Halogenovinyl sulfones. 6. Synthesis of condensed heterocycles by diastereoselective intramolecular Diels-Alder reactions of sulfonyl-substituted trienes

Article abstract of DOI:10.1021/jo980181b

Sulfonyl trienes having a chiral center on the allyl carbon of the diene moiety were prepared from L-amino acid as chiral building blocks. Intramolecular-Diels-Alder reaction of the sulfonyl trienes having E-geometry on the diene moiety proceeded on the si-face and exo-selectively to give cisisoindoles as a sole product in good yields. But using the sulfonyl trienes having Z-geometry on the diene part, the ratio of the diastereomers of the products decreased to about 80:20. The observed stereoselectivity can be explained by calculations with semiempirical and ab initio methods.

Full text of DOI:10.1021/jo980181b

7172
J . Org. Chem. 1998, 63, 7172-7179
Ha logen ovin yl Su lfon es. 6.1 Syn th esis of Con d en sed Heter ocycles
by Dia ster eoselective In tr a m olecu la r Diels-Ald er Rea ction s of
Su lfon yl-Su bstitu ted Tr ien es
Hideki Takeuchi,† Tetsuya Fujimoto,† Kenji Hoshino,† J iro Motoyoshiya,‡
Akikazu Kakehi,§ and Iwao Yamamoto*,†
Department of Functional Polymer Science, Faculty of Textile Science and Technology,
Shinshu University, Ueda, Nagano 386-8567, J apan, Department of Materials Creation Chemistry,
Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano 386-8567, J apan, and
Department of Chemistry and Material Engineering, Faculty of Engineering,
Shinshu University, Wakasato, Nagano 380-8553, J apan
Received February 3, 1998
Sulfonyl trienes having a chiral center on the allyl carbon of the diene moiety were prepared from
L-amino acid as chiral building blocks. Intramolecular Diels-Alder reaction of the sulfonyl trienes
having E-geometry on the diene moiety proceeded on the si-face and exo-selectively to give cis-
isoindoles as a sole product in good yields. But using the sulfonyl trienes having Z-geometry on
the diene part, the ratio of the diastereomers of the products decreased to about 80:20. The observed
stereoselectivity can be explained by calculations with semiempirical and ab initio methods.
Many reports about Diels-Alder reactions of dienes
Resu lts
with sulfonyl-substituted dienophiles can be found in the
literature, because vinyl sulfones have higher reactivity
than the other electron-withdrawing groups such as nitro,
cyano, esters, and ketones and the sulfonyl substituents
of the products are easily removed under mild condi-
tions.2 That complex molecules can be constructed in a
single step under mild conditions stereo- and regioselec-
tively via intramolecular Diels-Alder reactions of vinyl
sulfones might be expected; however, examples of the
reactions are rare.3 Recently, we reported the synthesis
of racemic mixtures of dibenzopyran derivatives via a
diastereoselective intramolecular Diels-Alder reaction of
vinyl sulfones.1 We were interested in this procedure
because it might be applied to the diastereoselective
synthesis of heterocyclic compounds having more than
one chiral center.
Generally, facial selectivity of cycloaddition can be
influenced by a chiral building block in which one face
of the diene or dienophile is blocked preferentially. In-
corporation of a single stereogenic center in an allylic
position of either a dienophile or a diene, particularly,
when a heteroatom is present, is known to exert a di-
rection influence.4 In this paper, we wish to report highly
diastereoselective intramolecular Diels-Alder reactions
of vinyl sulfones with dienes having a chiral building
block at the allylic position.
Syn th esis of Su lfon yl Tr ien es a n d Th eir In tr a m o-
lecu la r Diels-Ald er Rea ction s. Reaction of N-ben-
zylphenylalaninol (1c)5 with 1,3-dichloro-2-(phenylsulfo-
nyl)propane6 in the presence of triethylamine at room
temperature gave alcohol 2c in 76% yield. A Swern
oxidation of the alcohol 2c using oxalyl chloride, dimethyl
sulfoxide, and triethylamine afforded aldehyde 3c quan-
titatively. A Wittig reaction of 3c with phosphonium salt
6 in the presence of potassium tert-butoxide in THF at
room temperature gave desired sulfonyl triene 4c in 36%
yield.
The 1H NMR spectrum of 4c showed the signals of
olefinic protons at 5.84 and 5.40 ppm with a coupling
constant of 15.6 Hz which correspond to E geometry. No
signals assigned to a Z-diene were observed.
The intramolecular Diels-Alder reaction of 4c was
performed in boiling benzene to give isoindole deriva-
tive 5c in 83% yield as a single diastereomer ([R]26
)
D
+69.74°). The structure of 5c was determined by spectral
data and confirmed by X-ray analysis that indicated the
absolute configuration of bridge head methine carbon was
S and that of the other bridge head carbon was R (Fig-
ure 1). Intramolecular Diels-Alder reactions under the
same conditions using 4a ,b instead of 4c gave 5a ,b in
79% and 69% yields, respectively. The 13C NMR spectra
of these products 5a ,b were similar to that of 5c, which
suggested that these compounds had the same configu-
ration (Table 1).
† Department of Functional Polymer Science.
‡ Department of Materials Creation Chemistry.
§ Department of Chemistry and Material Engineering.
(1) Yamamoto, I.; Kohara, T.; Fujimoto, T.; Ohta, K. Phosphorus,
Sulfur, Silicon 1996, 116, 203.
On the basis of the above results, these reactions
proceeded exo- and π-face (si-face)-selectively7 to give
isoindoles having the same configuration, and the ste-
reoselectivity did not depend on the bulk of the substitu-
ent at the allylic position.
(2) (a) Trost, B. M.; Arndt, H. C.; Strege, P. E.; Verhorven, T. R.;
Tetrahedron Lett. 1976, 3477. (b) J ulia, M.; Mark, J . Tetrahedron Lett.
1973, 4833.
(3) (a) Craig, D.; Fiacher, S. A.; Kemal, O.; Plessner, T. Tetrahedron
Lett. 1988, 29, 6369. (b) Kametani, T.; Aizawa, M.; Nemoto, H.
Tetrahedron 1981, 37, 2547. (c) J ung, M. E.; Truc, V. C. Tetrahedron
Lett. 1988, 29, 6059.
(4) (a) Tripathy, R.; Franck, R.; Onan, L. D. J . Am. Chem. Soc. 1988,
110, 3257. (b) Fisher, M. J .; Hehre, W. J .; Kahn, S. D.; Overman, L. E.
J . Am. Chem. Soc. 1988, 110, 4625. (c) Datta, S. C.; Frank, R. R. J .
Chem. Soc., Perkin Trans. 1 1989, 2023. (d) Bloch, R.; Chaptal-Gradoz,
N. J . Org. Chem. 1994, 59, 4162.
(5) Davidsen, S. K.; Chu-Moyer, M. Y. J . Org. Chem. 1989, 54,
5558.
