Synthesis of functionalized chromanes via a formal [3 + 3] cycloaddition of allene sulfonamides to phenols

Article abstract of DOI:10.3987/COM-09-S(S)54

The Bronsted acid catalyzed formal [3 + 3] cycloaddition reaction of allene sulfonamides 1 with phenols 2 provides functionalized chromanes. This formal [3 + 3] cycloaddition reaction is proposed to proceed via a stepwise process involving intermolecular hydroarylation followed by intramolecular cyclization.

Full text of DOI:10.3987/COM-09-S(S)54

HETEROCYCLES, Vol. 80, No. 1, 2010
187
HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 187 - 198. © The Japan Institute of Heterocyclic Chemistry
Received, 15th July, 2009, Accepted, 18th August, 2009, Published online, 19th August, 2009
DOI: 10.3987/COM-09-S(S)54
SYNTHESIS OF FUNCTIONALIZED CHROMANES VIA A FORMAL [3
+ 3] CYCLOADDITION OF ALLENE SULFONAMIDES TO PHENOLS
Ken Hashimoto, Yoshikazu Horino,* and Shigeyasu Kuroda*
Department of Chemistry, Graduate School of Science and Engineering
University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan; E-mail:
horino@eng.u-toyama.ac.jp, kuro@eng.u-toyama.ac.jp
Abstract – The Brønsted acid catalyzed formal [3 + 3] cycloaddition reaction of
allene sulfonamides 1 with phenols 2 provides functionalized chromanes. This
formal [3 + 3] cycloaddition reaction is proposed to proceed via a stepwise
process involving intermolecular hydroarylation followed by intramolecular
cyclization.
The transition metal catalyzed intramolecular addition of phenolic oxygen nucleophiles to alkenes1 and
the hydroarylation2 of oxygen-tethered arene-ene substrates are two of the most promising strategies for
the synthesis of chromanes, which are of great interest due to their potentially broad range of biological
activities.3 Furthermore, intermolecular reactions, which are an attractive and much simpler strategy for
the synthesis of chromanes from commercially available phenols and allylic alcohols4 or 1,3-dienes,5 have
also been extensively studied. A few approaches for the synthesis of chromanes which do not involve
metal based catalysts, such as direct aromatic carbon-oxygen bond formation using tertiary phosphines,6
8
amines7 or Ipy2BF4 as a catalyst, or stoichiometric amount of hypervalent iodine reagent,9 have also been
reported. However, Brønsted acid catalyzed approaches are particularly rare.10 We envisioned that
regioselective intermolecular hydroarylation at the terminal sp2 carbon atom of an allene possessing an
electron withdrawing group (EWG) with phenols could be a straightforward approach to the direct
formation of the corresponding chromanes upon intramolecular addition of the phenolic hydroxy group to
the internal allenic double bond (eq. 1). However, selective intermolecular nucleophilic addition to the
terminal sp2 carbon atom rather than the central carbon atom of allenes is usually difficult11 as the vinyl
anion generated is less stable.12

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HETEROCYCLES, Vol. 80, No. 1, 2010
H+
+
(1)
+
EWG HO
EWG HO
EWG
O
H+
EWG
HO
To overcome this problem, we decided to use the easily prepared allene sulfonamides 113 as their terminal
sp2 carbon double bond has been found to behave as an enone toward heteronucleophiles.13b Thus, allene
sulfonamide 1a reacts with phenol to form a carbon-oxygen bond at the terminal sp2 carbon atom of the
allene. During the course of our study aimed at the synthesis of chromanes by a formal [3 + 3]
cycloaddition reaction as shown in equation (1), we found that addition of a catalytic amount of a
Brønsted acid to a mixture of 1a and p-cresol (2a; 2.0 equiv) completely suppresses carbon-oxygen bond
formation at the terminal sp2 carbon atom of the allene bond to give 4, and the only product of the
reaction (3a) is that resulting from a formal [3 + 3] cycloaddition reaction via a hydroarylation/cyclization
pathway (Table 1).
Table 1. Catalyst screening for the synthesis of chromane derivative 3aa)
Me
O
Me
OH
Me
O
5% catalyst
O
NTs
O
NTs
O
NTs
o
CH Cl , 50 C
2
2
O
O
O
1a
2a
3a
4
entry
1
catalyst
none
CSAb)
time
3a (%)
9
4 (%)
2 h
55
0
2
12 h
62
3
p-TsOH c)
TfOH d)
Tf2NH e)
Tf2NH
45 min
<5 min
5 min
60 min
15 min
67
0
4
78
0
5
82
0
6 f)
7 g)
79
0
Tf2NH
81
0
a) A mixture of 1a (1.0 equiv), 2a (2.0 equiv) and catalyst (0.05 equiv) in CH2Cl2 at 50 oC. b) Camphor
sulfonic acid. c) p-Toluenesulfonic acid. d) Trifluoromethanesulfonic acid. e) Trifluoromethanesulfonimde. f)
2% of Tf2NH was used. g) Reaction was carried out at room temperature.
