One-step palladium-catalyzed synthesis of substituted dihydrofurans from the carbonate derivatives of γ-hydroxy-α,β-unsaturated sulfones

Article abstract of DOI:10.1021/jo981391r

The palladium-catalyzed nucleophilic allylic substitution of the carbonate derivatives of γ-hydroxyα,β-unsaturated sulfones (2) with soft carbon nucleophiles such as malonates, β-keto esters, 1,3-diketones, and α- sulfonyl ketones took place cleanly and with full regiocontrol (γ- substitution). Typical optimized conditions are Pd₂(dba)₃ (5 mol %), dppe (20 mol %), molecular sieves, in toluene-THF at 100 °C. Unexpectedly, when β-keto esters, 1,3-diketones, and α-sulfonyl ketones were used as nucleophiles a cascade process occurred, via initial γ-regioselective allylic substitution and further intramolecular conjugate addition of the enol moiety to the α,β-unsaturated sulfone, to give 2,3,4,5- tetrasubstituted dihydrofurans (13-25) in moderate to good yields. Moreover, the cyclization step is highly stereoselective giving predominantly or exclusively the 4,5-dihydrofuran of trans configuration. From readily available enantiopure (S)-2, this one-step procedure of synthesis of substituted dihydrofurans has been applied to the synthesis of enantiomerically pure tetrasubstituted tetrahydrofurans.

Full text of DOI:10.1021/jo981391r

9406
J . Org. Chem. 1998, 63, 9406-9413
On e-Step P a lla d iu m -Ca ta lyzed Syn th esis of Su bstitu ted
Dih yd r ofu r a n s fr om th e Ca r bon a te Der iva tives of
γ-Hyd r oxy-r,â-u n sa tu r a ted Su lfon es
J ose´ L. Garrido, Ine´s Alonso, and J uan C. Carretero*
Departamento de Quı´mica Orga´nica, Universidad Auto´noma de Madrid, 28049-Madrid, Spain
Received J uly 17, 1998
The palladium-catalyzed nucleophilic allylic substitution of the carbonate derivatives of γ-hydroxy-
R,â-unsaturated sulfones (2) with soft carbon nucleophiles such as malonates, â-keto esters, 1,3-
diketones, and R-sulfonyl ketones took place cleanly and with full regiocontrol (γ-substitution).
Typical optimized conditions are Pd2(dba)3 (5 mol %), dppe (20 mol %), molecular sieves, in toluene-
THF at 100 °C. Unexpectedly, when â-keto esters, 1,3-diketones, and R-sulfonyl ketones were used
as nucleophiles a cascade process occurred, via initial γ-regioselective allylic substitution and further
intramolecular conjugate addition of the enol moiety to the R,â-unsaturated sulfone, to give 2,3,4,5-
tetrasubstituted dihydrofurans (13-25) in moderate to good yields. Moreover, the cyclization step
is highly stereoselective giving predominantly or exclusively the 4,5-dihydrofuran of trans
configuration. From readily available enantiopure (S)-2, this one-step procedure of synthesis of
substituted dihydrofurans has been applied to the synthesis of enantiomerically pure tetrasubsti-
tuted tetrahydrofurans.
In tr od u ction
nucleophile attack takes place exclusively at the terminus
of the allyl unit not bearing the electron-withdrawing
group.2 This regiochemical outcome has been usually
explained in terms of electronic (attack to the most
electron deficient position) rather than steric reasons.
γ-Oxygenated-R,â-unsaturated sulfones are interesting
and readily available starting compounds for stereo-
selective synthesis mainly due to their excellent proper-
ties as Michael acceptors,3 which allows an efficient
functionalization at the â position and subsequently at
the R position by treatment of its R-sulfonyl carbanion
with electrophiles. From a synthetic point of view, this
type of compound would even be more versatile in organic
synthesis if it was possible to substitute the oxygenated
function at the γ position by a wide variety of nucleo-
philes, to afford a new vinyl sulfone suitable for further
functionalization at â and R positions. In a preliminary
communication we reported that the carbonate deriva-
tives of γ-hydroxy-R,â-unsaturated sulfones undergo a
regioselective allylic substitution at the γ position under
appropriate palladium-catalyzed conditions.4 We now
give a full account of this work, reporting additional
examples as well as the scope and limitations of the
process and its application to the synthesis of enantio-
merically pure tetrahydrofurans.
During the last two decades, the palladium-catalyzed
nucleophilic substitution of allylic oxygenated com-
pounds, mainly esters, carbonates, and epoxides, has
become a crucial method for the formation of carbon-
carbon and carbon-heteroatom bonds.1 The impressive
range of allylic systems and nucleophile partners that
can be used, as well as the high levels of chemo- and
stereoselectivity usually attained in this kind of process,
explains its widespread use in modern organic synthesis.
Despite the huge literature on allylic metal-catalyzed
nucleophilic substitutions, it is worth noting that unlike
allylic systems substituted with alkyl, aryl, or electron-
donating substituents, those substituted with electron-
withdrawing groups at the double bond such as ester,
carbonyl, or cyano groups, have been much less studied.2
This is due to their usually lower reactivity toward the
Pd(0) catalysts, their tendency to undergo conjugate
addition of the nucleophile, and the easier deprotonation
of the π-allylpalladium intermediate (â-elimination) to
give 1,3-dienes. On the other hand, it is known that in
these cases when the allylic substitution occurs, the
(1) For some recent reviews, see: (a) Trost, B. M.; Van Vranken, D.
L. Chem. Rev. 1996, 96, 395. (b) Williams, J . M. J . Synlett 1996, 705.
(c) Tsuji, J . Palladium Reagents and Catalysis; J ohn Wiley & Sons:
New York, 1995; pp 290-422. (d) Godleski, S. A. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I.; Semmelhack, M. F., Eds;
Pergamon Press: Oxford, 1991; Vol. 4, Chapter 3.3.
(2) For palladium-catalyzed allylic substitutions in γ-oxygenated-
R,â-unsaturated esters, see: (a) Suzuki, T.; Sato, T.; Hirama, M.
Tetrahedron Lett. 1990, 31, 4747. (b) Tanikaga, R.; J un, T. X.; Kaji, A.
J . Chem. Soc., Perkin Trans 1 1990, 1185. (c) Tsuda, T.; Horii, Y.;
Nakagawa, Y.; Ishida, T.; Saegusa, T. J . Org. Chem. 1989, 54, 977. (d)
Tanikaga, R.; Takeuchi, J .; Takyu, M.; Kaji, A. J . Chem. Soc., Chem.
Commun. 1987, 386. (e) Tsuji, J .; Ueno, H.; Kobayashi, Y.; Okumoto,
H. Tetrahedron Lett. 1981, 22, 2573. For substitutions on π-allylpal-
ladium complexes substituted with carbonyl or cyano groups, see for
instance: (f) Sugiura, M.; Yagi, Y.; Wei, S.-Y.; Nukai, T. Tetrahedron
Lett. 1998, 39, 4351. (g) Hunt, D. A.; Quante, J . M.; Tyson, R. L.;
Dasher, L. W. J . Org. Chem. 1984, 49, 5262. (h) Tsuji, J .; Ueno, H.;
Kobayashi, Y.; Okumoto, H. Tetrahedron Lett. 1981, 22, 2573. (i)
J ackson, W. R.; Strauss, J . U. Aust. J . Chem. 1977, 30, 553.
It is interesting to point out that to the best of our
knowledge the only previous studies on metal-promoted
allylic substitutions in γ-oxygenated-R,â-unsaturated sul-
fones dealt with the stoichiometric reaction of their
(3) (a) Isobe, M. Perspectives in the Organic Chemistry of Sulfur;
Zwanenburg, B., Klunder, A. J . H., Eds.; Elsevier: New York, 1987;
pp 209-229. (b) Fuchs, P. L.; Braish, T. F. Chem. Rev. 1986, 86, 903.
See also: (c) Carretero, J . C.; Go´mez Arraya´s, R.; Storch de Gracia, I.
Tetrahedron Lett. 1996, 37, 3379. (d) Carretero, J . C.; Go´mez Arraya´s,
R. J . Org. Chem. 1995, 60, 6000. (e) De Blas, J .; Carretero, J . C.;
Dom´ınguez, E. Tetrahedron Lett. 1994, 35, 4603. (f) Dom´ınguez, E.;
Carretero, J . C. Tetrahedron 1994, 50, 7557. (g) Dom´ınguez, E.;
Carretero, J . C. Tetrahedron Lett. 1993, 34, 5803.
(4) Alonso, I.; Carretero, J . C.; Garrido, J . L.; Magro, V.; Pedregal,
C. J . Org. Chem. 1997, 62, 5682.
10.1021/jo981391r CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/19/1998

Pd-Catalyzed Synthesis of Substituted Dihydrofurans
J . Org. Chem., Vol. 63, No. 25, 1998 9407
Sch em e 1
cationic tetracarbonyl(η3-allyl)iron derivatives with nu-
cleophiles.5 Also, as a related precedent in this field, the
formation and isolation of π-allyl palladium chloride
dimers substituted at R-position with a sulfonyl group,
by stoichiometric reaction of allyl sulfones with palladium
dichloride, have been described.6
Resu lts a n d Discu ssion
The starting γ-hydroxy vinyl sulfones 1 were readily
prepared following the reported one-step procedure based
on the piperidine-catalyzed condensation of phenylsul-
fonyl arylsulfinyl methanes with aldehydes.7 First we
studied the reaction of their acetates with sodium di-
methyl malonate (1.1 equiv) in the presence of catalytic
amounts of Pd2(dba)3 (3-6 mol %) and phosphine ligands
(6-20 mol %). However, it was observed that, regardless
of the solvent (THF, toluene or DMF), temperature (from
-30 °C to 68 °C), and ligand [PPh3, P(OEt)3, dppe, dppp]
used, the main or sole product was the Michael adduct
instead of the desired γ-substituted product. In an
attempt to increase the rate of formation of the π-al-
lylpalladium complex by increasing the reactivity of the
leaving group, the corresponding chloroacetates were
studied. In fact, it has been previously described that the
palladium-catalyzed allylic substitution in γ-oxygenated-
R,â-unsaturated esters occurred satisfactorily from their
chloroacetates but not from the corresponding acetates.2b
Disappointingly, in our case the chloroacetates evolved
in a manner similar to that of the acetates, giving again
predominantly the Michael adduct.
