An o-iminothioquinone: Its cycloaddition to produce an indologlycoside and its self-dimerization to form a dithio-diazocycloctane, the structure assignment of which is based on the DFT prediction of its IR spectrum

Article abstract of DOI:10.1021/jo034800e

An unusual heterodiene, an indolothiono quinone, undergoes cycloaddition with a glycal to form an indole-N-glycoside. A novel dimer of the indolothionoquinone is assigned its structure on the basis of a match between its predicted and observed IR spectrum

Full text of DOI:10.1021/jo034800e

S-1
Supporting Information
Experimental Descriptions of all compounds S1-S15
Tables of Reaction Conditions attempted in cycloadditions S-16-S-18
Selected NMR and IR Spectra S-19-S27
An Ortho-Iminothio Quinone: Its Cycloaddition to Produce an Indologlycoside and its
Self-dimerization to Form a Dithio-Diazocycloctane, the Structure Assignment of which
is Based on the DFT Prediction of its IR Spectrum
Vinh Diep%, J. J. Dannenberg. Richard W. Franck*, Department of Chemistry, Hunter
College of CUNY, 695 Park Ave., New York City, New York 10021 and the Graduate
Center of CUNY, 365 Fifth Ave., New York City, New York 10016.
Experimental
All reactions were carried out under a dry argon/nitrogen atmosphere at ambient
temperature unless otherwise stated. Analytical thin layer chromatography (TLC) was
performed on pre-coated silica gel 60 F254 (E. Merck) plates unless otherwise stated, and
short/long wave ultraviolet (UV) light was used to visualize the spots. Flash column
chromatography was carried out on silica gel 60 (230-400 mesh). Chromatotron (radial
chromatography) plates were prepared by using Kiesegel 60 F254 gipshaltig (E. Merck).
Petroleum ether, dichloromethane, and ethyl acetate used as eluting solvents were ACS
reagent grade. Molecular sieves (Aldrich Chemical Co.) were activated by heating in an
oven (>100 oC) overnight or by heating them with a Bunsen burner under high vacuum.
The following reaction solvents were purified and dried by using standard distillation
procedures: tetrahydrofuran (THF, refluxing over sodium metal with benzophenone as
indicator), ether (refluxing over sodium metal with benzophenone as indicator), and
%
Taken in part from doctoral thesis submitted by V.D. to the Graduate School of CUNY in 2002.

S-2
methylene chloride (CH2Cl2, refluxing over P2O5. NMR spectra were measured at 300
MHz with CDCl3 as the solvent unless otherwise stated. Infrared spectra were recorded
on a Perkin-Elmer 1310 spectrophotometer. Melting points were determined on a Fisher-
Johns melting point apparatus.
N
BOC
tert-Butylcarbazole-9-carboxylate. Carbazole (1.00 g, 5.99 mmol, 1.0 eq) was dissolved
in dry acetonitrile(25 mL). Di-tert-butyldicarbonate (2.60 mL, 11.32 mmol, 1.9 eq) was
added as a neat liquid. DMAP (0.735 g, 6.01 mmol, 1.0 eq) was added in one portion.
The reaction mixture was stirred for 1h 45min. After column chromatography (2% ethyl
acetate/ pet. ether), a colorless oil was obtained in quantitative yield. 1H NMR (300 MHz,
CDCl3) __1.76 (9H, s, t-Bu), 7.34 (2H, t, J = 7.5 Hz), 7.46 (2H, t, J = 7.8 Hz), 7.96 (2H, d,
13
J = 7.8 Hz), 8.30 (2H, d, J = 8.4 Hz); C NMR (300 MHz, CDCl3) __28.7, 84.1, 116.4,
119.7, 123.1, 125.9, 127.2, 138.7, 151.2.