We examined several Brønsted acids and found that the reaction rate increased with the acidity of the
Brønsted acid (TfOH > Tf2NH > p-TsOH > CSA). The use of a strong Brønsted acid such as
trifluoromethanesulfonic acid (TfOH) or trifluoromethanesulfonimide (Tf2NH) gave the best catalytic
activity (entries 4 and 5). Furthermore, the use of Tf2NH as a catalyst allowed a lower catalyst loading
with no effect on the yield of 3a (entry 6). It should be noted that the reaction could be carried out at room

HETEROCYCLES, Vol. 80, No. 1, 2010
189
temperature (entry 7). To the best of our knowledge, there are no reports of the Brønsted acid catalyzed
hydroarylation of allenes at room temperature.14
Table 2. Formal [3 + 3] cycloaddition of 1a or 1b to phenolsa)
OH
X
2.5% Tf NH
2
O
CH Cl
2
2
O
N
O
N
room temp. 1-2 h
Ts
Ts
X
O
O
1a (R = Ts)
2
3
1b (R = Bz)
Entry
1
Phenols
OH
Products (%)
X
1
2
3
4
5
1a
1a
1a
1a
1b
2b (X = OMe)
2c (X = Br)
2d (X = I)
2e (X = Bpin)
2a (X = Me)
3b (X = OMe, 85)
3c (X = Br, 30)
3d (X = I, 45)
3e (X = Bpin, 43)
3f (X = Me, 79)
O
O
O
N
N
R
X
OH
OH
6
1a
2f
O
O
HO
HO
O
Ts
3g (69)
OH
O
O
O
7
1a
1a
2g
O
N
N
O
N
Ts
Ts
5a (40)
3h (24)
HO
R
8
9
2h (R = Me)
2i (R = OH)
O
O
O
O
O
R
N
O
Ts
Ts
3j (15)
3i (R = Me, 36)
3k (R = OH, 59)
OH
OH
10
11
1a
1a
2j
O
O
O
O
N
O
N
Ts
Ts
5b (27)
3l (24)
HO
2k
O
O
O
N
Ts
3m (82)
a) 1a or 1b (1.0 equiv), 2a (2.0 equiv) and Tf2NH (0.025 equiv) were used.15

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HETEROCYCLES, Vol. 80, No. 1, 2010
Under the optimized reaction conditions in hand, the scope of the reaction was investigated with a variety
of functionalized phenols (see Table 2). The reaction feature has turned out to occur dependently of the
electronic nature of the substituent on the benzene ring. For example, substrates containing electron
donating group afforded the desired products 3b in excellent yield (entry 1), whereas the presence of an
electron withdrawing group resulted in a much longer reaction time and the corresponding products were
obtained in only modest yield (entries 2-4). The structure of 3a was confirmed unequivocally by X-ray
diffraction (Figure 1). Likewise, an electron-withdrawing group on the nitrogen of 1a is essential for the
present reaction. Thus, while the use of 1b, which possesses a benzoyl group on nitrogen, also provided
the corresponding chromanes 3f in high yield (entry 5), changing this substituent to a benzyl group
resulted in none of the desired product being obtained. Trimethylhydroquinone (2f), which is used in the
synthesis of tocopherol,10 also gave the corresponding chromane 3g in excellent yield (entry 6). As for
asymmetrical substrates, o-cresol (2g) afforded the desired product 3h in low yield along with the
hydroarylation product 5a (entry 7). The stereochemistry of 5a was determined to be E by NOE
experiments. A similar result was obtained with m-cresol (2h; entry 8), whereas resorcinol (2i) gave 3k in
rather better yield (entry 9). 1-Naphthol (2j) also reacted in a similar manner to 2a to give a mixture of 3l
and 5b respectively (entry 10). In contrast, the reaction with 2-naphthol (2k) afforded the desired tricyclic
product 3m selectively in excellent yield (entry 11).
O
O
O
S
N
O
S
O
O
N
O
O
O
Figure 1. X-Ray structure of 3a (left, CCDC 739400) and 3n (right, CCDC 739401).
Interestingly, substrates 1c and 1d, which possess a substituent at the C5 position on the 2-oxazolidinone
ring, reacted with 2a to give desired products 3n and 3o, respectively, in good to excellent yield (Scheme
1). Compound 3n was obtained with very high diastereoselectivity, thereby suggesting that a
carbocationic intermediate generated via an enamide is involved in the intramolecular addition of the
hydroxyl group of 2a in the second step. The structure of 3n was also confirmed by X-ray diffraction
analysis (Figure 1).

