A general synthesis of methylenecyclopentanes by a stereoselective [3 + 2] approach

Article abstract of DOI:10.1021/jo960089k

The [3 + 2] cyclopentanation involving 3-(phenylsulfonyl)-2-(bromomethyl)-1-propene (1) and representative (E) α,β-unsaturated acyclic esters and ketones has been studied. High yields and complete stereoselectivity were observed in all reactions leading to tri- or tetrasubstituted methylenecyclopentanes. The anti-diastereoselectivity in the first, Michael addition step is rationalized by a chelation-controlled transition state in which MO interactions of the two π systems are involved. The Michael reactions of methallyl sulfone 8 with (E) enoates in the absence and presence of HMPA confirms the influence of chelation on the diastereomeric ratio of adducts. Cyclopentanations involving 1 with cyclohexenone, 2(5H)-furanone, and 5,6-dihydro-2-pyranone, respectively, were also studied with emphasis on the factors influencing the stereochemical outcome of the annulation process.

Full text of DOI:10.1021/jo960089k

J . Org. Chem. 1996, 61, 4959-4966
4959
A Gen er a l Syn th esis of Meth ylen ecyclop en ta n es by a
Ster eoselective [3 + 2] Ap p r oa ch
Eugene Ghera,* Tamar Yechezkel, and Alfred Hassner*,1
Department of Chemistry, Bar-Ilan University, Ramat Gan 52900, Israel
Received J anuary 12, 1996X
The [3 + 2] cyclopentanation involving 3-(phenylsulfonyl)-2-(bromomethyl)-1-propene (1) and
representative (E) R,â-unsaturated acyclic esters and ketones has been studied. High yields and
complete stereoselectivity were observed in all reactions leading to tri- or tetrasubstituted
methylenecyclopentanes. The anti-diastereoselectivity in the first, Michael addition step is
rationalized by a chelation-controlled transition state in which MO interactions of the two π systems
are involved. The Michael reactions of methallyl sulfone 8 with (E) enoates in the absence and
presence of HMPA confirms the influence of chelation on the diastereomeric ratio of adducts.
Cyclopentanations involving 1 with cyclohexenone, 2(5H)-furanone, and 5,6-dihydro-2-pyranone,
respectively, were also studied with emphasis on the factors influencing the stereochemical outcome
of the annulation process.
In tr od u ction
paper we report the results of tandem MIRC of 1 with
acyclic R,â-unsaturated esters and ketones leading to
cyclopentanation in a process characterized by high
effectivity and diastereoselectivity.10,11 A rationalization
of the stereochemical outcome of these reactions is
proposed. The scope of this [3 + 2] process was further
extended by its application to R,â-unsaturated lactones
and cyclic enones.
Five-membered carbocycles are important building
blocks for the synthesis of cyclopentanoid natural prod-
ucts. Among the growing number of methodologies
developed during recent years for the construction of
cyclopentanes, the [3 + 2] strategy has been widely
explored because it offers the possibility of forming two
carbon-carbon bonds under the same reaction condi-
tions.2,3 Practical interest in such methodology may
depend on several factors such as (a) the scope of the
process, (b) ready availability of utilized substrates, (c)
simplicity of experimental procedures, (d) regio- and
stereoselectivities of the process, and (e) eventual pos-
sibility of enantioselective construction of cyclopentanes.4
Among the reported [3 + 2] cyclopentanations, many of
which fail to fulfill several of the above conditions, the
utilization of trimethylenemethane (TMM) and its orga-
nometallic complexes as the three-carbon moiety deserves
special attention.5,6
Resu lts a n d Discu ssion
Cyclop en ta n a tion s w ith Acyclic Accep tor s. The
readily prepared bromo allyl sulfone 1 was deprotonated
by lithium diisopropylamide (LDA) in THF solution at
low temperature (-95 °C). Addition of representative
acyclic (E) R,â-unsaturated esters and ketones to lithiated
1 resulted in a rapid and effective conversion into the
corresponding methylenecyclopentanes via conjugate ad-
dition followed by ring closure (eq 1 and Table 1). All
We recently investigated the utilization of a TMM
equivalent, which does not undergo self-destruction
under basic conditions, namely, 3-(phenylsulfonyl)-2-
(bromomethyl)-1-propene (1), in 3 + 2 anionic cyclopen-
tanations. We reported on the Michael-initiated ring
closure (MIRC)7 involving 1 with nitroolefins8 and 2-(phen-
ylsulfonyl) enones,9 respectively, as acceptors. In this
X Abstract published in Advance ACS Abstracts, J uly 1, 1996.
(1) Synthetic Methods. 47. For part 46, see: Hassner, A.; Nam-
boothiri, I. N. N. J . Organomet. Chem. In press.
(2) For a review, see: Hudlicky, T.; Price, J . D. Chem. Rev. 1989,
89, 1467.
(3) For [3 + 2] cyclopentanations (not included in ref 2), see, inter
alia: Becker, D. A.; Danheiser, R. L. J . Am. Chem. Soc. 1989, 111,
389 and references therein. Feldman, K. S.; Romanelli, A. L.; Ruckle,
R. E.; Miller, R. F. J . Am. Chem. Soc. 1988, 110, 3300. Curran, D. P.;
Chen, M. H. J . Am. Chem. Soc. 1987, 109, 6558. Herndon, J . W. J .
Am. Chem. Soc. 1987, 109, 3165. Yamago, S.; Nakamura, E. J . Am.
Chem. Soc. 1989, 111, 7285. Lee, T. V.; Richardson, K. A.; Ellis, K. L.;
Visani, N. Tetrahedron 1989, 45, 1167. Panek, J . S.; J arom, N. F. J .
Org. Chem. 1993, 58, 2345. Kno¨lker, H. J .; Graf, R. Synlett 1994, 131.
Hudlicky, T.; Heard, N. E.; Fleming, A. J . Org. Chem. 1990, 55, 2570.
Molander, G. A.; Schubert, D. C. J . Am. Chem. Soc. 1986, 108, 4683
and references therein.
(4) Our results in this direction will be reported elsewhere.
(5) For a review, see: Trost, B. M. Angew. Chem., Int. Ed. Engl.
1986, 25, 1.
(6) Shimizu, I.; Ohashi, Y.; Tsuji, J . Tetrahedron Lett. 1984, 25, 5183.
Breuilles, P.; Uguen, D. Tetrahedron Lett. 1988, 29, 201. Trost, B. M.;
Mignani, S. M.; Nanninga, T. N. J . Am. Chem. Soc. 1988, 110, 1602.
Trost, B. M.; Seoane, P.; Mignani, S.; Acemoglu, M. J . Am. Chem. Soc.
1989, 111, 7487.
(7) For this term, see: Little, D. R.; Dawson, J . R. Tetrahedron Lett.
1980, 21, 2609.
(8) Ghera, E.; Yechezkel, T.; Hassner, A. J . Org. Chem. 1993, 58,
6717.
(9) Yechezkel, T.; Ghera, E.; Ostercamp, D.; Hassner, A. J . Org.
Chem. 1995, 60, 5135.
(10) For a preliminary report of a part of this work, see: Ghera, E.;
Yechezkel, T.; Hassner A. Tetrahedron Lett. 1990, 25, 3653.
(11) Subsequent to our preliminary report (ref 10), a MIRC process
involving the dilithiated chloro analog of 1 was reported to give
stereomeric mixtures of methylcyclopentenes: Najera, C.; San Sano,
J . Mo. Tetrahedron 1994, 50, 3491.
S0022-3263(96)00089-8 CCC: $12.00 © 1996 American Chemical Society

4960 J . Org. Chem., Vol. 61, No. 15, 1996
Ghera et al.
Ta ble 1. Cyclop en ta n a tion s by Rea ction of 1 w ith
Ta ble 2. Rea ction s of 8 w ith (E) En oa tes (9a ,b).