(6) Anzeveno, P. B.; Mattews, D. P.; Barney, C. L.; Barbuch, R. J .
J . Org. Chem. 1989, 49, 3134.
(7) Franck, R. W.; Argade, S.; Subramaniam, C. S.; Frechet, D. M.
Tetrahedron Lett. 1985, 27, 3187.
S0022-3263(98)00181-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/22/1998

Halogenovinyl Sulfones
J . Org. Chem., Vol. 63, No. 21, 1998 7173
a isomerically pure diene is shown in Scheme 2. Protec-
tion of the amino group followed by an oxidation of the
hydroxy group gave aldehyde 11c which reacted with
phosphonium salt 9 to give diene 12c. A deprotection of
12c by trimethylsilyl iodide9 and methanol gave a geo-
metrical mixture of amino diene 13c in 45% yield, which
was separated to two components. One of them was a
mixture of (3E,5E)- and (3Z,5E)-diene, and the other was
pure (3Z,5E)-diene.
A reaction of (3Z,5E)-diene 13c with 1,3-dichloro-2-
(phenylsulfonyl)propane in the presence of triethylamine
gave a desired sulfonyl triene (3Z,5E)-14 in 79% yield.
An intramolecular Diels-Alder reaction of (3Z,5E)-14 in
boiling toluene for 72 h gave two isoindoles in 98% yield
in the ratio of 80 to 20, which were separated by column
chromatography to give white crystals (major) and a pale
yellow syrup (minor).
The structure and stereochemistry of the major product
was determined by spectral data and confirmed by X-ray
crystal analysis (Figure 2). A NOESY spectrum of the
compound, cis-â-15, indicated that the each pair of H2
and H15, H1 and H5, and H2 and H11 was in a cis
relation as shown in Figure 3.
On the other hand, the NOESY spectrum of a minor
product, cis-R-15, showed a typical NOE between H1 and
H2 and H2 and H15 which was compatible to the
configuration assigned to cis-R-15. On the basis of these
results, the product cis-â-15 would come from endo-
cycloaddition of vinyl sulfone to the si-face attack on the
diene, and cis-R-15 would come from endo-re-face attack
on the diene moiety.
To clarify these stereoselectivities, we further exam-
ined the reactions of sulfonyl trienes having no substit-
uents on dienyl group. The geometric mixture of amino
diene 18, obtained from a Wittig reaction of aldehyde 11c
and phosphonium salt 19, was separated by column
chromatography, and each diene, E-18 and Z-18, was
transformed to sulfonyl triene E-21 and Z-21, as shown
in Scheme 3.
F igu r e 1. X-ray crystal structures of 5c and 8c.
An intramolecular Diels-Alder reaction of E-21 in
boiling toluene for 17 h gave cis-â-isoindoles, cis-â-22 in
83% yield as a single diastereomer, and a reaction of Z-21
under the same conditions gave a mixture of â-isoindoles,
cis-â-22, and R-isoindoles, cis-R-22, in 96% yield in the
ratio of 84 to 16 (Scheme 3). The structure of cis-â-22
was determined by spectral data and confirmed by X-ray
analysis (Figure 2), and that of cis-R-22 was determined
by comparing its NMR spectrum with that of cis-R-15.
Similarly, we performed an intramolecular Diels-
Alder reaction using D-N-benzylphenylalaninol as a
starting material (Scheme 1) resulting in formation of
the desired 8c in 88% yield. The spectral data showed
the same results as that of 5c except for specific rotation.
The compound 8c showed a specific rotation of -69.51°.
Furthermore, the X-ray analysis showed the absolute
configuration of 8c was that of an enantiomer of 5c
(Figure 1). This result suggests that the reaction would
proceed by the attack on re-face of diene, selectively.
Rela tion sh ip betw een Ster eoselectivity a n d Ge-
om etr y a n d /or Su bstitu en ts of Dien es. With the
hypothesis that the exo-orientation of cycloadditions in
the above reactions might be the result of steric repulsion
between the phenylsulfonyl group and methyl group on
the 4-position of the diene, we tried to examine the
intramolecular Diels-Alder reaction of sulfonyl trienes
having a methyl group on the terminal position of diene
moiety. A Wittig reaction of aldehyde 3c with phospho-
nium salt 9 in the presence of n-butyllithium and lithium
bromide,8 however, gave geometrical isomers, which
could not be separated. An alternative method to obtain
Discu ssion
Intramolecular Diels-Alder reactions of sulfonyl triene
having an E-configuration on the diene part proceeded
in a manner of si-face selective exo-cycloaddition, and the
reaction having a Z-configuration on the diene part
proceeded in a manner of si-face selective endo-cycload-
dition.
Asymmetric Diels-Alder reactions using chiral dienes
have been a subject of interest. The effect of an allylic
center on dienes which influences diastereoselectivity
stimulated the interest, and many theoretical discussions
(9) (a) Olah, G. A.; Narang, S. C. Tetrahedron 1982, 38, 2225. (b)
Rawal, V. H.; Michoud, C.; Monestel, R. F. J . Am. Chem. Soc. 1993,
115, 3030. (c) J ung, M. E.; Lyster, M. A. J . Chem. Soc., Chem. Commun.
1978, 315. (d) Lott, R. S.; Chauhan, V. S.; Stammer, C. H. J . Chem.
Soc., Chem. Commun. 1979, 495.
(8) (a) Vedejs, E.; Meier, G. P.; Snoble, K. A. J . J . Am. Chem. Soc.
1981, 103, 2823. (b) Hooper, D. L.; Gragan, S. J . Org. Chem. 1994, 59,
1226.

7174 J . Org. Chem., Vol. 63, No. 21, 1998
Takeuchi et al.
Ta ble 1. P r oton NMR a n d Ca r bon -13 NMR Ch em ica l Sh ifts a n d J Va lu es (Hz) for 5 in CDCl3
13C Data
carbon
1
2
3
4
5
6
7
8
9
10
5a
5b
5c
66.54
75.07
72.49
46.90
40.86
44.05
118.93
121.75
120.20
136.05
135.77
135.00
26.86
26.64
26.76
28.01
28.70
27.87
67.82
68.36
68.50
62.09
61.62
61.35
56.76
58.22
57.58
23.87
24.04
23.62
1H Data
proton
vinyl proton 3
methylene proton 8 or 9
methylene proton 9 or 8
5a
5b
5c
5.50-5.48 (multiplet)
5.62-5.42 (multiplet)
5.08-4.90 (multiplet)
3.81 (J gem ) 13.40)
2.82 (J gem ) 13.20)
3.91 (J gem ) 13.07)
2.80 (J gem ) 12.97)
4.00 (J gem ) 13.08)
2.91 (J gem ) 13.07)
3.42 (J gem ) 12.30)
2.04 (J gem ) 11.70)
3.42 (J gem ) 11.98)
2.11 (J gem ) 12.19)
3.34 (J gem ) 11.54)
2.11 (J gem ) 11.64)
have been reported in the past decade.10-13 Tripathy et
al.14 and Scott et al.15 reported that the selectivity of
Diels-Alder reactions of chiral dienes depended on the
conformational stability of the chiral center.
large enough to control the π-facial selectivity. The
reversal found in PM3 and ab initio method would be
due to the different appreciation of the repulsion of dipole
moments between the sulfonyl and amino groups, which
take the places more closely in TS-2 than in TS-1. In
addition, the heat of formation of the E-exo-si conformer
was 22.9 kcal/mol and that of E-exo-r e was 24.37 kcal/
mol. The more stabilized E-exo-si conformer also sup-
ports the predominant cyclization to give cis-â-isoindoles.