HETEROCYCLES, Vol. 80, No. 1, 2010
191
Me
2
2
R
R
OH
1
1
R
R
2% Tf NH
O
2
N
O
N
O
Ts
CH Cl
Ts
2
2
o
50 C
O
O
Me
1
2
1
2
2a (2.0 equiv.)
1c (R =H, R =Ph)
3n (R =H, R =Ph, 73%, >99:1 dr)
1
2
1
2
1d (R =R =Me)
3o (R =R =Me, 68%)
Scheme 1. Substituent effects at the C5 position in 1c and 1d.
In conclusion, we have demonstrated that allene sulfonamides 1a-d undergo a formal [3 + 3]
cycloaddition with phenols under mild reaction condition in the presence of a catalytic amount of a
Brønsted acid to give the corresponding functionalized chromanes in good to excellent yield. This
reaction follows a hydroarylation/cyclization pathway and is a rare example of a selective intermolecular
hydroarylation at the terminal sp2 carbon atom of an allenic double bond which does not require the
presence of a metal based catalyst. Further work concerning the scope of this reaction is currently
underway and will be reported in due course.
ACKNOWLEDGEMENTS
We gratefully acknowledge the Center for Instrument Analysis in University of Toyama.
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14. The reaction of N-benzyl-N-(1,2-propadienyl) p-toluenesulfonamide, 1-triphenylsilyl-1,2-
propadiene or 6-phenyl-1,2-hexadiene with p-cresol did not give the desired product under the
optimized reaction condition.
15. All melting points were obtained on a YANAKO melting apparatus and are uncorrected. Infrared
1
spectra were recorded on a Perkin Elmer FT/IR PARAGON 1000 spectrometer. The H NMR
spectra were determined in CDCl3 using CHCl3 as an internal reference with a JEOL-GX 400 FT
13
NMR. C NMR spectra were recorded on a JEOL-GX 400 spectrometer operating at 100 MHz

HETEROCYCLES, Vol. 80, No. 1, 2010
193
with complete proton decoupling and referenced to CDCl3 (77.0 ppm). High resolution mass spectra
were taken with a JEOL MStation JMS-700. Unless otherwise noted, all commercial materials were
used without purification. TLC analysis of reaction mixture was performed on Merck silica gel 60
F254 TLC plates. Flash chromatography was carried out on Merck 60 silica gel (32-63 m):
Spiro[6-methyl-3,4-dihydrochroman-2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3a): White
solid, mp 187.2-187.7 oC, Rf = 0.62 (50% EtOAc/hexane), purified by column chromatography over
silica gel (20% EtOAc/hexane) (82%); IR (KBr) 1085, 1125, 1164, 1193, 1283, 1377, 1498, 1596,
1789 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.26 (s, 3H), 2.27 (ddd, J = 2.0, 5.6, 13.6 Hz, 1H), 2.46
(s, 3H), 2.73 (ddm, J = 5.6, 17.2 Hz, 1H), 2.94 (dm, J = 17.2, 1H), 3.28 (dt, J = 5.6, 13.6 Hz, 1H),
4.12 (d, J = 9.2Hz, 1H), 4.23 (d, J = 9.2 Hz, 1H), 6.62 (d, J = 8.4 Hz, 1H), 6.94 (s, 1H), 6.98 (d, J
= 8.4 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ
20.5, 21.7, 22.6, 29.2, 73.2, 92.9, 116.9, 119.7, 128.9, 129.2, 129.6, 129.8, 131.4, 135.1, 145.6,
149.5, 152.3; HRMS: (EI) m/z Calcd. for C19H19NO5S: 373, Found (relative intensity): 373 (M+,
100), 155 (71); Anal. Calcd for C19H19NO5S: C, 61.11; H, 5.13; N, 3.75; S, 8.59, Found: C, 61.29;
H, 5.17; N, 3.78; S, 8.62. Spiro[6-methoxyl-3,4-dihydrochroman-2,4'-(3'-p-toluensulfonyl)-
