Synthesis of cyclic enol ethers from alkenyl-β-dicarbonyl compounds

Article abstract of DOI:10.1021/jo011089+

In this work we describe the cyclofunctionalization of eleven differently substituted alkenyl-β-dicarbonyl compounds, employing three electrophilic reagents, namely, iodine, ρ-methoxyphenyl-tellurium trichloride, and phenylselenenyl bromide. The reactions occur through the enolic form of the substrates, to afford the corresponding iodo-, telluro-, or selenocyclic enol ethers. Substrates bearing trisubstituted double bonds failed in reacting with the selenium and tellurium reagents. In general, β-diketones reacted faster than β-keto esters with the three studied electrophiles.

Full text of DOI:10.1021/jo011089+

4122
J . Org. Chem. 2002, 67, 4122-4126
Syn th esis of Cyclic En ol Eth er s fr om Alk en yl-â-d ica r bon yl
Com p ou n d s
Helena M. C. Ferraz,* Myrian K. Sano, Marta R. S. Nunes, and Graziela G. Bianco
Instituto de Quı´mica, Universidade de Sa˜o Paulo, CEP 05508-900, Sa˜o Paulo-SP, Brazil
hmferraz@iq.usp.br
Received November 19, 2001
In this work we describe the cyclofunctionalization of eleven differently substituted alkenyl-â-
dicarbonyl compounds, employing three electrophilic reagents, namely, iodine, p-methoxyphenyl-
tellurium trichloride, and phenylselenenyl bromide. The reactions occur through the enolic form of
the substrates, to afford the corresponding iodo-, telluro-, or selenocyclic enol ethers. Substrates
bearing trisubstituted double bonds failed in reacting with the selenium and tellurium reagents.
In general, â-diketones reacted faster than â-keto esters with the three studied electrophiles.
Sch em e 1
In tr od u ction
Cyclic ethers constitute important building blocks in
organic synthesis, being the core of several natural
products, such as polyether antibiotics1 and annonaceous
acetogenins.2
The electrophilic cyclofunctionalization of unsaturated
carboxylic acids and alcohols, leading to the correspond-
ing lactones and cyclic ethers, has been exhaustively
reported in the literature.3-6 â-Keto esters and â-dike-
tones bearing a double bond suitably positioned can also
react with electrophiles, probably through their enolic
forms,7 to give the corresponding product of an O-
cyclization, as shown in the general equations of Scheme
1.
Nevertheless, the use of alkenyl-â-dicarbonyl com-
pounds as substrates for the electrophilic cyclization is
less common than might be expected. Thus, Antonioletti
et al.8,9 reported the iodocyclization of a series of R-alk-
enylated substrates such as I, which led to the corre-
sponding iodocyclic ethers II in very good yields. The
selenocyclization of various substrates of general formu-
las I and III has already been studied by Ley et al.,7,10,11
as well as by Tiecco et al.,12,13 using different selenium
electrophiles. In all the conditions studied, the seleno-
cyclic ethers II and IV were obtained in reasonable to
good yields. In a preliminary communication,14 we re-
ported the iodo- and tellurocyclization of some â-keto
esters analogous to I or III, as will be discussed in the
next section. The tellurocyclization of I (R1 ) Me, R2 )
OEt) has also been described by us.15
The synthetic utility of the above-mentioned kind of
products stimulated us to undertake the present work,
to establish the scope and limitations of different elec-
trophiles toward the cyclofunctionalization reaction. We
chose â-dicarbonyl derivatives bearing allylic and ho-
moallylic chains, with different patterns of substitution
in the double bond, which would give diversely function-
alized five- and six-membered ring enol ethers.
(1) Boivin, T. L. B. Tetrahedron 1987, 43, 3309.
(2) Zeng, L.; Ye, Q.; Oberlies, N. H.; Shi, G.; Gu, Z. M.; He, K.;
McLaughlin, J . L. Nat. Prod. Rep. 1996, 275.
(3) Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321.
(4) Harmange, J . C.; Figade`re, B. Tetrahedron: Asymmetry 1993,
4, 1711.
(5) Petragnani, N.; Stefani, H. A.; Valduga, C. J . Tetrahedron 2001,
57, 1411.
Resu lts a n d Discu ssion
(6) Gruttadauria, M.; Meo, P. L.; Noto, R. Tetrahedron 2001, 57,
1819.
(7) J ackson, W. P.; Ley, S. V.; Morton, J . A. J . Chem. Soc., Chem.
Commun. 1980, 1028.
(8) Antonioletti, R.; Bonadies, F.; Scettri, A. Tetrahedron Lett. 1988,
29, 4987.
(9) Antonioletti, R.; Cecchini, C.; Ciani, B.; Magnanti, S. Tetrahedron
Lett. 1995, 36, 9019.