Sch em e 2
These results showed that the conjugate addition of
the malonate anion was a much faster process than the
allylic substitution and, consequently, the impossibility
of generating the π-allylpalladium intermediate under
these conditions. Trying to avoid this competitive conju-
gate addition we turned our attention to the carbonate
derivatives 2 (Tsuji’s method),8 which were readily
prepared in high yield by reaction of 1 with ethyl
chloroformate (pyridine, DMAP, THF, rt). These sub-
strates allow the reaction to be carried out in the presence
of diethyl malonate instead of its anion, generating in
situ the required nucleophile only after formation of the
π-allylpalladium complex and subsequent release of the
alkoxide, which would deprotonate the malonate. Now,
if the attack of the malonate anion to the π-allylpalla-
dium intermediate was faster than the conjugate addition
to 2, the desired allyl-substituted product would be the
main product of the reaction.
were 1-(phenylsulfonyl)-1,3-butadiene (5),9 likely formed
by â-elimination on the π-allylpalladium intermediate,
and the starting alcohol 1a , presumably formed as a
result of the hydrolysis of the carbonate 2a . Interestingly,
2a was cleanly converted into the allylic product 4a (79%
yield) when the reaction was carried out in the presence
of powdered molecular sieves (4 Å) and dppe as phosphine
ligand. Likely the bidentate phosphine ligand increases
the stability of the π-allylpalladium complex (3), while
the molecular sieves prevent the hydrolysis of the car-
bonate. Under these conditions, the reaction worked well
also for other γ-substituted carbonates such as 2b (R )
i
nHex) and 2c (R ) Pr), affording with complete regio-
control the corresponding γ-substituted products 4b and
4c (68% and 64% yields, respectively) regardless of the
size of the substitution at γ-position (Scheme 1).
On the contrary, unsatisfactory results were obtained
when 2a was treated with other stabilized nucleophiles
usually used in palladium-catalyzed allylic substitutions
(Schemes 2 and 3). Thus, the reactions with methyl
diethylmalonate10 and nitroethane11 led mainly to the
elimination product 5, probably due to the poorer nu-
cleophilic character of their anions compared to the
malonate anion. In the case of the reaction with di-
phenylglycine imine12 a mixture of the desired γ-substi-
tuted product 6 (46% as a 1:1 mixture of stereoisomers)
We were pleased to find that the reaction of 2a (R )
Me) with diethyl malonate in the presence of Pd2(dba)3
(5 mol %) and PPh3 (20 mol %) in THF at reflux afforded
a mixture of three products in which the Michael adduct
was not detected. The major product was the desired
γ-substituted product 4a , and the other minor products
(5) (a) Enders, D.; J andeleit, B.; Raabe, G. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1949. (b) Enders, D.; Von Berg, S.; J andeleit, B. Synlett
1996, 18.
(6) Ogura, K.; Shibuya, N.; Takahashi, K.; Iida, H. Bull. Chem. Soc.
J pn. 1984, 57, 1092. See also: Muzart, J .; Pale, P,; Pete, J . Tetrahedron
Lett. 1983, 24, 4567.
(7) (a) Dom´ınguez, E.; Carretero, J . C. Tetrahedron 1990, 46, 7197.
(b) Trost, B. M.; Grese, T. A. J . Org. Chem. 1991, 56, 3189.
(8) (a) Tsuji, J .; Shimizu, I.; Minami, I.; Ohashi, Y.; Sugiura, T.;
Takahashi, K. J . Org. Chem. 1985, 50, 1523. (b) Tsuji, J .; Shimizu, I.;
Minami, I.; Ohashi, Y. Tetrahedron Lett. 1982, 23, 4809. Reviews: (c)
Tsuji, J .; Minami, I. Acc. Chem. Res. 1987, 20, 140. (d) Tsuji, J .
Tetrahedron 1986, 42, 4361.
(9) (a) Eisch, J . J .; Galle, J . E.; Hallenbeck, L. E. J . Org. Chem. 1982,
47, 1608. (b) Crumbie, R. L.; Ridley, D. D. Aust. J . Chem. 1981, 34,
1017.
(10) See, for instance: Vicart, N.; Cazes, B.; Gore´, J . Tetrahedron
Lett. 1995, 36, 535.
(11) See, for instance: (a) Genet, J . P.; Ferroud, D. Tetrahedron Lett.
1984, 25, 3579. (b) Wase, P. A.; Morrow, S. D.; Hardinger, S. A. J .
Org. Chem. 1982, 47, 365.

9408 J . Org. Chem., Vol. 63, No. 25, 1998
Ta ble 1. P a lla d iu m -Ca ta lyzed Rea ction of Ca r bon a tes 2 w ith Acid Keton esa
Garrido et al.
substrate
Ar
nucleophile
product
entry
2
R1
Me
R2
R3
trans/cisb
yldc
1
2
2a
2a
2a
2a
2a
2b
2b
2b
2c
2c
2c
2d h
2d h
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
p-Tol
p-Tol
CO2Et
CO2Et
COMe
Me
Ph
Me
13
14
15
16
17
18
19
20
21
22
23
24
25
78/22
83/17
75/25
80/20
75/25
76d
63d
79d
89d
80d
79
57
67
38
14
Me
Me
Me
Me
nHex
nHex
nHex
iPr
3d
4
-CO-(CH2)3-
5e
6
PhSO2
CO2Et
CO2Et
COMe
CO2Et
CO2Et
COMe
CO2Et
Me
Me
Ph
Me
Me
Ph
>98/<2
>98/<2
>98/<2
>98/<2
>98/<2
>98/<2
-
7
8
9f
10
11
12g
13g
iPr
iPr
Me
Me
14
41
42
H
H
-CO-(CH2)3-
-
a
Reaction conditions: 2, R2CH2COR3 (4 equiv), Pd2(dba)3 (5 mol %), dppe (20 mol %), powdered molecular sieves 4 Å in 1:1 mixture of
THF-toluene (0.1 M solution of 2) at 100 °C. Determined by 1H NMR on the crude mixtures. c In pure product after silica gel
b
chromatography. The cis+trans mixture could not be separated by chromatography. e dppf was used as ligand instead of dppe.17 f Reaction
d
carried out in THF at reflux. 10 mol % of dppe was used.18 The precursor alcohol 1d was prepared according to a reported procedure.19
g
h
Sch em e 3
π-allylpalladium complex 3a to give the expected trisul-
fone 8, that would be unstable under the reaction
conditions, eliminating phenylsulfinate to afford diene 9.
Furthermore, addition of phenylsulfinate anion to com-
plex 3a would lead to the disulfone 10, which would
isomerize to the most substituted olefin 11.
Much more synthetically useful results were obtained
in the case of the palladium-catalyzed reaction of carbon-
ates 2 with acid ketones such as â-keto esters, 1,3-
diketones,14 and R-sulfonyl ketones (Table 1). Unexpect-
edly, with all these nucleophiles, tetrasubstituted dihydro-
furans 13-25 were obtained as the major products when
the reactions were performed at 100 °C in a 1:1 mixture
of toluene:THF. These results show that a tandem
process, based on an initial γ-allylic substitution leading
to intermediates 12, followed by their cyclization via
intramolecular conjugate addition of the enolate to the
vinyl sulfone moiety had taken place.15 The participation
of intermediates 12 in this cascade process was unam-
biguously proved by isolation of 12a (R1 ) Me, R2 ) CO2-
Et, R3 ) Me). Thus, by performing the palladium-
catalyzed reaction of 2a with ethyl acetoacetate under
milder conditions (26 h at room temperature), we isolated
along with the unexpected δ-substituted regioisomer 7
(23% yield) was obtained. Compound 7 would likely be
the result of the nucleophilic addition of the diphenylg-
lycine imine anion to C-4 of the intermediate diene 5
(Scheme 2).
(14) As it is shown below, the cyclization step is hardly regioselective
from non symmetrically substituted 1,3-diketones (like benzoylac-
etone).
On the other hand, the reaction of 2a with bis-
(phenylsulfonyl)methane13 led to a mixture of the 1,4-
disulfone 9 and the 1,3-disulfone 11 (ratio 9:11 ) 48:52
1
determined by H NMR on the crude mixture) (Scheme
3). This result might be explained by initial attack of the
bis(phenylsulfonyl)methane anion to the γ-position of the
(15) For other recent synthesis of dihydrofurans based on tandem
processes, see: (a) Lee, Y. R.; Kim, B. S. Tetrahedron Lett. 1997, 38,
2095. (b) Hagiwara, H.; Sato, K.; Suzuki, T.; Ando, M. Tetrahedron
Lett. 1997, 38, 2103. (c) Hayashi, T.; Yamane, M.; Ohno, A. J . Org.
Chem. 1997, 62, 204. (d) Hayashi, T.; Ohno, A.; Lu, S.-J .; Matsumoto,
Y.; Fukuyo, E.; Yanagi, K. J . Am. Chem. Soc. 1994, 116, 4221. For a
iodine-catalyzed cyclization of unsaturated 1,3-diketones, see: Anto-
nioletti, R.; Cecchine, C.; Ciani, B; Magnanti, S. Tetrahedron Lett. 1995,
36, 9019.
(12) See, for instance: (a) Genet, J . P.; J uge, S.; Besnier, I.; Uziel,
J .; Ferroud, D.; Kardos, N.; Achi, S.; Ruiz-Montes, J .; Thorimbert, S.
