Supplementary Material (ESI) for Perkin Transactions
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Supplementary data
Experimental
Flash chromatography was performed on silica gel (Merck Kiesegel 60 F254 230-400 mesh).
TLC was performed on aluminium backed silica plates (60 F254) which were developed using
standard visualizing agents: UV fluorescence (254 and 366 nm), molybdic acid / ,
anisaldehyde / , permanganate / . Melting points were determined on a Khöfler hot stage.
Infrared spectra were recorded as solutions (in CDCl3, unless otherwise specified) on a
Perkin-Elmer 157G Grating FT-IR spectrometer. Only selected absorbancies (max) are
reported. 1H NMR spectra were recorded at either 250 or 400 MHz on Bruker AC-250, or
Bruker AM-400 instruments respectively. Chemical shifts (H) are quoted in parts per million
(ppm), referenced to the appropriate residual solvent peak. 13C NMR spectra were recorded at
either 63 or 101 MHz on Bruker AC-250, or Bruker AM-400 instruments respectively.
Chemical shifts (C) are quoted in parts per million (ppm). Low resolution mass spectra (m/z)
were recorded on either VG Platform or VG Prospec spectrometers, with only molecular ions
(M+), and major peaks being reported with intensities quoted as percentages of the base peak.
High-resolution mass spectra were recorded on a VG Prospec spectrometer. Enantiomeric
excesses were determined by chiral HPLC using a Chiralcel OD column. Ratios of
enantiomers were determined at 254 nm. Solvents and reagents were purified prior to use
according to standard procedures and benzaldehyde was always distilled before use. All
reactions were conducted under a nitrogen atmosphere. Microanalyses were performed using
a Perkin Elmer 2400 CHN elemental analyzer by A. H. Jones, Department of Chemistry,
University of Sheffield.
Imine Synthesis
Preparation of Non-enolisable N-Sulfonyl Imines
The N-Ts and N-SES imines were prepared by reaction of the sulfonamide with the
corresponding aldehyde and BF3Et2O under Dean-Stark conditions using toluene as described
by Proctor (Scheme 1, Table 1, Entries 1-6).1 The N-Ts and the N-SES imines were purified
by recrystallisation from petroleum ether/dichloromethane or by column chromatography. A
range of non-enolisable N-SES and N-Ts imines was prepared by this method.
1
Supplementary Material (ESI) for Perkin Transactions
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H2N SO2R2
O
0.1 eq BF 3.Et2O
N
SO2R2
+
R1
Dean-Stark
R
Toluene, Reflux
Scheme 1: Synthesis of N-Sulfonyl Imines.
Table 1 N-Sulfonyl imines
R1
R2
Purification
Yield/%
New
Imine
Ph1
C6H4CH3
Recrystallisation
65
Noa
p-MeO-C6H41
C6H4CH3
Recrystallisation
56
Noa
p-Cl-C6H4
C6H4CH3
Recrystallisation
70
Noa
p-NO2-C6H41
C6H4CH3
Recrystallisation
80
Noa
Ph
CH2CH2SiMe3
Column Chromatography
72
Yes
p-Cl-C6H4
CH2CH2SiMe3
Column Chromatography
57
Yes
p-Me-C6H4
CH2CH2SiMe3
Column Chromatography
77
Yes
PhCH=CH
CH2CH2SiMe3
Column Chromatography
95
Yes
t-Bu
CH2CH2SiMe3
Recrystallisation
20
Yes
a
Data in agreement with lit.[Ref. 1]
Preparation of N--trimethylsilylethanesulfonyl imines
Preparation of N--trimethylsilylethanesulfonamide
A solution of the crude N--trimethylsilylethanesulfonyl chloride2,3 (18.63 g, 92.9 mmol) in
dichloromethane (50 ml) was added dropwise to a saturated ethanolic ammonia solution (400
ml) at 0 oC. The reaction mixture was stirred overnight before the solvents were removed in
vacuo. The residue was partitioned between a NaHCO3 (aq.) solution (100 ml) and
dichloromethane (100 ml). The aqueous phase was extracted (3  50 ml) with
dichloromethane and the combined extracts were dried over Na2SO4. Removal of the solvent
2
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in vacuo gave the crude N--trimethylsilylethanesulfonamide which was recrystallised from
dichloromethane and petroleum ether to give the title compound a flaky white crystals (4.98
g, 31%), m. p. 76-78 oC; (Found C, 33.01; H, 8.34; N, 7.51%. C5H15NO2SSi requires C,
33.15, H, 8.29; N, 7.73%); max(KBr)/cm-1 1149 (SO2); H(250 MHz; CDCl3) 0.04 (9H, s,
Si(CH3)3), 1.05-1.15 (2H, CH2Si(CH3)3), 2.95 (2H, m, SO2CH2), 4.78 (2H, br s, NH2); C(63
MHz; CDCl3) –2.0, 11.0, 51.6; m/z (CI) 182 (MH+, 13%), 73 (Si(CH3)3), 100), (Found MH+,