S-3
N
BOC
Bu3Sn
tert-Butyl-1-(1,1-dibutyl-1-stannapentyl)carbazole-9-carboxylate. Under an argon
atmosphere, a 1.3 M solution of s-BuLi in cyclohexane (1.35 mL, 1.76 mmol, 1.57 eq)
was added dropwise to a stirred solution of tert-butylcarbazole-9-carboxylate 0.298 g,
1.12 mmol, 1.0 eq) and TMEDA (0.22 mL, 1.47 mmol, 1.3 eq) in 5 mL of ether at -78 oC.
After stirring for 1 hour, Bu3SnCl (0.46 mL, 1.6 mmol, 1.5 eq) was added as a neat liquid
o
via a syringe. After stirring for another 30 minutes at -78 C, the reaction mixture was
removed from the dry ice-acetone bath and was allowed to stir for an additional 1 hour.
The reaction mixture was quenched with water and the products were extracted with
ether (3 x 15 mL). The combined ether extracts were washed with water (25 mL) and
then with saturated NaCl solution (25 mL), dried over Na2SO4, and evaporated. This
compound was purified by basic alumina column chromatography (petroleum ether) to
1
give a colorless oil (10%). H NMR (300 MHz, CDCl3) __0.87 (9H, t, J = 7.05 Hz), 1.08
(6H, t, J = 8.25 Hz), 1.33 (6H, sextet, J = 7.32 Hz), 1.55 (6H, quintet, J = 7.51 Hz), 1.72
(9H, singlet), 7.32 (2H, t, J = 7.46 Hz), 7.40 (1H, t, J = 7.87 Hz), 7.64 (1H, d, J = 6.95
13
Hz), 7.93 (2H, t, J = 7.69 Hz), 8.07 (1H, d, J = 8.43 Hz); C NMR (300 MHz, CDCl3)

S-4
__13.9, 14.0, 27.9, 28.8, 29.5, 84.3, 117.1, 119.4, 119.5, 123.3 (2), 126.0, 126.7, 126.7,
131.4, 137.2, 138.4, 146.1, 152.2.
N
BOC
PhthNS
tert-Butyl-1-(1,3-dioxoisointolin-2-ylthio)carbazole-9-carboxylate. To
a
stirred
solution of tert-butyl-1-(1,1-dibutyl-1-stannapentyl)carbazole-9-carboxylate, 69.8 mg,
0.125 mmol, 1.0 eq) and 2,6-lutidine (0.0145 mL, 0.124 mmol, 1.0 eq) in methylene
chloride (1 mL, dry) under reflux was added phthalimide-N-sulfenyl chloride (115 mg,
0.54 mmol, 4.35 eq, in 3 mL of dry methylene chloride). After stirring for 1.5 hours with
reflux, the reaction mixture was quenched with saturated aqueous ammonium chloride
solution (10 mL), separated, and the aqueous layer was washed with CH2Cl2 (3 x 10 mL).
The CH2Cl2 layers were combined, washed with potassium fluoride solution (10 g
KF/100 mL H2O solution), dried over anhydrous Na2SO4, and concentrated with a rotary
evaporator. Purification was done using silica gel column chromatography (25% ethyl
1
acetate/petroleum ether) to give 38.1 mg (68%) of the desired product. H NMR (300
MHz, CDCl3) __1.75 (9H, s), 7.22 (2H, m), 7.35 (1H, t, J = 7.51 Hz), 7.48 (1H, t, J = 8.43

S-5
Hz), 7.76 (3H, t of d, J = 2.93 Hz, J = 5.86 Hz), 7.91 (3H, m), 8.08 (1H, d, J = 8.05 Hz);
13C NMR (300 MHz, CDCl3) __28.5, 85.6, 116.5, 118.6, 120.1, 123.7, 124.1, 124.8,
125.4, 126.0, 126.3, 127.5, 127.6, 132.3, 134.7, 136.8, 139.4, 152.5, 168.3.
N
H
PhthNS
2-Carbazolylthioisoindoline-1,3-dione 30. To a solution of tert-butyl-1-(1,3-
dioxoisointolin-2-ylthio)carbazole-9-carboxylate, 26.7 mg, 0.060 mmol, 1.0 eq) in
methylene chloride (1 mL) was added trifluoroacetic acid (0.50 mL, 0.65 mmol, 11 eq).
After stirring for 23 hours at room temperature, the reaction mixture was quenched with
saturated sodium carbonate solution. The aqueous layer was washed 3 times with
methylene chloride and the organic layers were combined, dried over anhydrous sodium
sulfate, concentrated, and after column chromatography (10% ethyl acetate/petroleum
ether), the desired product was obtained (13.8 mg, 67%). Rf 0.33 (20% ethyl acetate/pet.
ether); 1H NMR (300 MHz, CDCl3) __7.20 (1H, t, J = 7.69 Hz), 7.26 (1H, t, J = 3.45 Hz),
7.48 (1H, t of d, J = 8.1 Hz, J = 1.2 Hz), 7.64 (1H, d, J = 8.1 Hz), 7.71 (2H, dd, J = 5.4