Bull. Soc. Chim. Fr. 1990, 127, 781. (b) Ferroud, D.; Genet, J . P.; Kiolle,
R. Tetrahedron Lett. 1986, 27, 23.
(13) See, for instance: Trost, B. M.; Varhoeven, T. R.; Fortunak, J .
M. Tetrahedron Lett. 1979, 2301.

Pd-Catalyzed Synthesis of Substituted Dihydrofurans
J . Org. Chem., Vol. 63, No. 25, 1998 9409
Sch em e 4
Sch em e 5
F igu r e 1. Significant chemical shifts (CDCl3) and NOESY
correlations of cis and trans dihydrofurans 13-23.
a mixture of the dihydrofuran 13 and its intermediate
12a 16 which were readily separated by chromatography
(25% and 43% yields, respectively). Dihydrofurans 13-
25 were isolated after chromatographic purification in
moderate to good yields (41-89%), excepting in the case
of the substrate with the bulkiest alkyl chain at γ-posi-
tion, 2c (R ) iPr), which afforded much lower yields (14-
38%, entries 9-11) due to the major formation of 4-methyl-
1-(phenylsulfonyl)-1,3-pentadiene (24-37%) as a result
of the competitive â-elimination process on its sterically
more demanding π-allylpalladium intermediate.
would lead to the minor cis dihydrofuran. On the other
hand, taking into account that the relative thermody-
namic unstability of conformer B with respect to A would
increase with the steric size of the R1 alkyl chain, this
model could also explain the higher trans-stereoselectiv-
ity observed from 2b and 2c compared with 2a .
As enantiomerically pure γ-hydroxyvinyl sulfones 1 can
be readily prepared by enzymatic enantioselective acety-
lation of racemic 1 in the presence of Lipase-PS,21 the
results shown in Table 1 should represent a new access
into enantiomerically pure substituted dihydrofurans and
their corresponding tetrahydrofurans22 after further
CdC reduction.
Concerning the stereoselectivity of the cyclization, it
should be pointed out that this occurred in all cases with
a remarkable trans-stereoselectivity. The stereocontrol
was nearly complete from substrates 2b and 2c (R1
)
i
nHex and Pr respectively, de > 98%), although signifi-
cantly lower from the less sterically demanding substrate
2a (R1 ) Me, de ) 50-66%). The cis/ trans configuration
of dihydrofurans 13-23 has been established by NMR.
Particularly useful diagnostic criteria are the chemical
shifts of H4 and H5 and the coupling constants between
them which are much higher in the cis isomers than in
the trans ones, and the strong NOESY cross-peaks
observed between H4 and H5 in the cis isomers and its
absence in the case of the trans ones. In the latter case,
the trans stereoselectivity was also confirmed by the
presence of significant NOE correlations between H4 and
the sulfonylmethyl group and between H5 and the alkyl
chain at C-4 (Figure 1).
First, we proved that as expected the palladium-
catalyzed allylic substitution of substrates 2 took place
with complete retention of configuration. Thus, reaction
of (S)-2a with dimethyl malonate under the usual pal-
ladium-catalyzed conditions [Pd2(dba)3 (5 mol %), dppe
(20 mol %), molecular sieves, THF, 68 °C] afforded the
1
known compound (R)-2623 [ee > 96%, determined by H
NMR with Pr(hfc)3] (Scheme 5).
As an example of the straightforward application of the
cyclization procedure to the enantioselective synthesis of
tetrasubstituted tetrahydrofurans, the palladium-cata-
lyzed reaction of (S)-2b with ethyl acetylacetate afforded
(4R,5R)-18 (79% yield) which was transformed in 70%
yield into a 86:14 mixture of enantiomerically pure
tetrahydrofurans 27:28 by reduction with Et3SiH in TFA
at 60 °C24 (Scheme 6). The stereochemical assignments
This high trans-stereoselectivity might be explained on
the basis of the ground state conformers of the acyclic
intermediates 12 (Scheme 4). Thus conformer A, which
leads to the trans isomer, should be the most stable
because minimizes the allylic 1,3-strain between R and
γ positions20 whereas the cyclization of the less stable
conformer B, having a R1/HR 1,3-allylic interaction,
1
of 27 and 28 were established by H NMR, particularly
by NOESY experiments (Figure 2). Thus, in the case of
the major adduct 27 the strong NOE correlations H3/H5
and H3/Me(C-2) define their corresponding syn relation-
(16) 13 was quantitatively formed when 12a was treated with a
catalytic amount of NaH (5 mol %, THF, reflux), showing that the
cyclization is a base-catalyzed process that takes place via the enolate
of 12a . On the other hand, in the absence of added base, 12a also
cyclized cleanly into 13 in the presence of both dppe and Pd2(dba)3 in
THF at reflux, but not in the absence of either the phosphine or the
palladium catalyst (no conversion was observed after 24 h in THF at
68 °C). It seems plausible that in the presence of the palladium catalyst
the phosphine might undergo the conjugate addition to the R,â-
unsaturated sulfone to form a zwitterionic intermediate, which would
act as a base converting 12a into its enolate. For metal-promoted
Michael reactions requiring the presence of free phosphine, see:
Go´mez-Bengoa, E.; Cuerva, J . M.; Mateo, C.; Echavarren, A. M. J . Am.
Chem. Soc. 1996, 118, 8553. For other phosphine-catalyzed nucleophile
additions, see: (a) Zhang, C.; Lu, X. Synlett. 1995, 645. (b) Trost, B.
M.; Li, C.-J . J . Am. Chem. Soc. 1994, 116, 10819. (c) Kim, B.; Kodomari,
M.; Regen, S. L. J . Org. Chem. 1984, 49, 3233. (d) Baraldi, P. TG.;
Guarneri, M.; Pollini, G. P.; Simoni, D.; Barcon, A.; Benetti, S. J . Chem.
Soc., Perkin Trans. 1 1984, 2501. (e) White, D. A.; Baizer, M. M.
Tetrahedron Lett. 1973, 3597.
(17) In the reaction of 2a with (phenylsulfonyl)acetone in the
presence of Pd2(dba)3 (5 mol %) and dppe as ligand (20 mol %), besides
the dihydrofuran 17 (25% yield) significant amounts of disulfone 11
(40%) and 4-methyl-6-(phenylsulfonyl)hex-3,5-dien-2-one (12%) were
detected. These side products would be likely the result of the
competitive sulfonyl elimination on the π-allylpalladium intermediate.
(18) Under the usual conditions (20 mol % of dppe) the yield in
dihydrofurans 24 and 25 is lower due to the formation of an important
amount of ethyl (E)-3-(p-tolylsulfonyl)-1-propen-1-yl carbonate.
(19) Culvenor, C. C. J .; Davies, W.; Savige, W. E. J . Chem. Soc. 1949,
2198.
(20) Hoffmann, R. W. Chem. Rev. 1989, 89, 1841.
(21) Carretero, J . C.; Dom´ınguez, E. J . Org. Chem. 1992, 57, 3867.
(22) For a review on the synthesis of substituted tetrahydrofurans,
see: Bolvin, T. L. B. Tetrahedron 1987, 43, 3309.
(23) J andeleit, B. Ph.D. Dissertation, Aachen (Germany), 1995 (see
also ref 5a).
(24) Baldwin, J . E.; Bamford, S. J .; Fryer, A. M.; Rudolph, M. P.
W.; Wood, M. E. Tetrahedron 1997, 53, 5255.

9410 J . Org. Chem., Vol. 63, No. 25, 1998
Garrido et al.
pyridine, and DMAP. N-(Diphenylmethylene)glycine methyl
ester was prepared according to a previously reported proce-
dure.25
E t h yl (E)-1-(P h en ylsu lfon yl)-1-b u t en -3-yl Ca r b on a t e
(2a ). Eluent: ethyl acetate-hexane (1:4), Rf ) 0.11. Yield:
95%. 1H NMR (300 MHz, CDCl3) δ: 7.84-7.70 (m, 2 H), 7.51-
7.32 (m, 3 H), 6.75 (dd, 1 H, J ) 4.0 and 15.4 Hz), 6.39 (dd, 1
H, J ) 2.0 and 15.4 Hz), 5.23-5.17 (m, 1 H), 3.97 (q, 2 H, J )
7.3 Hz), 1.24 (d, 3 H, J ) 6.9 Hz), 1.21 (t, 3 H, J ) 7.3 Hz). 13
C
NMR (75 MHz, CDCl3) δ: 153.5, 143.3, 139.5, 133.4, 129.4,
129.1 127.4, 71.2, 64.0, 19.1, 13.8. Anal. Calcd for C13H16O5S:
C, 54.91; H, 5.67; S, 11.28. Found: C, 55.32; H, 5.23; S, 11.60.
F igu r e 2. Significant NOESY correlations (CDCl3 and C6D6)
of compounds 27 and 28.
[(S)-2a , [R]25 ) -4.9 (c ) 0.92, CHCl3) (prepared from (S)-
D
Sch em e 6
1a 21)].
Eth yl (E)-1-(P h en ylsu lfon yl)-1-n on en -3-yl Ca r bon a te
(2b). Eluent: ethyl acetate-hexane (1:4), Rf ) 0.25. Yield:
89%. 1H NMR (200 MHz, CDCl3) δ: 7.90-7.84 (m, 2 H), 7.66-
7.49 (m, 3 H), 6.92 (dd, 1 H, J ) 4.4 and 15.1 Hz), 6.51 (dd, 1
H, J ) 1.6 and 15.1 Hz), 5.34-5.25 (m, 1 H), 4.16 (q, 2 H, J )
7.1 Hz), 1.75-1.65 (m, 2 H), 1.38-1.23 (m, 8 H), 1.27 (t, 3 H,
J ) 7.0 Hz), 0.88-0.82 (m, 3 H). 13C NMR (50 MHz, CDCl3) δ:
153.8, 142.8, 139.7, 133.3, 130.8, 129.1, 127.4, 74.8, 64.1, 33.3,
31.2, 28.5, 24.2, 22.2, 13.9, 13.8. MS: 355 (2, M+ + 1), 265 (100,
M+ + 1 - CO2 - EtOH). HRMS: exact mass calcd for
ships. This assignment is also supported by the presence
of significant NOE correlations H2/CH2SO2Ph, H3/CH2-
(C-4) and H5/CH2(C-4). On the other hand, the stereo-
chemistry of the minor isomer 28 (epimer of 27 at C-2)
was tentatively assigned taking into account the strong
NOESY cross-peaks H2/H5 and H3/H5.
C
18H27O5S (M+ + 1) 355.1579, found 355.1565. [(S)-2b, [R]25
D
) +6.3 (c ) 1.13, CHCl3) (prepared from (S)-1b21)].
Eth yl (E)-4-Meth yl-1-(ph en ylsu lfon yl)-1-pen ten -3-yl Car -
bon a te (2c). Eluent: ethyl acetate-hexane (1:5), Rf ) 0.18.
1
Yield: 90%. H NMR (200 MHz, CDCl3 ) δ: 7.88-7.84 (m, 2
H), 7.66-7.48 (m, 3 H), 6.91 (dd, 1 H, J ) 4.7 and 15.2 Hz),
6.51 (dd, 1 H, J ) 1.6 and 15.1 Hz), 5.15 (ddd, 1 H, J ) 1.6,
1.6 and 4.7 Hz), 4.15 (q, 2 H, J ) 7.1 Hz), 2.10-1.94 (m, 1 H),
1.26 (t, 3 H, J ) 7.0 Hz), 0.93 (d, 3 H, J ) 6.9 Hz), 0.92 (d, 3
H, J ) 6.9 Hz). 13C NMR (50 MHz, CDCl3) δ: 154.2, 141.6,
139.7, 133.4, 131.6, 129.1, 127.4, 79.1, 64.2, 31.9, 17.6, 17.3,
13.9. Anal. Calcd for C15H20O5S: C, 57.67; H, 6.45; S, 10.26.
Found: C, 58.16; H, 6.50; S, 10.80.
Con clu sion s
In summary, it has been demonstrated that under
appropriate conditions the carbonate derivatives of the
readily available γ-hydroxy-R,â-unsaturated sulfones (1)
can be used as efficient substrates in Pd(0)-catalyzed
regioselective γ-allylic substitutions with soft carbon
nucleophiles. Interestingly, a cascade process occurred
when â-keto esters, 1,3-diketones, and R-sulfonyl ketones
were used as nucleophiles, leading directly to tetrasub-
stituted dihydrofurans in a highly stereoselective man-
ner. Likely, this process takes place by initial γ-allylic
substitution and further cyclization by conjugate addition
of the enol moiety to the R,â-unsaturated sulfone.
Taking into account that sulfones 1 can be readily
prepared in enantiomerically pure form and that the
palladium-catalyzed γ-allylic substitution takes place
with complete retention of configuration, the procedure
described here constitutes a new, short, and efficient
approach to the enantioselective synthesis of substituted
dihydrofurans and, hence, to the synthesis of substituted
tetrahydrofurans after C-C double bond reduction.
Eth yl (E)-1-(p-Tolylsu lfon yl)-1-p r op en -3-yl Ca r bon a te
(2d ). Eluent: ethyl acetate-hexane (1:3), Rf ) 0.6 in ethyl
acetate-hexane (1:1). Yield: 98%. Mp: 39-41 °C. 1H NMR (300
MHz, CDCl3) δ: 7.76 (d, 2 H, J ) 8.3 Hz), 7.34 (d, 2 H, J ) 8.1
Hz), 6.94 (dt, 1 H, J ) 3.8 and 15.2 Hz), 6.60 (dt, 1 H, J ) 2.0
and 15.2 Hz), 4.82 (dd, 2 H, J ) 2.0 and 3.8 Hz), 4.20 (q, 2 H,
J ) 7.2 Hz), 2.44 (s, 3 H), 1.30 (t, 3 H, J ) 7.2 Hz). 13C NMR
(75 MHz, CDCl3) δ: 154.3, 144.7, 138.0, 136.8, 131.8, 130.0,
127.9, 64.8, 64.5, 21.6, 14.2. Anal. Calcd for C13H16O5S: C,
54.92; H, 5.68; S, 11.25. Found: C, 55.07; H, 5.81; S, 11.58.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed Re-
a ction of Ca r bon a tes 2 w ith Nu cleop h iles. A solution of
0.18 mmol of carbonate 2 and the corresponding nucleophile
(4 equiv) in THF (1.5 mL) or in a mixture of THF (0.5 mL)
and toluene (1 mL) was added to a stirred suspension of Pd2-
(dba)3 (5 mol %), dppe (20 mol %), and powdered molecular
sieves 4 Å (40 mg) in THF (0.5 mL). The reaction was
immediately heated at reflux or 100 °C [depending on the
solvent used: THF or THF-toluene (1:1), respectively] under
argon atmosphere until the carbonate disappeared by TLC (2-
24 h). Then, the reaction mixture was diluted with ethyl
acetate and filtered through a Florisil column. The solvent was
concentrated, and the residue was purified by flash chroma-
tography.
Exp er im en ta l Section
1H NMR (200 or 300 MHz) and 13C NMR (50 or 75 MHz)
spectra were recorded in CDCl3 or C6D6. Both chemical shifts
(ppm downfield from internal tetramethylsilane) and coupling
constants (Hz) were obtained by first-order analysis of spin
patterns. Mass spectra (MS) and high-resolution mass spectra
(HRMS) were recorded by using FAB technique. Mass data
are reported in mass units (m/z), and values in brackets show
the relative intensity from the base peak (as 100%). Analytical
thin-layer chromatography was performed on DC-Alufolien 0.2
mm silica gel 60-F plates (Merck). Visualization was ac-
complished with UV light and ethanolic phosphomolybdic acid
solution followed by heating. Flash chromatography was
performed on silica gel Merck-60 (230-400 mesh). All solvents
were dried before use. THF was distilled from sodium-
benzophenone under argon. Toluene was distilled from P2O5
and stored over sodium. Carbonates 2 were prepared by
straightforward reaction of alcohols 1 with ethyl chloroformate,2b
Diet h yl 2-[(E)-1-Met h yl-3-(p h en ylsu lfon yl)-2-p r op en -
1-yl]m a lon a te (4a ). Carbonate: 2a . Nucleophile: diethyl
malonate. Solvent: THF. Reaction time: 4 h. Eluent: ethyl
acetate-hexane [1:5 and 1:3 (Rf ) 0.25)]. Yield: 79%. 1H NMR
(200 MHz, CDCl3) δ: 7.87-7.83 (m, 2 H), 7.64-7.47 (m, 3 H),
6.96 (dd, 1 H, J ) 7.9 and 15.1 Hz), 6.35 (dd, 1 H, J ) 0.8 and
15.1 Hz), 4.15 (q, 2 H, J ) 7.1 Hz), 4.06 (q, 2 H, J ) 7.2 Hz),
3.34 (d, 1 H, J ) 8.2 Hz), 3.21-3.04 (m, 1 H), 1.21 (t, 3 H, J )
7.1 Hz), 1.17 (t, 3 H, J ) 7.1 Hz), 1.15 (d, 3 H, J ) 6.9 Hz). 13
C
NMR (50 MHz, CDCl3) δ: 167.4, 147.0, 140.2, 133.3, 131.2,
129.2, 127.5, 61.6, 56.4, 35.6, 16.9, 13.9. MS: 355 (100, M+
+
(25) O’Donnell, M. J .; Polt, R. L. J . Org. Chem. 1982, 47, 2663.

Pd-Catalyzed Synthesis of Substituted Dihydrofurans
J . Org. Chem., Vol. 63, No. 25, 1998 9411
1), 195 (13, M+ + 1 - EtCO2CH2CO2Et). HRMS: exact mass
calcd for C17H23O6S (M+ + 1) 355.1215, found 355.1220.
Dieth yl 2-[(E)-1-Hexyl-3-(p h en ylsu lfon yl)-2-p r op en -1-
yl]m a lon a te (4b). Carbonate: 2b. Nucleophile: diethyl mal-
onate. Solvent: THF. Reaction time: 4.5 h. Eluent: ethyl
acetate-hexane [1:6 and 1:3 (Rf ) 0.15)]. Yield: 68%. 1H NMR
(300 MHz, CDCl3) δ: 7.86-7.83 (m, 2 H), 7.61-7.48 (m, 3 H),
6.85 (dd, 1 H, J ) 9.7 and 15.0 Hz), 6.35 (d, 1 H, J ) 15.4 Hz),
4.11 (q, 2 H, J ) 7.1 Hz), 4.01 (dq, 2 H, J ) 1.3 and 7.2 Hz),
3.39 (d, 1 H, J ) 8.3 Hz), 2.99-2.88 (m, 1 H), 1.58-1.34 (m, 2
H), 1.21-1.12 (m, 8 H), 1.18 (t, 3 H, J ) 7.2 Hz), 1.15 (t, 3 H,
J ) 7.1 Hz), 0.85-0.80 (m, 3 H). 13C NMR (75 MHz, CDCl3) δ:
167.4, 167.2, 146, 140.4, 133.2, 132.5, 129.1, 127.5, 61.6, 61.5,
55.6, 41.4, 31.7, 30.8, 28.7, 26.8, 22.4, 13.9. MS: 425 (100, M+
+ 1), 265 (30, M+ + 1 - EtCO2CH2CO2Et). HRMS: exact mass
calcd for C22H33O6S (M+ + 1) 425.1998, found 425.1989.