The alkenyl-â-keto esters were prepared from ethyl
acetoacetate, by previously described methods. Thus, the
γ-alkenylated substrates 1, 8, 9, and 18 were obtained
employing the procedure described by Huckin and Weil-
er,16 while the R-alkenyl-â-keto esters 2, 10, and 17 were
prepared as described by Ranu and Bhar.17 These sub-
strates were then submitted to the electrophilic cycliza-
(10) J ackson, W. P.; Ley, S. V.; Whittle, A. J . J . Chem. Soc., Chem.
Commun. 1980, 1173.
(11) Brussani, G.; Ley, S. V.; Wright, J . L.; Williams, D. J . J . Chem.
Soc., Perkin Trans. 1 1986, 303.
(12) Tiecco, M.; Testaferri, L.; Tingoli, M.; Bartoli, D.; Balducci, R.
J . Org. Chem. 1990, 55, 429.
(14) Ferraz, H. M. C.; Sano, M. K.; Scalfo, A. C. Synlett 1999, 567.
(15) Ferraz, H. M. C.; Comasseto, J . V.; Borba, E. B.; Brandt, C. A.
Quı´m. Nova 1992, 15, 298.
(13) Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A. Synth.
Commun. 1998, 28, 1769.
(16) Huckin, S. N.; Weiler, L. J . Am. Chem. Soc. 1974, 96, 1082.
(17) Ranu, B. C.; Bhar, S. J . Chem. Soc., Perkin Trans. 1 1992, 365.
10.1021/jo011089+ CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/09/2002

Synthesis of Cyclic Enol Ethers
J . Org. Chem., Vol. 67, No. 12, 2002 4123
Ta ble 1. Electr op h ilic Cycliza tion of â-Keto Ester s
Ta ble 2. Electr op h ilic Cycliza tion of â-Keto Ester s
Bea r in g a Mon osu bstitu ted Dou ble Bon d
Bea r in g a Disu bstitu ted Dou ble Bon d
a
b
Ar ) p-MeOPh. Previously communicated in ref 14.
tion reactions, whose results are summarized in Tables
1 and 2 and in Scheme 2.
The iodocyclization of the alkenyl-â-keto esters was
performed under kinetic conditions, to avoid a reversible
process and, consequently, the formation of any C-
cyclization product. The reactions occurred in a clean
fashion, giving exclusively the expected product of a
Markovnikov addition to the double bond (Table 1,
entries 1, 2, and 5; Table 2, entries 1, 4, and 7). The only
exceptions were the substrates 17 and 18 (Scheme 2),
which bear trisubstituted double bonds.
a
b
Ar ) p-MeOPh. Different times (1-24 h) and temperatures
(room temperature to reflux) were tried for these reactions.
c Previously communicated in ref 14.
Sch em e 2
The â-keto ester 17 gave an isomeric mixture of the
six-membered and five-membered ring enol ethers 19
(Markovnikov product) and 20 (anti-Markovnikov prod-
uct), which were isolated in 66% and 22% yields, respec-
tively. On the other hand, the iodocyclization of 18 did
not follow Markovnikov’s rule, since the major product
of the reaction was the five-membered ring ether 21,
accompanied by minor amounts of the endocyclic enol
ether 22.18 Probably, this behavior is due more to steric
than to electronic factors.
The next set of reactions was the selenocyclization,
using phenylselenenyl bromide as the electrophilic re-
agent. The substrates 2, 9, and 10 (Table 1, entry 7; Table
2, entries 6 and 9) furnished the expected products 7,
13, and 16, respectively, although the yields of these
reactions were always lower than those of the corre-
sponding iodocyclizations. The â-keto esters 8 and 17
gave a complex mixture of products. The reaction of 18
with phenylselenenyl chloride has already been reported
in the literature.19 Using acetonitrile or dichloromethane
as solvent, the authors obtained a mixture containing
predominantly the product of addition to the double bond,
while running the reaction in the presence of aluminum
trichloride afforded the C-cyclization product in 84%
yield. In view of these observations, as well as the
negative results obtained with the substrates 8 and 17,
(18) The cyclic ethers 19-22 are very unstable, decomposing on
storage, but their structures could be clearly deduced by NMR
spectroscopy; their tendency for losing iodine (or iodide) is so high that
we could not obtain pure samples for elemental analysis. NMR data
for product 22: 1H NMR (300 MHz, CDCl3) δ 1.19 (t, J ) 7.1 Hz, 3H),
1.34 (s, 3H), 1.38 (s, 3H), 2.63-2.68 (m, 2H), 2.92 (m, 2H), 4.07 (q, J
) 7.1 Hz, 2H), 4.06-4.17 (m, 1H), 4.41 (t, J ) 3.6 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 14.1, 22.9, 27.2, 32.8, 33.3, 40.2, 60.7, 76.6, 97.5,
146.3, 169.9.
