The reactions of N-substituted 2-(dimethylallyl)aniline compounds with phenylselanyl halides

Article abstract of DOI:10.1071/CH99109

Cyclization of the carbamate of 2-(dimethylallyl)aniline with phenylselanyl chloride (benzeneselenenyl chloride) gave a 1 : 1 mixture of a dihydroindole and a tetrahydroquinoline. With phenylselanyl bromide only the dihydroindole was obtained. Addition of

Full text of DOI:10.1071/CH99109

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Volume 53, 2000
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Aust. J. Chem., 2000, 53, 123–129
The Reactions of N-Substituted 2-(Dimethylallyl)aniline
Compounds with Phenylselanyl Halides
Matthew A. Cooper,A Craig L. Francis,A Jeffrey W. Holman,A Bruno Kasum,A
Thomas Taverner,A Edward R. T. TiekinkA and A. David WardA,B
A Department of Chemistry, The University of Adelaide, Adelaide, S.A. 5005.
B Author to whom inquiries should be addressed (david.ward@adelaide.edu.au).
Cyclization of the carbamate of 2-(dimethylallyl)aniline with phenylselanyl chloride (benzeneselenenyl chloride)
gave a 1: 1 mixture of a dihydroindole and a tetrahydroquinoline. With phenylselanyl bromide only the dihydroin-
dole was obtained. Addition of methanol to the silica used in the procedure trapped the reaction at the non-cyclized
stage forming
a
3-methoxy-3-methyl-2-(phenylselanyl)butyl side chain. The sulfonamide of 2-
(dimethylallyl)aniline only formed the dihydroindole with phenylselanyl chloride. The corresponding trifluoroac-
etamide derivative did not form any cyclized product under the same conditions. The dihydroindole could be
converted into the corresponding alkene by oxidative removal of the phenylseleno group. 4-Ethoxycarbonyl-2-(3,3-
dimethylallyl)aniline cyclized with mercuric nitrate to give, after
a
reductive workup,
a
2,2-dimethyltetrahydroquinoline. The X-ray crystal structures of ethyl N-{2-[3-methoxy-3-methyl-2-(phenylse-
lanyl)butyl]phenyl}carbamate and 2-[1-methyl-1-(phenylselanyl)ethyl]-1-[(4-methylphenyl)sulfonyl]indoline are
reported.
Keywords. Synthesis; X-ray crystallography; phenylselanyl halide; virantmycin; cyclization.
Introduction
pounds which had larger allylic substituents either failed to
produce any cyclized product or formed only very small
amounts of these desired products. Reactions involving mer-
curic salts were unsuccessful in producing substituted
tetrahydroquinolines but gave non-substituted products after
a reductive workup. We have recently reported our results
using a copper-catalysed cyclization process to form 2,2-di-
substituted 1,2-dihydroquinolines.16 We now report the
results obtained from the use of selenium-containing
reagents as the electrophilic species for the cyclization
process.
We have been investigating synthetic approaches to the
novel antibiotic virantmycin (1)1–3 for some time. While
other groups4–11 have focused on the total synthesis of virant-
mycin we have been investigating general routes to structural
analogues of virantmycin for use in structure–activity
relationships. One of our methodologies involves
the electrophile-initiated cyclization of 2-(3,3-disubsti-
tuted allyl)aniline systems (Scheme 1).12–15
Results and Discussion
Treatment of the carbamate (2)17 with 1 equiv. of
phenylselanyl chloride, dry silica gel and anhydrous potas-
sium carbonate in dichloromethane at –78° for 15 min and
then at room temperature for 3 days produced a 1 : 1 mixture
of the dihydroindole (3) and the tetrahydroquinoline (4)
which could not be separated by chromatography (Scheme
2). A cleaner reaction product was obtained by using chlo-
roform as the solvent rather than the more usual
dichloromethane.17,18 It was also found that higher yields of
product were obtained when the selenium reagent was added
at low temperature and the reaction mixture subsequently
allowed to warm to room temperature than when the reagent
was added at ambient temperature. This competition
between endo and exo cyclization processes has also been
observed by Clive.17
Our early results on model compounds in this area of elec-
trophile-initiated cyclization have been reported.12–15 While
simple model compounds underwent iodine-initiated
cyclization to produce iodotetrahydroquinolines, com-
Manuscript received 6 September 1999
© CSIRO 2000
10.1071/CH99109
0004-9425/00/020123

124
M. A. Cooper et al.
When the carbamate (2) was treated with phenylselanyl
chloride, dry silica gel and anhydrous potassium carbonate
in chloroform at –78° for 30 min, then at room temperature
for 6 days, the only product observed was the dihydroin-
dole (3). Reaction of (2) with phenylselanyl bromide, dry
silica gel and anhydrous potassium carbonate in
dichloromethane at –78° for 30 min then at room tempera-
ture for 6 days also gave only the dihydroindole (3).
1H n.m.r. analysis revealed that the signal from the C 2
hydrogen of (3) appeared as a doublet of doublets at ꢀ 4.6
and that the two methyl resonances are widely spaced at ꢀ
1.42 and 1.02. The methyl resonances of (4) are much more
closely spaced, appearing at ꢀ 1.80 and 1.67.
Fig. 1. Molecular structure and crystallographic numbering scheme
for (5).
from which it was possible to isolate the chlorodihydroin-
dole (7) by chromatography. Reaction of selenides (3) and
(4) with phenylselanyl chloride at either room temperature or
–78° also gave a mixture of products, from which it was pos-
sible to isolate, by h.p.l.c., the chloride (7) and a solid which
1
rapidly decomposed. The H n.m.r. spectrum of this solid
indicated the presence of 14 aromatic hydrogens and this and
the mass spectrum were consistent with the solid being the
selenonium salt (8) although no molecular ion was observed.
When the reaction was followed by h.p.l.c., it was seen that
the salt (8) decomposed to a complex mixture of products
rather than form the corresponding chloride.
A mixture of dihydroindole (3) and tetrahydroquino-
line (4) in chloroform was refluxed overnight in the presence
of potassium carbonate and silica gel. No change in the ratio
of the two heterocycles was observed.
Treatment of the carbamate (2) with phenylselanyl chlo-
ride, anhydrous potassium carbonate and silica gel contain-
ing pre-absorbed methanol in dichloromethane afforded
(Scheme 3) the methoxy selenide (5), the structure of which
was confirmed by X-ray crystallography (Fig. 1). An analo-
gous reaction using dry silica gel, but with a small amount of
added water present, gave a mixture of starting alkene and
products that could not be separated by chromatography.
Mass spectroscopic and n.m.r. data were inconclusive as to
whether the non-alkene-containing components of this
mixture were the alcohol (6) and/or either of the possible
cyclized products.
The effect of the para-toluenesulfonamide protecting
group on the selenium-induced cyclization reaction was also
studied (Scheme 5). Treatment of the sulfonamide (9) with
phenylselanyl chloride, dry silica gel and anhydrous potas-
sium carbonate at room temperature for 64 h gave only the
dihydroindole (10), the structure of which was confirmed by
X-ray crystallography (Fig. 2).
It was of interest to see whether the selenides (3) and (4)
could be converted (Scheme 4) into their chloro-substituted
derivatives by using our previously established methodol-
ogy.18,19 However, reaction of the selenide mixture with
tetrabutylammonium chloride and chlorine at either room
temperature or –22° gave a complex mixture of products,

Reactions of N-Substituted 2-(Dimethylallyl)aniline
125
The methyl carbamate analogue of (2) and the sulfon-
amide (9) have been cyclized to a dihydroquinoline21 and a
dihydroindole22 system respectively, by using palladium cat-
alysts.
Treatment of the trifluoroacetamide (13)13 with phenylse-
lanyl chloride, dry silica gel17 and anhydrous potassium car-
bonate in dichloromethane produced no cyclized material
after 4 days reaction time but it was possible to isolate the
hydroxy selenide (15) from the reaction product in low yield
by chromatography (Scheme 7). This compound may arise
from displacement of the chloro group of (14) on silica.
In our previous paper,13 we reported that organomercury
acetates, formed by treatment of the corresponding allylani-
lines with mercuric acetate, could not be converted into the
desired 3-halotetrahydroquinolines in spite of numerous
attempts with a variety of conditions (Scheme 8). However,
reductive workup with alkaline sodium borohydride pro-
vided non-functionalized tetrahydroquinolines in high
yield.13
The allylanilino ester (18) (prepared as shown in Scheme
9) was treated with 3 equiv. of mercuric acetate, followed by
reductive workup to form the tetrahydroquinoline (19). This
sequence shows that the mercury(II)-induced cyclization is
tolerant of an electron-withdrawing substituent.
Attempts to functionalize the heterocyclic ring at the 3-
position, using an amidomercuration/oxidative demercura-
tion procedure23 on both the carbamate (2) and 2-allylaniline,
were unsuccessful.Attempted conversion of the intermediate
organomercury derivative from 2-allylaniline into the
bromide using potassium bromide resulted in the immediate
precipitation of mercury and recovery of the allylaniline.
Fig. 2. Molecular structure and crystallographic numbering scheme
for (10).
1
The H n.m.r. spectrum of (10) was markedly different
from that of the ethyl carbamate analogue (3). Whereas the
benzylic hydrogens of (3) appear as a multiplet centred at ꢀ
3.37, the two benzylic hydrogens of (10) have quite different
chemical shifts with one centred at ꢀ 2.36 and the other at ꢀ
3.15. The C 2 hydrogen of (3) appears at ꢀ 4.62; the same
hydrogen is found at ꢀ 4.03 in the spectrum of (10). The car-
bamate group of (3) is planar and this would require the two
methyl groups of the side chain at C 2 to align themselves so
that they are directed away from the carbamate group. This
leaves the selenium atom nearest to the carbamate group and
positions the attached phenyl ring away from any ring hydro-
gen. In the case of (10) the nitrogen of the sulfonamido group
is pyramidal, not trigonal planar, and the methyl groups of
the side chain can occupy the space beneath the indole ring
system with the sulfonyl portion above. This places the
phenyl of the phenylselenide group in a shielding position to
the C 2 hydrogen. The structure of (10) (Fig. 2) shows the
proximity of this phenyl ring to the C 2 hydrogen. It also
shows that the aromatic ring of the arylsulfonyl system is
sufficiently close to one of the benzylic hydrogens to make
them magnetically non-equivalent.
Experimental
General experimental conditions have been described previously.15
N.m.r. spectra were determined in (D)chloroform solution. High-per-
formance liquid chromatography (h.p.l.c.) was carried out with a
Waters 501 solvent delivery system and a U6K injector with a Waters
481 absorbance detector. Analyses were performed by using a Waters
Z-module with a Waters Radial-PAK™ C18 reverse-phase cartridge
(10 cm by 8 mm), with a gradient of methanol/water as eluent.
Ethyl N-[2-(3-Methylbut-2-enyl)phenyl]carbamate (2)
Ethyl chloroformate (1.08 g, 9.9 mmol) was added dropwise over
5 min to an emulsified mixture of 2-allylaniline17 (2.75 g, 17 mmol) in
water (10 ml) at 0°. The mixture was stirred vigorously for 10 min, and
then a solution of sodium hydroxide (0.8 g, 20 mmol) in water (5 ml)
was added, immediately followed by more ethyl chloroformate (1.08 g,
9.9 mmol). The resulting mixture was stirred at 0° for a further 2 h and
extracted with dichloromethane (2×30 ml). The organic extracts were
dried (Na2SO4) and evaporated and the residue was distilled to give the
carbamate (2)17 (3.56 g, 90%) as a light brown oil, b.p. 120°/0.1 mm
(lit.17 120°/0.1 mm). ꢁmax (film) 3325, 1715, 1585, 1510, 1220 cm–1.
1H n.m.r. ꢀ 1.28, t, J 7 Hz, CH2; 1.78, s, (CH3)2; 3.32, d, J 7.2 Hz,
ArCH2; 4.20, q, J 7.1 Hz, CO2CH2; 5.20, t, J 6.5 Hz, C=C–H; 6.72, s,
NH; 6.80–7.78, m, ArH. Mass spectrum m/z 233 (M).
Since the selenides (3) and (10) could be prepared cleanly
and in high yield, it was of interest to determine if they could
be further manipulated to remove the seleno moiety.20 By
using a two-phase dichloromethane/hydrogen peroxide
system at room temperature, the selenides (3) and (10) were
converted cleanly, via the corresponding selenoxide, into the
alkenes (11) and (12) respectively (Scheme 6). Compounds
such as (11) and (12) are of potential synthetic interest as the
isoprenoid unit inherent in these molecules occurs widely in
natural products.
Ethyl 2-[1-Methyl-1-(phenylselanyl)ethyl]indoline-1-carboxylate (3)
and Ethyl 2,2-Dimethyl-3-(phenylselanyl)-1,2,3,4-tetrahydroquin-
oline-1-carboxylate (4)
A solution of phenylselanyl chloride (170 mg, 0.87 mmol) in dry
dichloromethane (6 ml) was added dropwise to a stirred mixture of the
carbamate (2) (200 mg, 0.85 mmol), anhydrous potassium carbonate
(1.18 g, 8.5 mmol) and silica gel (Merck 60, 230–400 mesh, oven-dried,

126
M. A. Cooper et al.
400 mg) in dry dichloromethane (5 ml) at –78° under an atmosphere of
nitrogen. The mixture was stirred at this temperature for a further
15 min and then at room temperature in darkness for 74 h. The solution
was then filtered through Celite, the Celite washed with ethyl acetate
(10 ml) and the solvent evaporated to give a light yellow oil which was
purified by chromatography (ethyl acetate/hexane; 1: 9) to give a chro-
matographically homogeneous product consisting of a mixture of the
selenides17 (3) and (4) (0.302 g, 91%) in the ratio 1: 1 (Found
m/z, 389.0882. Calc. for C20H23NO280Se: m/z, 389.0894). ꢁmax (CCl4)
1715, 1600, 1590 cm–1. 1H n.m.r. ꢀ [for (3)] 1.02, s, CH3; 1.2, t,
J 7.2 Hz, CH2CH3; 1.42, s, CH3; 3.37, br d, J 7.8 Hz, ArCH2; 4.15, q,
J 7.2 Hz, CH2CH3; 4.62, dd, J 3.3, 7.8 Hz, NCH; 6.75–7.80, m, ArH.
1H n.m.r. ꢀ [for (4)] 1.25, t, J 7 Hz, CH2CH3; 1.67, s, CH3; 1.80, s, CH3;
2.91–3.30, m, CH2CH(SePh); 4.2, q, J 7 Hz, CH2CH3; 6.75–7.80, m,
ArH. Mass spectrum m/z 389 (M).
Reaction of (2) with Phenylselanyl Chloride and Wet Silica Gel
Using the procedure described above but with silica gel to which a
few drops of water had been added, gave, after chromatography, a frac-
tion that appeared to be mainly a mixture of several carbamates and the
starting alkene. 1H n.m.r. for the carbamates showed overlapping
signals at ꢀ 1.2, CH2CH3; 1.3 and 1.4, CH3; 2.9 and 3.2, both m, 2H;
4.1, q and m, OCH2CH3 and 1H; 6.8–7.4, m, ArH. The mass spectrum
showed a peak at m/z 250 (M+H) which indicated the presence of (6) in
the mixture.
Ethyl 2-[1-Methyl-1-(phenylselanyl)ethyl]indoline-1-carboxylate (3)
A solution of phenylselanyl bromide (147 mg, 0.56 mmol) in dry
dichloromethane (6 ml) was added to a rapidly stirred mixture of the
carbamate (2) (100 mg, 0.43 mmol), anhydrous potassium carbonate
(590 mg, 4.3 mmol) and silica gel (Merck 230–400 mesh, oven-dried,
300 mg) in dry dichloromethane (5 ml) at –78° under an atmosphere of
nitrogen. The mixture was stirred at this temperature for 30 min, at
room temperature in darkness for 6 days, and then filtered through
Celite. The Celite was washed with ethyl acetate (10 ml), the combined
organic phases were evaporated and the residue was purified by
reverse-phase h.p.l.c. (water/methanol; 20 : 80) to give the
selenide (3)17 (120 mg, 72%) as a colourless oil (Found: C, 61.3; H, 5.9;
N, 3.6%; m/z, 389.0891. Calc. for C20H23NO280Se: C, 61.7; H, 6.0; N,
3.6%; m/z, 389.0894). ꢁmax (film) 1700, 1600, 1480, 1270 cm–1.
1H n.m.r. ꢀ 1.02, s, CH3; 1.2, t, J 7.2 Hz, CH2CH3; 1.42, s, CH3; 3.37,
br d, J 7.8 Hz, ArCH2; 4.15, q, J 7.2 Hz, CH2CH3; 4.62, dd, J 3.3,
7.8 Hz, NCH; 6.75–7.80, m, ArH. Mass spectrum m/z 389 (M, 4%), 232
(100).
Ethyl N-{2-[3-Methoxy-3-methyl-2-(phenylselanyl)butyl]phenyl}-
carbamate (5)
Using a similar procedure to that described above but with silica gel
to which a few drops of methanol had been added gave, after chro-
matography, a fraction which was crystallized from hexane to give the
carbamate (5) as white crystals, m.p. 83–85°, whose structure was con-
firmed by X-ray structure analysis. ꢁmax (CHCl3) 3320, 1730 cm–1. 1H
n.m.r. ꢀ 1.29 and 1.33, both s, CH3; 1.31, overlapping t, CH2CH3; 2.61,
dd, JAB 14, JA,C 9.5 Hz, HA of methylene; 2.85, d, JAC 9.5, JBC 0 Hz,
CHSe; 3.37, s, OMe; 3.47, d, JAB 14, JBC 0 Hz, HB of methylene; 4.20,
overlapping q, OCH2CH3; 6.97–7.14 and 7.25–7.37, both Ar. 13C n.m.r.
ꢀ 14.58, 19.05, 24.00, 31.55, 33.90, 50.28, 60.41, 60.43, 127.30,
127.40, 128.95, 130.92, 133.82. Some aromatic carbon signals and the
carbonyl signal were not observed.

Reactions of N-Substituted 2-(Dimethylallyl)aniline
127
Reactions of the Selenides (3) and (4)
yellow oil. Chromatography (ethyl acetate/hexane) gave a white solid
which was recrystallized from dichloromethane/hexane to give the
selenide (10) (183 mg, 78%) as translucent crystals, m.p. 122–122.5°
(Found: C, 61.2; H, 5.2; N, 3.0. C24H25NO2SSe requires C, 61.3; H, 5.4;
N, 3.0%). ꢁmax (CCl4) 1600, 1490, 1360, 1170 cm–1. 1H n.m.r. ꢀ 0.97, s,
CH3; 1.70, s, CH3; 2.33, s, ArCH3; 2.36, dd, JAX 8.7, JBX 16.5 Hz, CHN;
3.15, d, JBX 16.5 Hz, ArCHAHB; 4.03, d, JAX 8.7 Hz, ArCHAHB;
6.98–7.48, m, C6H4 and C6H5Se; 7.37 and 7.60, d, J 6.9 Hz, C6H4SO2.
Mass spectrum m/z 471 (M, 5%), 314 (23), 272 (65), 91 (100).
(i) With chlorine and tetrabutylammonium chloride at room temper-
ature. Chlorine in carbon tetrachloride (1.8 M, 0.3 ml, 0.56 mmol) was
added to a stirred solution of the selenides (3) and (4) (210 mg,
0.5 mmol) in dry acetonitrile (10 ml). Tetrabutylammonium chloride
(140 mg, 0.5 mmol) was then added. The mixture was stirred at room
temperature for 40 h, then quenched by the addition of hydrogen per-
oxide (28%, 0.3 ml, 2.5 mmol). The mixture was extracted with
dichloromethane (2×10 ml) and the solvent evaporated to give a yellow
oil. Chromatography (ethyl acetate/hexane) gave ethyl 2-(1-chloro-1-
methylethyl)indoline-1-carboxylate (7) as a light yellow oil (40 mg,
30%) (Found: m/z, 267.1036. C14H18ClNO2 requires m/z, 267.1026).
ꢁmax (film) 1700, 1600, 1270 cm–1. 1H n.m.r. ꢀ 1.24, s, (CH3)2; 1.25, t,
J 9 Hz, CH2CH3; 3.28, d, JBX 9 Hz, ArCHAHB; 3.35, d, JAX 4 Hz,
ArCHAHB; 4.25, q, J 7 Hz, CH2CH3; 4.75, dd, JAX 4, JBX 9 Hz, CHN;
7.1–7.6, m, ArH. Mass spectrum m/z 267 (M, 3%), 232 (28), 190 (74),
118 (100). Further elution with ethyl acetate gave a complex mixture of
products.
2-Isopropenyl-1-[(4-methylphenyl)sulfonyl]indoline (12)
A mixture of the selenide (10) (230 mg, 0.5 mmol) and hydrogen
peroxide (28%, 5.4 g, 60 mmol) in dichloromethane (30 ml) was stirred
at room temperature for 4 h. The mixture was washed with water, the
organic phase dried (Na2SO4) and evaporated to give a white solid
which was recrystallized from dichloromethane/hexane to give the
alkene (12) (118 mg, 76%) as white needles, m.p. 107–107.5° (Found:
C, 69.0; H, 6.3; N, 4.6%; m/z, 313.1147. C18H19NO2S requires C, 69.0;
H, 6.1; N, 4.5%; m/z, 313.1139). ꢁmax (CCl4) 1655, 1600, 1580,
1360 cm–1. 1H n.m.r. ꢀ 1.66, s, CH3; 2.33, s, ArCH3; 2.62, dd, JAX 3.9,
JAB 16.2 Hz, ArHAHB; 2.91, dd, JBX 10.2, JAB 16.2 Hz, ArCHAHB; 4.55,
dd, JAX 3.9, JBX 10.2 Hz, CHN; 4.76 and 4.97, both s, C=CH2; 6.9, m,
ArH; 7.10 and 7.50, d, J 8.4 Hz, C6H4SO2; 7.60, d, J 7.8 Hz, ArH. Mass
spectrum m/z 313 (M, 100%), 272 (21), 158 (73).
(ii) With chlorine and tetrabutylammonium chloride at –23°. The
reaction was carried out as above except that the mixture was stirred at
–23° for 30 min, then warmed to room temperature and the crude
product purified by preparative reverse-phase h.p.l.c. (methanol/water
gradient). This yielded the chloride (7) (50 mg, 30%) (spectroscopic
data as above).
(iii) With phenylselanyl chloride at room temperature. Phenyl-
selanyl chloride (80 mg, 0.40 mmol) in dry dichloromethane (6 ml) was
added to a stirred mixture of the selenides (3) and (4) (150 mg,
0.38 mmol) and silica gel (Merck 60, 230–400 mesh, 1.0 g) in dry
dichloromethane (20 ml) at room temperature under an atmosphere of
nitrogen. The mixture was stirred at room temperature for 8 h, and then
filtered through Celite. The Celite was washed with ethyl acetate and
Ethyl 2-Isopropenylindoline-1-carboxylate (11)
In a similar manner to that described above the carbamate (3) was
converted into the alkene (11) which was isolated as a colourless oil,
b.p. 150°/0.4 mm. The n.m.r. spectrum indicated that the material, while
largely the required alkene (11), was not pure (Found: m/z, 231.1251.
Calc. for C14H17NO2: m/z, 231.1255). 1H n.m.r. [for (11)] ꢀ 1.27, t, J 7
Hz, OCH2CH3; 1.67, d, J 1 Hz, CH3C=C; 2.52–3.48, m, CH2, CHN;
4.25, q, J 7 Hz, OCH2; 4.78, br d, J 2.4 Hz, C=CH2; 6.92–7.35, m, ArH.
the combined filtrate concentrated to give
a
yellow oil.
Chromatography (ethyl acetate/hexane) gave the chloride (7) (51 mg,
50%) as a yellow oil (spectroscopic data as above).
2,2,2-Trifluoro-N-{2-[3-hydroxy-3-methyl-2-
(phenylselanyl)butyl]phenyl}acetamide (15)
(iv) With phenylselanyl chloride at –78°. The reaction was carried
out as above except that the mixture was stirred at –78° for 1 h, and then
allowed to warm to room temperature over 30 min. Preparative reverse-
phase h.p.l.c. (water/methanol; 30: 70) gave the chloride (7) (52 mg,
51%) as a yellow oil and the selenonium salt (8) (40 mg, 39%) as an
unstable, white solid. 1H n.m.r. ꢀ 1.25, t, J 7 Hz, CH2CH3; 1.67, s, CH3;
1.80, s, CH3; 2.91–3.30, m, CH2CH(SePh); 4.2, q, J 7 Hz, CH2CH3;
6.75–7.80, m, ArH. F.a.b. mass spectrum m/z 389 (M–SePh).
Phenylselanyl chloride (191 mg, 1 mmol) in dry dichloromethane
(6 ml) was added to a stirred mixture of the trifluoroacetamide (13)13
(257 mg, 1 mmol), silica gel (Merck 60, 230–400 mesh, oven-dried,
500 mg) and anhydrous potassium carbonate (1.2 g, 10 mmol) in dry
dichloromethane (10 ml) at –78° under an atmosphere of nitrogen. The
mixture was stirred at –78° for 20 min, and then at room temperature in
darkness for 4 days. The mixture was filtered through Celite, the Celite
washed with ethyl acetate (20 ml), and the filtrate evaporated to give a
yellow oil which was flash-chromatographed on silica gel. Elution with
ethyl acetate/hexane gave the hydroxy selenide (15) (90 mg, 21%) as a
light yellow oil (Found: m/z, 432.0675. C19H20F3NO280Se requires M+H,
432.0689). ꢁmax (film) 3380, 3360, 1720, 1590, 1160 cm–1. 1H n.m.r. ꢀ
1.40, s, CH3; 1.44, s, CH3; 2.37, s, OH; 2.88, dd, JAX 14.7, JBX 9.9 Hz,
CHXSe; 3.05, dd, JBX 9.9, JAB 2.7 Hz, ArCHAHB; 3.40, dd, JAX 14.7,
JAB 2.7 Hz, ArCHAHB; 6.9–7.3, m, ArH; 7.82, d, J 8.1 Hz, ArH; 9.33, s,
NH. Mass spectrum m/z 432 (M+H, 12%), 373 (100), 335 (14).
4-Methylphenyl N-[2-(3-Methylbut-2-enyl)phenyl]sulfamate (9)
Tosyl chloride (1.78 g, 9.3 mmol) was added to a stirred mixture of
2-allylaniline17 (1 g, 6.2 mmol) in dry pyridine (10 ml) under an atmo-
sphere of nitrogen. The mixture was stirred at room temperature for
48 h, diluted with ethyl acetate, washed with dilute hydrochloric acid
(1 M, 2×40 ml), and then with saturated sodium bicarbonate solution
(2×30 ml). The organic phase was dried and evaporated and the residue
purified by chromatography (hexane) to give a fraction which on crys-
tallization from dichloromethane/hexane gave the sulfonamide (9)
(1.71 g, 87%) as white crystals, m.p. 75–77°, b.p. 121–124°/0.02 mm
(Found: C, 68.2; H, 6.6; N, 4.4. C18H21NO2S requires C, 68.5; H, 6.7;
N, 4.4%). ꢁmax (CCl4) 3280, 1660, 1600, 1495, 1335, 1160 cm–1.
1H n.m.r. ꢀ 1.63, s, CH3; 1.68, s, CH3; 2.29, s, PhCH3; 3.00, br d, J 7 Hz,
PhCH2; 4.94, t, J 7 Hz, C=C–H; 7.36 and 7.58, d, J 9 Hz, ArH. Mass
spectrum m/z 315 (M, 2%), 201 (100), 173 (39), 161 (30), 156 (45).
Attempted Amidomercuration/Oxidative Demercuration of
Carbamate (2)
Mercuric nitrate (0.376 g, 1.1 mmol) was added to a stirred mixture
of the carbamate (2) (0.173 g, 0.74 mmol), sodium bicarbonate (62 mg,
0.74 mmol) and dry acetonitrile (10 ml) under an atmosphere of nitro-
gen and the resulting mixture stirred at room temperature for 1 h.
Saturated, aqueous potassium bromide solution (5 ml) was added and
the mixture stirred for a further 2 h. The mixture was extracted with
ethyl acetate (30 ml) and the organic phase dried and evaporated. The
residue was dissolved in dimethylformamide (5 ml) and added drop-
wise to a mixture of sodium borohydride (28 mg, 0.74 mmol) and
dimethylformamide (6 ml) through which oxygen had been bubbled for
20 min. Sulfuric acid (0.05 M, 20 ml) was added and the mixture shaken
and extracted with dichloromethane (2×20 ml). The combined organic
layers were dried and evaporated to return the starting carbamate (2) in
nearly quantitative yield.
2-[1-Methyl-1-(phenylselanyl)ethyl]-1-
[(4-methylphenyl)sulfonyl]indoline (10)
Phenylselanyl chloride (98 mg, 0.51 mmol) in dry dichloromethane
(6 ml) was added dropwise to a stirred mixture of the sulfonamide (9)
(157 mg, 0.5 mmol), potassium carbonate (600 mg, 5 mmol) and silica
gel (Merck 60, 230–400 mesh, oven-dried, 300 mg) in dry
dichloromethane (10 ml) at –78° under an atmosphere of nitrogen. The
mixture was stirred at –78° for 15 min, and then at room temperature in
darkness for 64 h. The mixture was filtered through Celite, the Celite
washed with ethyl acetate (20 ml) and the solvent evaporated to give a

128
M. A. Cooper et al.
Attempted Amidomercuration/Oxidative Demercuration of
2-Allylaniline
oil that was purified by flash chromatography (ethyl acetate/hexane;
1: 9) to give the ester (19) as a white solid (73 mg) after crystallization
from hexane, m.p. 87–88° (Found: C, 72.0; H, 8.5; N, 5.9%; m/z,
233.1420. C14H19NO2 requires C, 72.1; H, 8.2; N, 6.0%; m/z,
233.1416). ꢁmax (Nujol) 3376, 1679, 1604, 1512 cm–1. 1H n.m.r. ꢀ 1.23,
s, (CH3)2; 1.35, t, J 6.9 Hz, CH3; 1.70, t, J 6.5 Hz, CH2; 2.79, t, J 6.5 Hz,
CH2; 4.13, br s, NH; 4.30, q, J 6.9 Hz, OCH2; 6.38, d, J 8.1 Hz, ArH;
7.66, m, ArH; 7.70, br s, ArH. Mass spectrum m/z 233 (M, 51%), 218
(100), 190 (29).
2-Allylaniline (0.17 g, 1.13 mmol) in acetone (1 ml) was added to a
stirred suspension of mercuric acetate (1.05 g, 3.3 mmol) in acetone
(4 ml) and water (1 ml) and the resulting mixture stirred at room tem-
perature for 10 min. Sodium borohydride (0.13 g, 3.51 mmol) in
acetone (1 ml) was slowly added whilst oxygen gas was bubbled
through the mixture. After stirring for 1 min, the mixture was filtered,
diluted with water (5 ml) and extracted with dichloromethane. The
combined organic phases were dried and evaporated to give a complex
product mixture.
Crystallography
Intensity data were measured for transparent crystals of (5) and (10)
(0.08×0.48×0.57 mm3 for (5) and 0.40×0.40×0.40 mm3 for (10)) at
room temperature on a Rigaku AFC6R diffractometer for (5) and an
Enraf–Nonius CAD diffractometer for (10), each fitted with graphite
Ethyl 4-[(1,1-Dimethylallyl)amino]benzoate (17)
Amixture of the alkyne16 (16) (507 mg), Lindlar catalyst (0.149 mg)
and quinoline (100 mg) in ethyl acetate (15 ml) was stirred under
hydrogen for 10 min. The solution was filtered and the filtrate evapo-
rated to give an off-white solid which was recrystallized from
dichloromethane/hexane to give the alkene (17) (464 mg, 91%), m.p.
102.5–104° (Found: C, 71.9; H, 8.0; N, 6.1. C14H19NO2 requires C,
72.1; H, 8.2; N, 6.0%). ꢁmax (Nujol) 3310, 1680, 1600, 1510 cm–1.
1H n.m.r. ꢀ 1.35, t, J 7.5 Hz, CH3; 1.45, s, (CH3)2; 4.25, s, NH; 4.35, q,
J 7.5 Hz, CH2; 5.2, dd, Jtrans 17, Jgem 1 Hz, C=CHAHB; 5.3, dd, Jcis 10,
Jgem 1 Hz, C=CHAHB; 6.05, dd, Jcis 10, Jtrans 17 Hz, CH=CH2; 6.8, d,
J 9 Hz, ArH; 7.9, d, J 9 Hz, ArH. Mass spectrum m/z 233 (M, 88%), 218
(100), 206 (51), 188 (34).
Table 2. Fractional atomic coordinates for (5)
Atom
x
y
z
Se(23)
O(11)
O(11Ј)
O(24)
N(11)
C(1)
C(2)
C(3)
C(4)
C(5)
0.18657(4)
0.8245(3)
0.8107(2)
0.5341(2)
0.6334(3)
0.5425(4)
0.4088(4)
0.3181(4)
0.3627(6)
0.4936(6)
0.5850(4)
0.7635(4)
0.9461(4)
0.9756(4)
0.3592(3)
0.3613(3)
0.4031(3)
0.5995(4)
0.4139(3)
0.3117(4)
0.2322(4)
0.3124(4)
0.3382(5)
0.2797(8)
0.1979(9)
0.1729(6)
0.27799(3)
0.0996(2)
0.0953(2)
0.1558(2)
0.1341(2)
0.1495(2)
0.1455(2)
0.1626(3)
0.1816(3)
0.1838(4)
0.1687(3)
0.1097(3)
0.0633(3)
0.0430(3)
0.1251(2)
0.2167(2)
0.1956(2)
0.1116(3)
0.2888(3)
0.1218(3)
0.4130(3)
0.4413(3)
0.5394(4)
0.6062(4)
0.5784(5)
0.4805(4)
0.52271(3)
0.4423(2)
0.5920(2)
0.6632(2)
0.4909(2)
0.4066(3)
0.4081(3)
0.3263(3)
0.2474(3)
0.2466(3)
0.3246(3)
0.5017(4)
0.6160(4)
0.7151(4)
0.4952(2)
0.5563(2)
0.6594(2)
0.7460(3)
0.7143(2)
0.6931(2)
0.5151(3)
0.4593(3)
0.4503(4)
0.4966(4)
0.5495(4)
0.5604(3)
Ethyl 4-Amino-3-(3-methylbut-2-enyl)benzoate (18)
C(6)
A mixture of the alkene (17) (1.5 g, 6.5 mmol), p-toluenesulfonic
acid (200 mg), acetonitrile (200 ml) and water (50 ml) was stirred at 65°
for 16 h. The cooled solution was extracted with ethyl acetate
(2×50 ml), dried (Na2SO4), the solvent evaporated and the residue
flash-chromatographed on silica gel. Elution with ethyl acetate/hexane)
gave the allylaniline (18) (1.36 g, 91%) as a light brown oil (Found:
m/z, 233.1416. C14H19NO2 requires m/z, 233.1416). ꢁmax 3445, 3300,
1690, 1615, 1600, 1500 cm–1. 1H n.m.r. ꢀ 1.29, t, J 6.0 Hz, CH3; 1.69,
br s, (CH3)2; 3.16, d, J 6.9 Hz, ArCH2; 4.21, s, NH2; 4.25, q, J 6.0 Hz,
CH2; 5.17, m, C=C–H; 6.56, dd, J 7.5, 0.9 Hz, ArH; 7.67, m, ArH. Mass
spectrum m/z 233 (M, 100%), 218 (26), 178 (71), 160 (40).
C(11)
C(12)
C(13)
C(21)
C(22)
C(24)
C(25)
C(26)
C(27)
C(231)
C(232)
C(233)
C(234)
C(235)
C(236)
Ethyl 2,2-Dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate (19)
A mixture of the alkene (18) (96 mg, 0.41 mmol), mercuric acetate
(400 mg, 1.26 mmol), acetone (4 ml) and water (1 ml) was vigorously
stirred at room temperature for 10 min. Sodium borohydride (65 mg,
1.72 mmol) in aqueous sodium hydroxide solution (10%, 1 ml) was
then added dropwise, the solution diluted with water (5 ml) and the
resultant mixture extracted with dichloromethane (2×10 ml). The
organic extracts were dried (Na2SO4) and evaporated to give a brown
Table 3. Fractional atomic coordinates for (10)
Atom
x
y
z
Se(21)
S(10)
O(10a)
O(10b)
N(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(22)
C(23)
C(24)
C(25)
C(26)
C(27)
0.20238(3)
0.65808(7)
0.7194(2)
0.6460(2)
0.5047(2)
0.4293(2)
0.4159(3)
0.4411(2)
0.4211(3)
0.4507(3)
0.4968(3)
0.5179(3)
0.4914(2)
0.7410(2)
0.7862(3)
0.8470(3)
0.8660(3)
0.8191(3)
0.7572(3)
0.9355(3)
0.2974(3)
0.2016(3)
0.3230(3)
0.3351(3)
0.3323(3)
0.4243(4)
0.5205(4)
0.5239(3)
0.4311(3)
0.33969(3)
0.15622(6)
0.0858(2)
0.1246(2)
0.1793(2)
0.2667(2)
0.3581(2)
0.3031(2)
0.3387(2)
0.2697(3)
0.1667(3)
0.1304(2)
0.2006(2)
0.2813(2)
0.3232(2)
0.4238(3)
0.4815(2)
0.4386(2)
0.3395(2)
0.5898(3)
0.2204(2)
0.1838(3)
0.1284(2)
0.3787(2)
0.3329(3)
0.3628(3)
0.4373(3)
0.4823(2)
0.4547(2)
0.16655(2)
0.10580(4)
0.0577(1)
0.1803(1)
0.0643(1)
0.0992(1)
0.0408(2)
–0.0307(1)
–0.1032(2)
–0.1594(2)
–0.1431(2)
–0.0705(2)
–0.0150(1)
0.1093(1)
0.0464(2)
0.0491(2)
0.1159(2)
0.1780(2)
0.1758(1)
0.1198(2)
0.1205(1)
0.0529(2)
0.1760(2)
0.2487(2)
0.3178(2)
0.3774(2)
0.3675(2)
0.2986(2)
0.2397(2)
Table 1. Crystallographic data for (5) and (10)
(5)
(10)
Formula
M
C21H27NO3Se
420.4
C24H25NO2SSe
470.5
Crystal system
Space group
a (Å)
b (Å)
c (Å)
monoclinic
P21/n
monoclinic
P21/n
10.262(2)
13.611(5)
14.760(4)
101.26(2)
2022.1(9)
4
10.121(2)
12.368(3)
18.031(6)
97.40(2)
2238.3(9)
4
ꢂ (deg)
V (Å3)
Z
D
c (g cm–3
)
1.381
1.396
F (000)
ꢃ (cm–1
872
18.77
968
17.91
)
No. unique reflns meas.
4898
3833
ꢄmax (deg)
27.9
25.0
No. reflns used
2025
2263
R
0.044
0.043
g
Rw
0.00002
0.036
0.39
0.0001
0.054
0.67
ꢅmax (e Å–3
)

Reactions of N-Substituted 2-(Dimethylallyl)aniline
129
5
6
monochromatized Mo Kꢆ radiation, ꢇ 0.7107 Å. The ꢈ: 2ꢄ scan tech-
nique was employed to measure data which were corrected for Lorentz
and polarization effects24 and for (5), for absorption by using an empir-
ical procedure.25 The structures were solved by direct methods26 and
refined by a full-matrix least-squares procedure based on F.24 Hydrogen
atoms were included in each model at their calculated positions and
non-hydrogen atoms were refined with anisotropic displacement
parameters. After the inclusion of a weighting scheme of the form
w = 1/[ꢉ2(F)+g|F|2], each refinement was continued until convergence
using reflections with I ≥ 3.0ꢉ(I). Crystal data and refinement details
are collected in Table 1 and fractional atomic coordinates are listed in
Tables 2 and 3; the numbering schemes employed are shown in Figs 1
and 2 which were drawn with ORTEP at the 35% probability level.27
Evidence of some dynamic disorder in (5) can be seen in the
shapes/sizes of the thermal ellipsoids in Fig. 1. Crystallographic
Information Files (CIFs) and listings of structure factors for the struc-
tures have been deposited with the Australian Journal of Chemistry,
P.O. Box 1139, Collingwood, Vic. 3066, and are available until 31
December 2005.
Hill, M. L., and Raphael, R. A., Tetrahedron, 1990, 46, 4587.
Morimoto, Y., Oda, K., Shirahama, H., Matsumoto, T., and Omura,
S., Chem. Lett., 1988, 909.
Morimoto, Y., Matsuda, F., and Shirahama, H., Tetrahedron Lett.,
1990, 31, 6031.
Morimoto, Y., Matsuda, F., and Shirahama, H., Synlett, 1991, 201.
Pearce, C. M., and Sanders, J. K. M., J. Chem. Soc., Perkin Trans.
1, 1990, 409.
Morimoto, Y., Matsuda, F., and Shirahama, H., Tetrahedron, 1996,
52, 10609.
Morimoto, Y., and Shirahama, H., Tetrahedron, 1996, 52, 10631.
Raner, K. D., Skelton, B. W., Ward, A. D., and White, A. H., Aust. J.
Chem., 1990, 43, 609.
Raner, K. D., and Ward, A. D., Aust. J. Chem., 1991, 44, 1749.
De Silva, A. N., Francis, C. L., and Ward, A. D., Aust. J. Chem.,
1993, 46, 1657.
Francis, C. L., and Ward, A. D., Aust. J. Chem., 1994, 47, 2109.
Williamson, N. M., March, D. R., and Ward, A. D., Tetrahedron
Lett., 1995, 36, 7721.
7
8
9
10
11
12
13
14
15
16
17
Clive, D. L. J., Farina, V., Singh, A., Wong, C. K., Kiel, W. A., and
Menchen, S. M., J. Org. Chem., 1980, 45, 2120.
Morella, A. M., and Ward, A. D., Tetrahedron Lett., 1984, 25, 1197.
Morella, A. M., and Ward, A. D., Aust. J. Chem., 1995, 48, 445.
Paulmier, C., ‘Selenium Reagents and Intermediates in Organic
Synthesis’ (Pergamon Press: Oxford 1986).
Acknowledgments
18
19
20
M.A.C. acknowledges an Australian Postgraduate
Research Award (priority), C.L.F. acknowledges an
Australian Postgraduate Research Award and T.T. acknowl-
21
22
23
24
Hegedus, L. S., Allen, G. F., Bozell, J. J., and Waterman, E. L., J.
Am. Chem. Soc., 1978, 100, 5800.
Larock, R. C., Hightower, T. R., Hasvold, L. A., and Peterson, K. P.,
J. Org. Chem., 1996, 61, 3584.
Harding, K. E., Marman, T. H., and Nam, D., Tetrahedron, 1988, 44,
5605.
teXsan: Structure Analysis Software, Molecular Structure
Corporation, Texas, U.S.A.
Walker, N., and Stuart, D., Acta Crystallogr., Sect. A, 1983, 39, 158.
Sheldrick, G. M., SHELXS86, Program for the Automatic Solution of
Crystal Sructure, University of Göttingen, Göttingen, Germany,
1986.
Johnson, C. K., ORTEP, Report ORNL-5138, Oak Ridge National
Laboratory, TN, U.S.A., 1976.
edges
a University of Adelaide Summer Research
Scholarship. We thank the Australian Research Council for
support of the crystallographic facility.
References
1
Omura, S., Nakagawa, A., Hashimoto, H., Oiwa, R., Iwai, Y.,
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4