S-6
Hz, J = 3.0 Hz), 7.87 (2H, dd, J = 5.4 Hz, J = 3.0 Hz), 7.99 (1H, dd, J = 7.69 Hz, J = 1.10
Hz), 8.03 (1H, d, J = 7.8 Hz), 8.15 (1H, d, J = 7.69 Hz or 7.8 Hz), 9.92 (1H, s, N-H).
1-(tert-Butoxycarbonyl)indoline 18. To a stirred solution of indoline (1.7 mL, 15
mmol1.0 eq) in THF (18 mL) was added di-tert-butyldicarbonate (3.7 mL, 16 mmol, 1.1
eq). The reaction mixture was stirred overnight (25 1/3 h) at room temperature and the
solvent was removed with a rotary evaporator. The residual liquid was distilled under
reduced pressure (Kugelrohr distillation) to give the product as a colorless oil (3.14 g,
o
94%), bp 148 C (oven temperature)/0.20-0.15 mmHg, which on standing solidifies. Rf
o
o
1
0.5 (20% ethyl acetate/petroleum ether); mp 44-45 C (lit. 42-45 C)9; H NMR (300
MHz, CDCl3) d 1.57 (9H, s, t-Bu), 3.09 (2H, t, J = 8.7 Hz, H-3), 3.97 (2H, t, J = 8.7 Hz,
H-2), 6.92 (1H, t, J = 7.5 Hz, H-5), 7.13-7.18 (2H, m, H-4, H-6), 7.3-7.8 (1H, broad, H-
13
7); C NMR (300 MHz, CDCl3) d 27.4, 28.6, 47.7, 80.7, 114.7, 122.1, 124.7, 127.3,
131.2, 142.5, 152.6; IR (KBr, cm-1) 1703.7.
1-(tert-Butoxycarbonyl)-7-phenylthioindoline 19. Under an argon (or nitrogen)
atmosphere, a 1.3 M solution of s-BuLi in cyclohexane (1.2 mL, 1.6 mmol, 1.3 eq) was
added dropwise to a stirred solution of 1-(tert-butoxycarbonyl)indoline (tert-
butylindoline carboxylate, 0.27 g, 1.2 mmol, 1.0 eq) and TMEDA (0.25 mL, 1.7 mmol,
o
1.4 eq, dry) in 6 mL of ether at -78 C. A yellow-orange mixture was formed. After
stirring for 1 hour, phenyl disulfide (0.40 g, 1.8 mmol, 1.5 eq) was added as an ether (2

