, A. Isr. J. Chem.
32. Organ, M. G.; Miller, M.; Konstantinou, Z. J. Am. Chem. Soc.
1998, 120, 9283–9290.
1991, 31, 17–24.
¨
48. Granberg, K. L.; Backwall, J.-E. J. Am. Chem. Soc. 1992, 114,
33. Chowdhury, C.; Kundu, N. G. J. Chem. Soc., Chem. Commun.
1996, 1067–1068.
6858–6863.
34. Chowdhury, C.; Chaudhuri, G.; Guha, S.; Mukherjee, A. K.;
Kundu, N. G. J. Org. Chem. 1998, 63, 1863–1871.
35. Labrosse, J.-R.; Lhoste, P.; Sinou, D. Tetrahedron Lett. 1999,
40, 9025–9028.
49. Kurosawa, H.; Kajimaru, H.; Ogoshi, S.; Yoneda, H.; Miki, K.;
Kasai, N.; Murai, S.; Ikeda, I. J. Am. Chem. Soc. 1992, 114,
8417–8424.
50. Ogoshi, S.; Kurosawa, H. Organometallics 1993, 12,
2869–2871.
36. Labrosse, J.-R.; Lhoste, P.; Sinou, D. J. Org. Chem. 2001, 66,
6634–6642.
51. Kurosawa, H.; Ogoshi, S. Bull. Chem. Soc. Jpn 1998, 71,
973–984.
37. Labrosse, J.-R.; Lhoste, P.; Sinou, D. Org. Lett. 2000, 2,
527–529.
52. Yoshida, M.; Fujita, M.; Ihara, M. Org. Lett. 2003, 5,
3325–3327.
38. Labrosse, J.-R.; Lhoste, P.; Sinou, D. Eur. J. Org. Chem. 2002,
1966–1971.
53. Yoshida, M.; Ohsawa, Y.; Ihara, M. J. Org. Chem. 2004, 69,
1590–1597.
39. Ma, S. Eur. J. Org. Chem. 2004, 1175–1183.
40. Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96,
395–422.
54. Nakamura, K.; Takenaka, K.; Ohno, A. Tetrahedron:
Asymmetry 1998, 9, 4429–4439.
41. Damez, C.; Labrosse, J.-R.; Lhoste, P.; Sinou, D. Tetrahedron
Lett. 2003, 44, 557–560.