Improved synthesis of N-sulfonylformamidine derivatives promoted by thionyl chloride

Article abstract of DOI:10.1080/10426507.2017.1284843

An improved synthesis of N-sulfonylformamidine derivatives has been developed involving direct condensation of various sulfonamides and formamides in the presence of thionyl chloride using chloroform as solvent. Detailed synthetic studies indicate that th

Full text of DOI:10.1080/10426507.2017.1284843

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Improved Synthesis of N-Sulfonylformamidine Derivatives Promoted by Thionyl Chloride
Ruzeahong Hudabaierdi, Abudureheman Wusiman*, Ayinigeer Mulati
School of Chemistry and Chemical Engineering, Xinjiang Normal University, Urumqi 830054,
People’s Republic of China.
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Abstract: An improved synthesis of N-sulfonylformamidine derivatives has been developed
involving direct condensation of various sulfonamides and formamides in the presence of thionyl
chloride using chloroform as solvent. Detailed synthetic studies indicate that this procedure gives
the desired products in high yields under mild conditions.
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Keywords: Sulfonamide, formamidine, thionyl chloride, Vilsmeier reaction
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tertiary
amines
with
or
Introduction
N,N-dibromosulfonamides
N-Sulfonylformamidines are
a
unique
NBS/sulfonamides,7 direct condensation of
sulfonamides with DMF in the presence of
structural motif with fascinating chemical
properties and are widely used as efficient
NaI/TBHP,8
NaI-catalyzed
oxidative
1
coordinating ligands
and synthetic
tetrahydrogenative cross-coupling between
N,N-dimethylaniline and sulfonamides,9 as
well as other approaches.10 All these reactions
have drawbacks, which can include limited
substrate scope; a requirement for special
reactants or catalysts such as sulfonyl azides,
diethyl azodicarboxylate (DEAD) and
transition-metal catalysts or oxidants (TBHP);
and/or elevated temperature and longer
reaction time.
intermediates2 to generate compounds of
immense biological and pharmacological
importance.3
Traditional
methods
for
have
preparing
been
N-sulfonylformamidines
supplemented in recent years4 with several
new protocols based, for example, on
Cu-catalyzed imidation of tertiary amines
with sulfonyl azides,5 oxidative dehydration
of tertiary amines and tandem reaction with
sulfonylazides,6 selective haloform reaction of
In theory, direct condensation of
sulfonamide and formamide should provide
the most straightforward and atom-economic
* Address correspondence to this author
at the School of Chemistry and
Chemical
Engineering,
Xinjiang
Normal University, P.O. Box: 830054,
Urumqi, People’s Republic of China;
Tel/Fax: +86-158-991-27270, E-mails:
arahman@xjnu.edu.cn.
method
for
the
synthesis
of
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N-sulfonylformamidines.
But
reported
suggesting that more polar solvents are
needed to improve the sulfonamide reactivity
and to increase the product yield in this
approach. Herein we describe our efforts to
achieve a gentle, simple, cheap and very
efficient procedure for the preparation of
N-sulfonylformamidines in chloroform by use
the of common and cheap reagent thionyl
chloride. Our newly improved procedure does
syntheses following this approach, based on
4i
4c
POCl3,4b (COCl)2 or SOCl2 show the same
drawbacks as the above mentioned protocols.
N-Sulfonylformamidine, for instance, can be
obtained by condensation of sulfonamide and
formamide in the presence of corrosive POCl3,
but only in 26% yield. The (COCl)2-mediated
reaction is convenient and provides good
yields, but it requires 2.5 equiv. of (COCl)2
and formamidine. The SOCl2-triggered
reaction requires heating the reaction partners
in toluene or xylene at higher temperature,
and it provides products in only low to
moderate yields. Recently, our group reported
a facile one-pot procedure for synthesizing
cyclic N-sulfonyl amidines.11 We found that
most sulfonamides showed poor solubility in
toluene or xylene even at higher temperatures,
not
involve
any
transition
metal
catalyst/oxidants or potentially explosive
materials, and can be carried out under mild
conditions.
Results and discussion
Reaction conditions were explored by use
of the model reaction of tosylamide (1a) with
DMF (2a) (Table 1). In the presence of 1.0
equiv.
of
phosphoryl
chloride
in
chlorobenzene, the desired product 3a was
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obtained in 90% yield at 80 °C after 2 h (entry
1). To our delight, using SOCl2 under the
same conditions gave 3a in 88% yield (entry
2). Oxalyl chloride gave lower yield (entry 3).