182.0680. C5H16NO2SSi requires m/z 182.0671).
General procedure1
A solution of aldehyde (1.0 eq., 3.44 mmol), -trimethylsilylethanesulfonamide (1.0 eq., 3.44
mmol) and boron trifluoride etherate (0.1 eq., 0.34 mmol) in toluene was refluxed (1 g
sulfonamide in 10 ml) employing a Dean-Stark apparatus. When the theoretical amount of
water had been removed, the reaction was then allowed to cool to room temperature. The
mixture was then poured into a saturated NaHCO3 (aq) solution and extracted with
dichloromethane (3  20 ml). The organic extracts were washed with brine (20 ml), dried over
Na2SO4 and the solvent removed in vacuo. The crude imine was purified by column
chromatography, eluting with 9:1 petroleum ether:ethyl acetate to give a white solid which
was triturated with pentane.
N-Benzylidene--trimethylsilylethanesulfonamide
Benzaldehyde (0.35 ml, 3.44 mmol), -trimethylsilylethanesulfonamide (624 mg, 3.44 mmol)
and boron trifluoride etherate (44 l, 0.34 mmol) were reacted in toluene according to the
general procedure. The title compound was isolated as a white solid (667mg, 72%). m.p. 4344 oC; max(KBr)/cm-1 1609 (C=N); H(250 MHz; CDCl3) 0.01 (9H, s, Si(CH3)3), 0.98-1.18
(2H, CH2Si(CH3)3), 3.08-3.22 (2H, m, SO2CH2), 7.42-7.53 (2H, m, Ar), 7.55-7.62 (1H, m,
Ar), 7.88-8.00 (2H, m, Ar), 9.00 (1H, NCH); C(63 MHz; CDCl3) –2.0, 9.5, 48.9, 129.2
131.3, 135.0, 172.3; m/z (FAB) 270 (MH+, 100%), (Found MH+, 270.0977. C12H20NO2SSi
requires m/z 270.0984).
N-(p-Chlorobenzylidene)--trimethylsilylethanesulfonamide
p-Chlorobenzaldehyde (483 mg, 3.44 mmol), -trimethylsilylethanesulfonamide (624 mg,
3.44 mmol) and boron trifluoride etherate (44 l, 0.34 mmol) were reacted in toluene
3
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according to the general procedure. The title compound was isolated as a white solid (592 mg,
57%). m.p. 65-66 oC; max(KBr)/cm-1 1610 (C=N); H(250 MHz; CDCl3) 0.05 (9H, s,
Si(CH3)3), 0.92-1.06 (2H, CH2Si(CH3)3), 3.05-3.16 (2H, m, SO2CH2), 7.48 (2H, m, Ar), 7.68
(2H, m, Ar), 8.95 (1H, NCH); C(63 MHz; CDCl3) –2.0, 9.5, 49.0, 129.7, 132.3, 170.8; m/z
(FAB) 304 (MH+, 100%), (Found MH+, 304.0593. C12H19NO2SSiCl requires m/z 304.0594).