S-7
o
mL) solution via a syringe. The reaction mixture was stirred for 30 minutes at -78 C,
then the dry ice-acetone bath was removed and the reaction mixture was stirred for an
additional 1 hour. The reaction mixture was quenched with water and the products were
extracted with ether (4 x 10 mL). The combined ether extracts were washed with water
(50 mL) and then with saturated NaCl solution (50 mL), dried over Na2SO4, and
evaporated. Separation was performed using a 2-mm chromatotron plate (2-10% ethyl
acetate in petroleum ether) to give a white solid after removal of the solvent (0.24 g,
60%). Rf 0.29 (10% ethyl acetate in petroleum ether; 0.55 in CH2Cl2); mp 114-116 oC (lit.
o
1
114-115 C)9; H NMR (300 MHz, CDCl3) d 1.57 (9H, s, t-Bu), 3.04 (2H, t, J = 7.8 Hz,
H-3), 4.14 (2H, t, J = 7.8 Hz, H-2), 6.87 (1H, dd, J = 7.8 Hz, 7.0 Hz, H-5), 6.92 (1H, dd, J
= 7.8 Hz, 0.9 Hz, H-6), 7.02 (1H, dd, J = 7.0 Hz, 0.9 Hz, H-4), 7.20-7.30 (3H, m, SPh),
13
7.30-7.36 (2H, m, SPh); C NMR (300 MHz, CDCl3) d 28.6, 29.9, 51.0, 81.7, 122.5,
124.9, 127.2, 129.1, 130.5, 132.4, 134.7, 137.3, 142.6, 154.0.
1-(tert-Butoxycarbonyl)-7-tributylstannylindoline 20. Under an argon atmosphere, a
1.3 M solution of s-BuLi in cyclohexane (3.0 mL, 3.9 mmol, 1.3 eq) was added dropwise
to a stirred solution of 1-(tert-butoxycarbonyl)indoline 18 (0.66 g, 3.0 mmol, 1.0 eq) and
o
TMEDA (0.59 mL, 3.9 mmol, 1.3 eq, dry) in 15 mL of ether at -78 C. After stirring for 1
hour, Bu3SnCl (4.6 mmol, 1.5 eq) was added as a neat liquid via a syringe. After stirring
o
for another 30 minutes at -78 C, the reaction mixture was removed from the dry ice-
acetone bath and was allowed to stir for an additional 1 hour. The reaction mixture was

S-8
quenched with water and the products were extracted with ether. The combined ether
extracts were washed with water and then with saturated NaCl solution, dried over
anhydrous sodium sulfate, and evaporated. This compound was purified by basic alumina
column chromatography (petroleum ether) to give a colorless oil (73%). Rf 0.58
1
(petroleum ether, on neutral alumina), H NMR (300 MHz, CDCl3) d_0.87( 9H, t, J= 7.2
Hz) , 0.97 (6H, m, -CH2- of Bu), 1.32 (6 H, sextet, J = 7.2 Hz, -CH2- of Bu), 1.4-1.6 (6H,
m), 1.51 (9H, s, t-Bu), 3.00 (2H, t, J = 8.4 Hz, H-3), 3.96 (2H, t, J = 8.4 Hz, H-2), 6.93
(1H, t, J = 7.2 Hz, H-5), 7.10 (1H, dd, J = 7.5 Hz, 1.2 Hz, H-4), 7.32 (1H, dd, J = 6.6 Hz,
13
1.2 Hz, H-6); C NMR (300 MHz, CDCl3) d13.2, 14.0, 27.9, 28.2, 28.8, 29.6, 48.2, 80.7,
122.8, 124.5, 130.5, 131.5, 136.6, 149.2, 153.7; IR (KBr, cm-1) 1693.8; MS Calcd for
C25H43NO2Sn: 507.2312. Found m/z 506.1 (36), 507.2 (31), 508.1 (71), 509.1 (38), 510.2
(98), 511.2 (25), 512.2 (15), 513.2 (6), 514.2 (14).
tert-Butyl-7-(1,3-dioxoisoindolin-2-ylthio)indoline carboxylate 21. To a stirred
solution of 1-(tert-butoxycarbonyl)-7-tributylstannyl indoline 20 (0.27 g, 0.53 mmol, 1.0
eq) and 2,6-lutidine (0.1 mL, 0.86 mmol, 1.6 eq) in methylene chloride (1 mL, dry) was
added phthalimide-N-sulfenyl chloride (0.57 g, 2.3 mmol, 4.3 eq). After stirring for 2.5
hours at room temperature, the reaction mixture was quenched with saturated aqueous
ammonium chloride solution, separated, and the aqueous layer was washed with CH2Cl2.
The CH2Cl2 layers were combined, washed with potassium fluoride solution (10 g
KF/100 mL H2O solution), dried over anhydrous sodium sulfate, and concentrated with a