The IMDA reactions of 4a -c gave compounds 5a -c
as a sole product (Scheme 1). These products came from
the results of exo attack of the vinyl sulfone moiety.
Furthermore, in the IMDA of (3E)-21 we observed exo-
addition, which would suggest that the methyl substitu-
ent on the diene moiety did not affect the topography
(endo or exo) of the reactions. To clarify these stereose-
lectivities, we performed calculations of each transition
state with the CAChe MOPAC PM3 method. The activa-
tion energy of the exo-addition of the vinylsulfonyl group
on the si-face of diene in E-triene (E-exo-si to TS-1) was
26.23 kcal/mol (Figure 4). On the contrary, the activation
energies of the endo-additions (E-en d o-si to TS-3 and
E-en d o-r e to TS-4), which should give trans-fused
isoindoles, were 34.52 and 33.04 kcal/mol, respectively.
These values are much larger than that of E-exo-si to
TS-1 and suggest that the reactions could not proceed
via endo-additions. In the case of exo-addition of the
vinylsulfonyl group on the re-face of diene, the activa-
tion energy was 25.40 kcal/mol, which was 0.83 kcal/
mol smaller than E -exo-si to TS-1. As this did not
agree with the experimental results, we calculated
again these transition state energies with the ab initio
(3-21G*) method based on the structures located by PM3.
The energies of TS-1 and TS-2 were estimated as
-1213.181 320 and -1213.173 066 au, respectively, from
whose values the difference in energies between TS-1 and
TS-2 was calculated to be 0.008 245 au (5.18 kcal/mol)
On the other hand, in the case of the IMDA of Z-triene,
the ratio of si-face to re-face selectivity was about 80 to
20. In the IMDA of (3Z)-14 and (3Z)-21, the reactions
proceeded through the endo-transition states, selectively.
These results suggest that the terminal methyl substitu-
ent does not affect the stereoselectivity of the reactions.
Every product was a cis-fused condensed heterocycle
which has the same skeleton. In this case, the preferable
transition states in the cycloaddition would be TS-5 and
TS-6. The activation energy of TS-5 from Z-en d o-si was
29.64 kcal/mol, and that of TS-6 was 30.85 kcal/mol
(Figure 5). The difference between these energies (1.21
kcal/mol) would predict that the si-face attack would be
predominant. The exo transition state for the Z-triene
is geometrically impossible for the dienophile to approach
both termini of the diene simultaneously, which was
indicated by inspection of molecular models. Further-
more, the cyclization reactions of E-trienes (∆Ea ) 26.23
kcal/mol) proceeded in boiling benzene. In the case of
Z-triene (∆Ea ) 29.64 kcal/mol), the reactions did not
proceed in the same conditions but required higher
temperature (boiling toluene). The difference in activa-
tion energies, 3.41 kcal/mol, should affect the reaction
conditions.
(10) Houk, K. N.; Bock, C. W. J . Org. Chem. 1992, 57, 4862.
(11) Raimondi, L.; Brown, F. K.; Gonzalez, J .; Houk, K. N. J . Am.
Chem. Soc. 1992, 114, 4796.
(12) Houk, K. N.; Moses, S. R.; Wu, Y. D.; Rondan, D. G.; J ager, V.;
Schohe, R.; Fronczek, F. R. J . Am. Chem. Soc. 1984, 106, 3880.
(13) Brieger, G.; Bennett, J . N. Chem. Rev. 1980, 80, 63 and
references cited therein.
(14) Tripathy, R.; Franck, R. W.; Onan, K. D. J . Am. Chem. Soc.
1988, 110, 3257.
(15) Scott, D. K.; Warrem, J . H. Tetrahedron Lett. 1985, 26, 3647.
Exp er im en ta l Section
N -Be n zyl-N -[(2S )-5-m e t h yl-3,5-h e xa d ie n -2-yl]-N -[2-
(p h en ylsu lfon yl)-2-p r op en -1-yl]a m in e (4a ). To potassium
tert-butoxide (0.59 g, 4.75 mmol) was added dropwise a solution
of (2-methyl-1-propenyl)triphenylphosphonium perchlorate (2.18
g, 5.23 mmol) in THF (50 mL) at room temperature, and the

Halogenovinyl Sulfones
Sch em e 1
J . Org. Chem., Vol. 63, No. 21, 1998 7175
Sch em e 2
chromatographed on silica gel (2:5EtOAc/n-hexane): IR (neat)
2990, 1450, 1310, 1140, 1080, 980, 750, 680 cm-1 1H NMR
;
(90 MHz, CDCl3) δ 7.90-7.35 (m, 5H, SO2Ph), 7.12(S, 5H, Ph),
6.42 (s, 1H, H11), 6.30 (s, 1H, H11), 5.73 (d, 1H, H5, J H3H2
)
14.0 Hz), 5.25 (d, d, 1H, H4, J H2H1 ) 9.0 Hz, J H2H3 ) 14.4 Hz),
4.90 (s, 1H, H7 or H7′), 4.81 (s, 1H, H7 or H7′), 3.97-2.87 (m,
4H, H8, H9), 2.43(t, 1H, H3, J H1H2 ) 9.0 Hz, J H1H6 ) 9.0 Hz),
2.07-1.50 (m, 4H, H2, CH3), 1.00 (d, 3H, CH3, J ) 7.0 Hz),
0.70 (d, 3H, CH3, J ) 7.0 Hz); 13C NMR (22.63 MHz, CDCl3/
TMS) δ 149.28, 141.31, 139.19, 137.58, 133.42, 129.20, 128.63,
128.52, 128.35, 128.13, 127.03, 126.16, 124.67, 116.20, 68.67,
54.28, 48.19, 29.90, 20.759, 18.74; [R]25D) +3.95° (c ) 0.50,
CHCl3); HRMS m/z calcd for C25H31NSO2, M, 409.2073. Found,
M+, 409.2051.