o
oxazolidin]-2'-one (3b): White solid, mp 190.0-190.8 C, Rf = 0.51 (50% EtOAc/hexane), purified
by column chromatography over silica gel (20% EtOAc/hexane) (85%); IR (KBr): 1037, 1165,
1217, 1282, 1336, 1497, 1794 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.29 (ddd, J = 2.0, 5.2, 13.2 Hz,
1H), 2.48 (s, 3H), 2.78 (ddm, J = 5.2, 16.8 Hz, 1H), 2.97 (ddd, J = 2.0, 5.2, 16.8 Hz, 1H), 3.30 (dt,
J = 13.2, 5.2 Hz, 1H), 3.77 (s, 3H), 4.14 (d, J = 9.6 Hz, 1H), 4.25 (d, J = 9.6 Hz, 1H), 6.65 (d, J =
2.8 Hz, 1H), 6.67 (d, J = 8.8 Hz, 1H), 6.76 (dd, J = 2.8, 8.8 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 8.05
(d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 21.7, 22.9, 29.1, 55.7, 73.0, 92.9, 113.5, 114.5,
117.9, 120.6, 129.2, 129.7, 135.0, 145.5, 145.6, 152.3, 154.5; HRMS: (EI) m/z Calcd. for
C19H19NO6S: 389.0933, Found: 389.0926. Spiro[6-bromo-3,4-dihydrochroman-2,4'-(3'-p-
o
toluensulfonyl)oxazolidin]-2'-one (3c): White solid, mp 201.1-202.0 C, Rf = 0.58 (50%
EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (30%);
1
IR (KBr): 1087, 1124, 1164, 1205, 1279, 1378, 1477, 1792 cm-1; H NMR (CDCl3, 400 MHz): δ
2.32 (ddd, J = 2.0, 5.6, 13.6 Hz, 1H), 2.48 (s, 3H), 2.78 (ddm, J = 5.6, 17.2 Hz, 1H), 2.97 (ddd, J =
2.0, 5.6, 17.2 Hz, 1H), 3.30 (dt, J = 13.6, 5.6 Hz, 1H), 4.16 (d, J = 9.2 Hz, 1H), 4.24 (d, J = 9.0 Hz,
1H), 6.64 (d, J = 9.2 Hz, 1H), 7.28 (s, 1H), 7.29 (d, J = 9.2 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 8.03
(d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 21.8, 22.4, 28.8, 73.1, 92.9, 114.3, 118.9,
122.1, 129.3, 129.7, 131.3, 131.9, 134.9, 145.9, 150.8, 152.0; HRMS: (EI) m/z Calcd. for
C18H16BrNO5S:
436.9933,
Found:
436.9939.
Spiro[6-iodo-3,4-dihydrochroman-2,4'-
o
(3'-p-toluensulfonyl)oxazolidin]-2'-one (3d): White solid, mp 198.3-199.1 C, Rf = 0.55 (50%

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HETEROCYCLES, Vol. 80, No. 1, 2010
EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (45%);
1
IR (KBr): 1084, 1124, 1164, 1204, 1279, 1376, 1474, 1793 cm-1; H NMR (CDCl3, 400 MHz): δ
2.29 (ddd, J = 2.0, 5.2, 13.2 Hz, 1H), 2.48 (s, 3H), 2.78 (ddm, J = 5.2, 16.8 Hz, 1H), 2.97 (ddd, J =
2.0, 5.2, 16.8 Hz, 1H), 3.30 (dt, J = 5.6, 13.2 Hz, 1H), 4.14 (d, J = 9.6 Hz, 1H), 4.25 (d, J = 9.6 Hz,
1H), 6.52 (d, J = 9.2 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.45-7.48 (m, 2H), 8.02 (d, J = 8.4 Hz, 2H).
13C NMR (CDCl3, 100 MHz): δ 21.8, 22.2, 28.7, 73.1, 84.4, 92.9, 119.3, 122.7, 129.3, 129.6, 134.8,
137.1, 137.9, 145.8, 151.6, 152.0; HRMS: (EI) m/z Calcd. for C18H16INO5S: 484.9794, Found:
484.9783.
Spiro[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)-2,4'-(3'-p-toluensulfonyl)-
o
oxazolidin]-2'-one (3e): White solid, mp 232.2-235.3 C, Rf = 0.52 (50% EtOAc/hexane), purified
by column chromatography over silica gel (20% EtOAc/hexane) (43%); IR (KBr): 1084, 1164,
1
1274, 1359, 1795 cm-1; H NMR (CDCl3, 400 MHz): δ 1.34 (s, 12H) 2.33 (ddd, J = 1.6, 5.2, 13.6
Hz, 1H), 2.48 (s, 3H), 2.78 (ddm, J = 5.6, 16.8 Hz, 1H), 3.02 (ddd, J = 1.6, 4.4, 16.8 Hz, 1H), 3.31