Dieth yl 2-[(E)-1-Isopr opyl-3-(ph en ylsu lfon yl)-2-pr open -
1-yl]m a lon a te (4c). Carbonate: 2c. Nucleophile: diethyl ma-
lonate. Solvent: THF. Reaction time: 4 h. Eluent: ethyl
acetate-hexane [1:10 and 1:8 (Rf ) 0.05)]. Yield: 64%. 1H
NMR (200 MHz, CDCl3) δ: 7.83-7.77 (m, 2 H), 7.58-7.41 (m,
3 H), 6.90 (dd, 1 H, J ) 10.6 and 15.1 Hz), 6.30 (d, 1 H, J )
15.1 Hz), 4.01 (q, 2 H, J ) 6.9 Hz), 3.96 (q, 2 H, J ) 7.2 Hz),
3.53 (d, 1 H, J ) 8.7 Hz), 2.74 (ddd, 1 H, J ) 5.7, 8.7, and 10.5
Hz), 1.89-1.72 (m, 1 H), 1.12 (t, 3 H, J ) 7.1 Hz), 1.11 (t, 3 H,
J ) 7.0 Hz), 0.85 (d, 3 H, J ) 6.2 Hz), 0.81 (d, 3 H, J ) 6.2
Hz). 13C NMR (50 MHz, CDCl3) δ: 167.5, 167.1, 143.7, 140.3,
133.3, 133.1, 129.0, 127.4, 61.5, 61.4, 53.8, 47.4, 29.2, 20.9, 18.0,
13.8. MS: 383 (100, M+ + 1), 223 (23, M+ + 1 - EtCO2CH2-
CO2Et). HRMS: exact mass calcd for C19H27O6S (M+ + 1)
383.1528, found 383.1536.
Meth yl (E)-2-[N-(Dip h en ylm eth ylen e)a m in o]-3-m eth -
yl-5-(p h en ylsu lfon yl)-4-p en ten oa te (6). Carbonate: 2a . Nu-
cleophile: N-(Diphenylmethylene)glycine methyl ester. Solvent:
THF-toluene (1:1). Reaction time: 4.5 h. Eluent: ethyl
acetate-hexane (1:7, 1:5 and 1:3), Rf ) 0.36 in ethyl acetate-
hexane (1:2). Yield: 46%. Diastereoisomer ratio 6A/6B ) 56:
44. Diastereoisomer 6A: 1H NMR (300 MHz, CDCl3) δ: 7.87-
7.82 (m, 2 H), 7.60-7.26 (m, 11 H), 7.11-7.07 (m, 2 H), 7.08
(dd, 1 H, J ) 8.0 and 15.0 Hz), 6.39 (dd, 1 H, J ) 1.2 and 15.1
Hz), 4.04 (d, 1 H, J ) 5.6 Hz), 3.61 (s, 3 H), 3.22-3.07 (m, 1
H), 1.01 (d, 3 H, J ) 6.9 Hz). 13C NMR (75 MHz, CDCl3) δ:
171.8, 170.9, 148.2, 140.4, 138.9, 135.8, 133.1, 130.6, 129.1,
128.8, 128.7, 128.6, 128.1, 127.7, 127.6, 127.5, 69.4, 52.1, 39.7,
16.2. Diastereoisomer 6B: 1H NMR (300 MHz, CDCl3) (sig-
nificant signals) δ: 6.85 (dd, 1 H, J ) 7.4 and 15.1 Hz), 6.32
(dd, 1 H, J ) 1.2 and 15.1 Hz), 4.10 (d, 1 H, J ) 5.5 Hz), 1.19
(d, 3 H, J ) 6.8 Hz). 13C NMR (75 MHz, CDCl3) (significant
signals) δ: 172.0, 170.8, 140.6, 139.0, 135.9, 133.2, 130.9, 130.8,
68.4, 39.8, 14.7. MS (mixture 6A+6B): 448 (100, M+ + 1).
HRMS (mixture 6A+6B): exact mass calcd for C26H26NO4S
(M+ + 1) 448.1582, found 448.1583.
Meth yl (E)-2-[N-(Dip h en ylm eth ylen e)a m in o]-6-(p h en -
ylsu lfon yl)-4-h exen oa te (7). Carbonate: 2a . Nucleophile:
N-(Diphenylmethylene)glycine methyl ester. Solvent: THF-
toluene (1:1). Reaction time: 4.5 h. Eluent: ethyl acetate-
hexane (1:7, 1:5, and 1:3), Rf ) 0.28 in ethyl acetate-hexane
(1:2). Yield: 23%. 1H NMR (300 MHz, CDCl3) δ: 7.78-7.74
(m, 2 H), 7.63-7.29 (m, 11 H), 7.16-7.11 (m, 2 H), 5.55-5.38
(m, 2 H), 4.08 (dd, 1 H, J ) 5.6 and 7.3 Hz), 3.71 (bd, 2 H, J
) 6.5 Hz), 2.69-2.51 (m, 2 H). 13C NMR (75 MHz, CDCl3) δ:
171.8, 171.0, 138.3, 136.8, 136.1, 133.5, 130.5, 129.0, 128.9,
128.8, 128.6, 128.4, 128.1, 127.7, 119.0, 64.7, 59.9, 52.2, 36.8.
MS: 448 (73, M+ + 1), 306 (13, M+ + 1 - PhSO2H).
1,4-Bis(ph en ylsu lfon yl)-2-m eth yl-1,3-bu tadien e (9). Car-
bonate: 2a . Nucleophile: bis(phenylsulfonyl)methane. Solvent:
THF-toluene (1:1). Reaction time: 3 h. Eluent: ethyl acetate-
hexane (2:7), Rf ) 0.1. Isomer ratio (1E,3E)-9/(1Z,3E)-9 ) 75:
25. Yield: 30%. Isomer (1E,3E)-9: 1H NMR (significant signals)
(200 MHz, CDCl3) δ: 7.13 (d, 1H, J ) 15.1 Hz), 6.69 (d, 1 H,
J ) 15.1 Hz), 6.61 (bs, 1H) and 2.23 (d, 3 H, J ) 1.1 Hz). Isomer
(1Z,3E)-9: Yield: 7% (in pure product after chromatography).
1H NMR (200 MHz, CDCl3) δ: 8.54 (bd, 1 H, J ) 15.1 Hz),
7.98-7.89 (m, 4 H), 7.69-7.53 (m, 6 H), 6.65 (d, 1 H, J ) 15.6
Hz), 6.46 (bs, 1 H) and 1.97 (d, 3 H, J ) 1.1 Hz). MS: 349 (61,
M+ + 1), 207 (8, M+ + 1 - PhSO2H). HRMS: exact mass calcd
for C17H17O4S2 (M+ + 1) 349.0568, found 349.0566.
(E)-1,3-Bis(p h en ylsu lfon yl)-2-bu ten e (11). Eluent: ethyl
acetate-hexane (2:7), Rf ) 0.07. Yield: 38% (in pure product
1
after chromatography). H NMR (200 MHz, CDCl3) δ: 7.85-
7.41 (m, 10 H), 6.77 (tq, 1 H, J ) 1.6 and 8.1 Hz), 3.94 (d, 2 H,
J ) 8.1 Hz) and 1.57 (bs, 3 H). MS: 337 (80, M+ + 1).
Eth yl (E)-2-Acetyl-3-m eth yl-5-(p h en ylsu lfon yl)-4-p en -
ten oa te (12a ). Carbonate: 2a . Nucleophile: ethyl acetoacetate.
Solvent: THF at room temperature. Reaction time: 18 h.
Eluent: ethyl acetate-hexane (1:15), Rf ) 0.39 in ethyl
acetate-hexane (1:3). Yield: 43%. Isomer ratio 12A/12B ) 55:
45. Diastereoisomer 12A: 1H NMR (300 MHz, CDCl3) δ: 7.85-
7.82 (m, 2 H), 7.63-7.49 (m, 3 H), 6.89 (dd, 1 H, J ) 8.1 and
15.1 Hz), 6.34 (dd, 1 H, J ) 1.1 and 15.1 Hz), 4.01 (q, 2 H, J
) 7.1 Hz), 3.43 (d, 1 H, J ) 9.0 Hz), 3.20-3.13 (m, 1 H), 2.21
(s, 3 H), 1.15 (t, 3 H, J ) 7.1 Hz), 1.09 (d, 3 H, J ) 8.1 Hz). 13
C
NMR (75 MHz, CDCl3) δ: 200.6, 167.6, 147.0, 140.3, 133.4,
131.2, 129.2, 127.6, 64.2, 63.7, 34.9, 29.8, 16.6, 13.9. Diaste-
reoisomer 12B: 1H NMR (300 MHz, CDCl3) (significant
signals) δ: 6.88 (dd, 1 H, J ) 8.0 and 15.1 Hz), 6.33 (dd, 1 H,
J ) 1.1 and 15.1 Hz), 4.13 (q, 2 H, J ) 7.1 Hz), 3.46 (d, 1 H,
J ) 8.4 Hz), 2.14 (s, 3 H), 1.23 (t, 3 H, J ) 7.1 Hz), 1.07 (d, 3
H, J ) 8.0 Hz). 13C NMR (75 MHz, CDCl3) (significant signals)
δ: 200.8, 167.5, 147.4, 140.2, 61.8, 35.1, 29.9, 17.1, 14.0.
3-(Eth oxyca r bon yl)-2,4-d im eth yl-5-[(p h en ylsu lfon yl)-
m eth yl]-4,5-d ih yd r ofu r a n (13). Carbonate: 2a . Nucleophile:
ethyl acetoacetate. Solvent: THF-toluene (1:1). Reaction time:
3.5 h. Eluent: ethyl acetate-hexane (1:15), Rf ) 0.24 in ethyl
acetate-hexane (1:3). Yield: 76%. Isomer ratio trans-
13(4R*,5R*)/cis-13(4R*,5S*) ) 78:22. Diastereoisomer trans-
13: 1H NMR (200 MHz, CDCl3) δ: 7.98-7.91 (m, 2 H), 7.71-
7.52 (m, 3 H), 4.61 (ddd, 1 H, J ) 4.8, 4.8 and 8.6 Hz), 4.26-
4.01 (m, 2 H), 3.47 (dd, 1 H, J ) 8.1 and 14.5 Hz), 3.24 (dd, 1
H, J ) 4.8 and 14.5 Hz), 3.02-2.89 (m, 1 H), 1.90 (bs, 3 H),
1.26 (t, 3 H, J ) 7.0 Hz) and 1.20 (d, 3 H, J ) 7.0 Hz). 13C
NMR (50 MHz, CDCl3) δ: 166.1, 165.4, 139.9, 133.9, 129.1,
128.2, 107.3, 82.4, 60.2, 59.5, 42.7, 19.5, 14.2 and 13.7.