S-9
rotary evaporator. Purification was done using silica gel column chromatography (20%
ethyl acetate/petroleum ether) (0.20 g, 94%). Rf 0.37 (30% ethyl acetate/petroleum ether);
mp ~140 oC (decomposition); 1H NMR (300 MHz, CDCl3) d 1.57 (9H, s, t-Bu), 3.07 (2H,
t, J = 8.1 Hz, H-3), 4.15 (2H, t, J = 8.1 Hz, H-2), 6.86 (1H, t, J = 7.5 Hz, H-5), 6.93 (1H,
d, J = 7.5 Hz, H-4), 6.99 (1H, d, J = 6.9 Hz, H-6), 7.76-7.79 (4H, m, Phth-H); 13C NMR
(300 MHz, CDCl3) d 28.5, 29.4, 49.5, 82.3, 123.3, 125.5, 124.0, 125.2, 126.1, 132.5,
133.7, 134.5, 140.5, 154.7, 168.6; IR (KBr, cm-1) 1734.8; MS Calcd for C21H20N2O4S:
396.1144. Found: m/z 397 (M+H+), 414 (M+NH4+); Anal. Calcd for C21H20N2O4S: C,
63.62; H, 5.08; N, 7.07; S, 8.09. Found: C, 62.85; H, 5.05; N, 6.80; S, 8.00.
2-Indolin-7-ylthioindoline-1,3-dione 14. To a solution of tert-butyl-7-(1,3-
dioxoisoindolin-2-ylthio)indolinecarboxylate (21, 1.35 g, 3.40 mmol, 1.0 eq) in
methylene chloride (25 mL) was added trifluoroacetic acid (2.6 mL, 34 mmol, 10 eq).
After stirring for 2 hours at room temperature, the reaction mixture was quenched with
saturated sodium carbonate solution. The aqueous layer was washed 4 times with
methylene chloride and the organic layers were combined, dried over anhydrous sodium
sulfate, concentrated, and after column chromatography (15% ethyl acetate/petroleum
ether), the desired product was obtained (0.703 g, 70%). Rf 0.48 (20% ethyl
acetate/petroleum ether); mp 160-170 oC (decomposition); 1H NMR (300 MHz, CDCl3)
d 3.06 (2H, t, J = 8.5 Hz, H-3), 3.66 (2H, t, J = 8.5 Hz, H-2), 5.69 (1H, broad singlet, N-

S-10
H), 6.52 (1H , t, J = 7.35 Hz, H-5), 7.08 (1H, d, J = 7.2 Hz, H-6), 7.47 (1H, d, J = 8.1 Hz,
H-4), 7.72-7.89 (4H, m, Phth-H); 13C NMR (300 MHz, CDCl3) d 30.8, 46.9, 110.8, 117.6,
124.1, 128.1, 130.5, 132.4, 134.7, 136.0, 156.7, 168.8; IR (KBr, cm-1) 3357.8 (broad),
1728.1, 1703.1; MS Calcd for C16H12N2O2S: 296.0619. Found m/z 297 (M+H+); Anal.
Calcd for C16H12N2O2S: C, 64.85; H, 4.08; N, 9.45; S, 10.82. Found: C, 64.97; H, 4.24; N,
9.35; S, 10.83.
Cycloaddition to form N-glycoside 22 Method A-In a typical experiment, heterodiene
precursor 21 and 3,4,6-tri-O-benzyl-D-glucal 7(1-5 eq) were dissolved in dry CH2Cl2.
The appropriate silica gel (10 x mass of 3,4,6-Tri-O-benzyl-D-glucal) was then added.
The solvent was then removed to dryness using a rotary evaporator. The flask containing
the dry mixture of diene precursor 21, 3,4,6-tri-O-benzyl-D-glucal 7, and silica gel was
subject to low pressure by attaching it to a vacuum pump and heated to 50-55 oC for the
desired reaction time.(see Table in Supporting Information for sets of other conditions)
Method B Cycloaddition between 2-indolin-7-ylthioindoline-1,3-dione (14) and 3,4,6-tri-
O-benzyl-D- glucal (7). When silica gel was used, the procedure was the same as that for
the cycloaddtition between 21 and glucal. When no silica gel was used, a typical
procedure was as follows: 2-Indolin-7-ylthioindoline-1,3-dione (14, 45 mg, 0.15 mmol,
1.0 eq) and 3,4,6-tri-O-benzyl glucal 7 (127 mg, 0.31 mmol, 2.0 eq) were dissolved in
methylene chloride (1 mL, dry) and stirred at room temperature for 3 days. The reaction
mixture was concentrated and after separation on a 1-mm chromatotron plate, 8.1 mg