Acyclic (E) Accep tor s
In flu en ce of HMP A on th e Dia ster eom er ic Ra tioa
a
Standard reaction conditions (-95 °C, 15 min) were used
b
except for entry 4 (-95 to -70 °C, 30 min). 24% of unreacted
ethyl cinnamate was recovered.
dence (absence of alternative vinylic protons in the
spectrum of the crude products, with 1% limit of detec-
tion).
In order to rationalize the anti-diastereoselective12
outcome of the initial conjugate addition step, the well-
documented sensitivity of Michael reactions to the steric
environment13 should be taken into account along with
chelation control in the transition state (TS), via coordi-
nation of the lithium counterion with the oxygens of the
sulfone and the carbonyl group.14
Ion pair dissociation, favored by addition of a solvating
agent (HMPA) to the reaction mixture, should provide
information about the influence of the chelation factor
in the TS, for instance, by significantly altering the
diastereomeric ratio of products. Since the lithiated
bromo sulfone 1 in THF solution was unstable in the
presence of HMPA, we examined the analogous methallyl
sulfone 8 in conjugate additions with ethyl (E)-crotonate
(9a ) and ethyl (E)-cinnamate (9b). Indeed, the anti/syn
diastereomeric ratio (10:11) was significantly affected in
the presence of HMPA, with the preference shifting
drastically in favor of the syn-diastereomer (Table 2). The
preponderance of a chelated TS was thus substantiated.
It is noteworthy that in the presence of HMPA the
conjugate addition of 8 to ethyl cinnamate, via a non-
additions occurred in a regioselective manner at the
R-phenylsulfonyl terminus of the allylic carbanion and
were characterized by complete stereoselectivity at the
three stereogenic centers of the resulting methylenecy-
clopentanes 2-7. The stereochemical assignments for
the stereohomogeneous products were made on the basis
of spectral evidence and consistent NOE data shown in
eq 1. The presence of additional substitution in the
acceptor, leading to the tetrasubstituted methylenecy-
clopentane derivative 7 (entry 6), did not affect the
effectivity and stereoselectivity of the cyclopentanation.
Open-chain intermediates formed in the conjugate addi-
tion step could not be detected even when we attempted
to slow down the ring closure, e.g., by addition of hexane
to the reaction mixture. Similarly, very fast quenching
of the reaction at low temperature provided solely cy-
clized product 2-7 together with unreacted sulfone 1. It
can therefore be assumed that the ring closure step
occurs faster than the rate-determining Michael addition
to form b (eq 1). The formation of trans-trans products
2-6 requires that the first step, Michael addition to a,
lead to the anti12 diastereomer of b. The outcome of the
ring closure step to c can be thermodynamically rational-
ized. The complete stereoselectivity in these high-yield
cyclopentanations was substantiated by 1H NMR evi-
(12) Syn and anti designations are based on the extended form
including both anion-stabilizing groups (SO2 and CdO). See: Oare,
D. A.; Heathcock, C. H. In Topics in Stereochemistry; Eliel, E. L., Wilen,
S. H., Eds.; Wiley: New York, 1989; Vol. 19, p 227. In an early report
(ref 10) we made opposite designations for syn and anti. For monocyclic
products (such as 15), the designations erythro and threo have been
used in order to avoid misunderstandings.
(13) Chapdelaine, M. J .; Hulce, M. Org. React. 1990, 38, 225.
(14) Binns, M. R.; Haynes, R. K.; Katsifis, A. G.; Schober, P. A.;
Vonwiller, S. C. J . Org. Chem. 1989, 54, 1960.

Synthesis of Methylenecyclopentanes
J . Org. Chem., Vol. 61, No. 15, 1996 4961
Sch em e 1.a Ba se-In d u ced Rea ction of 1 w ith
Dieth yl Ma lea te
F igu r e 1.
chelated TS, is slower and less effective (entry 4) than
in the chelation-assisted addition (entry 3).
It is reasonable to assume that, as for sulfone 8, the
analogous reactions of bromo sulfone 1 with acyclic (E)
unsaturated carbonyl compounds likewise involve a
chelated TS. However, the chelation factor alone proved
insufficient to account for the stereochemical outcome of
conjugate additions involving 1 and 8, respectively.
Thus, consideration of the four “cyclic” TS (A-D, Figure
1) leads at first glance to the conclusion that the TS (C)
should be the sterically favored one, having anti-
positioned hydrogens at the two vicinal stereocenters.
However, (C) leads to the syn-diastereomer. The pref-
erential formation (as in 10a ) or the sole formation (as
in 10b and 2-7) of the anti-diastereomer can be rational-
ized by considering an additional factor, namely, a
secondary orbital interaction involving a HOMO-LUMO
complex between the (E) enoate moiety and the allylic
anion in the transition state. Calculations have shown
that such interactions resulting from overlap of the two
π systems, may compensate for the repulsions due to a
hindered approach of reactants.15 Careful inspection of
models visualizes that such overlap takes place better
in TS (A) than in (D). Moreover, in TS (A) the “cisoid”
chelation with the counterion leading to anti-addition
should be favored over the “transoid” chelation in TS (D).
a
Reaction conditions: (a) -95 to -50 °C, 1 h; (b) -95 to -30
°C, 1.5 h.
The Li-O coordination can also have a negative
influence on the outcome of conjugate additions as
evidenced in reactions with (Z) enoates: in sharp contrast
to the effectivity of cyclopentanations with (E) acceptors,
the reactions of 1 with (Z)-crotonate and -cinnamate,
respectively, did not afford the desired conjugate adducts
and resulted mainly in polymerization. The association
of the lithiated reagent with the ester group is probably
hindering the conjugate attack on the same (R-substi-
tuted) face of the double bond. The reaction of 1 with
diethyl maleate led however to cyclopentanation (Scheme
1): chelation involving the sulfone and one of the
carboxylate groups facilitates the attack on the unsatur-
ated carbon nearest to the site of chelation with a
resulting cis-relationship between the phenylsulfonyl
group and the vicinal carboxylate (15% NOE for the
related protons in 13). The minor product (5) probably
results from equilibration: increase in the time and
F igu r e 2. Conformational and stereochemical data for com-
pounds 14 and 17-20.
temperature of the reaction resulted in more equilibra-
tion to 5, as shown in Scheme 1. The ring closure to 13
is not as rapid as for (E) enoates and the open-chain
adduct 12 also was isolated. Its tentatively assigned
stereochemistry can be anticipated because the other
diastereomer would close at once to 5, as observed in
reactions of 1 with diethyl fumarate (Table 1, entry 4).
The conjugate addition step in the reactions sum-
marized in Table 1 seems kinetically controlled because
under the given reaction conditions neither base-induced
equilibration nor a retro-Michael reaction should account
(15) Sevin, A.; Tortajada, J .; Pfau, M. J . Org. Chem. 1986, 51, 2671.

4962 J . Org. Chem., Vol. 61, No. 15, 1996
Ta ble 3. Cyclop en ta n n u la tion s by Rea ction of 1 w ith Cyclic Accep tor s
Ghera et al.
for the formation of a sole diastereomer. Hence the slow
equilibration observed for 13 f 5 (Scheme 1, b).
Cyclopentanations of unsaturated lactones (entries 3
and 4, Table 3) were more effective and afforded 18 and
20, respectively, as the major products. The trans-fusion
for 18 as well as the expected cis-fusion in 20 was secured
by NOE data (Figure 2). Threo-configuration was as-
signed for the minor adduct 19 (Figure 2) and for 22 (by
analogy).