(dt, J = 13.6, 5.6 Hz, 1H), 4.16 (d, J = 9.6 Hz, 1H), 4.24 (d, J = 9.6 Hz, 1H), 6.73 (d, J = 8.4 Hz,
1H), 7.37 (d, J = 8.4 Hz, 2H), 7.62 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 2H). 13C
NMR (CDCl3, 100 MHz): δ 21.8, 22.3, 24.81, 24.84, 29.2, 73.3, 83.8, 93.1, 116.6,, 119.4, 129.3
129.7, 134.9, 135.0, 136.3, 145.7, 152.2, 154.3; HRMS: (EI) m/z Calcd. for C24H28BNO7S:
485.1680, Found: 485.1685. Spiro[6-methyl-3,4-dihydrochroman-2,4'-(3'-benzoyl)oxazolidin]-
o
2'-one (3f): White solid, mp 100-100.5 C, Rf = 0.45 (50% EtOAc/hexane), purified by column
chromatography over silica gel (20% EtOAc/hexane) (79%); IR (KBr): 1088, 1126, 1219, 1306,
1
1340, 1382, 1450, 1498, 1699, 1794 cm-1; H NMR (CDCl3, 400 MHz): δ 2.16 (ddd, J = 2.4, 5.2,
13.2 Hz, 1 H), 2.28 (s, 3 H), 2.81 (ddm, J = 5.6, 16.8 Hz, 1 H), 2.96 (ddd, J = 2.4, 6.0, 16.8 Hz, 1
H), 3.13 (dt, J = 6.0, 13.2 Hz, 1H), 4.27 (d, J = 9.2 Hz, 1 H), 4.42 (d, J = 9.2 Hz, 1 H), 6.82 (d, J =
8.4 Hz, 1 H), 6.93 (s, 1H), 6.98 (d, J = 8.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.58 (d, J = 7.6 Hz,
1H), 7.71 (d, J = 7.6 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 20.5, 22.4, 26.9, 73.1, 117.4, 119.6,
128.1, 128.8, 129.1, 129.3, 131.0, 132.9, 133.7, 149.9, 153.7, 169.3; HRMS: (EI) m/z Calcd. for
C19H17NO4: 323.1158, Found: 323.1153. Spiro[5,7,8-trimethyl-6-hydroxy-3,4-dihydrochroman-
2,5'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3g): White solid, mp 196.2-197.0 oC, Rf = 0.50 (50%
EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (69%);
1
IR (KBr): 1087, 1160, 1278, 1371, 1456, 1636, 1788, 2924, 3566 cm-1; H NMR (CDCl3, 400
MHz): δ 1.89 (s, 3H), 2.13 (s, 3H), 2.15 (s, 3H), 2.34 (ddd, J = 1.6, 6.0, 13.2 Hz, 1H), 2.46 (s, 3H),
2.58 (ddm, J = 6.0, 16.8 Hz, 1H) ), 2.99 (dd, J = 5.2, 16.8 Hz, 1H), 3.28 (dt, J = 6.0, 13.2 Hz, 1H),
4.10 (d, J = 9.6 Hz, 1H), 4.29 (d, J = 9.6 Hz, 1H), 4.40 (brs, 1H), 7.34 (d, J = 8.4 Hz, 1H), 8.08 (d,
J = 8.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 11.5, 11.9, 12.2, 21.3, 21.7, 29.2, 72.3, 92.7, 116.5,
118.6, 122.3, 123.2, 129.3, 129.6, 135.2, 143.5, 145.5, 146.4, 152.5; HRMS: (EI) m/z Calcd. for

HETEROCYCLES, Vol. 80, No. 1, 2010
195
C21H23NO6S: 417.1246, Found 417.1235. Spiro[8-methyl-3,4-dihydrochroman-2,4'-(3'-p-
o
toluensulfonyl)oxazolidin]-2'-one (3h) : White solid, mp 161.0-162.0 C, Rf = 0.51 (50%
EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (24%);
1
IR (KBr): 1086, 1125, 1163, 1280, 1376, 1468, 1794 cm-1; H NMR (CDCl3, 400 NHz): δ 2.03 (s,
3H), 2.33 (ddd, J = 1.6, 5.6, 13.2 Hz, 1H), 2.46 (s, 3H), 2.79 (ddm, J = 5.6, 17.2 Hz, 1H), 3.03 (ddd,
J = 1.6, 5.6, 17.2 Hz, 1H), 3.32 (dt, J = 5.6, 13.2 Hz, 1H), 4.16 (d, J = 9.6 Hz, 1H), 4.25 (d, J = 9.6
Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H), 6.97 (d, J = 7.2 Hz, 1H), 7.02 (d, J = 7.2 Hz, 1H), 7.35 (d, J =
8.0 Hz, 2H), 8.09 (d, J = 8.0 Hz, 2H).13C NMR (CDCl3, 100 MHz): δ 15.8, 21.7, 22.8, 29.1, 73.1,
93.1, 119.6, 121.6, 126.77, 126.80, 129.3, 129.5, 129.6, 135.2, 145.6, 149.9, 152.3; HRMS: (EI) m/z
Calcd. for C19H19NO5S: 373.0984, Found: 373.0987. Spiro[7-methyl-3,4-dihydrochroman-