(19) Alderdice, M.; Weiler, L. Can. J . Chem. 1981, 59, 2239.

4124 J . Org. Chem., Vol. 67, No. 12, 2002
Ferraz et al.
Sch em e 3
Sch em e 4
Sch em e 5
we did not submit the â-keto ester 18 to the selenocy-
clization reaction.
The reactions of tellurocyclization of the â-keto esters
were performed using p-methoxyphenyltellurium trichlo-
ride. The substrates bearing di- and trisubstituted double
bonds (with the exception of 10, Table 2, entry 8) always
furnished a complex mixture of products. It should be
mentioned that almost all the tellurocyclizations of
unsaturated carboxylic acids and alcohols described in
the literature20 were performed on substrates bearing
monosubstituted double bonds. Accordingly, the â-keto
esters 1a , 1b, and 2 (Table 1, entries 3, 4, and 6) gave
good yields of the cyclic products.
The bicyclic products 12-16 (Table 2) exhibit cis-fused
rings, assigned by NMR spectroscopy14 and by analogy
with related compounds.21,22 The cis arrangement of the
rings, as well as the trans relationship between the
electrophile and the ring oxygen atom, is a direct
consequence of the mechanism of the electrophile-
promoted cyclization, which is believed to proceed via a
trans-diaxial addition to the double bond.23
similar hydration of the cyclic products. The incorpora-
tion of the hydroxyl group only in the products of
cyclization of 23 can be understood considering that an
enol ether such as 24b is more prone to hydration than
the earlier compounds, which are all substituted 3-alkoxy
acrylates.
Finally, in a preliminary experiment, the reaction of
26 with DBU furnished the bicyclic ketal 28, in a
nonoptimized yield of 53% (Scheme 5).
To compare the behavior of alkenyl-â-keto esters and
â-diketones toward electrophilic cyclization, the R-allyl-
â-cyclohexanediones 30 and 31 were submitted to treat-
ment with the three electrophilic reagents. The cycliza-
tion reactions occur smoothly, giving the tetrahydro-
benzofuranones in very good yields, as summarized in
Table 3.26
Con clu sion s
In addition to the substrates already discussed, the
â-keto ester 23 (R ) Et) was also submitted to the
cyclization reactions. It is noteworthy that Ley and co-
workers24 were able to isolate a 9:1 mixture of the double
bond isomers 24b (R ) Me) and 24a (R ) Me), by treating
23 (R ) Me) with N-phenylselenophthalimide and a trace
amount of SnCl4. Nevertheless, under the conditions
employed by us, the only characterizable product of
selenocyclization of 23 (R ) Et) was the hemiketal 25,
probably formed from 24b (Scheme 3).
In a similar fashion, treatment of 23 (R ) Et) with
iodine and p-methoxyphenyltellurium trichloride led to
the corresponding hemiketals 26 and 27, respectively, in
moderate yields (Scheme 4).25 It must be noted that in
all the other examples studied, we did not observe any
The results shown in this work extend the usefulness
of the electrophile-mediated cyclization of alkenyl-
substituted â-keto esters and ketones, especially when
iodine is employed as the electrophile. With few excep-
tions, only the substrates bearing monosubstituted double
bonds react cleanly with phenylselenenyl bromide and
p-methoxyphenyltellurium trichloride. Nevertheless, the
methodology herein presented provides access to cyclic
ethers and tetrahydrobenzofuranones differently func-
tionalized, in yields ranging from moderate to very good.
Moreover, these products can be submitted to further
elimination or reduction reactions, as described previ-
ously for the compounds 3a and 4a .14 Studies toward
these kinds of reactions are in progress in our laboratory.
(20) Petragnani, N.; Comasseto, J . V. Synthesis 1991, 897.
(21) Ferraz, H. M. C.; Pereira, F. L. C.; Leite, F. S.; Nunes, M. R.
S.; Arru´a, M. E. P. Tetrahedron 1999, 55, 10915.
(22) Husebye, S.; Meyers, E. A.; Zingaro, R. A.; Comasseto, J . V.;
Petragnani, N. Acta Crystallogr. 1987, C43, 1147.
(23) Dowle, M. D.; Davies, D. I. Chem. Soc. Rev. 1979, 8, 171.
(24) Ley, S. V.; Lygo, B.; Molines, H. J . Chem. Soc., Perkin Trans.
1 1984, 2403.
Exp er im en ta l Section
The â-keto esters and â-diketones were prepared by previ-
ously described methods.16,17,27 Column chromatography was
performed using 230-400 mesh silica gel. TLC analyses were
performed with silica gel plates, using vanillin solution or
iodine for visualization.