Lowering the reaction temperature to 60 °C
and changing the solvent to chloroform gave
the highest yield of 95% after 2 h (entry 6).
Changing the solvent to DMF without
changing the other reaction conditions led to
only a trace amount of desired product (entry
6). We attribute this result to a reaction
between the electrophilic Vilsmeier complex
and DMF itself, which formed an inactive
complex.12 Decreasing the temperature
reduced the yield of 3a and necessitated
longer reaction times (entries 8 and 9).
Exposure to air did not affect the reaction
(entry 10), while the desired product were be
obtained in comparable yields (entries 11 and
12) by use of 2 mL or 5mL of solvent. After
removal of the chlorinating agent, no reaction
at all occurred (entry 13).
Using the optimized conditions (Table 1,
entry 12), we conducted SOCl2-mediated
direct condensation of various substituted
sulfonamides and formamides (Table 2).
Sulfonamides with electron-neutral or
electron-donating groups on aryl rings such as
methyl, tert-butyl and methoxy groups reacted
with DMF to form the corresponding
sulfonylamidines 3a−3d in excellent yield
(Table 2, entries 1-4). While electron-
withdrawing groups such as chloro and nitro
substituents on the aromatic ring had varying
influence, and yields ranging from 50% to 75%
(entries 5-7) of the corresponding products 3
were obtained. These results indicate that the
electronic nature of the sulfonamide
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obviously effects the reaction. In addition,
(1S)-camphorsulfonylimine as byproduct in
13% yield.13 In contrast, the reaction of
tosylamide with formanilide (1l) gave a
complex product mixture (entry 17).
heterocyclic
derivatives
such
as
and
also
thiophene-2-sulfonamide
5-methylpyridine-2-sulfonamide
participated in the reaction under the
optimized conditions and provided the
corresponding amidines 3h and 3i in 70% and
50% respectively (entries 8 and 9). Various
formamides including N,N-diethylformamide,
N,N-diisopropylformamide,
N-methyl-N-phenylformamide,
N-formyl-piperidine, and 4-formylmorpholine
were examined and gave products in excellent
yield (entries 10-14). Methane sulfonamide
reacted smoothly to afford the desired 3o in
80% yield (entry 15). Using chiral substrates
such as (1S)-10-camphorsulfonamide (1k) led
to the corresponding amidine enantiomer 3p
in 84% yield (entry 16), together with
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The structure of 3p was confirmed by a
single-crystal X-ray diffraction analysis
(Figure 1). The structural features of 3p are
the same as observed in the previously cited
N-sulfonylformamidine derivative.10c The
lengths of the two C-N bonds [N1-C11,
1.316(3) Å; N2-C11, 1.320(2) Å] are similar,
which is indicative of the delocalized nature
of the C=N double bond. The N1-C11-N2
angle is 122.11° which discloses an E-isomer
of the generated C=N double bond.14
isolated yield. This result indicates that the
formation of 3a presumably underwent a
Vilsmeier reaction pathway.15
Conclusion
In summary, we have improved an
efficient
procedure
for
synthesizing
under mild
N-sulfonylformamidines
conditions. Aliphatic and (hetero)aromatic
sulfonamides are well tolerated in this
transformation and the desired products were
obtained in good to excellent yields.
Experimental
To confirm the reaction pathway of the
described transformations, we treated 1a with
the commercially accessible Vilsmeier reagent
Reagents
were
purchased
from
commercial sources and used without further
purification unless otherwise specified.
Dichloromethane (DCM), chlorobenzene
(PhCl), 1,2-dichloroethane (DCE) and
chloroform (CHCl3) were distilled from CaH2.
chloromethylenedimethyliminium
chloride
(Scheme 1) under the standard reaction
conditions. As we had anticipated, the
reactions led to the same product 3a with 96%
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Other solvents were used without additional
purification. Purification of the reaction
products was carried out by flash column
chromatography using 200-300 mesh silica
gel. Visualization on TLC (analytical thin
layer chromatography) was achieved by the
use of UV light (254 nm) and treatment with
phosphomolybdic acid or anisaldehyde stain
followed by heating. High-resolution mass
spectra were recorded on a Bruker BIO TOF
Q mass spectrometer. 1H and 13C NMR
spectra were recorded in CDCl3 on a Varian
multiplet), coupling constant(s) in Hz,
integration. Single-crystal X-ray diffraction
was carried out on a diffractometer using a
Rigaku AFC12/Saturn 724 CCD fitted with
Mo Kα radiation (λ = 0.71073 Å) at 298 K.