Cyclop en ta n a tion w ith Cyclic Accep tor s. Cy-
cloalkenones and R,â-unsaturated lactones reacted in a
similar manner by a MIRC process with bromo sulfone
1 to afford bicyclic products (Table 3). The regiochemical
outcome, such as with acyclic acceptors, is characterized
by the conjugate addition of the allylic carbanion reacting
primarily from the R-terminus of the allyl sulfone, except
for the case when the hindering group on the acceptor
(4,4-dimethoxycyclohexadienone, entry 2) forced the ad-
dition via the less hindered γ-terminus to provide 17, a
potentially interesting synthetic intermediate. The ster-
eochemical assignments for 17 rely on NOE data (Figure
2). Previously reported reactions of other allylic sulfones
with cyclohexenone at low temperature and in the
absence of HMPA afforded mainly 1,2-carbonyl addition
products.14,16 We did not detect such products, but the
selectivity of this conjugate addition was not as high as
with acyclic acceptors: along with 14, originating from
the cyclization of the erythro-diastereomeric adduct,
minor amounts of open-chain adduct 15, with the tenta-
tively assigned threo-configuration,12,17 and of the vinylic
sulfone 16 (a γ-adduct) were also isolated. The assigned
cis-fusion for the hydrindanone derivative 14 (entry 1)
is based on NOE data (Figure 2).
As mentioned for acyclic acceptors, the Z geometry of
the double bond should make the intermediacy of a cyclic
TS in which the sulfone and carbonyl oxygens are
coordinated via the lithium counterion more difficult, and
the same should hold for (Z) double bonds in cyclic
systems. Haynes and co-workers14 assumed that an
“extended” ten-membered cyclic TS (via γ-attack) is
conformationally less viable for conjugate additions of
allylic sulfones to cyclohexenone than to cyclopentenone.
An eight-membered transition state, as required for the
formation of adducts 14, 15, and 18-22, via an R-attack,
would appear even more hindered. We assume, there-
fore, that steric effects and MO interactions (π-π attrac-
tion) are largely responsible for the stereochemical
outcome of conjugate additions with cyclic acceptors. The
TS (E), which is less hindered than (F), leads to the
prevalence of the erythro-diastereomer (Figure 3).
The role of possible Li-O coordination in the above
reactions was examined by using again methallyl sulfone
8 as the donor which enables the conjugate additions to
be carried out in the presence of HMPA (Table 4).
Interestingly, only 25% of adducts along with recovered
(16) Hirama, M. Tetrahedron Lett. 1981, 22, 1905.
(17) Steric obstruction between the cyclohexane ring and the phen-
ylsulfonyl group probably prevent the cyclization of 15.

Synthesis of Methylenecyclopentanes
J . Org. Chem., Vol. 61, No. 15, 1996 4963
F igu r e 3.
Ta ble 4. In flu en ce of HMP A on th e Ou tcom e of
Rea ction s of 8 w ith Cyclic Accep tor sa
F igu r e 4. Stereochemical Data for Compounds 23a ,b and
25a ,b
assignments for 23a ,b and 25a ,b (Figure 4) are based
on NOE data in conjunction with J values: diaxial
coupling (J 1,2 ) 12 Hz) and anti-arrangement of the
protons at the stereogenic centers (H-2 and CHSO2Ph,
see Experimental Section for the corresponding J values).
Con clu sion
The foregoing results of base-induced additions of
allylic bromo sulfone 1 to acyclic (E) enoates and enones
demonstrate that the cyclopentanations leading to trisub-
stituted methylenecyclopentanes via anti-adducts take
place with excellent effectivity and diastereoselectivity.
Molecular orbital π-π interactions need to be taken into
account along with a “cyclic” chelated transition state in
order to rationalize the anti-diastereoselectivity observed
in the conjugate addition step. Reactions of a halogen-
devoid analog of 1, namely, methallyl sulfone 8 with (E)
enoates, in the presence of HMPA, gave rise to drastic
changes of the diastereomeric ratio, thus confirming the
role of chelation. Although the (Z) geometry of acyclic
acceptors proved unfavorable for performing the studied
Michael additions, cyclopentanations were successful
when cyclohexenone and R,â-unsaturated lactones were
used as the acceptors for 1. The presence of the ad-
ditional oxygen in lactones had a favorable effect on the
yields of additions involving 1 and 8, respectively.
a
All reactions were conducted under the same conditions (-95
°C, 20 min).
Exp er im en ta l Section
starting material were obtained in the reaction with
cyclohexenone (entry 1), whereas in the presence of
HMPA and under the same conditions this reaction was
found as effective as previously reported for propenyl
sulfone.16 Adduct 23 was obtained as a 3:1 erythro/ threo
mixture of diastereomers 23a and 23b. In contrast to
cyclohexenone, the yields obtained in the reaction with
5,6-dihydro-2-pyranone (entries 3 and 4) revealed only
slight dependence on the presence or absence of HMPA,
although differences in the ratio of diastereomers 25a
and 25b were observed. The improvement of reactivity
in the latter reaction due to Li coordination with the
noncarbonylic oxygen seems therefore minimal. How-
ever, the presence of ring oxygen in an enone has been
shown previously to improve reactivity in conjugate
additions18 due to the lowering of the LUMO energy by
interaction with the π system.19 The stereochemical
General experimental techniques and analytical measure-
ments were applied as previously described.20 Melting points
are uncorrected. Mass spectra (CI) were recorded at 60 eV.
Methallyl sulfone 8 was prepared as reported.21 Reactions
with cooling at -95 °C were performed using a mixture of
liquid nitrogen and MeOH.
2-(Br om om eth yl)-3-(p h en ylsu lfon yl)-1-p r op en e (1). A
mixture containing 2-(chloromethyl)-3-(phenylsulfonyl)-1-pro-
pene22 (5 g, 0.02 mol) and sodium bromide (2.06 g, 0.02 mol)
in 120 mL of 2:1 (v/v) DMF:CH2Br2 was stirred overnight at
100 °C (external temperature, preheated oil bath). After
removal of the solvents under reduced pressure, the residue
was dissolved in CH2Cl2. The organic layer washed with water
(3 × 50 mL) and brine, dried over MgSO4, and evaporated
under reduced pressure to give a white solid. Recrystallization
(19) Frazer-Reid, B.; Underwood, R.; Osterhout, M.; Grossman, J .
A.; Liotta, D. L. J . Org. Chem. 1986, 51, 2152.
(20) Ghera, E.; Yechezkel, T.; Hassner, A. J . Org. Chem. 1990, 55,
5977.
(18) Frazer-Reid, B.; Holder, N. L.; Hicks, D. R.; Walker, D. L. Can.
J . Chem. 1977, 55, 3986.
(21) Trost, B. H.; Schmuff, N. S. J . Am. Chem. Soc. 1985, 107, 396.
(22) Breuilles, P.; Uguen, D. Tetrahedron Lett. 1987, 28, 6053.

4964 J . Org. Chem., Vol. 61, No. 15, 1996
Ghera et al.
(diisopropyl ether) gave the pure product (1), stable at ambient
temperature (4.4 g, 80%): mp 53 °C; 1H NMR δ 7.99-7.82 (m,
2H), 7.74-7.49 (m, 3H), 5.49 (s, 1H), 5.00 (s, 1H), 4.13 (s, 2H),
3.79 (s, 2H); 13C NMR δ 137.95 (s), 133.88 (d), 133.71 (s), 129.08
(d, 2 × CH), 128.23 (d, 2 × CH), 124.45 (t), 59.65 (t), 35.02 (t);
MS (CI/NH3) m/z 294, 292 (MNH4+, 100, 98), 248 (8).
116.27 (t), 70.10 (d), 61.58 (t), 61.20 (t), 48.70 (d), 47.23 (d),
38.21 (t), 14.11 (q) 13.94 (q); MS (CI/CH4) m/z 367 (MH+, 100),
321 (16), 293 (26), 225 (19). Anal. Calcd for C18H22O6S: C,
59.00; H, 6.05; S, 8.75. Found: C, 58.73; H, 5.87; S, 8.45.