Gen er a l P r oced u r e for Iod ocycliza tion . A mixture of
I2 (1.5 mmol), anhydrous Na2CO3 or NaHCO3 (1.5 mmol), and
the â-dicarbonyl compound (1 mmol) in dry CH2Cl2 (20 mL)
was stirred at room temperature till the starting material
disappeared (GC). Then AcOEt was added, the organic phase
(25) The relative configuration of the hemiketals 25-27 could not
be unequivocally assigned. An equilibrium involving hydration/
dehydration was observed in CDCl3 solution, during the compilation
of the spectra. The products of hydrolysis of 25 and 26 were identified
as the â-keto esters 25′ and 26′, respectively. The telluro-containing
product 27 is more stable, and allowed the acquisition of 2D spectra
(1H-1H and 1H-13C COSY).
(26) Preliminary results of this study were communicated at the 8th
International Conference on the Chemistry of Selenium and Tellurium,
Sao Paulo, Brazil, 2000.
(27) Barrios, H.; Rock, M. C.; Salmon, M.; Walls, F. Bol. Inst. Qu´ım.
Univ. Me´xico 1969, 21, 146.

Synthesis of Cyclic Enol Ethers
J . Org. Chem., Vol. 67, No. 12, 2002 4125
Ta ble 3. Electr op h ilic Cycliza tion of
Alk en yl-â-d ik eton es
27.4, 31.1, 33.6, 59.7, 77.9, 100.0, 163.2, 167.0. Data for 20:
IR (film) νmax 1693, 1649, 1223 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 1.24 (t, J ) 7.1 Hz, 3H), 1.86 (s, 3H), 1.87 (s, 3H),
2.15 (t, J ) 1.6 Hz, 3H), 2.70-2.78 (m, 1H), 2.90-3.00 (m, 1H),
4.02-4.12 (m, 1H), 4.13 (q, J ) 7.1 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 13.9, 14.4, 31.8, 33.1, 35.1, 50.2, 59.5, 89.6, 102.0,
165.7, 167.3.
[5-(1-Iod o-1-m eth yleth yl)d ih yd r ofu r a n -2-ylid en e]a ce-
tic Acid Eth yl Ester (21). The crude product was chromato-
graphed on silica gel (hexane/ethyl acetate (9:1) as eluent),
giving 21 (unstable oil) in 70% yield: IR (film) νmax 1696, 1654,
1
1144 cm-1; H NMR (200 MHz, CDCl3) δ 1.26 (t, J ) 7.4 Hz,
3H), 1.87-2.11 (m, 1H), 1.92 (s, 3H), 1.94 (s, 3H), 2.24-2.41
(m, 1H), 2.89-3.09 (m, 1H), 3.32-3.47 (m, 1H), 3.84 (t, J )
7.3 Hz, 1H), 4.12 (q, J ) 7.4 Hz, 2H), 5.32 (t, J ) 2.2 Hz, 1H);
13C NMR (50 MHz, CDCl3) δ 14.4, 28.3, 30.3, 32.7, 33.8, 49.1,
59.1, 89.8, 91.3, 168.3, 175.7.
(2-H yd r oxy-6-iod om et h ylt et r a h yd r op yr a n -2-yl)a ce-
tic Acid Eth yl Ester (26). The crude product was chromato-
graphed on silica gel (hexane/ethyl acetate (9:1) as eluent),
giving 26 (oil) in 55% yield: 1H NMR (300 MHz, CDCl3) δ
1.16-1.43 (m, 2H), 1.31 (t, J ) 7.2 Hz, 3H), 1.57-2.02 (m, 4H),
2.55 and 2.64 (AB system, J ) 15.0 Hz, 2H), 3.09 (dd, J )
10.0 and 6.9 Hz, 1H), 3.15 (dd, J ) 10.0 and 5.1 Hz, 1H), 3.89-
3.97 (m, 1H), 4.16-4.30 (m, 2H), 5.02 (d, J ) 2.4 Hz, 1H); the
other signals in the 1H NMR spectrum correspond to the
product 26′, formed by hydrolysis of the hemiketal in CDCl3
solution, during the compilation of the spectrum; 13C NMR (75
MHz, CDCl3) δ 10.2, 14.2, 18.4, 30.6, 34.1, 45.1, 61.0, 69.7,
95.7, 172.1; the minor signals (14.1, 15.9, 19.5, 35.6, 42.5, 49.3,
61.4, 70.7, ca.167, ca. 202) correspond to the product 26′;
HRMS m/z calcd for C10H17IO4 328.01716, found 328.01533.