The Supplemental Materials contains sample
1H and 13C NMR spectra for the products 3
(Figures S 1 – S 34).
General procedure for the preparation of
N-sulfonylformamidines 3a–3p.
A mixture of sulfonamide 1 (2.0 mmol,
1.0 equiv.), formamide 2 (2.0 mmol, 1.0
equiv.) and thionyl chloride (0.236g, 145 µL,
2.0 mmol) in CHCl3 (10 mL) was stirred at
60°C for the indicated reaction time (see
Table 2). Then, the solvent was evaporated
under vacuum to give the products in
excellent yields or the residue was purified by
silica gel column chromatography (petroleum
13
Inova spectrometer (1H NMR: 400 MHz, C
NMR: 100 MHz) with solvent resonance as
the internal standard (1H NMR: CDCl3 at 7.27
1
ppm; 13C NMR: CDCl3 at 77.23 ppm). H
NMR data are reported as follows: chemical
shifts, multiplicity (s = singlet, d = doublet, t
= triplet, dd = doublet of doublet, m =
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ether and ethyl acetate) to give the desired
products.
NMR: δ 162.3, 159.0, 134.4, 128.6, 113.9,
55.6, 41.5, 35.5.
(E)-N'-(4-tert-butylphenylsulfonyl)-N,N-
dimethylformimidamide (3d): White powder;
mp: 166-167°C; 1H NMR: δ 8.14 (s, 1H), 7.81
(d, J = 8.6 Hz, 2H), 7.47 (d, J = 8.6 Hz, 2H),
3.12 (s, 3H), 3.02 (s, 3H), 1.32 (s, 9H); 13C
NMR: δ 159.2, 155.5, 139.5, 126.4, 125.8,
41.5, 35.6, 35.1, 31.2; HRMS calcd. for
C13H20N2NaO2S [M+Na]+; 291.1143; found
291.1138.
(E)-N,N-dimethyl-N'-tosylformimidamide
(3a):8 White powder; mp: 131-132°C; H
1
NMR: δ 8.13 (s, 1H), 7.78 (d, J = 8.2 Hz, 2H),
7.26 (d, J = 8.0 Hz, 2H), 3.12 (s, 3H), 3.01 (s,
13
3H), 2.40 (s, 3H); C NMR: δ 158.2, 141.6,
138.7, 128.5, 125.7, 40.6, 34.7, 20.6.
(E)-N,N-dimethyl-N'-(phenylsulfonyl)-
formimidamide (3b): White powder; mp:
1
134-136°C; H NMR: δ 8.14 (s, 1H), 7.89 (d,
(E)-N,N-dimethyl-N'-(4-nitrophenylsulfonyl)
J = 6.8 Hz, 2H), 7.52-42 (m, 3H), 3.13 (s, 3H),
3.02 (s, 3H); 13C NMR: δ 159.3, 142.5, 131.9,
128.8, 126.6, 41.6, 35.7.
8
formimidamide (3e): White powder; mp:
1
193-194°C; H NMR: δ 8.30 (d, J = 8.6 Hz,
2H), 8.15 (s, 1H), 8.06 (d, J = 8.6 Hz, 2H),
(E)-N'-(4-methoxyphenylsulfonyl)-N,N-
dimethylformimidamide (3c):8 White powder;
mp: 155-156°C; 1H NMR: δ 8.11 (s, 1H), 7.81
(d, J = 8.6 Hz, 2H), 6.92 (d, J = 8.6 Hz, 2H),
3.83 (s, 3H) 3.12 (s, 3H), 3.00 (s, 3H); 13C
13
3.17 (s, 3H), 3.04 (s, 3H); C NMR: δ 159.5,
149.7, 148.3, 127.9, 124.1, 41.6, 35.9.
(E)-N,N-dimethyl-N'-(2-nitrophenylsulfonyl)
formimidamide (3f): White powder; mp:
11
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1
135-136°C; H NMR: δ 8.27 (d, J = 7.6 Hz,
calcd.
241.0081; found 241.0088.