Diastereoisomer cis-13: 1H NMR (200 MHz,CDCl3) (significant
signals) δ: 4.93 (ddd, 1 H, J ) 4.8, 8.6 and 8.6 Hz), 4.26-4.01
(m, 2 H), 3.56 (dd, 1 H, J ) 8.1 and 14.5 Hz), 3.43 (dd, 1 H, J
) 4.3 and 15.1 Hz), 3.30-3.15 (m, 1 H), 2.01 (bs, 3 H), 1.25 (t,
3 H, J ) 7.0 Hz) and 0.98 (d, 3 H, J ) 7.0 Hz). 13C NMR (50
MHz, CDCl3) (significant signals) δ: 166.9, 165.3, 139.4, 108.7,
78.7, 56.6, 39.4 and 13.8. MS: 325 (100, M+ + 1), 279 (20, M+
+ 1 -EtOH). HRMS: exact mass calcd for C16H21O5S (M+ + 1)
325.1109, found 325.1106.
3-(Eth oxyca r bon yl)-4-m eth yl-2-p h en yl-5-[(p h en ylsu l-
fon yl)m eth yl]-4,5-d ih yd r ofu r a n (14). Carbonate: 2a . Nu-
cleophile: ethyl benzoylacetate. Solvent: THF-toluene (1:1).
Reaction time: 4 h. Eluent: ethyl acetate-hexane (1:15), Rf )
0.25 in ethyl acetate-hexane (1:5). Yield: 63%. Isomer ratio:
trans-14(4R*,5R*)/cis-14(4R*,5S*) ) 83:17. Diastereoisomer
1
trans-14: H NMR (200 MHz, CDCl3) δ: 7.98-7.89 (m, 2H),
7.63-7.18 (m, 8H), 4.75 (ddd, 1H, J ) 4.3, 4.3 and 8.0 Hz),
4.10 (q, 2 H, J ) 7.0 Hz), 3.62 (dd, 1 H, J ) 8.1 and 14.5 Hz),
3.31 (dd, 1 H, J ) 4.3 and 14.5 Hz), 3.15 (dq, 1 H, J ) 4.3 and
7.0 Hz), 1.32 (d, 3 H, J ) 6.5 Hz), 1.17 (t, 3 H, J ) 7.0 Hz).13
C
NMR (75 MHz, CDCl3) δ: 164.7, 163.2, 139.9, 133.8, 130.5,
129.4, 129.3, 129.1, 128.4, 128.3, 127.4, 107.5, 81.9, 60.5, 59.9,
1
44.5, 19.8, 14.1. Diastereoisomer cis-14: H NMR (200 MHz,
CDCl3) (significant signals) δ: 5.10 (ddd, 1 H, J ) 4.3, 8.0 and
8.0 Hz), 4.12 (q, 2 H, J ) 7.0 Hz), 3.66 (dd, 1 H, J ) 8.1 and
15.1 Hz), 3.51 (dd, 1 H, J ) 4.3 and 15.1 Hz), 3.51-3.33 (m, 1
H), 1.19 (d, 3 H, J ) 7.0 Hz), 1.14 (t, 3 H, J ) 7.0 Hz). 13C
NMR (75 MHz, CDCl3) (significant signals) δ: 163.7, 139.5,
130.6, 129.2, 128.2, 109, 78.6, 56.7, 41.3, 14.3. MS: 387 (55,
M+ + 1), 341 (92, M+ + 1 - EtOH), 245 (19, M+ + 1 -
PhSO2H). HRMS (cis-14+trans-14): exact mass calcd for
C
21H23O5S (M+ + 1) 387.1266, found 387.1251.
3-Acetyl-2,4-d im eth yl-5-[(p h en ylsu lfon yl)m eth yl]-4,5-
d ih yd r ofu r a n (15). Carbonate: 2a . Nucleophile: 2,4-pen-
tanedione. Solvent: THF. Reaction time: 2.5 h. Eluent: ethyl
acetate-hexane [1:5 (Rf ) 0.05)]. Yield: 79%. Isomer ratio
trans-15(4R*,5R*)/cis-15(4R*,5S*) ) 75:25. Diastereoisomer

9412 J . Org. Chem., Vol. 63, No. 25, 1998
Garrido et al.
1
trans-15: H NMR (300 MHz, CDCl3) δ: 7.94-7.89 (m, 2 H),
(4R*,5R*)-3-(E t h oxyca r b on yl)-4-n -h exyl-2-p h en yl-5-
[(ph en ylsu lfon yl)m eth yl]-4,5-dih ydr ofu r an (tr a n s-19). Car-
bonate: 2b. Nucleophile: ethyl benzoylacetate. Solvent: THF-
toluene (1:1). Reaction time: 5 h. Eluent: ethyl acetate-hexane
(1:15), Rf ) 0.28 in ethyl acetate-hexane (1:5). Yield: 57%.
1H NMR (300 MHz, CDCl3) δ: 7.98-7.90 (m, 2 H), 7.66-7.18
(m, 8 H), 4.91 (ddd, 1 H, J ) 3.7, 3.7, 8.9 Hz), 4.16-4.05 (m,
2H), 3.64 (dd, 1 H, J ) 8.9 and 14.9 Hz), 3.24 (dd, 1 H, J ) 3.6
and 14.5 Hz), 3.08-3.03 (m, 1 H), 1.80-1.50 (m, 2 H), 1.40-
1.10 (m, 8 H), 1.16 (t, 3 H, J ) 6.9 Hz), 0.89-0.78 (m, 3 H).
13C NMR (75 MHz, CDCl3) δ: 164.6, 163.3, 140.0, 133.7, 130.5,
129.4, 129.3, 128.5, 128.3, 127.3, 106.0, 79.8, 61.1, 59.8, 49.5,
33.4, 31.6, 29.2, 25.9, 22.6 and 14.0. MS: 457 (30, M+ + 1),
411 (69, M+ + 1 - EtOH). HRMS: exact mass calcd for
C26H33O5S (M+ + 1) 457.2049, found 457.2030.
(4R*,5R*)-3-Acet yl-4-n -h exyl-2-m et h yl-5-[(p h en ylsu l-
fon yl)m eth yl]-4,5-d ih yd r ofu r a n (tr a n s-20). Carbonate: 2b.
Nucleophile: 2,4-pentanedione. Solvent: THF-toluene (1:1).
Reaction time: 3 h. Eluent: ethyl acetate-hexane (1:15), Rf )
0.10 in ethyl acetate-hexane (1:10). Yield: 67%. 1H NMR (300
MHz, CDCl3) δ: 7.95-7.90 (m, 2 H), 7.70-7.51 (m, 3 H), 4.76
(ddd, 1 H, J ) 3.9, 3.9 and 8.6 Hz), 3.45 (dd, 1 H, J ) 8.6 and
14.9 Hz), 3.17 (dd, 1 H, J ) 3.9 and 14.9 Hz), 2.94-2.89 (m, 1
H), 2.19 (s, 3 H), 1.91 (bs, 3 H), 1.69-1.40 (m, 1 H), 1.39-1.14
(m, 9 H), 0.95-0.83 (m, 3 H). 13C NMR (75 MHz, CDCl3) δ:
193.8, 165.6, 140.0, 133.7, 129.1, 128.1, 116.4, 80.3, 60.6, 48.3,
33.2, 31.6, 29.2, 29.1, 25.9, 22.5, 14.8, 14.0. MS: 365 (100, M+
+ 1), 223 (29, M+ + 1 - PhSO2H). HRMS: exact mass calcd
for C20H29O4S (M+ + 1) 365.1786, found 365.1779.
(4R*,5R*)-3-(Eth oxyca r bon yl)-4-isop r op yl-2-m eth yl-5-
[(ph en ylsu lfon yl)m eth yl]-4,5-dih ydr ofu r an (tr a n s-21). Car-
bonate: 2c. Nucleophile: ethyl acetoacetate. Solvent: THF-
toluene (1:1). Reaction time: 6 h. Eluent: ethyl acetate-hexane
(1:15), Rf ) 0.35 in ethyl acetate-hexane (1:3). Yield: 38%.
1H NMR (200 MHz, CDCl3) δ: 7.96-7.91 (m, 2 H), 7.70-7.51
(m, 3 H), 4.86 (ddd, 1 H, J ) 3.2, 3.2, and 9.1 Hz), 4.24-4.01
(m, 2H), 3.49 (dd, 1 H, J ) 9.1 and 15.0 Hz), 3.10 (dd, 1 H, J
) 3.2 and 15.1 Hz), 2.83-2.80 (m, 1 H), 2.18-2.00 (m, 1 H),
1.84 (d, 3 H, J ) 1.1 Hz), 1.24 (t, 3 H, J ) 7.5 Hz), 0.88 (d, 3
H, J ) 7.0 Hz), 0.74 (d, 3 H, J ) 7.0 Hz). 13C NMR (75 MHz,
CDCl3) δ: 166.6, 165.6, 140.2, 133.7, 129.3, 129.2, 128.2, 127.7,
127.6, 104.5, 76.7, 61.5, 59.6, 53.8, 32.2, 29.7, 28.9, 19.9, 16.3,
14.3, 13.7. MS: 307 (44, M+ + 1 - EtOH). HRMS: exact mass
calcd for C18H25O5S (M+ + 1) 353.1423, found 353.1420.