2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3i): Isolated as an inseparable mixture of 3j; white
solid, Rf = 0.42 (50% EtOAc/hexane), purified by column chromatography over silica gel (20%
EtOAc/hexane) (36%); IR (KBr): 1084, 1121, 1180, 1281, 1377, 1458, 1792 cm-1; 1H NMR (CDCl3,
400 NHz): δ 2.27-2.33 (m, 1 H), 2.31 (s, 3H), 2.49 (s, 3H), (ddm, J = 5.2, 16.4 Hz, 1H), 2.96 (dm, J
= 16.4 Hz, 1H), 3.29 (dt, J = 5.6, 13.6 Hz, 1H), 4.15 (d, J = 9.6 Hz, 1H), 4.26 (d, J = 9.6 Hz, 1H),
6.57 (s, 1H), 6.78 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 8.07 (d, J =
8.4 Hz, 2H); HRMS: (EI) m/z Calcd. for C19H19NO5S: 373.0984, Found: 373.0988. Spiro[5-
methyl-3,4-dihydrochroman-2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3j): Isolated as an
inseparable mixture of 3i; white solid, Rf = 0.42 (50% EtOAc/hexane), purified by column
1
chromatography over silica gel (20% EtOAc/hexane) (15%): H NMR (CDCl3, 400 NHz): δ
2.27-2.33 (m, 1 H), 2.31 (ddm, J = 5.2, 16.4 Hz, 1H), 2.96 (dm, J = 16.4 Hz, 1H), 3.29 (dt, J = 5.6,
13.6 Hz, 1H), 4.15 (d, J = 9.6 Hz, 1H), 4.26 (d, J = 9.6 Hz, 1H), 6.57 (s, 1H), 6.78 (d, J = 7.6 Hz,
1H), 7.01 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 8.4 Hz, 2H).
Spiro[7-hydroxy-3,4-dihydrochroman-2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3k): White
solid, mp 215.3-216.1 oC, Rf = 0.34 (50% EtOAc/hexane), purified by column chromatography over
silica gel (20% EtOAc/hexane) (59%); IR (film): 1084, 1163, 1272, 1366, 1456, 1624, 1782, 3465
cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.29 (ddd, J = 2.0, 5.2, 13.6 Hz, 1H), 2.47 (s, 3H), 2.70 (ddm,
J = 5.2, 16.8 Hz, 1H), 2.92 (ddm, J = 5.2, 16.8 Hz, 1H), 3.28 (dt, J = 6.0, 13.6 Hz, 1H), 4.15 (d, J =
9.6 Hz, 1H), 4.26 (d, J = 9.6 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H), 6.47 (dd, J = 2.4, 8.4 Hz, 1H), 6.97
13
(d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 2H); C NMR (CDCl3, 100
MHz): δ 21.7, 21.9, 29.3, 73.2, 93.0, 103.8, 109.8, 112.1, 129.3, 129.7, 130.0, 135.0, 145.7, 152.3,
152.5, 155.8; HRMS: (EI) m/z Calcd. for C18H17NO6S: 375.0777, Found: 375.0777.
Spiro[3,4-dihydrobenzo[h]chroman-2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3l) : White
solid, mp 214.7-215.3 oC, Rf = 0.50 (50% EtOAc/hexane), purified by column chromatography over

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HETEROCYCLES, Vol. 80, No. 1, 2010
silica gel (20% EtOAc/hexane) (24%); IR (film) 1085, 1160, 1280, 1372, 1457, 1508, 1542, 1791,
2924, 3566 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.44 (ddd, J = 2.0, 6.0, 13.6 Hz, 1H), 2.53 (s, 3H),
2.94 (ddm, J = 5.6, 13.6, 16.8 Hz, 1H), 3.13 (ddd, J = 2.0, 6.0, 16.8 Hz, 1H), 3.45 (dt, J = 6.0, 13.6
Hz, 1H), 4.20 (d, J = 9.6 Hz, 1H), 4.30 (d, J = 9.6 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.27-7.42 (m,
3H), 7.45-7.51 (m, 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H), 8.14 (dm, J = 8.4 Hz,
2H); 13C NMR (CDCl3, 100 MHz): δ 21.8, 22.9, 28.9, 73.0, 93.4, 114.2, 121.2, 121.7, 124.8, 125.6,
126.3, 126.7, 127.6, 129.5, 129.8, 133.4, 135.2, 145.7, 146.3, 152.5; HRMS: (EI) m/z Calcd. for
C22H19NO5S: 409.0984, Found 409.0982.