(1â,2r,3â)-1-Acetyl-2-m eth yl-4-m eth ylen e-3-(p h en ylsu l-
fon yl)cyclop en t a n e (6). Elution: EtOAc/petroleum ether
1:2. 6: mp 137-139 °C; 1H NMR δ 7.94-7.87 (m, 2H), 7.70-
7.62 (m, 1H), 7.60-7.51 (m, 2H), 5.25 (t, J ) 2 Hz, 1H), 5.11
(t, J ) 1.5 Hz, 1H), 3.58 (dq, J ) 8, 2 Hz, 1H), 2.85 (d quin, J
) 10, 7 Hz, 1H), 2.58-2.41 (m, 2H), 2.31-2.15 (m, 1H), 2.12
(s, 3H), 1.02 (d, J ) 7 Hz, 3H); 13C NMR δ 207.03 (s), 141.70
(s), 137.17 (s), 133.66 (d), 129.49 (d, 2 × CH), 128.85 (d, 2 ×
CH), 115.35 (t), 74.69 (d), 58.65 (d), 38.11 (t), 37.92 (d), 28.94
(q), 19.73 (q); MS (CI/isobutane) m/z 296 (M[H2O]+, 44), 279
(MH+, 100).
Eth yl (1r,1â,2r,3â)-3-(P h en ylsu lfon yl)-2-(eth oxyca r bo-
n yl)-1R-m eth yl-4-m eth ylen ecyclopen ta n eca r boxyla te (7).
Elution: EtOAc/petroleum ether 1:4. 7: 1H NMR δ 7.95-7.89
(m, 2H), 7.69-7.62 (m, 1H), 7.59-7.51 (m, 2H), 5.33 (ddd, J
) 3, 2, 1 Hz, 1H), 5.28 (ddd, J ) 3, 1.5, 0.5 Hz, 1H), 4.56 (dqd,
J ) 8.5, 2, 0.5 Hz, 1H), 4.23, 4.14 (ABq of q, J gem ) 10.5 Hz,
J vic ) 7 Hz, 2H), 4.04, 3.95 (ABq of q, J gem ) 10.5 Hz, J vic ) 7
Hz, 2H), 4.01 (d, J ) 8.5 Hz, 1H), 2.76 (dqq, J ) 14.5, 2, 0.8
Hz, 1H), 2.24 (d, J ) 14 Hz, 1H), 1.27 (t, J ) 7 Hz, 3H), 1.14
(t, J ) 7 Hz, 3H), 1.00 (s, 3H); 13C NMR δ 173.64 (s), 169.48
(s), 140.03 (s), 137.14 (s), 133.84 (d), 129.64 (d, 2 × CH), 128.94
(d, 2 × CH), 116.82 (t), 68.04 (d), 61.35 (t), 61.29 (t), 53.11 (d),
50.29 (s), 47.28 (t), 17.80 (q), 14.14 (q), 14.06 (q); MS (CI/CH4)
m/z 381 (MH+, 100), 335 (21), 307 (15), 239 (39), 165 (15). Anal.
Calcd for C19H24O6S: C, 59.99; H, 6.36; S, 8.43. Found: C,
59.84; H, 6.26; S, 8.35.
Rea ction s of Br om o Su lfon e 1 w ith (E) Un sa tu r a ted
Acyclic Ca r bon yl Com p ou n d s. Gen er a l P r oced u r e. To
a stirred solution of LDA, prepared at 0 °C from 0.17 mL (1.3
mmol) of diisopropylamine and 0.83 mL of n-BuLi (1.25 mmol,
1.5 M solution in hexane) in 5.5 mL of THF, was added
dropwise at -95 °C a solution of 1 (385 mg, 1.4 mmol)23 in 4.5
mL of THF. After the solution was stirr for 10 min at the
above temperature, the unsaturated carbonyl compound was
added (1 mmol) in 2.3 mL of THF. After completion of the
reaction (see Table 1), the reaction mixture was quenched with
aqueous (20%) AcOH, poured into water, and extracted with
CH2Cl2. The extracts were washed successively with saturated
NaHCO3 solution and water, dried (MgSO4), and evaporated
under reduced pressure. All the products were purified by
column chromatography over silica gel to afford the yields
indicated in Table 1.
Eth yl (1â,2r,3â)-2-Meth yl-4-m eth ylen e-3-(p h en ylsu lfo-
n yl)cyclop en ta n eca r boxyla te (2). Elution: EtOAc/petro-
leum ether 1:3. 2: 1H NMR δ 7.98-7.79 (m, 2H), 7.75-7.65
(m, 1H), 7.60-7.50 (m, 2H), 5.25 (ddt, J ) 3, 2, 1 Hz, 1H),
5.13 (ddt, J ) 3, 2, 1 Hz, 1H), 4.17 (q, J ) 7 Hz, 2H), 3.61 (dq,
J ) 7, 2 Hz, 1H), 2.81 (ddqd, J ) 10, 8, 7, 0.5 Hz, 1H), 2.55-
2.30 (m, 3H), 1.28 (t, J ) 7 Hz, 3H), 1.13 (d, J ) 7 Hz, 3H);
13C NMR δ 172.75 (s), 141.79 (s), 137.07 (s), 133.77 (d), 129.69
(d, 2 × CH), 128.92 (d, 2 × CH), 115.45 (t), 74.53 (d), 60.77 (t),
50.79 (d), 39.67 (d), 38.19 (t), 19.60 (q), 14.20 (q); MS (CI/CH4)
m/z 309 (MH+, 55), 263 (100), 169 (60). Anal. Calcd for
C16H20O4S: C, 62.31; H, 6.54. Found: C, 62.57; H, 6.62.
Eth yl (1â,2r,3â)-4-Meth ylen e-3-(p h en ylsu lfon yl)-2-p r o-
p ylcyclop en ta n eca r boxyla te (3). Elution: EtOAc/petro-
leum ether 1:5. 3: 1H NMR δ 7.95-7.86 (m, 2H), 7.70-7.62
(m, 1H), 7.59-7.51 (m, 2H), 5.19 (td, J ) 3, 1.5 Hz, 1H), 4.97
(td, J ) 3, 1.5 Hz, 1H), 4.17, 4.10 (ABq of q, J gem ) 10.5 Hz,
J vic ) 7 Hz, 2H), 3.60 (dq, J ) 6, 1.5 Hz, 1H), 2.97 (quin d, J
) 7, 2 Hz, 1H), 2.55-2.33 (m, 3H), 1.51-1.40 (m, 2H), 1.24 (t,
Rea ction s of Meth a llyl Su lfon e 8 w ith Eth yl Cr oton a te
(9a ) (Table 2).24 To a stirred solution of LDA, prepared from
0.13 mL (0.99 mmol) of diisopropylamine and 0.63 mL of
n-BuLi (0.95 mmol, 1.5 M solution in hexane) in 4 mL of THF,
was added dropwise at -95 °C a solution of methallyl phenyl
sulfone (8) (207 mg, 1.06 mmol) in 3.5 mL of THF. After 10
min, ethyl crotonate (86 mg, 0.75 mmol) in 2 mL of THF was
added and stirring was continued for 20 min at the above
temperature. Quenching (20% aqueous AcOH) and extraction
(CH2Cl2) as before was followed by evaporation under reduced
pressure. The diastereomeric ratio (10a /11a , 5.5:1) was
J ) 7 Hz, 3H), 1.32-1.18 (m, 2H), 0.85 (t, J ) 7.5 Hz, 3H); 13
C
1
NMR δ 177.33 (s), 142.24 (s), 136.92 (s), 133.54 (d), 129.62 (d,
2 × CH), 128.69 (d, 2 × CH), 115.24 (t), 73.91 (d), 60.60 (t),
49.10 (d), 43.25 (d), 38.12 (t), 37.50 (t), 19.71 (t), 13.96 (q), 13.79
(q); MS (CI/CH4) m/z 337 (MH+, 100), 291 (79), 263 (53), 195
(68). Anal. Calcd for C18H24O4S: C, 64.26; H, 7.19; S, 9.53.