N-Ben zyl-N-[(2S)-1-p h en yl-5-m et h yl-3,5-h exa d ien -3-
yl]-N-[2-(p h en ylsu lfon yl)-2-p r op en -1-yl]a m in e (4c). This
compound was obtained in 36% yield as yellow crystals, after
being chromatographed on silica gel (1:3EtOAc/n-hexane): mp
110.5-112.5 °C; IR (neat) Å@2900, 2800, 1580, 1440, 1290,
1120, 1060, 960, 870, 730, 680 cm-1; 1H NMR (90 MHz, CDCl3)
δ 7.97-6.80 (m, 15H, Ph × 3), 6.28 (s, 1H, H7 or H7′), 5.84 (d,
1H, H4, J H3H2 ) 15.6 Hz), 5.73 (s, 1H, H10), 5.40 (d, d, 1H,
H3, J H3H4 ) 15.6 Hz, J H2H3 ) 7.9 Hz), 4.94 (s, 1H, H6 or H6′),
4.85 (s, 1H, H6 or H6′), 3.79-2.58 (m, 6H, CH2 × 3), 1.88 (m,
4H, H2, CH3); 13C NMR (22.63 MHz, CDCl3/TMS) δ 149.04,
141.37, 139.27, 138.95, 136.41, 133.33, 129.52, 129.17, 128.48,
128.31, 128.20, 127.09, 126.77, 126.18, 125.10, 116.41, 63.10,
mixture was stirred for 30 min. Then a solution of 3a (1.63 g,
4.75 mmol) in THF (20 mL) was added dropwise to the solution
and stirred for 3 h. To the solution was added an aqueous
ammonium chloride, and then THF was evaporated in vacuo.
The residue was extracted CH2Cl2, and the organic extract was
washed with saturated NaCl solution and dried over anhy-
drous Na2SO4. The solvent was evaporated in vacuo, and the
residue was chromatographed on silica gel (1:40EtOAc/CHCl3)
to give 4a as yellow syrup in 31% (0.56 g) yield: IR (neat) 3000,
1450, 1300, 1140, 1080, 750, 680 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 7.83-6.97 (m, 10H, Ph × 2), 6.48 (s, 1H, H10), 6.26
(s, 1H, H10), 5.94 (d, 1H, H4, J H3H2 ) 15.8 Hz), 5.49 (dd, 1H,
H3, J H2H3 ) 7.1 Hz, J H3H4 ) 15.9 Hz), 4.93 (s, 1H, H6 or H6′),
4.86 (s, 1H, H6 or H6′), 3.46 (s, 1H, H7), 3.42 (s, 1H, H7), 3.36-
2.97 (m, 3H, H2, H8), 1.79 (s, 3H, Me), 1.07 (d, 3H, Me, J )
6.4 Hz); 13C NMR (22.63 MHz, CDCl3) δ 149.5, 141.5, 139.5,
139.4, 134.5, 133.5, 130.2, 129.3, 128.6, 128.4, 128.3, 127.1,
54.37, 48.43, 39.05, 18.61; [R]26 ) +8.34° (c ) 0.99, CHCl3).
D
Anal. Calcd for C29H31NSO2: C, 76.1; H, 6.83; N, 3.06. Found:
C, 75.7; H, 6.880; N, 3.24.
N-Ben zyl-N-[(2R)-1-p h en yl-5-m et h yl-3,5-h exa d ien -3-
yl]-N-[2-(p h en ylsu lfon yl)-2-p r op en -1-yl]a m in e (7c). This
compound was obtained in 28% yield as yellow crystals, after
being chromatographed on silica gel (1:3EtOAc/n-hexane); mp
125.4, 116.3, 55.9, 54.3, 48.6, 18.8, 16.1; [R]25 -32.857° (c )
D
110.3-112.5 °C; [R]29 ) -9.86° (c ) 1.11, CHCl3).
1.05, CHCl3). HRMS: calcd for C23H27NSO2, M 381.1761;
D
found M+, m/z 381.1793.
Isoin d ole 5a . A solution of sulfonyl triene 4a (0.47 g, 0.23
mmol) in benzene (30 mL) was refluxed for 24 h, and the
mixture was concentrated in vacuo. The residue was chro-
matographed on silica gel (1:3EtOAc/CHCl3) to give 5a (0.37
N-Ben zyl-N-[(2S)-2,6-d im eth yl-4,6-h exa d ien -3-yl]-N-[2-
(p h en ylsu lfo-n yl)-2-p r op en -1-yl]a m in e (4b). This com-
pound was obtained in 10% yield as a yellow syrup, after being

7176 J . Org. Chem., Vol. 63, No. 21, 1998
Takeuchi et al.
Sch em e 3
F igu r e 2. X-ray crystal structures of cis-â-15 and cis-â-22.
1.85 (m, 1H, H5 or H6), 1.75 (s, 3H, H10, 1.71-1.64 (m, 1H,
H5 or H6), 1.07 (d, 3H, H11, J ) 5.9 Hz); 13C NMR (22.63 MHz,
CDCl3) δ138.24(Cipso), 137.20 (Cipso), 136.05(C4), 133.19,
130.38, 128.88, 128.67, 128.62, 128.40, 128.25, 128.10, 126.95,
118.93 (C3), 67.86 (C7), 66.54 (C1), 62.09 (C8 or C9), 56.76
(C8 or C9), 46.90 (C2), 28.01 (C5 or C6), 26.86 (C5 or C6), 23.87
(C10), 17.20 (C11); [R]24D ) +66.18° (c ) 1.00, CHCl3); MS (m/
z) 381 (M+). HRMS (m/z): calcd for C23H26NSO2, M - 1,
380.1682; found, M+ - 1, 380.1641.
F igu r e 3. H-H NOE correlation of cis-â-15 and cis-R-15.
g, 79%) as a yellow syrup along with starting 4a (0.07 g, 15%
recovery): IR (neat) 2925, 1450, 1380, 1300, 1140, 1080, 750,
1
680 cm-1; H NMR (400 MHz, CDCl3) δ 7.76-6.97 (m, 10H,
Ph × 2), 5.50-5.48 (m, 1H, H3), 3.81 (d, 1H, H8 or H9, J gem
)
Isoin d ole 5b: 69% yield, yellow syrup; IR (neat) 2990, 1450,
1300, 1140, 1070, 730, 690 cm-1; 1H NMR (90 MHz, CDCl3) δ
7.98-7.01 (m, 10H, Ph × 2), 6.62-5.42 (m, 1H, H3), 3.91 (d,
13.4 Hz), 3.42 (d, 1H, H8 or H9, J gem ) 12.3 Hz), 2.82 (m, 1H,
H8 or H9, J gem ) 13.2 Hz), 2.75(br, 1H, H1), 2.44-2.37 (m,
1H, H5 or H6), 2.29-2.27 (m, 1H, H5 or H6), 2.06 (d, 1H, H2,
J H2H1 ) 14.9 Hz), 2.04 (d, 1H, H8 or H9, J gem ) 11.7 Hz), 1.90-
1H, H8 or H9, J gem ) 13.07 Hz), 3.42 (d, 1H, H8 or H9, J gem
)
11.98 Hz), 3.12-2.78 (m, 1H, H2), 2.80 (d, 1H, H8 or H9, J gem

Halogenovinyl Sulfones
J . Org. Chem., Vol. 63, No. 21, 1998 7177
F igu r e 5. Transiton states of Z-sulfonyl trienes calculated
by MOPAC PM3.