(4R*,5R*)-3-(Eth oxyca r bon yl)-4-isop r op yl-2-p h en yl-5-
[(ph en ylsu lfon yl)m eth yl]-4,5-dih ydr ofu r an (tr a n s-22). Car-
bonate: 2c. Nucleophile: ethyl benzoylacetate. Solvent: THF-
toluene (1:1). Reaction time: 6 h. Yield: 14%. 1H NMR (300
MHz, CDCl3) δ: 7.99-7.19 (m, 10H), 5.02 (ddd, 1H, J ) 3.2,
3.2, and 9.1 Hz), 4.09 (q, 2H, J ) 6.9 Hz), 3.68 (dd, 1H, J )
9.1 and 14.5 Hz), 3.16 (dd, 1H, J ) 3.2 and 14.6 Hz), 3.03 (t,
1H, J ) 3.2 Hz), 2.25-2.13 (m, 1H), 1.16 (t, 3H, J ) 7.3 Hz),
0.98 (d, 3H, J ) 6.9 Hz), 0.88 (d, 3H, J ) 6.9 Hz).
7.70-7.51 (m, 3 H), 4.58 (ddd, 1 H, J ) 3.6, 4.8 and 8.2 Hz),
3.42 (dd, 1 H, J ) 7.9 and 14.5 Hz), 3.23 (dd, 1 H, J ) 4.8 and
14.5 Hz), 3.04-2.97 (m, 1 H), 2.17 (s, 3H), 1.91 (s, 3 H), 1.18
(d, 3 H, J ) 6.8 Hz). 13C NMR (75 MHz, CDCl3) δ: 193.9, 165.6,
139.8, 133.8, 129.2, 128.1, 117.8, 82.5, 60.0, 43.1, 29.2, 20.0,
14.8. Diastereoismer cis-15: 1H NMR (300 MHz, CDCl3)
(significant signals) δ: 4.88 (ddd, 1 H, J ) 4.6, 8.2 and 8.2
Hz), 3.54 (dd, 1 H, J ) 8.1 and 14.6 Hz), 3.43 (dd, 1 H, J ) 4.6
and 14.5 Hz), 3.27-3.18 (m, 1 H), 2.20 (s, 3 H), 2.04 (s, 3 H)
and 0.97 (d, 3 H, J ) 6.9 Hz). 13C NMR (75 MHz, CDCl3)
(significant signals) δ: 193.6, 166.5, 139.4, 134.0, 128.2, 119.7,
78.8, 56.4, 39.9, 19.7 and 15.1. MS (cis-15+trans-15): 295 (100,
M+ + 1), 153 (18, M+ + 1 - PhSO2H). HRMS (cis-15+trans-
15): exact mass calcd for C15H19O4S (M+ + 1) 295.1004, found
295.0999.
4,5,6,7-Tetr ah ydr o-3-m eth yl-2-[(ph en ylsu lfon yl)m eth yl]-
4(2H)-ben zofu r a n on e (16). Carbonate: 2a . Nucleophile: 1,3-
cyclohexanedione. Solvent: THF-toluene (1:1). Reaction time:
20 h. Eluent: ethyl acetate-hexane (1:9, 1:5, and 1:2), Rf )
0.4 in ethyl acetate-hexane (1.1). Yield: 89%. Isomer ratio
trans-16(2R*,3R*)/cis-16(2R*,3S*) ) 75:25. Diastereoisomer
1
trans-16: H NMR (300 MHz, CDCl3) δ: 7.95-7.89 (m, 2 H),
7.68-7.51 (m, 3 H), 4.69 (ddd, 1 H, J ) 4.7, 4.7 and 8.0 Hz),
3.47 (dd, 1 H, J ) 8.0 and 14.6 Hz), 3.29 (dd, 1 H, J ) 4.5 and
14.6 Hz), 3.01-2.93 (m, 1 H), 2.30-1.87 (m, 6 H), 1.19 (d, 3
H, J ) 6.8 Hz). 13C NMR (75 MHz, CDCl3) δ: 195.2, 175.4,
139.6, 133.9, 129.2, 128.0, 117.0, 85.2, 60.3, 40.3, 36.6, 23.5,
21.5, 18.7. Diastereoisomer cis-16: 1H NMR (300 MHz, CDCl3)
(significant signals) δ: 5.08 (ddd, 1 H, J ) 3.7, 9.0 and 9.0 Hz),
3.53 (dd, 1 H, J ) 8.9 and 14.7 Hz), 3.41 (dd, 1 H, J ) 3.7 and
14.8 Hz), 3.32-3.25 (m, 1 H), 0.99 (d, 3 H, J ) 7.0 Hz). 13C
NMR (75 MHz, CDCl3) (significant signals) δ: 195.0, 175.7,
139.4, 133.9, 128.1, 118.1, 81.0, 56.6, 36.7, 36.5, 21.4, 13.7. MS
(cis-16+trans-16): 307 (100, M+ + 1), 165 (29, M+ + 1 -
PhSO2H). HRMS (cis-16+trans-16): exact mass calcd for
C
16H19O4S (M+ + 1) 307.1004, found 307.1019.
2,4-Dim et h yl-3-(p h en ylsu lfon yl)-5-[(p h en ylsu lfon yl)-
m eth yl]-4,5-d ih yd r ofu r a n (17). Carbonate: 2a . Nucleophile:
(phenylsulfonyl)acetone. Ligand: dppf (20 mol %). Solvent:
THF-toluene (1:1). Reaction time: 6.5 h. Eluent: ethyl acetate-
hexane (1:10, 1:8, and 1:5), Rf ) 0.28 in ethyl acetate-hexane
(1:1). Yield: 80%. Isomer ratio trans-17(4R*, 5R*)/cis-17(4R*,
5S*) ) 75:25. Diastereoisomer trans-17: 1H NMR (300 MHz,
CDCl3) δ: 7.92-7.79 (m, 4 H), 7.70-7.49 (m, 6 H), 4.57 (ddd,
1 H, J ) 4.9, 4.9 and 7.6 Hz), 3.34 (dd, 1 H, J ) 7.6 and 14.5
Hz), 3.12 (dd, 1 H, J ) 4.9 and 14.5 Hz), 2.95-2.90 (m, 1 H),
2.02 (d, 3 H, J ) 1.4 Hz) and 1.14 (d, 3 H, J ) 6.7 Hz). 13C
NMR (75 MHz, CDCl3) δ: 165.2, 142.7, 139.6, 133.0, 129.3,
129.2, 126.6, 114.2, 82.9, 59.8, 43.8, 19.3 and 13.4. Diastereo-
isomer cis-17: 1H NMR (300 MHz, CDCl3) (significant signals)
δ: 4.91 (ddd, 1 H, J ) 4.3, 8.5 and 8.5 Hz), 3.50 (dd, 1 H, J )
8.4 and 14.6 Hz), 3.35 (dd, 1 H, J ) 4.5 and 14.5 Hz), 3.15-
3.05 (m, 1 H), 2.09 (d, 3 H, J ) 1.2 Hz), 1.06 (d, 3 H, J ) 7.0
Hz). 13C NMR (75 MHz, CDCl3) δ: 165.7, 134.1, 134.0, 128.2,
128.1, 126.7, 115.6, 79.2, 56.2, 40.7, 14.4. MS (cis-17+trans-
17): 393 (44, M+ + 1), 251 (8, M+ + 1 - PhSO2H). HRMS (cis-
17+trans-17): exact mass calcd for C19H21O5S2 (M+ + 1)
393.0830, found 393.0836.
(4R*,5R*)-3-Acetyl-4-isop r op yl-2-m eth yl-5-[(p h en ylsu l-
fon yl)m eth yl]-4,5-d ih yd r ofu r a n (tr a n s-23). Carbonate: 2c.
Nucleophile: 2,4-pentanedione. Solvent: THF-toluene (1:1).
Reaction time: 7 h. Eluent: ethyl acetate-hexane (1:15), Rf )
0.10 in ethyl acetate-hexane (1:3). Yield: 14%. 1H NMR (200
MHz, CDCl3) δ: 7.96-7.92 (m, 2 H), 7.67-7.53 (m, 3 H), 4.88
(ddd, 1 H, J ) 3.8, 3.8 and 8.6 Hz), 3.46 (dd, 1 H, J ) 9.1 and
15.0 Hz), 3.11 (dd, 1 H, J ) 3.8 and 14.5 Hz), 2.95-2.90 (m, 1
H), 2.20 (s, 3 H), 2.11-2.02 (m, 1 H), 1.91 (d, 3 H, J ) 1.0 Hz),
0.91 (d, 3 H, J ) 7.0 Hz), 0.72 (d, 3 H, J ) 7.0 Hz). 13C NMR
(75 MHz, CDCl3) δ: 194.0, 165.9, 140.2, 133.8, 129.1, 128.2,
115.3, 76.4, 61.3, 54.3, 29.4, 28.8, 20.1, 16.0, 14.8. MS: 323
(74, M+ + 1), 181 (16, M+ + 1 - PhSO2H). HRMS: exact mass
calcd for C17H23O4S (M+ + 1) 323.1317, found 323.1325.
3-(E t h oxyca r b on yl)-2-m et h yl-5-[(p -t olylsu lfon yl)m e-
th yl]-4,5-d ih yd r ofu r a n (24). Carbonate: 2d . Nucleophile:
ethyl acetoacetate. Solvent: THF-toluene (1:1). Reaction time:
17.5 h. Eluent: ethyl acetate-hexane (1:7 and 1:3), Rf ) 0.3
(4R*,5R*)-3-(E t h oxyca r b on yl)-4-n -h exyl-2-m et h yl-5-
[(ph en ylsu lfon yl)m eth yl]-4,5-dih ydr ofu r an (tr a n s-18). Car-
bonate: 2b. Nucleophile: ethyl acetoacetate. Solvent: THF-
toluene (1:1). Reaction time: 4 h. Eluent: ethyl acetate-hexane
1
[1:15 (Rf ) 0.04)]. Yield: 79%. H NMR (300 MHz, CDCl3) δ:
7.94-7.90 (m, 2 H), 7.67-7.23 (m, 3 H), 4.75 (ddd, 1 H, J )
4.0, 4.0 and 8.9 Hz), 4.18-4.03 (m, 2 H), 3.46 (dd, 1 H, J ) 8.9
and 14.5 Hz), 3.17 (dd, 1 H, J ) 4.0 and 14.5 Hz), 2.85-2.82
(m, 1 H), 1.81 (bs, 3 H), 1.71-1.37 (m, 2 H), 1.36-1.16 (m, 8
H), 1.20 (t, 3 H, J ) 6.9 Hz), 0.88-0.84 (m, 3 H). 13C NMR (75
MHz, CDCl3) δ: 166.3, 165.5, 140.2, 133.7, 129.1, 128.2, 105.9,
80.4, 60.9, 59.6, 48.0, 33.0, 31.6, 29.2, 25.9, 22.6, 14.3, 14.1,
13.8. MS: 395 (24, M+ + 1), 349 (100, M+ + 1 - EtOH). HRMS:
exact mass calcd for C21H31O5S (M+ + 1) 395.1892, found
1
in ethyl acetate-hexane (1:1). Yield: 41%. mp: 89-93 °C. H
NMR (300 MHz, CDCl3) δ: 7.80 (d, 2 H, J ) 8.3 Hz), 7.35 (d,
2 H, J ) 8.3 Hz), 5.00 (dddd, 1 H, J ) 5.7, 6.9, 6.9 and 10.3
Hz), 4.13 (q, 2 H, J ) 7.2 Hz), 3.52 (dd, 1 H, J ) 6.9 and 14.3
395.1891. [(4R,5R)-18, [R]25 ) -56.5 (c ) 1.49, CHCl3)
D
(prepared from (S)-2b21)].

Pd-Catalyzed Synthesis of Substituted Dihydrofurans
J . Org. Chem., Vol. 63, No. 25, 1998 9413
Hz), 3.28 (dd, 1 H, J ) 5.6 and 14.4 Hz), 3.09 (ddq, 1 H, J )
1.6, 10.3 and 15.1 Hz), 2.65 (ddq, 1 H, J ) 1.6, 6.9, 15.0 Hz),
2.45 (s, 3 H), 1.98 (t, 3 H, J ) 1.6 Hz) and 1.24 (t, 3 H, J ) 7.2
Hz). 13C NMR (75 MHz, CDCl3) δ: 166.6, 165.5, 145.0, 136.7,
129.8, 128.2, 101.8, 75.5, 61.1, 59.6, 35.4, 21.6, 14.3 and 13.6.
MS: 325 (14, M+ + 1), 279 (100, M+ + 1 - EtOH). HRMS:
exact mass calcd for C16H21O5S (M+ + 1) 325.1110, found
325.1096.
4,5,6,7-Tet r a h yd r o-2-[(p -t olylsu lfon yl)m et h yl]-4(2H )-
ben zofu r a n on e (25). Carbonate: 2d . Nucleophile: 1,3 cyclo-
hexanedione. Solvent: THF-toluene (1:1). Reaction time: 18
h. Eluent: dichloromethane and dichloromethane-ethyl ac-
etate (10:1 and 4:1). Rf ) 0.23 in dichloromethane-ethyl
acetate (2:1). Yield: 42%. mp: 168-170 °C. 1H NMR (300 MHz,
CDCl3) δ: 7.79 (d, 2 H, J ) 8.3 Hz), 7.36 (d, 2 H, J ) 8.1 Hz),
5.96 (dddd, 1 H, J ) 5.3, 7.2, 7.2 and 10.2 Hz), 3.55 (dd, 1 H,
J ) 7.2, 14.4 Hz), 3.33 (dd, 1 H, J ) 5.3 and 14.5 Hz), 2.99
(ddt, 1 H, J ) 1.8, 10.4 and 14.9 Hz), 2.51 (ddt, 1 H, J ) 1.8,
7.2 and 14.9), 2.44 (s, 3 H), 2.41-2.16 (m, 4H), 2.02-1.89 (m,
2 H). 13C NMR (75 MHz, CDCl3) δ: 195.1, 176.3, 145.2, 136.5,
129.9, 128.1, 112.5, 78.5, 61.2, 36.3, 31.8, 23.5, 21.6, 21.4. MS:
307 (85, M+ + 1). HRMS exact mass calcd for C16H19O4S (M+
+ 1) 307.1004, found 307.1007.
MHz, CDCl3) δ: 7.95-7.90 (m, 2 H), 7.65-7.58 (m, 1 H), 7.55-
7.48 (m, 2 H), 4.22 (ddd, 1 H, J ) 3.2, 5.9 and 9.0 Hz), 4.11 (q,
2 H, J ) 7.1 Hz), 3.85 (qd, 1 H, J ) 6.0 and 8.1 Hz), 3.46 (dd,
1 H, J ) 8.6 and 14.5 Hz), 3.27 (dd, 1 H, J ) 3.3 and 14.5 Hz),
2.33-2.15 (m, 1 H), 2.23 (dd, 1 H, J ) 8.1 and 8.3 Hz), 1.52-
1.36 (m, 1 H), 1.29-1.16 (m, 9 H), 1.22 (t, 3 H, J ) 7.1 Hz),
1.10 (d, 3 H, J ) 6.1 Hz), 0.86 (t, 3 H, J ) 6.5 Hz). 13C NMR
(75 MHz, CDCl3) δ: 172.7, 140.1, 133.5, 128.9, 128.2, 78.0,
77.7, 60.9, 60.5, 57.9, 50.0, 33.2, 31.5, 29.2, 27.4, 22.5, 19.8,
1
14.1 and 14.0. H NMR (300 MHz, C6D6) δ: 7.98-7.91 (m, 2
H), 7.05-6.95 (m, 3 H), 4.40 (ddd, 1 H, J ) 4.3, 6.4 and 8.0
Hz), 4.00-3.81 (m, 1 H), 3.93 (dq, 2 H, J ) 1.1 and 7.0 Hz),
3.30 (dd, 1 H, J ) 8.1 and 14.5 Hz), 3.15 (dd, 1H, J ) 4.3 and
14.5 Hz), 2.48-2.36 (m, 1H), 2.21 (dd, 1 H, J ) 8.1 and 8.6
Hz), 1.31-1.19 (m, 10 H), 1.09 (d, 3 H, J ) 6.0 Hz), 0.95 (t, 3
H, J ) 7.0 Hz), 0.93 (t, 3 H, J ) 7.0 Hz). Isomer 28: 1H NMR
(300 MHz, CDCl3) (significant signals) δ: 4.16-4.09 (m, 1 H),
3.97 (ddd, 1 H J ) 3.4, 7.8, and 7.8 Hz), 3.53 (dd, 1 H, J ) 8.1
and 14.5 Hz), 3.40 (dd, 1 H, J ) 3.4 and 14.5 Hz), 2.66 (dd, 1
H, J ) 5.2 and 7.5 Hz) and 0.99 (d, 3 H, J ) 6.3 Hz). 13C NMR
(75 MHz, CDCl3) (significant signals) δ: 128.8, 128.4, 128.2,
78.2, 76.0, 61.0, 60.6, 54.1, 48.2, 32.5, 27.6, 16.8, 14.2. Anal.
Calcd for C21H32O5S (mixture 27+28): C, 63.61; H, 8.13 and
S, 8.08, found C, 64.14; H, 7.82 and S 8.09.
(R)-Dim eth yl 2-[(E)-1-Meth yl-3-(p h en ylsu lfon yl)-2-p r o-
p en -1-yl]m a lon a te [(R)-26]. [R]D ) -9.0 (c ) 1.03, CHCl3);
[R]D lit.23,5a ) -10.3 (c ) 1.02, CHCl3). ee >96% [determined
by 1H NMR with Pr(hfc)3]. 1H NMR (300 MHz, CDCl3) δ: 7.90-
7-84 (m, 2H), 7.66-7.51 (m, 3H), 6.97 (dd, 1H, J ) 8.1 and
15.2 Hz), 6.38 (dd, 1H, J ) 0.7 and 15.2 Hz), 3.69 (s, 3H), 3.59
(s, 3H), 3.42 (d, 1H, J ) 8.1 Hz), 3.20-3.07 (m, 1H), 1.17 (d,
3H, J ) 6.8 Hz).
Ack n ow led gm en t. Financial support from DGI-
CYT(Ministerio de Educacio´n y Cultura, project PB96-
0021) is gratefully acknowledged. The authors are also
greatly indebted to Dr. Concepcio´n Pedregal and Ms.
Virginia Magro for some previous work in this field and
to Prof. Dieter Enders for sending us the complete
characterization data of compound (R)-26.
(2S,3R,4R,5R)-3-(Eth oxyca r bon yl)-4-n -h exyl-2-m eth yl-
5-[(p h en ylsu lfon yl)m et h yl]t et r a h yd r ofu r a n (27) a n d
(2R,3R,4R,5R)-(28). To a stirred solution of 18 (71 mg, 0.18
mmol) in trifluoroacetic acid (3.44 mL) was added triethylsi-
lane (10 equiv, 320 µL). The reaction mixture was heated at
60 °C for 19 h. After cooling at room temperature, the mixture
was concentrated in vacuo and then azeotropic removal of
residual trifluoroacetic acid with toluene. The residue was
purified by flash chromatography (eluting with ethyl acetate-
hexane 1:7. Rf ) 0.37 in ethyl acetate-hexane 1:3) to give a
mixture of 27 and 28. Yield: 70%. Isomer ratio 27/28 ) 86:14.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 2a -d , 4a -c, 6, 7, 12a , 13-21, 24, 25,
and 27+28; 1H NMR spectra of 9Z, 11, 23, and 26; HRMS
spectra for 2b, 4a -c, 6, 9Z, 13-21, and 23-25 (83 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
[R]25 ) -25.1 (c ) 0.97, CHCl3). Isomer 27: 1H NMR (300
J O981391R
D