Found: C, 63.98; H, 6.99; S, 9.71.
established by the integration of the H NMR spectrum of the
crude mixture. Chromatographic purification on silica gel
(EtOAc/petroleum ether 1:5) gave an inseparable mixture of
10a and 11a (83%). The above reaction was repeated under
identical conditions by adding HMPA (0.4 mL in 0.2 mL of
THF) to the reaction mixture (10 min after the addition of 8),
prior (5 min) to ethyl crotonate. After extraction with Et2O,
Eth yl (1â,2r,3â)-4-m eth ylen e-2-p h en yl-3-(p h en ylsu lfo-
n yl)cyclop en ta n eca r boxyla te (4). Elution: EtOAc/petro-
leum ether 1:5. 4: 1H NMR δ 7.82-7.76 (m, 2H), 7.58-7.50
(m, 1H), 7.46-7.38 (m, 2H), 7.20-7.09 (m, 3H), 7.01-6.94 (m,
2H), 5.35 (dt, J ) 2, 1 Hz, 1H), 5.19 (dt, J ) 3, 1.5 Hz, 1H),
4.14 (qd, J ) 7, 2 Hz, 1H), 4.04 (qd, J ) 7, 1 Hz, 2H), 3.93 (dd,
J ) 10, 7 Hz, 1H), 2.91 (ddd, J ) 12, 10, 7 Hz, 1H), 2.81-2.61
(m, 2H), 1.13 (t, J ) 7 Hz, 3H); 13C NMR δ 172.18 (s), 141.71
(s), 141.19 (s), 137.28 (s), 133.60 (d), 129.28 (d, 2 × CH), 128.83
(d, 2 × CH), 128.54 (d, 2 × CH), 127.29 (d, 2 × CH), 126.99
(d), 115.72 (t), 75.09 (d), 60.80 (t), 52.29 (d), 49.66 (d), 38.68
(t), 14.08 (q); MS (EI) m/z 371 (MH+, 4), 325 (6), 228 (76), 155
(100).
1
the integration of the H NMR of the crude mixture showed a
1:1.5 ratio of 10a :11a . Chromatographic purification gave 80%
of the diastereomeric mixture.
Rea ction s of Meth a llyl Su lfon e 8 w ith Eth yl Cin -
n a m a te (9b) (Table 2). The reaction of 8 with 9b following
the procedure and amounts as described for ethyl crotonate
(9a ) gave a sole product (TLC, 1H NMR). Chromatographic
purification (EtOAc/petroleum ether 1:5) gave eth yl 5-m eth yl-
3-p h en yl-4-(p h en ylsu lfon yl)-5-h exen oa t e (10b; anti)
(87%): mp 132-134 °C; 1H NMR δ 7.52-7.41 (m, 3H), 7.34-
7.25 (m, 2H), 7.09 (s, 5H), 5.30-5.25 (m, 2H), 4.05 (d, J ) 9
Hz, 1H), 3.97 (td, J ) 9.5, 3.5 Hz, 1H), 3.91 (ABq of q, J gem
)
E t h yl (1â,2r,3â)-2-(E t h oxyca r b on yl)-4-m et h ylen e-3-
(p h en ylsu lfon yl)cyclop en ta n eca r boxyla te (5). Elution:
EtOAc/petroleum ether 1:4. 5: mp 56-58 °C; 1H NMR δ 7.96-
7.89 (m, 2H), 7.70-7.63 (m, 1H), 7.60-7.53 (m, 2H), 5.32 (td,
J ) 2, 1 Hz, 1H), 5.21 (td, J ) 2, 1 Hz, 1H), 4.44 (dq, J ) 7, 2
10 Hz, J vic ) 7 Hz, 2H), 2.91 (dd, J ) 16, 3.5 Hz, 1H), 2.61
(ddd, J ) 16, 9.5, 1.5 Hz, 1H), 1.80 (t, J ) 1 Hz, 3H), 1.03 (t,
J ) 7 Hz, 3H); 13C NMR δ 170.86 (s), 140.18 (s), 139.09 (s),
136.63 (s), 132.70 (d), 128.55 (d, 4 × CH), 128.95 (d, 2 × CH),
128.16 (d, 2 × CH), 127.30 (d), 121.10 (t), 75.91 (d), 60.38 (t),
41.06 (d), 38.94 (t), 22.47 (q), 13.97 (q); MS (CI/NH3) m/z 390
(MNH+4, 100), 373 (MH+, 5). Anal. Calcd for C21H24O4S: C,
67.71; H, 6.49. Found: C, 67.87; H, 6.46. The dominant
conformer of 10b, with anti-arranged methine hydrogens (J
) 9 Hz), exhibits 3% and 2% NOE at -CH2CO2Et upon
irradiation of the methyl and vinyl hydrogens, respectively.
Hz, 1H), 4.17 (q, J ) 7 Hz, 2H), 4.04, 3.96 (ABq of q, J gem
)
10.5 Hz, J vic ) 7 Hz, 2H), 3.69 (dd, J ) 10, 7 Hz, 1H), 2.93
(ddd, J ) 12, 10, 7 Hz, 1H), 2.67 (bdd, J ) 15, 7 Hz, 1H), 2.59
(ddq, J ) 15, 12, 2 Hz, 1H), 1.25 (t, J ) 7 Hz, 3H), 1.14 (t, J
) 7 Hz, 3H); 13C NMR δ 171.72 (s), 171.34 (s), 140.18 (s),
136.98 (s), 133.92 (d), 129.59 (d, 2 × CH), 129.01 (d, 2 × CH),
(23) An excess of 1 was found necessary in order to prevent the
formation of small amounts of a 1:2 donor/acceptor adduct originating
from a Michael-Michael reaction.
(24) The reactions of 8 with 9a were previously performed under
different conditions; see ref 8 for configurational, spectroscopic, and
analytical data of 10a and 11a .

Synthesis of Methylenecyclopentanes
J . Org. Chem., Vol. 61, No. 15, 1996 4965
Methallyl sulfone 8 was reacted with ethyl cinnamate (9b) in
the presence of HMPA under the conditions and amounts given
for ethyl crotonate. The reaction mixture was allowed to warm
to -70 °C during 30 min. Workup as described earlier and
1H NMR integration of the crude mixture showed a 1:4 ratio
of 10b:11b. Chromatographic purification (EtOAc/petroleum
ether 1:5) gave by order of elution unreacted ethyl cinnamate
(24%), 11b (45%), and 10b (10%).
(d, J ) 10.5 Hz, 1H), 3.70 (d, J ) 7.5 Hz, 1H), 3.56 (d, J ) 11
Hz, 1H), 3.02-1.44 (m, 9H). 16: 1H NMR δ 7.94-7.48 (m,
5H), 6.53 (s, 1H), 3.91 (s, 2H), 3.02-1.44 (m, 11H).
MS (15 + 16): CI (NH3) m/z 390, 388 (MNH4+, 100, 85),
308 (87).
Rea ction w ith 4,4-Dim eth oxy-2,5-cycloh exa d ien -1-on e.
Purification by column chromatography (EtOAc/petroleum
ether 2:3) gave (1â,6â-5,5-d im eth oxy-8-[((Z)-(p h en ylsu lfo-
n yl)m eth ylen e]bicyclo[4.3.0]n on -3-en -2-on e (17), 65%, mp
11b (syn): mp 157-159 °C; 1H NMR 7.88-7.83 (m, 2H),
7.64-7.57 (m, 1H), 7.55-7.46 (m, 2H), 7.25-7.13 (m, 5H), 4.72
(bs, 1H), 4.69 (ddd, J ) 2, 1, 0.5 Hz, 1H), 4.15 (d, J ) 11 Hz,
1H), 3.98 (td, J ) 10, 4 Hz, 1H), 3.95 (ABq of q, J gem ) 10 Hz,
J vic ) 7 Hz, 2H), 3.59 (dd, J ) 15.5, 4 Hz, 1H), 2.97 (dd, J )
15.5, 10 Hz, 1H), 1.29 (dd, J ) 1.5, 1 Hz, 3H), 1.07 (t, J ) 7
Hz, 3H); 13C NMR δ 171.06 (s), 140.35 (s), 138.99 (s), 137.61
(s), 133.40 (d), 129.12 (d, 2 × CH), 128.71 (d, 2 × CH), 128.56
(d, 2 × CH), 128.13 (d, 2 × CH), 127.02 (d), 121.38 (t), 75.16
(d), 60.20 (t), 41.61 (d), 40.31 (dd), 21.19 (q), 14.02 (q); MS (CI/
NH3) m/z 390 (MNH4+, 100), 373 (MH+, 13); on irradiation of
CH3 protons, a 10% NOE was observed at the phenyl group;
upon irradiation of the ortho proton of the PhSO2 group a 2%
NOE was exhibited at CH2COOEt.