Spiro[3,4-dihydrobenzo[f]chroman-2,4'-(3'-p-
o
toluensulfonyl)oxazolidin]-2'-one (3m) : White solid, mp 234.2-235.3 C, Rf = 0.53 (50%
EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (82%);
1
IR (KBr): 1084, 1164, 1280, 1378, 1596, 1793 cm-1; H NMR (CDCl3, 400 MHz): δ 2.49 (s, 3H),
2.50 (m, 1H), 2.90 (m, 1H), 3.41-3.50 (m, 2H), 4.24 (d, J = 10.0 Hz, 1H), 4.29 (d, J = 10.0 Hz, 1H),
6.94 (d, J = 8.8 Hz, 1H), 7.39-7.45 (m, 2H), 7.56 (dt, J = 1.2, 8.0 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H),
7.81-7.83 (m, 2H), 8.11 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 19.5, 21.8, 28.8, 72.8,
92.7, 112.4, 118.3, 122.0, 124.4, 127.1, 128.6, 129.1, 129.3, 129.5, 129.8, 132.2, 135.0, 145.7,
149.1, 152.3; HRMS: (EI) m/z Calcd. for C22H19NO5S: 409.0984, Found: 409.0978. Spiro[6-
methyl-3,4-dihydrochroman-2,4'-(5’-phenyl-3'-p-toluensulfonyl)oxazolidin]-2'-one (3n): White
solid, mp 188.9-189.6 oC, Rf = 0.65 (50% EtOAc/hexane), purified by column chromatography over
1
silica gel (20% EtOAc/hexane) (73%); IR (KBr): 1070, 1164, 1379, 1498, 1790 cm-1; H NMR
(CDCl3, 400 MHz): δ 1.99 (ddd, J = 2.0, 5.6, 14.0 Hz, 1H), 2.30 (s, 3 H), 2.38 (ddm, J = 6.0, 17.2
Hz, 1H), 2.49 (s, 3H), 2.56 (ddd, J = 2.0, 6.0, 17.2 Hz, 1H), 3.18 (dt, J = 6.0, 13.6 Hz, 1H), 5.21 (s,
1H), 6.67 (d, J = 8.4 Hz, 1H ), 6.89 (s, 3H), 7.00 (d, J = 8.4 Hz, 1H), 7.30 (dd, J = 1.6, 8.0 Hz, 2H),
7.35-7.47 (m, 5H), 8.07 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 20.5, 21.8, 21.9, 25.5,
85.3, 96.1, 116.9, 120.2, 127.8, 128.7, 129.0, 129.2, 129.6, 129.9, 130.3, 130.5, 133.0, 135.1, 145.6,
149.4, 152.6; HRMS: (EI) m/z Calcd. for C25H23NO5S: 449.1297, Found: 449.1291. Spiro[6-
methyl-3,4-dihydrochroman-2,4'-(5’,5’-dimethyl-3'-p-toluensulfonyl)oxazolidin]-2'-one (3o):
White solid, mp 185.2-185.9 oC, Rf = 0.60 (50% EtOAc/hexane), purified by column
chromatography over silica gel (20% EtOAc/hexane) (68%); IR (film): 899, 922, 991, 1085, 1174,
1221, 1276, 1350, 1376, 1453, 1497, 1596, 1784, 2924 cm-1; 1H NMR (400 MHz, CDCl3): δ 1.22 (s,
3 H), 1.52 (s, 3 H), 2.28 (s, 3 H), 2.40 (ddd, J = 2.8, 4.8, 14.0 Hz, 1 H), 2.47 (s, 3 H), 2.70 (ddm, J
= 5.2, 16.8 Hz, 1H), 2.94 (ddd, J = 2.4, 5.6, 16.8 Hz, 1H), 3.42 (dt, J = 6.0, 14.0 Hz, 1 H), 6.60 (d,
J = 8.4 Hz, 1 H), 6.91 (s, 1H), 6.98 (d, J = 8.4 Hz, 1 H), 7.33 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.4
Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 20.5, 21.7, 22.8, 22.9, 23.4, 24.8, 87.2, 97.2, 115.6, 119.9,
128.9, 129.0, 129.4, 129.9, 130.9, 135.3, 145.4, 150.9; HRMS: (EI) m/z Calcd. for C21H23NO5S:

HETEROCYCLES, Vol. 80, No. 1, 2010
197
401.1297,
Found:
401.1295.