Isoin d ole 8c: 88% yield; mp 167.6-169.5 °C; [R]28
-69.51° (c ) 1.03, CHCl3).
)
D
(2S)-2-(N-Ben zyl-N-(ter t-bu toxycar bon yl)am in o)-1-ph en -
yl-3,5-h ep ta d ien e (12c). To a solution of 2-butenyltriphen-
ylphosphonium perchlorate (9) (4.46 g, 10.7 mmol) and lithium
bromide (3.72 g, 47.2 mmol) in THF (80 mL) was added a 1.6
M solution of n-butyllithium in n-hexane (7.36 mL, 11.8 mmol,
1.1 equiv), and the solution was stirred at 0 °C for 30 min.
Then a solution of N-benzyl-N-Boc-phenylalaninal (11c) (3.6
g, 10.7 mmol) in THF (40 mL) was added to the mixture. After
the mixture was stirred for 24 h, a saturated ammonium
chloride solution (30 mL) was added and the solvent THF was
evaporated in vacuo. The residue was extracted with dichlo-
romethane, and the organic layer was washed with brine and
dried over anhydrous Na2SO4. The solvent was evaporated
in vacuo, and the residue was chromatographed on silica gel
(1:10EtOAc/CHCl3) to give 12c (1:1 geometrical mixture) in
83% (3.34 g) yield as a yellow syrup: IR (neat) 3000, 1690,
F igu r e 4. Transition states of E-sulfonyl trienes calculated
by MOPAC PM3.
1500, 1450, 1360, 1320, 1250, 1160, 1110, 980, 740, 700 cm-1
;
1H NMR (90 MHz, CDCl3) δ 7.40-6.90 (m, 10H, Ph × 2), 6.35-
5.34 (m, 4H, olefin proton), 5.18-4.65 (m, 1H, CH), 4.65-3.93
(m, 2H, CH2), 3.18-2.53 (m, 2H, CH2), 1.70 (d, 3H, CH3, J )
7.1 Hz), 1.38 (s, 9H, Boc); 13C NMR (22.63 MHz, CDCl3) δ
155.42 (CdO), 139.58 (Cipso), 139.45 (Cipso), 138.71 (Cipso),
138.51 (Cipso), 132.14, 131.60, 131.54, 131.05, 129.46, 129.30,
128.81, 128.24, 128.16, 128.00, 127.51, 127.33, 126.83, 126.70,
126.66, 126.40, 126.18, 79.74 (C-O), 60.41 (CH), 55.45 (CH),
49.41 (CH2), 48.63 (CH2), 40.65 (CH2), 39.55 (CH2), 28.41 (CH3),
18.25 (CH3), 18.01 (CH3); MS (m/z) 377 (M+).
) 12.97 Hz), 2.43-1.06 (m, 10H, H1, H2, H5, H6, H11, H8),
0.95 (d, 3H, H12, J ) 6.92 Hz), 0.79 (d, 3H, H12, J ) 6.81
Hz); 13C NMR (90 MHz, CDCl3) δ139.04 (Cipso), 137.61 (Cipso),
135.77 (C4), 133.33, 130.53, 128.79, 128.40, 127.21, 121.75
(C3), 75.07 (C1), 68.36 (C7), 61.62 (C8 or C9), 58.22 (C8 or
C9), 40.86 (C2), 28.70 (C5 or C6), 28.29 (C11), 26.64 (C5 or
C6), 24.04 (C10) 19.84 (C12), 17.24 (C12); [R]24 ) +80.98° (c
D
) 0.97, CHCl3); MS (m/z) 409 (M+). HRMS (m/z): calcd for
C25H31NSO2, M, 409.2074; found, M+, 409.2102.
(2S)-2-(N-Ben zyla m in o)-1-p h en yl-3,5-h ep ta d ien e (13c).
To a solution of N-Boc-amino diene 12c (2.50 g, 6.9 mmol) in
chloroform (30 mL) was added dropwise by syringe iodotri-
methylsilane (1.18 mL, 8.3 mmol, 1.2 equiv), and the mixture
was heated at 50 °C. After 30 min, 5 mL of methanol was
added, and the solvent was evaporated in vacuo. Then 40 mL
of ether and 40 mL of 30% aqueous acetic acid was added and
stirred for a few minutes. The solution was neutralized by
aqueous sodium bicarbonate and extracted with ether. The
ether layer was washed with brine and dried over anhydrous
Na2SO4. The solvent was evaporated in vacuo, and the residue
was chromatographed on silica gel (1:3EtOAc/n-hexane) to give
a 1:1 mixture of (3E,5E)- and (3E,5Z)-amino diene 13c (0.26
g) and pure (3Z,5E)-amino diene 13c (0.61 g).
Isoin d ole 5c: 83% yield; mp 167.5-169.4 °C; IR (KBr) 3025,
1
2900, 2800, 1440, 1370, 1290, 1140, 1070, 730, 690 cm-1; H
NMR (90 MHz, CDCl3) δ 7.71-6.79 (m, 15H, Ph × 3), 5.00
(m, 1H, H3), 4.00 (d, 1H, H8 or H9, J gem ) 13.08 Hz), 3.34 (d,
1H, H8 or H9, J gem ) 11.54 Hz), 3.05-1.70 (m, 8H, H1, H2,
H5, H6, H11), 2.91 (d, 1H, H8 or H9, J gem ) 13.07 Hz), 2.11
(d, 1H, H8 or H9, J gem ) 11.64 Hz), 1.64 (s, 3H, H10); 13C NMR
(22.63 MHz, CDCl3) δ138.51(Cipso), 138.32 (Cipso), 137.67
(Cipso), 135.00 (C4), 132.99, 130.47, 129.78, 128.65, 128.44,
128.26, 127.09, 126.36, 120.20 (C3), 72.49 (C1), 68.50 (C7),
61.35 (C9), 57.58 (C8), 44.05 (C2), 37.64 (C11), 27.87 (C5 or
C6), 26.76 (C5 or C6), 23.62(C10); [R]26 ) +69.74° (c ) 0.90,
D
CHCl3); MS (m/z) 366 (M - 91). Anal. Calcd for C29H31
-
NSO2: C, 76.11; H, 6.83; N, 3.06. Found: C, 76.40; H, 6.82;
N, 3.24.