Rea ction of Br om o Su lfon e 1 w ith Dieth yl Ma lea te.
The reaction was performed under conditions shown for 2-7,
and then the mixture was allowed to warm from -95 to -50
°C during 1 h. Workup as described earlier and chromato-
graphic purification (EtOAc/petroleum ether 1:3) gave by order
of elution 12, 13, and 5.
Eth yl 5-(br om om eth yl)-3-(eth oxyca r bon yl)-4-(p h en yl-
su lfon yl)-5-h exen oa te (12, syn , 11%): mp 93-95 °C; 1H
NMR δ 7.87-7.80 (m, 2H), 7.70-7.62 (m, 1H), 7.58-7.49 (m,
2H), 5.62 (s, 1H), 5.60 (bs, 1H), 4.32 (d, J ) 8 Hz, 1H), 4.24-
4.15 (m, 4H), 3.75 (s, 2H), 3.50 (ddd, J ) 10, 8, 4 Hz, 1H), 3.23
(dd, J ) 17, 4 Hz, 1H), 3.12 (dd, J ) 17, 10 Hz, 1H), 1.28 (t, J
) 7 Hz, 3H), 1.25 (t, J ) 7 Hz, 3H); 13C NMR δ 171.15 (s),
170.79 (s), 137.29 (s), 136.60 (s), 134.21 (d), 129.52 (d, 2 × CH),
128.99 (d, 2 × CH), 124.06 (t), 67.21 (d), 61.63 (t), 60.90 (t),
42.57 (d), 35.33 (t), 34.28 (t), 14.16 (q), 13.96 (q); MS m/z 449,
447 (MH+, 21, 19), 403, 401 (100, 95), 225 (95).
1
87-89 °C; H NMR δ 7.88-7.81 (m, 2H), 7.63-7.57 (m, 1H),
7.55-7.46 (m, 2H), 6.74 (dd, J ) 10, 2 Hz, 1H), 6.22 (dddd, J
) 3.5, 3, 2, 1.5 Hz, 1H), 6.00 (d, J ) 10 Hz, 1H), 3.32 (s, 3H),
3.29 (s, 3H), 3.27 (dddtd, J ) 19, 8, 2, 1.5, 0.5 Hz, 1H), 3.11
(dq, J ) 18, 1.5 Hz, 1H), 2.96 (td, J ) 11, 2.5 Hz, 1H), 2.91
(ddt, J ) 9, 6.5, 1.5 Hz, 1H), 2.64 (ddt, J ) 18, 8, 2.5 Hz, 1H),
2.50 (ddt, J ) 19, 11, 2.5 Hz, 1H); 13C NMR δ 198.31 (s), 159.44
(s), 146.80(d), 141.57 (s), 133.07 (d), 129.65 (d), 129.02 (d, 2 ×
CH), 126.90 (d, 2 × CH), 123.02 (d), 97.49 (s), 49.36 (q), 48.08
(q), 46.00 (d), 45.65 (d), 38.29 (dd), 31.37 (dd); MS (CI/NH3)
m/z 366 (MNH4+, 35), 334 (95), 317 (100).
Rea ction w ith 5,6-Dih yd r o-2H-p yr a n -2-on e. Chromato-
graphic purification of the crude mixture (EtOAc/petroleum
ether 1:1) gave by order of elution 19 and then 18.
(4a r,5r,7a â)-6-Met h ylen e-5-(p h en ylsu lfon yl)h exa h y-
d r ocyclop en ta [c]p yr a n -1-on e (18), 66%: mp 126-128 °C;
1H NMR δ 7.92-7.86 (m, 2H), 7.72-7.65 (m, 1H), 7.62-7.53
(m, 2H), 5.25 (dt, J ) 3, 2 Hz, 1H), 4.81 (dt, J ) 3, 2Hz, 1H),
4.32 (ddd, J ) 11.5, 4.5, 3.5 Hz, 1H), 4.24 (ddd, J ) 11.5, 11,
2.5 Hz, 1H), 3.71 (dq, J ) 4, 1.5 Hz, 1H), 3.35 (tdd, J ) 9.5, 7,
4 Hz, 1H), 3.16 (td, J ) 9, 4.5 Hz, 1H), 2.88, (ddt, J ) 16.5,
4.5, 1.5 Hz, 1H), 2.81 (ddtd, J ) 16.5, 9, 2.5, 1.5 Hz, 1H), 2.07
(dddd, J ) 14.5, 7, 4.5, 3.5 Hz, 1H), 1.65 (dddd, J ) 14.5, 11,
10, 4.5 Hz, 1H); 13C NMR δ 171.95 (s), 140.60 (s), 136.50 (s),
134.11 (d), 129.33 (d, 2 × CH), 129.11 (d, 2 × CH), 117.02 (t),
75.44 (d), 66.80 (t), 41.83 (d), 37.80 (t), 35.55 (t), 28.48 (t); MS
(CI/NH3) m/z 310 (MNH4+, 100), 293 (MH+, 56), 151 (7). Anal.
Calcd for C15H16O4S: C, 61.63; H, 5.51. Found: C, 61.78; H,
5.49.
(3′S*,4S*)-4-[2′-(Br om om et h yl)-3′-(p h en ylsu lfon yl)-1′-
p r op en -3′-yl]tetr a h yd r o-2H-p yr a n -2-on e (19), 12%, color-
less oil: 1H NMR δ 7.88-7.79 (m, 2H), 7.73-7.65 (m, 1H),
7.65-7.52 (m, 2H), 5.65 (bs, 1H), 5.41 (s, 1H), 4.44 (ddd, J )
11.5, 4.5, 3.5 Hz, 1H), 4.23 (td, J ) 11, 3.5 Hz, 1H), 3.77 (dd,
J ) 11, 1 Hz, 1H), 3.72 (d, J ) 9 Hz, 1H), 3.44 (dd, J ) 11, 1
Hz, 1H), 3.27 (ddd, J ) 17, 5, 2 Hz, 1H), 2.80 (tddd, J ) 11, 9,
5.5, 4.5 Hz, 1H), 2.65 (dd, J ) 17.5, 10.5 Hz, 1H), 2.14 (ddtd,
J ) 13.5, 7, 3.5, 2 Hz, 1H), 1.82 (dtd, J ) 13.5, 11, 5 Hz, 1H);
13C NMR δ 169.09 (s), 137.60 (s), 136.58 (s), 134.34 (d), 129.45
(d, 2 × CH), 129.23 (d, 2 × CH), 124.15 (t), 71.41 (d), 67.89 (t),
36.48 (t), 35.78 (dd), 32.25 (d), 27.15 (t); MS (CI/NH3) m/z 392
(MNH4+, 100), 374 (MH+, 0.5), 346 (6), 312 (8).