2-Iod om e t h yl-3,5,6,7-t e t r a h yd r o-2H -b e n zofu r a n -4-
on e (32). The crude product was purified by column chroma-
tography (hexane/ethyl acetate (6:4) as eluent), giving 32 (mp
74-77 °C) in 85% yield: IR (film) νmax 2950, 1633, 1617 cm-1
;
1H NMR (300 MHz, CDCl3) δ 2.05-2.10 (m, 2H), 2.35-2.40
(m, 2H), 2.43-2.48 (m, 2H), 2.60 (ddt, J ) 14.8, 6.7, and 1.9
Hz, 1H), 2.99 (ddt, J ) 14.8, 10.0, and 1.9 Hz, 1H), 3.3-3.4
(m, 2H), 4.80-4.89 (m, 1H); 13C NMR δ 8.1, 21.6, 23.9, 32.6,
36.4, 83.5, 112.9, 176.7, 195.4. Anal. Calcd for C9H11O2I: C,
38.87; H, 3.99. Found: C, 38.96; H, 4.29.
a
b
Ar ) p-MeOPh. Previously reported in ref 15.
was washed with sodium thiosulfate solution (0.1 N) and brine
and dried over anhydrous MgSO4, and the solvent was
evaporated.
6-Iod om et h yl-2-m et h yl-5,6-d ih yd r o-4H -p yr a n -3-ca r -
boxylic Acid Eth yl Ester (5). The crude product was purified
by column chromatography (hexane/ethyl acetate (9:1) as
eluent), giving 5 (oil) in 87% yield: IR (film) νmax 2975, 1704,
2-Iod om eth yl-6,6-d im eth yl-3,5,6,7-tetr a h yd r o-2H-ben -
zofu r a n -4-on e (35). The crude product was purified by
column chromatography (hexane/ethyl acetate (6:4) as eluent),
giving 35 (oil) in 69% yield: IR (film) νmax 2959, 1627 cm-1
;
1626 cm-1; H NMR (500 MHz, CDCl3) δ 1.27 (t, J ) 7.1 Hz,
1H NMR (300 MHz, CDCl3) δ 1.11 (s, 3H), 1.12 (s, 3H), 2.23
(s, 2H), 2.30 (br s, 2H), 2.60 (ddt, J ) 14.8, 6.7, and 1.9 Hz,
1H), 2.99 (ddt, J ) 14.8, 10.0, and 1.9 Hz, 1H), 3.35 (d, J )
5.3 Hz, 2H), 4.8-4.9 (m, 1H); 13C NMR (75 MHz, CDCl3) δ
8.6, 28.5, 28.9, 32.4, 34.1, 37.7, 50.9, 83.4, 111.4, 175.5, 194.5.
Anal. Calcd for C11H15O2I: C, 43.16; H, 4.94. Found: C, 43.17;
H, 4.96.
1
3H), 1.64-1.69 (m, 1H), 2.03-2.07 (m, 1H), 2.24 (s, 3H), 2.27-
2.29 (m, 1H), 2.40-2.44 (m, 1H), 3.28 (dd, J ) 6.0 and 10.4
Hz, 1H), 3.31 (dd, J ) 5.7 and 10.4 Hz, 1H), 3.85-3.88 (m,
1H), 4.15 (q, J ) 7.1 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ
7.1, 14.4, 20.1, 20.8, 26.6, 59.7, 75.1, 101.4, 163.9, 168.2. Anal.
Calcd for C10H15O3I: C, 38.73; H, 4.87. Found: C, 38.75; H,
4.85.
Gen er a l P r oced u r e for Tellu r ocycliza tion . A mixture
of the â-dicarbonyl compound (2 mmol) and p-methoxyphe-
nyltellurium trichloride (2.2 mmol) in 30 mL of recently
distilled chloroform was heated under reflux for the time
indicated in the tables or schemes. The solvent was evaporated
and the residue filtered through silica gel, using chloroform
as eluent.
[5-(1-Iodoeth yl)dih ydr ofu r an -2-yliden e]acetic Acid Eth -
yl Ester (11). The crude product was purified by column
chromatography (hexane/ethyl acetate (9:1) as eluent), giving
11 (mp 66-67 °C) in 71% yield: IR (film) νmax 2983, 1694, 1637,
1
1124 cm-1; H NMR (300 MHz, CDCl3) δ 1.19 (t, J ) 7.1 Hz,
3H), 1.80-1.90 (m, 1H), 1.87 (d, J ) 6.4 Hz, 3H), 2.25-2.34
(m, 1H), 2.84-2.97 (m, 1H), 3.23-3.33 (m, 1H), 4.05 (q, J )
7.1 Hz, 2H), 4.10-4.17 (m, 2H), 5.22 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 14.2, 24.2, 28.8, 29.3, 30.0, 59.0, 86.9, 89.9,
168.0, 175.4. Anal. Calcd for C10H15O3I: C, 38.73; H, 4.87.
Found: C, 38.57; H, 4.78.
6-(p-Meth oxyp h en yld ich lor otellu r o)m eth yl-2-m eth yl-
5,6-d ih yd r o-4H-p yr a n -3-ca r boxylic Acid Eth yl Ester (6).