S-11
(9%) of the cycloadduct was obtained .(see Table in Supporting Information for sets of
other conditions). 1H NMR (300 MHz, CDCl3) d 2.93 (2H, t, J = 9.5 Hz), 3.14 (1H,
quartet, J = 10.1 Hz), 3.35 (1H, dd, J = 10.8 Hz, 3.6 Hz), 3.58 (1H, m), 3.73 (3H, m), 3.91
(1H, m), 4.11 (1H, m), 4.52 (2H, t, J = 11.1 Hz), 4.65 (1H, d, J = 12.3 Hz), 4.78 (1H, d, J
= 10.5 Hz), 4.84 (1H, d, J = 10.8 Hz), 4.90 (1H, d, J = 3.6 Hz), 5.00 (1H, d, J = 10.2 Hz),
6.66 (1H, t, J = 7.5 Hz), 6.86 (2H, t, J = 8.7 Hz), 7.12-7.73 (15 H, m); 13C NMR (300
MHz, CDCl3) d 28.4, 46.4, 51.2, 69.1, 69.8, 71.8, 73.8, 75.3, 79.6, 81.4, 82.3, 112.2,
120.4, 121.2, 123.6, 127.9, 128.0, 128.1, 128.1, 128.2, 128.3, 128.6, 129.2, 130.2, 138.3,
138.4, 145.1; MS Calcd for C35H35NO4S: 565.2282. Found m/z 566 (M+H+), 434 (TBG +
NH4+); Anal. Calcd for C35H35NO4S: C, 74.31; H, 6.24; N, 2.48; S, 5.67. Found: C, 74.03;
H, 6.28; N, 2.35; S, 5.60.
Dimer 31 1H NMR (300 MHz, CDCl3) d 2.83 (2H, m), 3.06 (2H, m), 3.69 (4H, m), 6.64
(2H, t, J = 7.5 Hz), 7.03 (2H, d, J = 7.2 Hz), 7.23 (2H, d, J = 7.8 Hz); 13C NMR (300
MHz, CDCl3) d 29.1, 58.1, 118.6, 119.4, 127.2, 132.3, 135.9, 151.4; IR (KBr, cm-1)
739.1, 768.0, 948.8, 1057.7, 1216.9, 1244.2, 1418.2, 1592.1; MS Calcd for C16H14N2S2:
298.0598. Found m/z 299 (M+H+).
1-(tert-Butoxycarbonyl)-7-tributylstannyl-5-chloroindoline 25. Under an inert (N2)
atmosphere, a 1.3 M solution of s-BuLi in cyclohexane (2.0 mL, 2.6 mmol, 1.7 eq) was
added dropwise to a stirred solution of 1-(tert-butoxycarbonyl)-5-chloroindoline 24 (0.38

S-12
g, 1.5 mmol, 1.0 eq) and TMEDA (0.30 mL, 2.0 mmol, 1.3 eq, dry) in 15 mL of THF at -
78 oC. After stirring for 1 hour, Bu3SnCl (0.81 mL, 3.0 mmol, 2.0 eq) was added as a neat
liquid via a syringe. After stirring for another 30 minutes at -78 oC, the reaction mixture
was allowed to warm to room temperature and stirred for an additional 1 hour. The
reaction mixture was quenched with water and the products were extracted with ether.
The combined ether extracts were washed with water and then with saturated NaCl
solution, dried over anhydrous sodium sulfate, and evaporated. This compound was
purified by basic alumina column chromatography (petroleum ether) to give a colorless
oil (75%). 1H NMR (300 MHz, CDCl3) d 0.88 (9H, t, J = 7.2 Hz, CH3 of Bu), 0.98 (6H, t,
J = 8.2 Hz, -CH2- of Bu), 1.31 (6 H, sextet, J = 7.2 Hz, -CH2- of Bu), 1.4-1.6 (6H, m, -
CH2- of Bu), 1.51 (9H, s, CH3 of t-Bu), 2.97 (2H, t, J = 8.4 Hz, H-3), 3.96 (2H, t, J = 8.4
Hz, H-2), 7.05 (1H, d, J = 1.5 Hz, H-4), 7.24 (1H, d, J = 2.1 Hz, H-6). 13C NMR (300
MHz, CDCl3) d 13.3, 13.9, 27.7, 28.0, 28.7, 29.4, 48.3, 81.1, 124.5, 128.4, 132.7, 133.5,
135.8, 147.8, 153.7. IR (KBr, cm-1) 1694.0.
tert-Butyl-7-(1,3-dioxoisoindolin-2-ylthio)-5-chloroindolinecarboxylate 26. To a
stirred solution of 1-(tert-butoxycarbonyl)-5-chloro-7-tributylstannylindoline 25, 0.18 g,
0.32 mmol, 1.0 eq) and 2,6-lutidine (0.38 mL, 0.33 mmol, 1.0 eq) in methylene chloride
(2 mL, dry) under reflux was added phthalimide-N-sulfenyl chloride (0.19 g, 75% pure,
0.67 mmol, 2.1 eq, in 3 mL of dry methylene chloride). After stirring for 1 hour with

S-13
reflux, the reaction mixture was quenched with saturated aqueous ammonium chloride
solution, separated, and the aqueous layer was washed with CH2Cl2. The CH2Cl2 layers
were combined, washed with potassium fluoride solution (10 g KF/100 mL H2O
solution), dried over anhydrous sodium sulfate, and concentrated with a rotary
evaporator. Purification was done using silica gel column chromatography (20% ethyl
acetate/petroleum ether) (0.11 g, 82%). Rf 0.54 (1:1 ethyl acetate/pet. ether); 1H NMR
(300 MHz, CDCl3) d 1.56 (9H, s, t-Bu), 3.06 (2H, t, J = 8.1 Hz, H-3), 4.15 (2H, t, J = 8.1
Hz, H-2), 6.88 (1H, d, J = 1.5 Hz, H-4), 6.97 (1H, d, J = 1.5 Hz, H-6), 7.77-7.95 (4H, m,
Phth-H); 13C NMR (300 MHz, CDCl3) d 28.6, 29.4, 49.7, 82.7, 123.6, 124.2, 124.9,
127.4, 130.0, 132.3, 134.8, 135.4, 139.2, 154.5, 168.2; MS Calcd for C21H19ClN2O4S:
430.0754. Found m/z 453 (M+Na+).
2-(5-Chloroindolin-7-ylthio)isoindoline-1,3-dione 27. To a solution of tert-butyl-7-
(1,3-dioxoisoindolin-2-ylthio)-5-chloroindolinecarboxylate 26, 0.43 g, 0.99 mmol, 1.0
eq) in methylene chloride (18 mL) was added trifluoroacetic acid (1.5 mL, 19 mmol, 19
eq) via a syringe in one portion. After stirring for 1.5 hours at room temperature, the
reaction mixture was quenched with saturated aqueous sodium carbonate solution
(saturated). The aqueous layer was washed 3 times with methylene chloride and the
organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and
after column chromatography (20-25% ethyl acetate/pet. ether), quantitative yield of the