E t h yl (1r,2â,3â)-2-(et h oxyca r b on yl)-4-m et h ylen e-3-
(p h en ylsu lfon yl)cyclop en ta n eca r boxyla te (13, 46%): mp
1
92-94 °C; H NMR δ 7.89-7.83 (m, 2H), 7.68-7.61 (m, 1H),
7.58-7.49 (m, 2H), 5.12 (td, J ) 2.5, 1.5 Hz, 1H), 4.85 (td, J )
2.5, 1.5 Hz, 1H), 4.35 (dq, J ) 7, 1 Hz, 1H), 4.19, 4.05 (ABq of
q, J gem ) 10.5 Hz, J vic ) 7 Hz, 2H), 4.12 (q, J ) 7 Hz, 2H), 3.70
(ddd, J ) 12, 11, 9 Hz, 1H), 3.55 (dd, J ) 12, 7 Hz, 1H), 2.92
(ddtd, J ) 17, 10.5, 2.5, 1.5 Hz, 1H), 2.39 (ddt, J ) 17, 9, 2.5
Hz, 1H), 1.27 (t, J ) 7 Hz, 3H), 1.23 (t, J ) 7 Hz, 3H); 13C
NMR δ 173.51 (s), 168.78 (s), 140.70 (s), 137.81 (s), 133.94 (d),
129.67 (d, 2 × CH), 128.78 (d, 2 × CH), 116.65 (t), 72.35 (d),
61.45 (t), 61.02 (t), 49.53 (d), 42.88 (d), 33.83 (t), 14.12 (q), 13.97
(q); MS (CI/isobutane) m/z 384 ([MH2O]+, 45), 367 (MH+, 100),
321 (15).
Rea ction w ith 2(5H)-F u r a n on e. Chromatographic pu-
rification of the crude mixture (EtOAc/petroleum ether 1:1)
gave by order of elution 22, 20, and 21.
Rea ction s of Br om o Su lfon e 1 w ith Cyclic Ca r bon yl
Com p ou n d s. The general reaction conditions are as shown
for acyclic acceptors. For reaction time and temperature, see
Table 3.
(3a â,6a â,4â)-5-Met h ylen e-4-(p h en ylsu lfon yl)h exa h y-
d r ocyclop en ta [c]fu r a n -1-on e (20), 69%: mp 134-136 °C;
1H NMR δ 7.90-7.85 (m, 2H), 7.73-7.66 (m, 1H), 7.62-7.54
(m, 2H), 5.20 (dtd, J ) 3, 1.5, 1 Hz, 1H), 4.70 (dtd, J ) 3, 1.5,
1Hz, 1H), 4.53 (dd, J ) 10, 7 Hz, 1H), 4.09 (dd, J ) 10, 3 Hz,
1H), 3.83 (qd, J ) 3, 1 Hz, 1H), 3.72 (tt, J ) 8, 3 Hz, 1H), 3.17
(td, J ) 9, 2 Hz, 1H), 2.90 (dddd, J ) 16, 9.5, 3, 2 Hz, 1H),
2.70 (ddd, J ) 16, 2, 1 Hz, 1H); 13C NMR δ 177.93 (s), 140.69
(s), 136.11 (s), 134.25 (d), 129.37 (d, 2 × CH), 129.14 (d, 2 ×
CH), 117.65 (t), 75.72 (d), 71.76 (t), 43.34 (d), 40.89 (d), 36.12
(t); MS (CI/NH3) m/z 575 (M2NH4+, 15), 296 (MNH4+, 100).
(3aâ,6aâ)-5-Meth yl-4-(ph en ylsu lfon yl)-3,3a,6,6a-tetr ah y-
d r o-1H-cyclop en ta [c]fu r a n -1-on e (21), 7%: mp 102-104
°C; 1H NMR δ 7.90-7.77 (m, 2H), 7.69-7.47 (m, 3H), 4.76 (dd,
J ) 11, 3 Hz, 1H), 4.42 (dd, J ) 11, 7.5 Hz, 1H), 3.96-3.82
(m, 1H), 3.13 (ddd, J ) 8, 7, 5 Hz, 1H), 2.93 (bd, J ) 6 Hz,
2H), 2.15 (bs, 3H); 13C NMR δ 178.87 (s), 156.47 (s), 141.58
(s), 134.49 (s), 133.60 (d), 129.44 (d, 2 × CH), 126.88 (d, 2 ×
CH), 70.97 (dd), 48.29 (d), 43.11 (t), 39.65 (d), 15.50 (q); MS
(CI/NH3) m/z 296 (MNH4+).
Rea ction w ith 2-Cycloh exen -1-on e. Purification of the
crude mixture of products by chromatography (EtOAc/petro-
leum ether 2:3) gave (by order of elution) a mixture of 15 +
16 (1:1, 22%) and then (1â,6â,7â)-7-p h en ylsu lfon yl-8-
m eth ylen ebicyclo[4.3.0]n on a n -2-on e (14), 48%, mp 140-
142 °C; 1H NMR δ 7.91-7.85 (m, 2H), 7.70-7.65 (m, 1H),
7.60-7.52 (m, 2H), 5.26 (dt, J ) 3, 1.5 Hz, 1H), 4.98 (dt, J )
3, 1.5 Hz, 1H), 3.71 (dq, J ) 5, 2 Hz, 1H), 3.18 (tt, J ) 7.5, 5
Hz, 1H), 2.87 (td, J ) 8, 5 Hz, 1H), 2.77 (ddt, J ) 15.5, 5.5, 2
Hz, 1H), 2.44-2.32 (m, 2H), 2.32 (dd, J ) 13, 6.5 Hz, 1H),
1.95-1.78 (m, 3H), 1.64 (dddd, J ) 14, 10, 8, 2.5 Hz, 1H); 13
C
NMR δ 210.01 (s), 141.51 (s), 137.25 (s), 133.81 (d), 129.46 (d,
2 × CH), 128.96 (d, 2 × CH), 116.48 (t), 72.86 (d), 50.55 (d),
43.34 (d), 39.32 (t), 34.39 (t), 27.12 (t), 22.72 (t); MS (CI/
isobutane) m/z 291 (MH+, 35), 149 (100). Anal. Calcd for
C16H18O3S: C, 66.18; H, 6.25. Found: C, 66.01; H, 6.27.
Compounds 15 and 16 were characterized as an inseparable
1
mixture of isomers with overlap of some H NMR signals. 15:
(4R*,3′R*)-4-[2′-(Br om om et h yl)-3′(p h en ylsu lfon yl)-1′-
1H NMR δ 7.94-7.48 (m, 5H), 5.65 (bs, 1H), 5.51 (s, 1H), 3.78
p r op en -3′-yl]d ih yd r o-2H-fu r a n -2-on e (22), 8%: 1H NMR

4966 J . Org. Chem., Vol. 61, No. 15, 1996
Ghera et al.
δ 7.85-7.79 (m, 2H), 7.76-7.68 (m, 1H), 7.63-7.53 (m, 2H),
5.62 (bs, 1H), 5.17 (s, 1H), 4.33 (dd, J ) 10, 8 Hz, 1H), 4.07 (t,
J ) 9 Hz, 1H), 3.90 (d, J ) 11 Hz, 1H), 4.87 (d, J ) 11 Hz,
1H), 3.64 (dd, J ) 11, 1 Hz, 1H), 3.16 (tdt, J ) 11, 10, 8 Hz,
1H), 2.91 (dd, J ) 18, 8 Hz, 1H), 2.65 (dd, J ) 18, 11 Hz, 1H);
13C NMR δ 175.37 (s), 137.10 (s), 136.24 (s), 134.72 (d), 129.61
2.10 (bs, 3H), 2.08-2.00 (m, 2H), 1.94 (td, J ) 11, 1Hz, 1H),
1.82 (bd, J ) 14 Hz, 1H), 1.70-1.54 (m, 3H); 13C NMR δ 209.82
(s), 154.25 (s), 142.35 (s), 133.13 (d), 129.18 (d, 2 × CH), 128.11
(d), 127.08 (d, 2 × CH), 47.57 (t), 47.41 (t), 41.16 (t), 36.65 (d),
+
30.87 (dd), 24.79 (dd), 17.65 (q); MS (CI/NH3) m/z 310 (MNH4
,
100).