The crude product was purified by column chromatography
(hexane/ethyl acetate (7:3) as eluent), giving 6 (mp 139-142
°C) in 83% yield: IR (film) νmax 2943, 1708, 1630, 1257, 1091
1
5-Iod o-2,6,6-tr im eth yl-5,6-d ih yd r o-4H-p yr a n -3-ca r box-
ylic Acid Eth yl Ester (19) a n d 5-(1-Iod o-1-m eth yleth yl)-
2-m eth yl-4,5-d ih yd r ofu r a n -3-ca r boxylic Acid Eth yl Ester
(20). The crude product was chromatographed on silica gel
(hexane/ethyl acetate (9:1) as eluent), giving 19 (oil) in 66%
yield and 20 (oil) in 22% yield. Data for 19: IR (film) νmax 1703,
cm-1; H NMR (200 MHz, CDCl3) δ 1.29 (t, J ) 7.4 Hz, 3H),
1.69-1.82 (m, 1H), 2.05-2.13 (m, 1H), 2.30 (s, 3H), 2.26-2.62
(m, 2H), 3.81-3.86 (m, 2H), 3.86 (s, 3H), 4.17 (q, J ) 7.4 Hz,
2H), 4.67-4.80 (m, 1H), 7.03-7.10 (m, 2H), 8.03-8.11 (m, 2H);
13C NMR (50 MHz, CDCl3) δ 14.3, 19.9, 21.1, 27.4, 55.5, 56.9,
59.8, 71.3, 102.2, 115.6, 120.0, 135.1, 162.3, 163.1, 167.9. Anal.
Calcd for C17H22O4TeCl2: C, 41.77; H, 4.54. Found: C, 41.40;
H, 4.28.
1
1641 cm-1; H NMR (300 MHz, CDCl3) δ 1.24 (t, J ) 7.1 Hz,
3H), 1.37 (s, 3H), 1.44 (s, 3H), 2.16-2.17 (m, 3H), 2.80-2.90
(m, 1H), 2.97-3.05 (m, 1H), 4.11 (q, J ) 7.2 Hz, 2H), 4.14-
4.17 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 14.3, 20.2, 23.3,
[2-H y d r o x y -6-(p -m e t h o x y p h e n y ld ic h lo r o t e llu r o )-
m eth yltetr ah ydr opyr an -2-yl]acetic Acid Eth yl Ester (27).

4126 J . Org. Chem., Vol. 67, No. 12, 2002
Ferraz et al.
The crude product was purified by column chromatography
(hexane/ethyl acetate (7:3) as eluent), giving 27 (mp 90-91
°C) in 65% yield: IR (film) νmax 3421, 2943, 1743, 1700, 1260,
chromatographed on silica gel (hexane/ethyl acetate (9:1) as
eluent), giving 25 (oil) in 38% yield: IR (film) νmax 3457, 2939,
1739, 1714 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.19-1.44 (m,
2H), 1.30 (t, J ) 7.1 Hz, 3H), 1.59-1.96 (m, 4H), 2.53 and 2.62
(AB system, J ) 15.1 Hz, 2H), 2.90 (dd, J ) 12.0 and 5.6 Hz,
1H), 3.02 (dd, J ) 12.0 and 7.3 Hz, 1H), 4.10-4.18 (m, 1H),
4,20 (q, J ) 7.1 Hz, 2H), 4.92 (d, J ) 2.5 Hz, 1H), 7.19-7.28
1
1038 cm-1; H NMR (200 MHz, CDCl3) δ 1.19-2.07 (m, 6H),
1.28 (t, J ) 7.1 Hz, 3H), 2.58 and 2.70 (AB system, J ) 15.7
Hz, 2H), 3.59-3.82 (m, 2H), 3.76 (s, 3H), 4.13-4.29 (m, 2H),
4.69-4.79 (m, 1H), 5.09 (br s, 1H), 6.91-6.99 (m, 2H), 7.87-
7.98 (m, 2H); 13C NMR (50 MHz, CDCl3) δ 13.9, 18.3, 30.6,
33.4, 44.3, 55.3, 58.6, 61.1, 65.4, 96.3, 115.2, 120.7, 135.0, 161.7,
171.8. Anal. Calcd for C17H24O5TeCl2: C, 40.28; H, 4.77; Cl,
13.99. Found: C, 40.80; H, 4.74; Cl, 14.30.
2-(p-Meth oxyp h en yld ich lor otellu r o)m eth yl-3,5,6,7-tet-
r a h yd r o-2H-ben zofu r a n -4-on e (33). The crude product was
purified by column chromatography (hexane/ethyl acetate (7:
3) as eluent), giving 33 (mp 160-162 °C) in 81% yield: IR
(film) νmax 2916, 1646 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.05-
2.11 (m, 2H), 2.36-2.41 (m, 2H), 2.43-2.68 (m, 3H), 3.11-
3.20 (m, 1H), 3.80-3.91 (m, 2H), 3.87 (s, 3H), 5.55-5.65 (m,
1H), 7.03-7.08 (m, 2H), 8.04-8.09 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 21.6, 23.8, 32.8, 36.5, 55.6, 57.5, 79.5, 112.7, 115.8,
119.3, 135.1, 162.4, 176.2, 195.6. Anal. Calcd for C16H18O3-
TeCl2: C, 42.07; H, 3.97. Found: C, 41.77; H, 4.12.
Gen er a l P r oced u r e for Selen ocycliza tion . A mixture of
the â-keto ester (1 mmol) or â-diketone (2 mmol) and PhSeBr
(2 mmol) in dry THF was stirred at room temperature till the
starting material disappeared (GC). Then AcOEt was added,
the organic phase was washed with brine and dried over
anhydrous MgSO4, and the solvent was evaporated.
2-Meth yl-6-ph en ylselan ylm eth yl-5,6-dih ydr o-4H-pyr an -
3-ca r boxylic Acid Eth yl Ester (7). The crude product was
purified by column chromatography (hexane/ethyl acetate (9:
1) as eluent), giving 7 (oil) in 65% yield: IR (film) νmax 2931,
1703, 1623 cm-1; 1H NMR (500 MHz, CDCl3) δ 1.26 (t, J ) 7.1
Hz, 3H), 1.60-1.66 (m, 1H), 2.00-2.06 (m, 1H), 2.18 (t, J )
0.9 Hz, 3H), 2.23-2.26 (m, 1H), 2.37-2.41 (m, 1H), 3.00 (dd,
J ) 12.7 and 6.7 Hz, 1H), 3.19 (dd, J ) 12.7 and 6.0 Hz, 1H),
4.00-4.05 (m, 1H), 4.14 (q, J ) 7.1 Hz, 2H), 7.24-7.27 (m,
3H), 7.52-7.54 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 14.4,
20.2, 21.1, 26.3, 31.7, 59.6, 75.8, 101.3, 127.2, 129.1, 130.0,
132.9, 164.2, 168.4. Anal. Calcd for C16H20O3Se: C, 56.64; H,
5.94. Found: C, 56.36; H, 5.92.
1
(m, 3H), 7.46-7.54 (m, 2H); the other signals in the H NMR
spectrum correspond to the product 25′, formed by hydrolysis
of the hemiketal in CDCl3 solution, during the compilation of
the spectrum; 13C NMR (75 MHz, CDCl3) δ 14.1, 18.5, 30.6,
33.6, 34.2, 45.1, 60.9, 69.7, 95.4, 126.5, 128.9, 131.1, 132.3,
172.0; the minor signals (14.1, 19.7, 35.6, 37.0, 42.6, 49.2, 61.3,
69.5, 127.3, 129.2, 131.1, 133.0, ca. 167, ca. 203) correspond
to the product 25′.
2-P h en ylsela n ylm eth yl-3,5,6,7-tetr a h yd r o-2H-ben zofu -
r a n -4-on e (34). The crude product was purified by column
chromatography (hexane/ethyl acetate (8:2) as eluent), giving
34 (mp 69-70 °C) in 83% yield: IR (film) νmax 2935, 1633, 1613
1
cm-1; H NMR (300 MHz, CDCl3) δ 2.00 (q, J ) 6.5 Hz, 2H),
2.32 (t, J ) 6.5 Hz, 4H), 2.62 (ddt, J ) 14.7, 10.0, and 1.6 Hz,
1H), 2.91-3.00 (m, 1H), 3.07 (dd, J ) 12.7 and 5.8 Hz, 1H),
3.21 (dd, J ) 12.7 and 5.9 Hz, 1H), 4.92-4.97 (m, 1H), 7.25-
7.28 (m, 3H), 7.52-7.55 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
21.5, 23.7, 31.6, 32.5, 36.3, 84.2, 112.8, 127.3, 128.9, 129.1,
133.1, 176.7, 195.2. Anal. Calcd for C15H16O2Se: C, 58.64,H,
5.25. Found: C, 58.15; H, 5.08.
6,6-Dim eth yl-2-ph en ylselan ylm eth yl-3,5,6,7-tetr ah ydr o-
2H-ben zofu r a n -4-on e (37). The crude product was purified
by column chromatography (hexane/ethyl acetate (8:2) as
eluent), giving 37 (mp 47-48 °C) in 80% yield: IR (film) νmax
1
2955, 1625 cm-1; H NMR (300 MHz, CDCl3) δ 1.08 (s, 6H),
2.20 (br s, 4H), 2.64 (ddt, J ) 14.7, 10.0, and 1.6 Hz, 1H), 2.93-
3.02 (m, 1H), 3.08 (dd, J ) 12.7 and 6.7 Hz, 1H), 3.21 (dd, J )