(E)-N,N-dimethyl-N'-[(5-methylpyridin-2-
for
C7H10N2NaO2S2
[M+Na]+;
1H), 8.10 (s, 1H), 7.65 (m, 3H), 3.21 (s, 3H),
3.05 (s, 3H); 13C NMR: δ 160.8, 132.7, 132.0,
130.7, 123.9, 41.8, 35.7; HRMS calcd. for
C9H11N3NaO4S [M+Na]+; 280.0368; found
280.0361.
yl)sulfonyl]formimidamide
(3i):
White
1
powder; mp: 183-184°C; H NMR: δ 8.50 (s,
1H), 8.36 (s, 1H), 8.05 (d, J = 8.0 Hz, 2H),
(E)-N'-(4-chlorophenylsulfonyl)-N,N-
7.72 (d, J = 7.6 Hz, 2H), 3.20 (s, 3H), 3.03 (s,
13
dimethylformimidamide (3g):8 White powder; 3H), 2.42 (s, 3H); C NMR: δ 161.9, 154.2,
mp: 122-123°C; 1H NMR: δ 8.13 (s, 1H), 7.83
(d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H),
147.7, 140.7, 137.5, 122.6，42.0, 35.8, 18.5；
HRMS calcd. for C9H13N3NaO2S [M+Na]+;
250.0626; found 250.0620.
13
3.14 (s, 3H), 3.03 (s, 3H); C NMR: δ 159.3,
141.1, 138.2, 129.0, 128.1, 41.6, 35.7.
(E)-N,N-diethyl-N'-tosylformimidamide
(E)-N,N-dimethyl-N'-(thiophen-2-
1
(3j):8 White powder; mp: 71-72°C; H NMR:
ylsulfonyl)formimidamide
(3h):
White
δ 8.14 (s, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.25
(d, J= 8.0, 2H), 3.47 (q, J = 7.2 Hz, 2H), 3.37
(q, J = 7.2 Hz, 2H), 2.39 (s, 3H), 1.25 (t, J =
7.2 Hz, 3H), 1.14 (t, J = 7.2 Hz, 3H); 13C
NMR: δ 158.1, 142.3, 139.9, 129.3, 126.4,
47.1, 41.0, 29.8, 21.5, 14.6 12.2.
1
powder; mp: 95-96°C; H NMR: δ 8.13 (s,
1H), 7.59 (d, J = 3.6 Hz, 1H), 7.49 (d, J = 5.2
Hz, 1H), 7.02 (t, J = 4.4 Hz, 1H), 3.15 (s, 3H),
3.05 (s, 3H); 13C NMR: δ 159.2, 143.9,
130.67, 130.63, 126.9, 41.5, 35.6; HRMS
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(E)-N,N-diisopropyl-N'-tosylformimidamide
33.2, 21.6.
(3k):10b White powder; mp: 112-113°C; H
1
(E)-4-methyl-N-(piperidin-1-ylmethylene)be
NMR: δ 8.24 (s, 1H), 7.74 (d, J = 8.2 Hz, 2H),
7.24 (d, J = 8.3 Hz, 2H), 4.52 (dt, J = 13.6,
6.8 Hz, 1H), 3.67 (dt, J = 13.6, 6.8 Hz, 1H),
2.38 (s, 3H), 1.30 (d, J = 6.8 Hz, 6H), 1.20 (d,
nzenesulfonamide (3m):8 White powder; mp:
1
152-153°C; H NMR: δ 8.11 (s, 1H), 7.77 (d,
J = 8.2 Hz, 2H), 7.25 (d, J = 7.6 Hz, 3H), 3.59
(t, J = 5.6 Hz, 2H), 3.40 (t, J = 5.2 Hz, 2H),
13
J = 6.8 Hz, 6H); C NMR: δ 156.2, 142.0.4,
13
2.40 (s, 3H), 1.73-1.58 (m, 6H); C NMR: δ
139.9, 129.2, 126.2, 48.4, 47.8, 23.6, 21.4,
19.6.
157.3, 142.4, 139.8, 129.4, 126.6, 52.0, 44.8,
26.5, 25.0, 24.1, 21.6.
(E/Z)-N-methyl-N-phenyl-N'-
tosylformimidamide (3l):9 White powder; mp:
(E)-4-methyl-N-(morpholinomethylene)benz
enesulfonamide (3n):8 White powder; mp:
1
64-65°C; H NMR: δ 8.57 (s, 0.5H), 8.48 (s,
1
178-179°C; H NMR: δ 8.17 (s, 1H), 7.76 (d,
0.5H), 7.82 (dd, J = 8.1, 4.6 Hz, 1H), 7.43 (dd,
J = 14.6, 7.2 Hz, 2H), 7.3-7.28 (m, 2H), 7.19
(t, J = 8.4 Hz, 2H), 3.44 (s, 1.5H), 3.33 (s,
J = 8.2 Hz, 2H), 7.26 (d, J = 7.7 Hz, 2H), 3.74
(t, J = 4.8 Hz, 2H), 3.67 (s, 4H), 3.47 (t, J =
13
4.8 Hz, 2H), 2.39 (s, 3H); C NMR: δ 157.4,
13
1.5H), 2.43 (d, J = 5.8 Hz, 3H); C NMR: δ
142.6, 139.0, 129.3, 125.6, 66.7, 65.9, 50.2,
44.2, 21.4.
162.5, 158.52, 143.7, 143.4, 143.0, 139.0,
133.1, 131.4, 130.0, 129.8, 129.7, 129.5,
127.4, 126.9, 126.6, 126.5, 122.5, 122.2, 36.2,
(E)-N-methyl-N'-(methylsulfonyl)-N-
phenylformimidamide (3o):4i White powder;
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mp: 69-70°C; 1H NMR: δ 8.43 (s, 1H), 7.39 (t,
J = 8.0, Hz, 2H), 7.28 (t, J = 7.2 Hz, 1H), 7.18
(d, J = 7.6 Hz, 2H), 3.43 (s, 3H), 2.99 (s, 3H);
13C NMR: δ 158.4, 142.9, 129.6, 127.1, 121.9,
41.7, 35.8.
309.1249; found 309.1243.
(1S)-Camphorsulfonylimine:16 White powder;
1
mp: 224-226°C; H NMR (500 MHz): δ 3.18
(d, J = 13.3 Hz, 1H), 2.97 (d, J = 13.3 Hz,
1H), 2.76 (ddd, J = 19.3, 4.4, 2.2 Hz, 1H),
2.38 (d, J = 19.3 Hz, 1H), 2.25 (t, J = 4.2 Hz,
1H), 2.06 (ddd, J = 5.7, 4.7, 2.1 Hz, 2H), 1.76
(t, J = 9.1 Hz, 1H), 1.50-1.42 (m, 1H), 1.08 (s,
3H), 0.86 (s, 3H); 13C NMR (125 MHz): δ
195.56, 77.33, 77.08 (s), 76.82, 64.50, 49.39,
47.95, 44.58, 35.87, 28.36, 26.57, 19.40,
18.93.
(E)-N'-{[(1R,4R)-7,7-dimethyl-2-oxobicyclo[
2.2.1]hept-an-1-yl]methylsulfonyl}-N,N-
dimethylformimidamide (3p): White powder;
1
mp: 172-173°C; H NMR (500 MHz): δ 8.02
(s, 1H), 3.49-3.40 (m, 1H), 3.13 (d, J = 0.6 Hz,
3H), 3.00 (dd, J = 1.8, 1.1 Hz, 3H), 2.98-2.92
(m, 1H), 2.62 (t, J = 13.0 Hz, 1H), 2.33 (dd, J
= 18.4, 2.9 Hz, 1H), 2.11-1.98 (m, 2H), 1.89
(d, J = 18.3 Hz, 1H), 1.77-1.72 (m, 1H),
1.45-1.37 (m, 1H), 1.11 (s, 3H), 0.85 (s, 3H);
13C NMR (125 MHz): δ 215.39, 159.77, 58.51,
50.82, 48.03, 42.66 (d, J = 9.7 Hz), 41.35,
35.38, 26.99, 24.76, 19.94, 19.76; HRMS
Acknowledgments
This work was supported by the National
Natural Science Foundation of China
(21362038).
calcd.
for
C13H22N2NaO3S
[M+Na]+;
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Lu, C. S.; Zhang, Q. F.; Yao, N.; Li, X. N.
Org. Lett. 2010, 12, 897-899.
6. Xu, X. L.; Li, X. N.; Ma, L.; Ye, N.;
Weng, B. J. J. Am. Chem. Soc. 2008, 130,
11. Mulati, A.; Wusiman, A. Heterocycles
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2015, 91, 2163-2171.
12. (a) Linda, P.; Lucarelli, A.; Marino, G.;
Savelli, G. J. Chem. Soc., Perkin Trans. 2,
1974, 1610-1612; (b) Martin, J.; Poignant,
S.; Filleux, M. L.; Querneneur, M. T.
Tetrahedron Lett. 1970, 11, 5061-5064.
13. Piąteka, A.; Chapuis, C. Tetrahedron Lett.
2013, 54, 4247-4249.
14. X-Ray data deposited at the Cambridge
Crystallographic Data Centre under
CCDC 1502936. Unit cell parameters: a
7.9045(9) b 10.3888(12) c 8.8755(10) P21.
Experimental and refinement details can
be found in the Supplemental Materials.
15. Kikugawa, K.; Kawashima, T. Chem.
Pharm. Bull. 1971, 19, 2629-2630.
16. Towson, J. C.; Weismiller, M. C.; Sankar
Lal, G.; Sheppard, A. C.; Kumar, A.;
Davis, F. A. Org. Synth. 1990, 69, 158.
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Scheme 1. The reaction between 1a and
Vilsmeier reagent
18
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Figure 1. X-Ray crystal structure of 3p
19
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chloride in 10 mL of solvent, unless otherwise
b
noted.
Isolated yield after column
c
chromatography. Reaction was performed
Table 1. Optimization of the reaction
d
with a drying tube on top of the condenser.
conditions a
e
5.0 mL of solvent was used. 2.0 mL of
solvent was used. f No reaction.
Entr
y
Acid Solven Temp Tim Yiel
chlorid
e
POCl3
SOCl2
t
. (°C) e (h)
d
(%)b
90
1
2
3
PhCl
PhCl
80
80
80
2
2
8
88
(COCl) PhCl
50
2
4
5
6
7
8
9
SOCl2 DCM
40
60
60
60
40
rt
60
60
60
60
5
5
2
5
5
8
2
2
2
8
70
60
95
trace
70
50
SOCl2
DCE
SOCl2 CHCl3
SOCl2 DMF
SOCl2 CHCl3
SOCl2 CHCl3
SOCl2 CHCl3
SOCl2 CHCl3
SOCl2 CHCl3
10c
11d
12e
13
95
96
93
•-
CHCl3
NRf
a
Reactions were performed with 2.0 mmol of
TsNH2 (1.0 equiv.), 2.0 mmol DMF (1.0
equiv.) and 2.0 mmol, (1.0 equiv.) of acid
20
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a
1
a
1
a
1
a
c
2
d
2
e
12
13
14
15
16
4-MeC6H4
4-MeC6H4
4-MeC6H4
Me
Me Ph 4
95g
93
87
80
84h
0
3l
3
m
Table
2.
Preparation
of
(CH2)5
4
3
N-sulfonylformamidinesa
(C2H4)2
O
2f
3n
3o
3p
3q
2
d
2
a
2
g
Me Ph 4
Me Me 3
H Ph 5
1j
(1S)-10-camphor
1
k
yl
17
4-MeC6H4
1l
Yiel
d
a
Reactions were performed with 2.0 mmol of
sulfonamide 1 (1.0 equiv.) and 2.0 mmol
formamide 2 (1 equiv.) in 2.0 mL of
Tim
e
(h)
Entr
R1
R2 R3
1
2
3
y
(%)
b
1
a
1
b
1
c
1
d
1
e
2
a
2
a
2
a
2
a
2
a
2
a
2
a
2
a
2
a
2
b
2
1
2
3
4
5
6
7
8
9
4-MeC6H4
C6H5
Me Me 2
Me Me 3
Me Me 3
Me Me 3
Me Me 6
Me Me 6
Me Me 5
Me Me 8
Me Me 8
93
93
3a
3b
3c
3d
3e
3f
b
chloroform, unless otherwise noted. Isolated
c
yield after column chromatography. 28 % 1e
4-MeOC6H4
4-tBuC6H4
4-NO2C6H4
2-NO2C6H4
4-ClC6H4
2-thienyl
90
was recovered. d 37% 1f was recovered. e 23%
91
f
g
62c
50d
75
1h was recovered. 33% 1i was recovered.
h
The E and Z isomers ratio was 1:1. 13%
(1S)-camphorsulfonylimine was isolated.
1f
1
g
1
h
3g
3h
3i
70e
51f
5-methyl-2-pyrid
inyl
1i
1
a
1
10
11
4-MeC6H4
4-MeC6H4
Et Et 3
96
95
3j
i-Pri-Pr 3
3k
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