(E)-3-(p-Toluenesulfonyl)-4-(2-p-tolyloxyethylidene)-
oxazolidin-2-one (4): White solid, mp 104.2-105.0 oC, Rf = 0.52 (50% EtOAc/hexane), purified by
column chromatography over silica gel (20% EtOAc/hexane) (55%); IR (film): 1088, 1160, 1278,
1378, 1456, 1509, 1542, 1783, 2923 cm-1; 1H NMR(CDCl3, 400 MHz): δ 2.30 (s, 3H), 2.46 (s, 3H),
4.52 (dt, J = 5.6, 1.2 Hz, 2H), 4.94 (dt, J = 2.4, 1.2 Hz, 2H), 6.30 (tt, J = 2.4, 5.6 Hz, 1H), 6.77 (d, J
= 8.0, 2H), 7.09 (d, J = 8.0 Hz, 2H), 7.94 (d, J = 8.0 Hz, 2H); 13C NMR(CDCl3,100 MHz): δ 20.5,
21.7, 63.6, 66.1, 102.3, 114.5, 128.3, 129.9, 130.0, 130.1, 130.9, 134.2, 146.3, 151.5, 155.7; HRMS:
(EI) m/z Calcd. for C22H19NO5S: 373.0984, Found: 373.0985. (E)-4-[2-(4-Hydroxy-3-
methylphenyl)-ethylidene]-3-(p-toluenesulfonyl)-oxazolidin-2-one (5a): Yellow solid, mp
o
115.1-116.5 C, Rf = 0.29 (50% EtOAc/hexane), purified by column chromatography over silica gel
(20% EtOAc/hexane) (40%); 1H NMR(CDCl3, 400 MHz): δ 2.23 (s, 3H), 2.46 (s, 3H), 3.17 (d, J =
8.0 Hz, 2H), 4.78 (s, 1H), 4.82 (m, 2H), 6.16 (tt, J = 2.4, 8.0 Hz, 1H), 6.71 (d, J = 8.0 Hz, 1H), 6.84
(dm, J = 8.0 Hz, 1H), 6.88 (s, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H); 13C
NMR(CDCl3,100 MHz): δ 15.8, 21.7, 31.9, 65.7, 106.9, 115.1, 124.1, 126.5, 128.2, 128.6, 129.9,
130.60, 130.64, 134.3, 146.1, 151.9, 152.6; HRMS: (EI) m/z Calcd. for C19H19NO5S: 373.0984,
Found:
373.0986.
(E)-4-[2-(4-Hydroxy-1-naphthalenyl)-ethylidene]-3-(p-toluenesulfonyl)-
o
oxazolidin-2-one (5b): White solid, mp 112.5-113.5 C, Rf = 0.60 (50% EtOAc/hexane), purified
by column chromatography over silica gel (20% EtOAc/hexane) (27%); IR (film): 1086, 1163,
1267, 1373, 1457, 1508, 1542, 1771, 3567 cm-1; 1H NMR(CDCl3, 400 MHz): δ 2.44 (s, 3H), 3.61 (d,
J = 7.2 Hz, 2H), 4.79 (m, 2H), 4.82 (m, 2H), 5.44 (brs, 1H), 6.29 (tt, J = 2.8, 7.2 Hz, 1H), 6.75 (d, J
= 7.6 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 7.28 (dm, J = 8.0 Hz, 2H), 7.52-7.57 (m, 2H), 7.82 (m, 1H),
7.87 (d, J = 8.6 Hz, 1H), 8.27 (m, 1H); 13C NMR(CDCl3,100 MHz): δ 21.7, 29.8, 65.7, 106.5, 107.9,
122.6, 123.3, 124.9, 125.2, 125.5, 126.8, 126.9, 128.1, 128.9, 129.9, 132.6, 134.2, 146.1, 150.9,
151.9; HRMS: (EI) m/z Calcd. for C22H19NO5S: 409.0984, Found: 409.0984. X-Ray Crystal
Strucutuer Analysis of Compound 3a (CCDC 739400)16: C19H19NO5S, Mr = 373.42
g/mol,
colorless plate, crystal size 0.40 x 0.40 x 0.40 mm, monoclinic, space group P21/c (#), a
=
9.223(8) Å, b = 12.854(10) Å, c = 15.780(8) Å, = 90o,  = 105.43(5)o,  = 90o, V = 1803(2) Å3, T
= 296 K, Z = 4, Dcalc = 1.375 g/cm3, 0.71069 Å, F(000) = 784,  cm-1, 5799
measured reflections, 4114 reflections with I > 0.00, 235 parameters, R = 0.156, wR = 0.091,
residual electron density +0.48 / -0.43 e Å -3. X-Ray Crystal Strucutuer Analysis of Compound
3n (CCDC 739401) 16: C25H23NO5S, Mr = 449.52 g/mol, colorless prismatic, crystal size 0.20 x
0.20 x 0.30 mm, orthorhombic, space group Pbca (#61) a = 20.654(6) Å, b = 17.908(6) Å, c =
11.846(5) Å, = 90o,  = 105.43(5)o,  = 90o, V = 4381(4) Å 3, T = 296 K, Z = 84, Dcalc = 1.363

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HETEROCYCLES, Vol. 80, No. 1, 2010
g/cm3, 0.71069 Å, F(000) = 1888.00,  cm-1,7044 measured reflections, 1804
reflections with I > 3.00, 289 parameters, R = 0.047, wR = 0.061, residual electron density
+0.16 / -0.20 e Å -3.
16. Crystallographic data for the structures in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication number CCDC 739400 and CCDC
739401. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44(0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk].