Stereoselective transformation of amines via chiral 2,4,6-triphenylpyridinium intermediates

Article abstract of DOI:10.1016/S0957-4166(01)00343-3

We herein report the preparation and the nucleophilic substitution of the chiral 2,4,6-triphenylpyridinium tetrafluoroborates 2a and 2b. The triphenylpyridinium intermediates were generated from homochiral amines (1a, 1b) and 2,4,6-triphenylpyrylium tetrafluoroborate and used as substrates for stereoselective nucleophilic substitution. The degree of inversion in the substitution reactions has been studied. The alcohol (3a, 3b) and azide (4a, 4b) products were obtained with >99 and 96-98% inversion of configuration, respectively.

Full text of DOI:10.1016/S0957-4166(01)00343-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1947–1951
Stereoselective transformation of amines via chiral
2,4,6-triphenylpyridinium intermediates
Sadri A. Said and Anne Fiksdahl*
Organic Chemistry Laboratories, Norwegian University of Science and Technology, N-7491 Trondheim, Norway
Received 18 July 2001; accepted 30 July 2001
Abstract—We herein report the preparation and the nucleophilic substitution of the chiral 2,4,6-triphenylpyridinium tetra-
fluoroborates 2a and 2b. The triphenylpyridinium intermediates were generated from homochiral amines (1a, 1b) and 2,4,6-
triphenylpyrylium tetrafluoroborate and used as substrates for stereoselective nucleophilic substitution. The degree of inversion in
the substitution reactions has been studied. The alcohol (3a, 3b) and azide (4a, 4b) products were obtained with >99 and 96–98%
inversion of configuration, respectively. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
pyrylium salt I involves a fast base-catalyzed ring open-
ing reaction with primary amine RNH2 and an acid-
catalyzed rate-determining ring-closure step of the
open-chain intermediate II to give the pyridinium salt
III. When the counterion is non-nucleophilic, such
When homochiral amino compounds are more easily
accessible (e.g. from natural sources) than other alter-
native substrates like halides or alcohols there is a need
for suitable methods for the stereoselective transforma-
tion of amines into other functionalities. In our ongo-
ing effort to develop stereoselective transformation
reactions for chiral amines we have previously shown
that N,N-disulfonyl derivatives of chiral primary
amines may be transformed by nucleophilic substitution
reactions into the corresponding amines, alcohols and
aryl ethers with inversion of stereochemistry.1–9
−
as BF4 , a nucleophile can add to afford the displace-
ment product R-Nu IV and triphenylpyridine V. The
driving force for this reaction is the good leaving
group ability and high stability of 2,4,6-triphenyl-
pyridine V.
To our knowledge this method has not been used for
chiral substrates and the stereoselectivity of the dis-
placement reaction has therefore never been studied.
Our present work demonstrates the preparation and
nucleophilic substitution of the chiral 2,4,6-
triphenylpyridinium salts 2 formed from homochiral
amines 1 and 2,4,6-triphenylpyrylium salt (see Scheme 1
and Table 1). The degree of inversion in the substitu-
tion reactions has been studied for the formation of the
alcohol 3 and azide 4 products.
An alternative means of converting a primary amine
into a suitable leaving group is to transform the amine
RNH2 into the 2,4,6-triphenylpyridinium compound III
by treatment with 2,4,6-triphenylpyrylium salt I (see
Fig. 1). It has been demonstrated that the bulky 2,4,6-
triphenylpyridine ring acts as a good leaving group in
synthetic transformations.10–18 The conversion of the
Figure 1.
* Corresponding author.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00343-3

1948
S. A. Said, A. Fiksdahl / Tetrahedron: Asymmetry 12 (2001) 1947–1951
Scheme 1.
Table 1. Results for the reactions shown in Scheme 1
2. Results and discussion
fragmentation of triphenylpyridine from the molecular
ions of 2a, 2b. Due to the weak CꢀN-pyridinium bond,
the molecular ions were always absent in the mass
spectrum and the base peak was the neutral
The primary amines 1a and 1b reacted with 2,4,6-
triphenylpyrylium tetrafluoroborate by fast ring open-
ing to the vinylogous amide (II), which underwent slow
ring closure to the 1-substituted 2,4,6-triphenylpyri-
dinium cations 2a and 2b in 84–90% yield (see Scheme
1 and Table 1). Both steps of the reactions could be
followed by TLC and by characteristic changes of
colour from yellow to dark red/black and back to
yellow. The ring opening reaction was more rapid in
the presence of Et3N or using an excess of the amine (2
equivalents). It is believed that the base is needed to
remove the proton in one of the sub-steps in the
formation of the vinylogous amide.12,15,17 The cycliza-
tion step is strongly catalyzed by acetic acid. The
rate-enhancing effect was demonstrated by a manifold
increase in reaction rate, reducing the reaction time
from 7 days to 5 h by the addition of one equivalent of
acetic acid.
1
triphenylpyridine fragment. H NMR of the cyclohexyl
intermediate 2a showed a characteristic phenyl ring
current effect19 causing a high field resonance of two of
the cyclohexyl protons as can be observed for (S)-2a; l
0.37 and 0.63. This specific shielding effect can be
explained by the cyclohexyl ring conformation.
As can be seen from Table 1 the configuration of the
aliphatic amine substrates 1a and 1b were nearly com-
pletely inverted by the nucleophilic substitution of the
pyridinium intermediates 2a, 2b to give the alcohol 3a,
3b and azide 4a, 4b products. The azides 4a, 4b can be
further reduced to the primary amines and thus afford
the inverted amines. No attempts to optimize the yields
of the substitution products 3a, 3b and 4a, 4b (17–71%)
were made.
The mass spectra of the 2,4,6-triphenylpyridinium inter-
mediates demonstrate the energetically highly favoured
The following comments can be made on the advan-
tages of the 2,4,6-triphenylpyridinium intermediates as

S. A. Said, A. Fiksdahl / Tetrahedron: Asymmetry 12 (2001) 1947–1951
1949
substrates for stereoselective conversion of chiral
aliphatic primary amino groups into other functionali-
ties by means of nucleophilic displacement. The forma-
tion of the intermediates 2a, 2b was carried out at room
temperature. Less vigorous reaction conditions were
needed and higher yields of intermediates 2a, 2b (84–
90%) were obtained compared with previous N,N-disul-
fonylderivative intermediates.1–9 Triphenylpyridinium
derivatives 2a, 2b showed comparable reactivity (80–
100°C, 5 h) towards nucleophiles to ditosyl-, dimesyl-
and dinosyl-imides1–5 (120°C, 72 h). They needed more
vigorous reaction conditions than previous 1,2-benzene-
and naphthalene-disulfonylimides (0°C, 24 h).6–9 The
stereoselectivity and degree of inversion (96–99%) for
the substitution of intermediates 2a, 2b is comparable
to that of ditosylimides1–4 and is generally better than
other previously reported disulfonylimides.5–9
and azide 4a, 4b products were prepared by nucle-
ophilic substitution of the pyridium intermediates with
>99 and 96–98% inversion of stereochemistry, respec-
tively. A benzylic substrate afforded racemic alcohol,
azide and aryl ether products in one-pot reactions in
70–85% yield. This process provides a method of
achieving the stereoselective conversion of chiral
aliphatic primary amino groups into alcohols and
azides by means of nucleophilic displacement on the
activated derivative.
4. Experimental
2,4,6-Triphenylpyrylium tetrafluoroborate, (R/S)-1-
cyclohexylethylamine and (S)-a-methoxyphenylacetic
acid were obtained from Fluka, (R)-1-phenylethyl-
amine, potassium nitrite, triethylamine and acetic acid
from Acros, and (R)-1-methyl-3-phenylpropylamine
was prepared by optical resolution using diastereomeric
crystallization with (S)-N-acetylcystein as described
elsewhere.1 Phenol, 2-naphthol, sodium azide were
obtained from Merck. DMF was dried over activated
The benzylic racemic 1-phenylethylamine has previ-
ously been reported readily to form the triphenylpyri-
dinium salt.16 However, the intermediate pyridinium
salt could not be isolated and the corresponding alco-
hol product was formed directly. Presumably the ben-
zylic pyridinium intermediate rapidly dissociates by an
SN1 process to give the resonance stabilized secondary
carbocation which is trapped by water to give the
alcohol. Other products could not be prepared.
Racemic products were therefore expected for the
homochiral (R)-1-phenylethylamine 1c (see Scheme 2).
In addition to the alcohol 3c we were able to prepare
the azide 4c and the aryl ether products 5c and 5d by
one-pot procedures. However, all products had lost
their optical activity being almost racemic. Water is
generated in the ring-closure reaction for the formation
of the intermediate 2c and the alcohol 3c was always
present as a by-product for all reactions even in pre-
dried solvents. The yields were in general higher for the
nucleophilic substitution of 2c compared with 2a, 2b
and the benzylic products 3c, 4c, 5c and 5d were
obtained in 70–85% overall yields from the amine (R)-
1c.
,
molecular sieves (4 A). THF was distilled (N2) from the
sodium ketyl of benzophenone and used immediately.
Solvents: pro analysi quality. GLC: Carlo Erba Model
8130, split-injection, hydrogen, FID, column:
Chrompack CP-Sil 5 CB (25 m). Chiral GLC analysis:
Chrompack CP-CHIRADEX-CB fused silica WCOT
(25 m, 0.32 mm; 0.32 mm), carrier gas pressure 5–5.5
p.s.i. 1H/13C NMR: Bruker Avance DPX 300/75.47
MHz and 400/100.5 MHz spectrometers, chemical
shifts are reported in ppm downfield from TMS. MS:
MAT 95 XL. IR: Nicolet 20SXC FT-IR spectrometer.
[h]D: Perkin–Elmer 241 polarimeter (10 cm cell with a
total volume of 1 mL).
4.1. Preparation of 1-((R or S)-1-cyclohexylethyl)-
2,4,6-triphenylpyridinium tetrafluoroborate 2a from (R
or S)-1-cyclohexylethylamine 1a
(S)-1-Cyclohexylethylamine ((S)-1a, 1.49 mL, 10.1
mmol) was added to a yellow solution of 2,4,6-
triphenylpyrylium tetrafluoroborate (4.0 g, 10.1 mmol)
in dichloromethane (20 mL) effecting a colour change
of the mixture from yellow to red. Triethylamine (1.4
mL, 10 mmol, 1 equiv.) was added, and the deep red
mixture was stirred at rt for 15 min. Acetic acid (0.58
mL, 10.1 mmol, 1 equiv.) was added turning the colour
blackish. The reaction was further stirred for 8 h at rt
under nitrogen. The reaction was followed by TLC and
3. Conclusion
The stereoselective conversion of chiral primary amines
into alcohols and azides with inversion of configuration
has been demonstrated. The 2,4,6-triphenylpyridinium
derivatives 2a, 2b of the chiral primary aliphatic amines
1a and 1b were formed from 2,4,6-triphenylpyrylium
tetrafluoroborate in 84–90% yield. The alcohol 3a, 3b
Scheme 2.

1950
S. A. Said, A. Fiksdahl / Tetrahedron: Asymmetry 12 (2001) 1947–1951
was complete when the mixture was yellow. The crude
product solidified at rt and was purified by flash chro-
matography (gradient elution: dichloromethane, 5%
methanol/dichloromethane) to give the white crystalline
pyridinium tetrafluoroborate (S)-2a (4.6 g, 90%); mp
4.4. Preparation of (S)- or (R)-1-cyclohexylethyl azide
4a from 1-((R)- or (S)-1-cyclohexylethyl)-2,4,6-
triphenylpyridinium tetrafluoroborate 2a
((S)-1-Cyclohexylethyl)-2,4,6-triphenylpyridinium tetra-
fluoroborate ((S)-2a, 3.7 g, 7.3 mmol) and NaN3 (1.6 g,
24.6 mmol, 3.3 equiv.) in DMF (10 mL) was stirred and
heated to 100°C for 5 h under a nitrogen atmosphere.
The mixture was cooled to rt, diluted with water (50
mL), extracted with diethyl ether (2×50 mL) and washed
with brine. The solution was dried over Na2SO4. The
crude oily product which was obtained after evapora-
tion of the solvent, was purified by flash chromatogra-
phy (heptane) to give (R)-4a as a colourless oil (433 mg,
39%). [h]D −35.8 (c 2.0, CHCl3). (S)-4a was correspond-
ingly prepared in 37% yield from (R)-2a. The products
were characterized giving data in accordance with (S)-
and (R)-4a prepared previously.6 1H NMR (300 MHz,
CDCl3): l 0.90–1.80 (m, 11H), 1.25 (d, J=6.6 Hz, 3H),
3.27 (quintet, J=6.6 Hz, 1H); 13C NMR (75.47 MHz,
CDCl3): l 16.5, 26.2, 26.3, 26.5, 29.2, 29.4, 43.4, 63.2,
128.5, 129.3, 129.8, 131.2. The (R)- and (S)-azides 4a
were reduced by catalytic hydrogenation to the corre-
sponding amine and derivatized with (S)-a-methoxy-
phenylacetyl chloride. Enantiomeric purity of the azide
products (R)- and (S)-4a were based on GLC analysis
of the diastereomeric amide derivatives, indicating a
degree of inversion of 96–97% (R:S ratio: (R)-4a; 96:4
and (S)-4a; 3:97). The derivatized products coeluted
on GLC with the respective compounds prepared
previously.6
1
151–153°C; H NMR (400 MHz, CDCl3): l 0.37 (dq,
J=2 and 12 Hz, 1H), 0.63 (dq, J=3 and 12 Hz, 1H),
0.85–1.70 (m, 9H), 1.58 (d, J=7 Hz, 3H), 4.60 (dq, J=7
and 11 Hz, 1H), 7.46–7.78 (m, 17H); 13C NMR (75.47
MHz, CDCl3): l 21.1, 25.4, 25.59, 25.62, 30.2, 30.7,
42.4, 72.1, 128.5, 129.3, 129.8, 131.2, 132.3, 133.9, 155.3;
MS [m/z (% rel. int.)]: 307 (Ph3Pyr, 100%), 278 (1%),
230 (13%), 202 (6%), 110 (2%), 102 (2%), 81 (4%); IR
(KBr, cm−1): 3059 (w), 2929 (m), 2851 (m), 1619 (s),
1599 (m), 1562 (s), 1494 (m), 1411 (m), 1353 (s), 1082
(m), 1057 (s), 1034 (m), 892 (m), 763 (s), 702 (s), 532 (w),
521 (w). (S)-2a: [h]D +61.7 (c 2.0, CHCl3). (R)-2a was
correspondingly prepared in 84% yield from (R)-1a and
characterized; [h]D −59.1 (c 2.0, CHCl3).
4.2. Preparation of 1-((R)-1-methyl-3-phenylpropyl)-
2,4,6-triphenylpyridinium tetrafluoroborate 2b from (R)-
1-methyl-3-phenylpropylamine 1b
The preparation of (R)-2b from (R)-1b (96% e.e.) was
carried out as described above for the preparation of
(S)-2a. The crystalline product was obtained after flash
chromatography (same solvent gradient as 4.1, 89%
1
yield); mp 195–198°C; H NMR (300 MHz, CDCl3): l
1.42 (d, J=7 Hz, 3H), 1.73 (m, 1H), 2.15 (m, 2H), 2.34
(m, 1H), 4.86 (m, 1H), 6.84 (m, 2H), 7.13 (m, 3H), 7.46
(m, 10H), 7.65 (m, 7H); 13C NMR (75.47 MHz, CDCl3):
l 21.7, 32.5, 37.8, 66.1, 126.5, 128.1, 128.3, 128.8, 129.6,
130.9, 132.0, 133.8, 134.0, 139.0, 155.1, 157.3; MS [m/z
(% rel. int.)]: 307 (Ph3Pyr, 100%), 278 (3%), 230 (29%),
202 (15%), 152 (11%), 132 (10%), 117 (14%), 102 (8%),
91 (27%); IR (KBr, cm−1): 3058 (w), 3026 (w), 2924 (w),
1617 (s), 1599 (w), 1583 (m), 1495 (m), 1410 (m), 1059
(s), 1036 (m), 890 (m), 764 (s), 701 (s), 520 (w). (R)-2b
(96% e.e.); [h]D −53.7 (c 2.0, CHCl3).
4.5. Preparation of (S)-1-methyl-3-phenylpropanol 3b
from 1-((R)-1-methyl-3-phenylpropyl)-2,4,6-
triphenylpyridinium tetrafluoroborate 2b
The nucleophilic substitution for the preparation of
(S)-3b from (R)-2b (96% e.e.); and potassium nitrite was
carried out as described for the preparation of (R)-3a
from (S)-2a above. The oily product (41% yield)
obtained after flash chromatography (5% acetone in
heptane) was characterized giving data in accordance
with (S)-3b published elsewhere.3 13C NMR (75.47
MHz, CDCl3): l 23.9, 32.4, 41.1, 67.7, 126.0, 128.6,
142.3. The product coeluted on GLC with the respective
compound prepared previously.3 Chiral GLC indicated
an R:S ratio of 2:98 and a degree of inversion of >99%;
(S)-3b (96% e.e.).
4.3. Preparation of (S)- or (R)-1-cyclohexylethanol 3a
from 1-((R)- or (S)-1-cyclohexylethyl)-2,4,6-
triphenylpyridinium tetrafluoroborate 2a
((S)-1-Cyclohexylethyl)-2,4,6-triphenylpyridinium tetra-
fluoroborate ((S)-2a, 0.6 g, 1.19 mmol) and KNO2 (2 g,
23.5 mmol) in DMF (5 mL) was stirred and heated to
80°C for 5 h under a nitrogen atmosphere. The mixture
was cooled to rt, diluted with water (40 mL), extracted
with diethyl ether (2×25 mL) and washed with 0.5 M
NaOH, water and brine. The solution was dried over
Na2SO4. The yellowish crude oily product which was
obtained after evaporation of the solvent, was purified
by flash chromatography (5% acetone in heptane) to
give (R)-3a as a colourless oil (26 mg, 17%). (S)-3a was
correspondingly prepared in 21% yield from (R)-2a. The
products were characterized giving data in accordance
with (S)- and (R)-3a published elsewhere and coeluted
on GLC with the respective compounds prepared previ-
ously.4 Chiral GLC indicated a degree of inversion of
>99% for both reactions (R:S ratio: (R)-3a; >99:0.01
and (S)-3a; <0.01:99).
4.6. Preparation of (S)-1-methyl-3-phenylpropyl azide
4b from 1-((R)-1-methyl-3-phenylpropyl)-2,4,6-
triphenylpyridinium tetrafluoroborate 2b
The nucleophilic substitution for the preparation of
(S)-4b from (R)-2b (96% e.e.) and NaN3 was carried out
as described for the preparation of (R)-4a from (S)-2a
above. The oily product (71% yield) obtained after flash
chromatography (2% acetone in heptane) was character-
ized giving data in accordance with (S)-4b published
elsewhere.1 13C NMR (75.47 MHz, CDCl3): l 19.7, 32.5,
38.1, 57.4, 126.2, 128.6, 128.7, 141.4. The azide (S)-4b

S. A. Said, A. Fiksdahl / Tetrahedron: Asymmetry 12 (2001) 1947–1951
1951
was reduced by catalytic hydrogenation to the corre-
sponding amine and derivatized with (S)-a-methoxy-
phenylacetyl chloride. Enantiomeric purity of the
azide product (S)-4b was based on GLC analysis
of the diastereomeric amide derivatives, indicating an
R:S ratio of 96:4 and a degree of inversion of 98%;
(S)-4b (92% e.e.). The derivatized product coeluted on
GLC with the respective compound prepared previ-
ously.1
4.10. Preparation of 1-phenylethyl phenyl ether 5c and
1-phenylethyl 2-naphthyl ether 5d from (R)-1-
phenylethylamine 1c via 1-((R)-1-phenylethyl)-2,4,6-
triphenylpyrylium tetrafluoroborate 2c
The nucleophilic substitutions for the preparation of
the products 5c and 5d from (R)-1c and phenol and
2-naphthol, respectively, were carried out as described
above for the preparation of 3c from (R)-1c, replacing
the nucleophile KNO2 with phenol or 2-naphthol (3.3
equiv.). The oily products 5c (70%) and 5d (73% yield)
obtained after flash chromatography (3% acetone in
heptane) were characterized giving data in accordance
with 5c and 5d reported elsewhere and they coeluted on
GLC with the respective compounds prepared previ-
ously.8,9 The products showed no optical rotation and
the enantioseparation of the phenyl ether 5c on chiral
GLC indicated a racemic product (R:S ratio 1:1).
4.7. Preparation of 1-((R)-1-phenylethyl)-2,4,6-
triphenylpyrylium tetrafluoroborate 2c from (R)-1-
phenylethylamine 1c
The preparation of (R)-2c from (R)-1c and 2,4,6-
triphenylpyrylium tetrafluoroborate was carried out as
described above for the preparation of (S)-2a but the
nucleophile for the displacement reactions was added
from the beginning. The intermediate was thus not
isolated and the two-step reactions were carried out in
one-pot as described below:
References
1. Seljestokken, B.; Fiksdahl, A. Acta Chem. Scand. 1993,
47, 1050–1052.
2. Johansen, C.; Fiksdahl, A. Chirality 1994, 6, 161–164.
3. Oppedal, H.; Tveit, I. C.; Fiksdahl, A. Tetrahedron:
Asymmetry 1994, 5, 895–902.
4.8. Preparation of 1-phenylethanol 3c from (R)-1-
phenylethylamine 1c via 1-((R)-1-phenylethyl)-2,4,6-
triphenylpyrylium tetrafluoroborate 2c
4. Ileby, N.; Kuzma, M.; Heggvik, L. R.; Sørbye, K.;
Fiksdahl, A. Tetrahedron: Asymmetry 1997, 8, 2193–2198.
5. Heggvik, L. R.; Fiksdahl, A. Tetrahedron: Asymmetry
1997, 8, 2189–2192.
6. Sørbye, K.; Tautermann, C.; Carlsen, P. H.; Fiksdahl, A.
Tetrahedron: Asymmetry 1998, 9, 681–689.
7. Said, S. A.; Fiksdahl, A. Tetrahedron: Asymmetry 1999,
10, 2627–2633.
8. Said, S. A.; Fiksdahl, A.; Carlsen, P. H. Tetrahedron
Lett. 2000, 41, 5593–5596.
9. Said, S. A.; Fiksdahl, A. Tetrahedron: Asymmetry 2001,
12, 893–896.
10. Katritzky, A. R.; Gruntz, U.; Kenny, D. H.; Rezende, M.
C.; Sheikh, H. J. Chem. Soc., Perkin Trans. 1 1979,
430–432.
11. Katritzky, A. R.; Bapad, J. B.; Blade, R. J.; Leddy, B. P.;
Nie, P.-L.; Ramsden, C. A.; Thind, S. S. J. Chem. Soc.,
Perkin Trans. 1 1979, 418–425.
12. Katritzky, A. R. Tetrahedron 1980, 36, 679–699.
13. Katritzky, A. R.; Liso, G.; Lunt, E.; Patel, R. C.; Thind,
S. S.; Zia, A. J. Chem. Soc., Perkin Trans. 1 1980,
849–851.
To
a
solution of 2,4,6-triphenylpyrylium tetra-
fluoroborate (1 g, 2.5 mmol) and KNO2 (4.3 g, 50
mmol) in THF (10 mL) was added (R)-1-phenylethyl-
amine ((R)-1c, 0.32 mL, 2.5 mmol) and triethylamine
(0.34 mL, 2.5 mmol) using a syringe. The mixture was
stirred for 20 min and acetic acid (0.14 mL, 2.5 mmol)
was added. The reaction was completed after stirring
for a further 10 h at rt. The product, isolated by
standard procedure as a colourless oil (261 mg, 85%),
was characterized giving data in accordance with
3c published elsewhere. The product coeluted on
GLC with the respective compound prepared previ-
ously.4 Chiral GLC analysis indicated almost full
racemization of the product (R:S ratio 44:56; 12% e.e.
(S)-3c).
4.9. Preparation of 1-phenylethyl azide 4c from (R)-1-
phenylethylamine 1c via 1-((R)-1-phenylethyl)-2,4,6-
triphenylpyrylium tetrafluoroborate 2c
The nucleophilic substitution for the preparation of
the azide 4c from (R)-1c was carried out as described
above for the preparation of 3c from (R)-1c, replacing
the nucleophile KNO2 with NaN3 (5 equiv.). The oily
product (78% yield) obtained after flash chromatogra-
phy was characterized giving data in accordance with
4c published elsewhere and the derivatized product
coeluted on GLC with the respective compound pre-
pared previously.2 The product showed no optical
rotation and GLC of the diastereomeric amide deriva-
tives indicated full racemization of the product (R:S
ratio 1:1).
14. Katritzky, A. R.; Brownlee, R. T. C.; Musumarra, G.
Tetrahedron 1980, 36, 1643–1647.
15. Katritzky, A. R.; Manzo, R. H. J. Chem. Soc., Perkin
Trans. 1 1981, 571–575.
16. Katritzky, A. R.; Lloyd, J. M.; Patel, R. C. J. Chem.
Soc., Perkin Trans. 1 1982, 117–123.
17. Katritzky, A. R.; Marson, C. M. Angew. Chem., Int. Ed.
Engl. 1984, 23, 420–429.
18. Katritzky, A. R.; Brycki, B. J. Am. Chem. Soc. 1986, 108,
7295–7299.
19. Kolehmainen, E.; Rasala, D.; Bak, T.; Laihia, K.; Gaw-
necki, R. Spectrosc. Lett. 1995, 28, 621–639.