Mixtu r e of (3E,5E)-13c a n d (3Z, 5E)-13c: IR (neat) 3025,
2925, 2850, 1600, 1500, 1450, 1100, 1030, 980, 740, 700 cm-1
;

7178 J . Org. Chem., Vol. 63, No. 21, 1998
Takeuchi et al.
1H NMR (CDCl3, 400 MHz) δ 7.31-7.11 (m, 10H, Ph), 6.44-
6.37 (m, 2H, H4, H5), 6.11-5.99 (m, 1H, H6), 5.68-5.41 (m,
1H, H3), 3.83-3.77 (m, 1H, methylene proton H8), 3.61-3.56
(m, 1H, methylene proton H8), 3.40-3.28 (m, 1H, H2), 2.86-
2.70 (m, 2H, methylene proton H7), 1.75-1.71 (m, 3H, CH3),
1.26 (s, 1H, NH); 13C NMR (CDCl3) δ 140.54 (Cipso), 138.64
(Cipso), 135.66, 133.44, 131.91, 131.21, 129.44, 129.02, 128.82,
128.41, 128.33, 127.98, 126.82, 126.77, 126.75, 126.36, 126.34,
126.16, 61.07 (C2), 60.91 (C2), 51.29 (C8), 51.24 (C8), 42.83
(C1), 42.76 (C1), 18.11 (C7), 13.42 (C7); MS m/z 278 (M + 1),
210, 186, 171, 129, 91. HRMS (m/z): calcd for C20H24N, M +
1, 278.1909; found, M+ + 1, 278.1898.
for C29H31NSO2: C, 76.11; H, 6.83; N, 3.06. Found: C, 75.94;
H, 6.83; N, 3.06; [R]27 ) +93.06° (c ) 1.03, CHCl3).
D
Isoin d ole Der iva tive cis-r-15. Yellow syrup: IR (neat)
3040, 2960, 2940, 2870, 1450, 1300, 1220, 1150, 1080, 750, 700
cm-1 1H NMR (CDCl3, 400 MHz) δ 7.80-7.75 (m, 2H, Ph,
;
7.63-7.60 (m, 1H, Ph), 7.51-7.45 (m, 2H, Ph), 7.33-7.20 (m,
10H, Ph), 5.76 (d, 1H, H4, J H4H3 ) 10.03 Hz), 5.62-5.58 (m,
1H, H3), 4.09 (d, 1H, H9, J gem ) 13.26 Hz), 3.38-3.35 (m, 1H,
H1), 3.19 (d, 1H, H9, J gem ) 13.17 Hz), 3.13-3.02 (m, 2H, H2,
H11), 3.12 (d, 1H, H8, J gem ) 11.45 Hz), 2.84 (d, 1H, H8, J gem
) 11.73 Hz), 2.60-2.53 (m, 1H, H11), 2.27-2.23 (m, 1H, H5),
1.78-1.72 (m, 1H, H6), 1.48(t, 1H, H6, J gem ) 11.78 Hz), 0.95
(d, 3H, H10, J MeH5 ) 7.08 Hz); 13C NMR (CDCl3) δ 138.35
(Cipso), 138.14 (Cipso), 137.07 (Cipso), 136.61 (C4), 133.66,
130.49, 128.96, 128.74, 128.57, 128.43, 128.37, 128.23, 127.01,
126.25, 124.78 (C3), 69.69 (C7), 67.90 (C1), 59.33 (C8), 57.34
(C9), 41.06 (C2), 35.87 (C11), 29.72 (C6), 25.87 (C5), 21.25
(3Z,5E)-13c: IR (neat) 3025, 2925, 2850, 1600, 1500, 1450,
1100, 1030, 980, 940, 820, 740, 700 cm-1 1H NMR (CDCl3,
;
400 MHz) δ 7.29-7.13 (m, 10H, Ph), 6.45-6.04 (m, 2H, H4,
H5), 5.71-5.62 (m, 1H, H6), 5.18 (t, 1H, H3, J H3H4 ) 9.36 Hz),
3.83-3.75 (m, 1H, H2), 3.80 (d, 1H, methylene proton H8, J gem
) 13.55 Hz), 3.59 (d, 1H, methylene proton H8, J gem ) 13.58
Hz), 2.80-2.71 (m, 2H, methylene proton H1), 1.75-1.71 (m,
3H, CH3), 1.53 (s, 1H, NH); 13C NMR (CDCl3) δ 140.51 (Cipso),
138.59 (Cipso), 131.43 (C3), 130.69, 130.64, 129.45, 128.36,
128.26, 128.10, 128.04, 126.94, 126.74, 126.32, 55.39 (C2),
51.26 (C8), 42.50 (C1), 18.23 (CH3); [R]27D ) +12.56° (c ) 1.06,
CHCl3); MS m/z 278 (M + 1). HRMS (m/z): calcd for C20H24N,
M + 1, 278.1909; found, M+ + 1, 278.1866.
(C10); MS m/z 458 (M + 1). HRMS (m/z): calcd for C29H32
-
NSO2, M + 1, 458.2154; found, M+ + 1, 458.2119.
2-(N-Ben zylam in o)-1-ph en yl-3,5-h exadien e (18). Am in o
d ien e E-18: IR (neat) 3300, 3075, 3050, 3000, 2900, 2825,
1800, 1590, 1480, 1440, 1330, 1100, 1060, 1020, 990, 940, 890,
730, 680 cm-1; 1H NMR (CDCl3, 90 MHz) δ 7.41-6.90 (m, 10H,
Ph × 2), 6.57-5.98 (m, 2H, H4, H5), 5.60 (d, d, 1H, H3, J H3H4
) 14.35 Hz, J H3H2 ) 7.80 Hz), 5.30-5.00 (m, 2H, H6, H6′),
3.69 (d, d, 2H, methylene proton H7, J gem ) 13.51 Hz), 3.39-
3.23 (m, 2H, methylene proton H1), 1.62 (br, 1H, NH); 13C
NMR (CDCl3) δ 140.46 (Cipso), 138.43 (Cipso), 136.67, 132.19,
129.39, 128.37, 128.29, 127.92, 126.72, 126.33, 116.43 (C6),
N -B e n zyl-N-(1-p h e n y l-3Z,5E -h e p t a d ie n -2-y l)-N -[2-
(p h en ylsu lfon yl)-2-p r op en -1-yl]a m in e (14) ((3Z,5E)-14).
This compound was obtained from the reaction between amino
diene (3Z,5E)-13c (0.58 g, 2.1 mmol), triethylamine (0.42 g,
4.2 mmol, 2 equiv), and 1,3-dichloro-2-(phenylsulfonyl)propane
(0.53 g, 2.1 mmol) in the presence of hydroquinone (0.02 g,
0.21 mmol) in 79% (0.76 g) yield as a yellow syrup, after being
chromatographed on silica gel (1:3EtOAc/n-hexane): IR (neat)
3050, 3030, 2930, 2850, 1740, 1500, 1450, 1370, 1300, 1240,
60.74 (C2), 51.27 (C7), 42.60 (C1); [R]26 ) -1.57° (c ) 1.07,
D
CHCl3).
Am in o d ien e Z-18: IR (neat) 3300, 3075, 3050, 3000, 2900,
2825, 1800, 1720, 1590, 1480, 1440, 1350, 1320, 1280, 1190,
1060, 1020, 980, 960, 900, 740, 680 cm-1; 1H NMR (CDCl3, 90
MHz) δ 7.41-6.95 (m, 10H, Ph × 2), 6.63-5.99 (m, 2H, H3,
H4), 5.45-4.97 (m, 3H, H5, H6, H6′), 3.93-3.81 (m, 1H, H2),
3.69 (d, d, 2H, methylene proton H7, J gem ) 13.62 Hz), 2.76
(d, d, 2H, methylene proton H1, J gem ) 6.7 Hz), 1.70(br, 1H,
NH); 13C NMR (CDCl3) δ 140.23 (Cipso), 138.23 (Cipso), 134.42,
131.99, 131.12, 129.35, 128.31, 128.22, 128.07, 127.98, 127.25,
126.83, 126.75, 126.29, 118.21 (C5), 55.47 (C1), 51.18 (C7),
1180, 1140, 1080, 960, 740, 700 cm-1 1H NMR (CDCl3, 400
;
MHz) δ 7.84-7.80 (m, 2H, Ph), 7.62-7.58 (m, 1H, Ph), 7.52-
7.48 (m, 2H, Ph), 7.25-7.12 (m, 6H, Ph), 6.97-6.88 (m, 4H,
H11, Ph), 6.34 (s, 1H, H11), 6.09(t, 1H, H4, J H4H5 ) 10.64 Hz),
5.90 (s, 1H, H11), 5.71 (d, d, 1H, H5, J H4H5 ) 10.69 Hz, J H5H6
) 14.91 Hz), 5.61(q, d, H6, J H6Me ) 6.35 Hz, J H6H5 ) 14.91
Hz), 5.18(t, H3, J H3H4 ) 10.53 Hz), 3.69(1H, d, d, H2, J H1H2
)
7.58 Hz, J H2H3 ) 17.60 Hz), 3.54 (d, 1H, H9, J H8gem ) 16.92
Hz), 3.46 (d, 1H, H8, J H7gem ) 14.15 Hz), 3.24 (d, 1H, H8, J H7gem
) 14.13 Hz), 3.13 (d, 1H, H9, J H8gem ) 16.90 Hz), 2.76 (d, d,
H1, J H1gem ) 13.76 Hz, J H1H2 ) 6.85 Hz), 1.63 (d, 3H, Me, J MeH6
) 6.19 Hz); 13C NMR (CDCl3) δ 148.70 (Cipso), 139.15 (Cipso),
139.00 (Cipso), 138.68 (C10), 133.43, 132.72, 131.22 (C4),
129.54 (C6), 129.20, 128.48, 128.08, 128.04, 128.00, 126.96,
126.96, 126.86, 126.09, 125.32, 125.19 (C11), 57.33 (C2), 54.73
42.94 (C6); [R]26 ) +3.13° (c ) 0.82, CHCl3).
D
N-Ben zyl-N-[(2S)-1-p h en yl-3E,5-h exa d ien -2-yl]-N-[2-
(p h en ylsu lfon yl)-2-p r op en -1-yl]a m in e (E-21). This com-
pound was obtained from the reaction between amino diene
E-18 (0.21 g, 0.8 mmol), triethylamine (0.16 g, 1.6 mmol, 2
equiv), and 1,3-dichloro-2-(phenylsulfonyl)propane (0.20 g, 0.8
mmol) in the presence of hydroquinone (0.02 g, 0.21 mmol) in
90% (0.32 g) yield as a yellow syrup, after being chromato-
graphed on silica gel (1:3EtOAc/n-hexane): IR (neat) 3060,
3050, 3000, 2900, 2820, 1590, 1480, 1440, 1360, 1300, 1200,
1160, 1120, 1100, 1070, 1010, 990, 950, 740, 680 cm-1; 1H NMR
(CDCl3, 90 MHz) δ 7.90-6.85 (m, 15H, Ph × 3), 6.49-6.00 (m,
1H, olefin proton), 6.28 (s, 1H, H10 or H10′), 5.70 (s, 1H, H10
or H10′), 5.86-5.47 (m, 2H, olefin proton), 5.20-4.98 (m, 2H,
H6, H6′), 3.73-2.60 (m, 7H, H2, methylene proton H1, H7 and
H8); 13C NMR (CDCl3) δ 148.31, 139.08, 138.99, 138.64, 136.28,
134.29, 133.40, 130.82, 129.43, 129.17, 128.39, 128.22, 128.05,
127.81, 127.01, 126.14 (C9), 125.21 (C10), 117.30 (C6), 62.47
(C8), 47.52 (C9), 39.33 (C1), 18.11 (C6); [R]27 ) +67.66° (c )
D
1.05, CHCl3); MS m/z 458(M + 1). HRMS (m/z): calcd for
C
29H32NSO2, M + 1, 458.2154; found, M+ + 1, 458.2105.
Isoin d ole Der iva tive 15. A solution of (3Z,5E)-14 (0.85
g, 1.86 mmol) in toluene (20 mL) was refluxed for 72 h. Then
the solvent was evaporated and the residue was chromato-
graphed on silica gel to give a epimeric mixture of cis-â-15
and cis-R-15 (0.83 g, 98%, R-15/â-15 ) 80/20), which was
purified by chromatography again.
Isoin d ole d er iva tive cis-â-15: mp 150.1-152.6 °C; IR
(neat) 3050, 2975, 2950, 2800, 1680, 1500, 1450, 1300, 1220,
(C2), 53.78 (C7), 47.89 (C8), 38.66 (C1); [R]26 ) +1.23° (c )
D
1
1140, 1080, 1030, 760, 700 cm-1; H NMR (CDCl3, 400 MHz)
0.60, CHCl3).
δ 7.74-7.73 (m, 2H, Ph), 7.65-7.61 (m, 1H, Ph), 7.48-7.45
(m, 2H, Ph), 7.34-7.22 (m, 6H, Ph), 7.20-7.13 (m, 4H, H11,
Ph), 5.40 (d, 1H, H4, J H4H3 ) 9.82 Hz), 4.88-4.83 (m, 1H, H3),
3.90 (d, 1H, H9, J gem ) 12.77 Hz), 3.36 (d, 1H, H8, J gem ) 11.90
Hz), 2.96(t, 1H, H2, J ) 5.97 Hz), 2.91-2.86 (m, 1H, H8), 2.87
(d, 1H, H9, J gem ) 12.68 Hz), 2.34 (d, 1H, H8, J gem ) 11.91
Hz), 2.29-2.21 (m, 2H, H1, H11), 2.09-1.97 (m, 1H, H5), 1.78-
1.71 (m, 2H, H6), 1.01 (d, 3H, H10, J MeH5 ) 6.93 Hz); 13C NMR
(CDCl3) δ 138.35 (Cipso), 138.14 (Cipso), 137.07 (Cipso),
133.31, 132.76 (C4), 130.80,129.45, 129.13, 128.59, 128.57,
128.24, 127.29, 126.47, 74.85(C1), 71.09 (C7), 58.95 (C8), 58.11
(C9), 43.31 (C2), 39.40 (C11), 33.94 (C6), 25.98 (C5), 21.15
N-Ben zyl-N-[(2S)-1-p h en yl-3Z,5-h exa d ien -2-yl]-N-[2-
(p h en ylsu lfon yl)-2-p r op en -1-yl]a m in e (Z-21). This com-
pound was obtained from the reaction between amino diene
Z-18 (0.21 g, 0.8 mmol), triethylamine (0.16 g, 1.6 mmol,
2equiv), and 1,3-dichloro-2-(phenylsulfonyl)propane (0.20 g, 0.8
mmol) in the presence of hydroquinone (0.02 g, 0.21 mmol) in
76% (0.27 g) yield as a yellow syrup, after being chromato-
graphed on silica gel (1:3EtOAc/n-hexane): IR (neat) 3090,
3060, 2925, 2825, 1600, 1580, 1500, 1450, 1370, 1300, 1220,
1170, 1140, 1120, 1080, 1020, 1000, 970, 900, 740, 690 cm-1
;
1H NMR (CDCl3, 90 MHz) δ 7.87-6.80 (m, 15H, Ph × 3), 6.34
(s, 1H, H10 or H10′), 6.27-6.48 (m, 2H, olefin protons), 5.88
(s, 1H, H10 or H10′), 5.49-4.89 (m, 3H, olefin protons), 3.87-
2.40 (m, 7H, H2, methylene protons); 13C NMR (CDCl3) δ
(C10); MS m/z 458(M + 1). HRMS (m/z): calcd for C29H32
-
NSO2, M + 1, 458.2154; found, M+ + 1, 458.2144. Anal. Calcd

Halogenovinyl Sulfones
J . Org. Chem., Vol. 63, No. 21, 1998 7179
5.81 (m, 1H, H4), 5.62 (d, d, 1H, H3, J H3H2 ) 3.95 Hz, J H3H4
148.74, 139.23, 138.73, 138.56, 133.40, 133.05, 131.67, 129.46,
129.17, 128.83, 128.44, 128.35, 128.26, 128.13, 128.03, 127.01,
126.12, 125.19 (C10), 118.88 (C6), 57.69 (C2), 54.67 (C7), 47.85
)
10.34 Hz), 4.05 (d, 1H, H8 or H9, J gem ) 13.40 Hz), 3.20 (d,
1H, H8 or H9, J gem ) 12.96 Hz), 3.56-2.44 (m, 6H, H1, H2,
H8, H9, H10), 2.13-1.63 (m, 4H, H5, H6); 13C NMR (CDCl3) δ
139.12 (Cipso), 136.65 (Cipso), 133.59, 130.17, 129.37, 128.91,
128.76, 128.50, 128.35, 128.31, 126.94, 126.16, 124.97, 68.87
(C7), 67.85 (C1), 59.61 (C8), 57.45 (C10), 40.65 (C2), 36.23 (C9),
28.11 (C6), 20.82 (C5); MS (FAB) m/z 444 (M+ + 1). FAB
HRMS (m/z): calcd for C28H30NSO2, M + 1, 444.2013; found,
M+ + 1, 444.1997.
(C8), 39.33 (C1); [R]26 ) +17.18° (c ) 0.67, CHCl3).
D
Isoin d ole d er iva tive cis-â-22 (fr om E-21): 83% yield as
white crystals; mp 141.0-141.8 °C; IR (neat) 3030, 3020, 2980,
2820, 2800, 1740, 1610, 1590, 1500, 1450, 1300, 1220, 1040,
1080, 1030, 1000, 760, 700, 660 cm-1 1H NMR (CDCl3, 90
;
MHz) δ 7.72-6.84 (m, 15H, Ph × 3), 5.92-5.60 (m, 1H, H4),
5.23 (d, d, 1H, H3, J H3H2 ) 4.28 Hz, J H3H4 ) 10.60 Hz), 4.01
(d, 1H, H8 or H9, J gem ) 13.07 Hz), 3.32 (d, 1H, H8 or H9,
J gem ) 11.76 Hz), 3.05-1.45 (m, 8H, H1, H2, H5, H6, H10),
2.90 (d, 1H, H8 or H9, J gem ) 12.96 Hz), 2.12 (d, 1H, H8 or
H9, J gem ) 11.75 Hz); 13C NMR (CDCl3) δ 138.14 (Cipso),
137.80 (Cipso), 136.97 (Cipso), 133.01, 130.28, 129.61, 128.59,
128.48, 128.35, 128.16, 127.16, 127.01, 126.31, 126.18, 71.94-
(C1), 68.65 (C7), 61.00 (C8), 57.29 (C10), 43.04 (C2), 37.27 (C9),
26.89 (C6), 21.45 (C5). Anal. Calcd for C28H29NSO2: C, 75.81;
Ack n ow led gm en t. We thank Mr. Takeya Ando,
Osaka University, for useful suggestions for MOPAC
PM3 calculations and Kissei Pharmaceutical Co., Ltd.,
for NMR measurements and valuable discussions.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of each new compound, vibrational spectra, x-ray
crystallographic data for 7c, 9c, cis-â-16, and cis-â-23, and
synthetic procedures of 2a -c, 3a -c, and (2R)-2-{N-benzyl-N-
[2-(phenylsulfonyl)-2-propenyl]}amino-3-phenyl-1-propanal (73
pages). This material is contained 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.
H, 6.59; N, 3.16. Found: C, 76.00; H, 6.60; N, 3.16. [R]26
+1.47° (c ) 0.46, CHCl3).
)
D
Isoin d ole Der iva tives cis-â-22, a n d cis-r-22 fr om Z-21.
Isoin d ole d er iva tive cis-â-22: 81% yield as white crystals;
mp 138.4-140.3 °C.
Isoin d ole d er iva tive cis-r-22: 15% yield as a yellow syrup;
IR (neat) 3070, 3050, 2950, 2850, 1730, 1610, 1590, 1500, 1400,
1370, 1300, 1220, 1150, 1090, 1080, 1030, 1000, 750, 700 cm-1
;
1H NMR (CDCl3, 90 MHz) δ 7.97-7.00 (m, 15H, Ph × 3), 6.10-
J O980181B