(d, 2 × CH), 129.39 (d, 2 × CH), 123.45 (t), 69.97 (t), 69.56 (d),
Rea ction s w ith 5,6-Dih yd r o-2H-p yr a n -2-on e. In ab-
sence of HMPA, chromatographic purification of the crude
product (EtOAc/petroleum ether 1:1) gave by order of elution
25a (63%) and 25b (22%). Similar purification of the crude
product obtained in presence of HMPA gave 25a (71%) and
25b (12%).
+
36.29 (t), 34.91 (d), 34.11 (t); MS (CI/NH3) m/z 376 (MNH4
,
100), 359 (MH+, 3), 332 (15), 298 (48).
Rea ction s of Meth a llyl Su lfon e 8 w ith Cyclic Ca r bon yl
Com p ou n d s. The conditions and amounts were identical
with those used in reactions of 8 with ethyl crotonate, in the
absence or presence of HMPA. The diastereomeric ratio was
established by integration of the vinylic protons in the crude
mixture (Table 4).
Rea ction s w ith 2-Cycloh exen -1-on e. In the absence of
HMPA, chromatographic purification (EtOAc/petroleum ether
2:3) gave by order of elution 23a (9%), 23b (9%), and 24 (7%).
In the presence of HMPA, a similar purification gave 23a (61%)
and 23b (20%).
(4S*,1′R*)-4-[2′-Met h yl-3′-(p h en ylsu lfon yl)-1′-p r op en -
3′-yl]tetr a h yd r o-2H-p yr a n -2-on e (25a ), colorless oil: 1H
NMR δ 7.86-7.78 (m, 2H), 7.69-7.60 (m, 1H), 7.57-7.48 (m,
2H), 4.95 (bs, 1H), 4.83 (s, 1H), 4.53 (ddd, J ) 11.5, 5.5, 3.5
Hz, 1H), 4.36 (td, J ) 11.5, 3.5 Hz, 1H), 3.51 (d, J ) 10 Hz,
1H), 2.91 (dtdd, J ) 11, 10, 6, 4 Hz, 1H), 2.74 (dqd, J ) 16, 4,
2 Hz, 1H), 2.68 (ddd, J ) 18, 6.5, 2 Hz, 1H), 2.23 (dd, J ) 18,
10 Hz, 1H), 2.04 (dtd, J ) 16, 11, 5 Hz, 1H), 1.60 (bs, 3H); 13
C
(3S*,3′R*)-3-[2′-Met h yl-3′-(p h en ylsu lfon yl)-1′-p r op en -
3′-yl]cycloh exa n -1-on e (23a ): mp 94-96 °C; 1H NMR δ
7.86-7.79 (m, 2H), 7.66-7.58 (m, 1H), 7.55-7.47 (m, 2H),
4.96-4.91 (m, 1H), 4.86 (s, 1H), 3.57 (d, J ) 9 Hz, 1H), 2.79-
2.55 (m, 2H), 2.47 (ddt, J ) 14, 4, 2 Hz, 1H), 2.41 (ddt, J ) 14,
4, 2 Hz, 1H), 2.32 (ddd, J ) 7, 6, 1 Hz, 1H), 2.22-2.12 (m,
1H), 2.11 (ddd, J ) 14, 11.5, 1 Hz, 1H), 1.85-1.67 (m, 2H),
1.58 (bs, 3H); 13C NMR δ 209.28 (s), 138.83 (s), 136.64 (s),
133.34 (d), 128.62 (d, 2 × CH), 128.55 (d, 2 × CH), 121.00 (t),
76.03 (d), 45.32 (dd), 41.09 (t), 37.53 (d), 29.82 (dd), 24.57 (t),
21.15 (q); MS (CI/isobutane) m/z 310 ([M(H2O)]+, 20), 293
(MH+, 100), 151 (98).
(3S*,3′S*)-3-[2′-Meth yl-3′-(p h en ylsu lfon yl)-1′-p r op en -3′-
yl]cycloh exa n -1-on e (23b): mp 150-152 °C; 1H NMR δ
7.87-7.80 (m, 2H), 7.66-7.59 (m, 1H), 7.56-7.47 (m, 2H), 5.03
(bs, 1H), 4.93 (s, 1H), 3.49 (d, J ) 8 Hz, 1H), 2.88 (ddt, J ) 14,
4, 2 Hz, 1H), 2.71 (dddd, J ) 15, 11.5, 7.5, 3.5 Hz, 1H), 2.43
(dddd, J ) 14, 6, 3, 2 Hz, 1H), 2.37 (ddd, J ) 14, 12, 1 Hz,
1H), 2.26 (dddd, J ) 14, 8, 7, 2 Hz, 1H), 2.19-2.20 (m, 1H),
2.08 (ddq, J ) 9, 6.5, 3 Hz, 1H), 1.70-1.65 (m, 1H), 1.66 (bs,
3H), 1.57 (dddt, J ) 16, 13, 3, 2 Hz, 1H); 13C NMR δ 209.20
(s), 138.95 (s), 136.58 (s), 133.51 (d), 128.77 (d, 4 × CH), 121.27
(t), 76.12 (d), 46.45 (dd), 41.03 (t), 37.54 (d), 28.70 (t), 24.60
(t), 22.06 (q); MS (CI/isobutane) m/z 310 ([M(H2O)]+, 3), 293
(MH+, 55), 151 (100).
NMR δ 169.55 (s), 138.27 (s), 136.28 (s), 133.85 (d), 128.87 (d,
4 × CH), 121.93 (t), 75.86 (t), 68.21 (t), 34.40 (dd), 30.98 (d),
28.10 (dd), 20.77 (q); MS (CI/isobutane) m/z 312 ([M(H2O)]+,
98), 295 (MH+, 100).
(4S*,1′S*)-4-[2′-Met h yl-3′-(p h en ylsu lfon yl)-1′-p r op en -
3′yl]tetr a h yd r o-2H-p yr a n -2-on e (25b), colorless oil: 1H
NMR δ 7.87-7.79 (m, 2H), 7.68-7.61 (m, 1H), 7.57-7.48 (m,
2H), 5.02 (bs, 1H), 4.89 (s, 1H), 4.44 (ddd, J ) 12, 5, 4 Hz,
1H), 4.28 (td, J ) 11, 4 Hz, 1H), 3.53 (d, J ) 9 Hz, 1H), 3.23
(ddd, J ) 16, 6, 2 Hz, 1H), 2.91 (tddd, J ) 11, 9, 6, 4 Hz, 1H),
2.68 (dd, J ) 18, 11 Hz, 1H), 2.05 (dqd, J ) 15, 4, 2 Hz, 1H),
1.72 (dtd, J ) 16, 11, 5 Hz, 1H), 1.64 (bs, 3H); 13C NMR δ
169.26 (s), 138.17 (s), 136.12 (s), 133.70 (d), 128.76 (d, 2 × CH),
128.66 (d, 2 × CH), 121.79 (t), 75.49 (d), 67.84 (t), 35.42 (t),
30.95 (d), 26.78 (t), 21.31 (q); MS (CI/isobutane) m/z 312
([M(H2O)]+, 90), 295 (MH+, 100).
Ack n ow led gm en t. The authors thank Dr. Hugo E.
Gottlieb for valuable help with the NMR spectra.
Support of this research by Grant 353-94 from the Israel
Science Foundation is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra (14
pages). This material is available in libraries on microfiche,
immediately 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.
3-[(E)-(2′-Meth yl-1′-(p h en ylsu lfon yl)-1′-p r op en -3′-yl]cy-
1
cloh exa n -1-on e (24), colorless oil; H NMR δ 7.95-7.85 (m,
2H), 7.66-7.50 (m, 3H), 6.19 (q, J ) 1 Hz, 1H), 2.43-2.26 (m,
2H), 2.21 (bdd, J ) 15, 7 Hz, 1H), 2.14 (bd, J ) 8 Hz, 1H),
J O960089K