12.7 and 5.7 Hz, 1H), 4.93-5.02 (m, 1H), 7.26-7.28 (m, 3H),
7.52-7.55 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 28.6, 28.7,
31.6, 32.8, 34.0, 37.7, 50.9, 84.5, 111.4, 127.5, 129.1, 129.2,
133.3, 175.8, 194.7. Anal. Calcd for C17H20O2Se: C, 60.90,H,
6.01. Found: C, 60.66; H, 5.89.
P r ep a r a tion of (6,8-Dioxa bicyclo[3.2.1]oct-5-yl)a cetic
Acid Eth yl Ester (28). To a stirred solution of 26 (1 mmol,
328 mg) in dry toluene (8 mL) was added DBU (1.2 mmol, 182
mg). The mixture was refluxed for 1 h and then filtered
through a silica gel pad. The solvent was evaporated, and the
crude product was purified by column chromatography (hex-
ane/ethyl acetate (8:2) as eluent), giving 106 mg of 28: yield
53%; IR (film) νmax 2044, 1738, 1013 cm-1; 1H NMR (300 MHz,
CDCl3) δ 1.27 (t, J ) 7.1 Hz, 3H), 1.47-1.51 (m, 1H), 1.62-
1.67 (m, 1H), 1.75-1.93 (m, 4H), 2.74 (s, 2H), 3.86-3.89 (m,
1H), 3.94 (dd, J ) 6.6 and 0.6 Hz, 1H), 4.17 (q, J ) 7.1 Hz,
2H), 4.56-4.58 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 14.2,
16.8, 28.1, 33.9, 43.6, 60.6, 69.2, 75.2, 106.5, 169.1. The 1H
NMR data are in good agreement with those reported for the
analogous methyl ester.28
(7-P h en ylsela n ylh exa h yd r oben zofu r a n -2-ylid en e)a ce-
tic Acid Eth yl Ester (13). The crude product was purified
by column chromatography (hexane/ethyl acetate (9:1) as
eluent), giving 13 (oil) in 57% yield: IR (film) νmax 2934, 1701,
1
1643 cm-1; H NMR (300 MHz, CDCl3) δ 1.22-2.05 (m, 6H),
1.25 (t, J ) 7.2 Hz, 3H), 2.53-2.62 (m, 1H), 2.90-3.10 (m, 2H),
3.54 (br q, J ) 4.9 Hz, 1H), 4.11 (q, J ) 7.2 Hz, 2H), 4.38 (t,
J ) 4.9 Hz, 1H), 5.31 (t, J ) 1.4 Hz, 1H), 7.26-7.30 (m, 3H),
7.54-7.57 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 14.4, 20.4,
26.1, 27.7, 34.0, 36.9, 42.3, 59.1, 84.3, 91.4, 127.8, 128.6, 129.1,
134.5, 168.4, 175.4; the other signals in the spectra were
attributed to traces of the Z isomer of 13. Anal. Calcd for
C
18H22O3Se: C, 59.18; H, 6.07. Found: C, 58.84; H, 6.06.
2-Meth yl-7-p h en ylsela n yl-3a ,4,5,6,7,7a -h exa h yd r oben -
zofu r a n -3-ca r boxylic Acid Eth yl Ester (16). The crude
product was purified by column chromatography (hexane/ethyl
acetate (9:1) as eluent), giving 16 (oil) in 80% yield: IR (film)
Ack n ow led gm en t. The authors are indebted to
FAPESP, CNPq, and CAPES for financial support.
ν
max 2935, 1698, 1638 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.27
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 5, 13, 19, 20, 22, 25-28, 33-35, and
37, IR spectra for 25, 27, and 28, and MS spectra for 26 and
28. This material is available free of charge via the Internet
at http://pubs.acs.org.
(t, J ) 7.0 Hz, 3H), 1.22-1.40 (m, 1H), 1.46-1.55 (m, 2H),
1.78-1.87 (m, 1H), 1.94-2.05 (m, 2H), 2.15 (d, J ) 1.0 Hz,
3H), 3.11-3.19 (m, 1H), 3.66 (dd, J ) 10.5 and 4.5 Hz, 1H),
4.11-4.22 (m, 2H), 4.49 (dd, J ) 7.5 and 4.5 Hz, 1H), 7.24-
7.31 (m, 3H), 7.54-7.60 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
14.4, 14.5, 19.6, 27.1, 27.5, 39.2, 41.8, 59.4, 85.1, 109.6, 127.8,
128.9, 129.2, 134.7, 166.1, 168.2.
J O011089+
(2-H yd r oxy-6-p h en ylsela n ylm et h ylt et r a h yd r op yr a n -
2-yl)a cetic Acid Eth yl Ester (25). The crude product was
(28) Sum, P. E.; Weiler, L. Can. J . Chem. 1979, 57, 1475.