S-14
desired product was obtained; 1H NMR (300 MHz, CDCl3) d 3.05 (2H, t, J = 8.5 Hz. H-
3), 3.68 (2H, t, J = 8.5 Hz, H-2), 5.67 (1H, s, N-H), 7.01 (1H , s, H-4), 7.45 (1H, s, H-6),
7.73-7.90 (4H, m, Phth-H); 13C NMR (300 MHz, CDCl3) d 30.2, 47.2, 110.9, 121.2,
124.1, 128.3, 132.2, 132.3, 134.4, 134.7, 155.3, 168.5; Anal. Calcd for C16H11ClN2O2S: C,
58.09; H, 3.35; Cl, 10.72; N, 8.47; S, 9.69. Found: C, 57.89; H, 3.36; Cl, 11.14; N, 8.28;
S, 9.29; MS Calcd for C16H11ClN2O2S: 330.0230. Found m/z 331 (M+H+), 353 (M+Na+).
Cycloaddition to form N-glycoside 28). A typical experiment: 2-(5-chloroindolin-7-
ylthio)isoindoline-1,3-dione 27, 66.5 mg, 0.201 mmol, 1.0 eq) and 3,4,6-tri-O-benzyl-D-
glucal 7 (168.8 mg, 0.405 mmol, 2.0 eq) were dissolved in methylene chloride (2 mL,
dry) and stirred under reflux for 1 day. The reaction mixture was concentrated and after
silica gel column chromatography (pet ether to 5% ethyl acetate/pet ether), 70.4 mg
1
(58%) of the cycloadduct was obtained. Rf 0.41 (20% ethyl acetate/pet. ether); H NMR
(500 MHz, CDCl3) d 2.90 (2H, t, J = 10.4 Hz), 3.15 (1H, quartet, J = 10.3 Hz), 3.33 (1H,
dd, J = 10.8 Hz, 3.5 Hz), 3.58 (1H, t, J = 8.25 Hz), 3.72 (3H, m), 3.86 (1H, t, J = 9.7 Hz),
4.09 (1H, t, J = 7.8 Hz), 4.51 (1H, d, J = 10.7 Hz), 4.55 (1H, d, J = 12.4 Hz), 4.64 (1H, d,
J = 12.1 Hz), 4.79 (1H, d, J = 10.5 Hz), 4.83 (1H, d, J = 10.8 Hz), 4.87 (1H, d, J = 3.5
13
Hz), 4.96 (1H, d, J = 10.2 Hz), 6.81-7.41 (17 H, m); C NMR (300 MHz, CDCl3) d
28.23, 46.35, 51.31, 69.04, 71.94, 73.87, 75.34, 76.74, 79.62, 81.31, 82.10, 113.41,

S-15
121.48, 122.94, 124.85, 127.88, 127.99, 128.14, 128.26, 128.56, 128.63, 128.97, 131.50,
138.13, 138.18, 138.37, 143.68; Anal. Calcd for C35H34NO4S: C, 70.04; H, 5.71; N, 2.33.
Found: C, 69.10; H, 5.66; N, 2.14.
1-(tert-Butoxycarbonyl)-5-chloroindoline 24. A mixture of 5-chloroindoline (0.21 g,
1.4 mmol, 1.0 eq) and di-tert-butyl dicarbonate (0.38 mL, 1.7 mmol, 1.2 eq) in ether (5
mL) was stirred overnight at room temperature for 2 days. After silica gel column
chromatography (2.5 % ethyl acetate/petroleum ether), 0.34 g (96%) of the desired
o
product was obtained. Rf 0.58 (20% ethyl acetate/petroleum ether); mp 129-130 C (lit.
o
1
130-130.5 C)9; H NMR (300 MHz, CDCl3) d 1.55 (9H, s, t-Boc), 3.05 (2H, t, J = 8.7
Hz, H-3), 3.97 (2H, t, J = 8.7 Hz, H-2), 7.08 (1H, s, H-6), 7.09 (1H, d, J = 8.4 Hz, H-4),
13
7.73 (1H, broad singlet, H-7); C NMR (300 MHz, CDCl3) d 27.4, 28.7, 48.0, 81.0,
115.6, 124.9, 127.1, 127.3, 133.0, 142.0, 152.4; IR (KBr, cm-1) 1707.8, 1479.8, 1390.0,
1329.9, 1255.6, 1142.0, 1019.5, 873.6, 823.2, 762.5.