N-(p-Methylbenzylidene)--trimethylsilylethanesulfonamide
p-Methylbenzaldehyde (0.41 ml, 3.44 mmol), -trimethylsilylethanesulfonamide (624 mg,
3.44 mmol) and boron trifluoride etherate (44 l, 0.34 mmol) were reacted in toluene
according to the general procedure. The title compound was isolated as a white solid (754 mg,
77%). m.p. 99-100 oC; max(KBr)/cm-1 1601 (C=N); H(250 MHz; CDCl3) 0.01 (9H, s,
Si(CH3)3), 0.95-1.16 (2H, CH2Si(CH3)3), 2.38 (3H, s, ArCH3), 3.04-3.18 (2H, m, SO2CH2),
7.25 (2H, m, Ar), 7.54 (2H, m, Ar), 8.94 (1H, NCH); C(63 MHz; CDCl3) –2.0, 9.6, 22.0,
48.9, 129.8, 130.3, 131.4, 172.1; m/z (FAB) 284 (MH+, 100%), (Found MH+, 284.1139.
C13H22NO2SSi requires m/z 284.1141).
N-(Trans-3-phenylprop-2-enylidene)--trimethylsilylethanesulfonamide
Cinnamaldehyde (0.43 ml, 3.44 mmol), -trimethylsilylethanesulfonamide (0.624 g, 3.44
mmol) and boron trifluoride etherate (44 l, 0.34 mmol) were reacted in toluene according to
the general procedure. The title compound was isolated as a white solid (1.0 g, 95%), m.p. 8889 oC; (Found C, 56.68; H, 7.14; N, 4.93. C14H21NO2SSi requires C, 56.95; H, 7.12; N,
4.15%); max(KBr)/cm-1 1620 (C=N) 1583 (C=C); H(250; MHz CDCl3) 0.00 (9H, s,
Si(CH3)3), 0.90-1.07 (2H, m, CH2Si(CH3)3), 2.95-3.10 (2H, m, SO2CH2), 6.98 (1H, dd, J 9,
15, PhCH=CHCHN), 7.30-7.42 (3H, m, Ar) 7.50-7.60 (3H, m, Ar, PhCH=CHCHN), 8.20
(1H, d, J 9, PhCH=CHCHN); H(63 MHz; CDCl3) –2.0, 9.6, 48.9, 124.6, 128.7, 129.2, 131.7,
134.1, 154.1, 173.0; m/z (EI) 295 (M+, 23%) 73 (Si(CH3)3), 100), (Found M+, 295.1069.
C14H21NO2SSi requires m/z 295.1062).
N-(2,2-Dimethylpropylidene)- -trimethylsilylethanesulfonamide
Pivaldehyde (434 µL, 4.0 mmol), -trimethylsilylethanesulfonamide (724 mg, 4.0 mmol) and
boron trifluoride etherate (49 µL, 0.40 mmol) were reacted in toluene according to the above
procedure. The title compound was isolated as white crystals after recrystallisation from
4
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dichloromethane-petrol, Rf 0.58 (90:10 petroleum ether:ethyl acetate); mp 76˚C;max
(KBr)/cm-1 1637 (C=N), 1315 (SO2N), 1261 (SiMe3), 1140, 863; H(250 MHz; CDCl3) 0.00
(9H, s, Si(CH3)3), 0.87-0.98 (2H, m, CH2Si), 1.14 (9H, s, C(CH3)3), 2.92-3.06 (2H, m,
SO2CH2), 8.40 (1H, s, NCH); C(63 MHz; CDCl3) (quaternary carbon signal not visible) 2.0, 9.4, 26.1, 48.5, 186.4; m/z(CI) 250 (MH+ 14%), 73 (Si(CH3)3, 100) (Found: MH+,
250.1297. C10H24NO2SiS requires m/z 250.1289).
Preparation of Enolisable N-Sulfonyl Imines
For enolisable imines the method developed by Chemla4 was employed (Scheme 2, Table 2).
Although this method has only been described for the preparation of N-Ts imines we found
that it could be extended to include N-SES imines.
R1CHO
+
2
R SO2NH 2
+
p-TolSO2Na
HCOOH
HN
R1
H2O
SO2R2
SO2p-Tol
NaHCO 3
H2O/CH2Cl2
N
SO2R2
R1
Scheme 2: Synthesis of Enolisable N-Sulfonyl Imines.
Table 2 Enolisable N-Sulfonyl Imines
R1
a
R2
Purification
Yield/%
New Imines
n-Bu
C6H4CH3
None
60
Noa
Cy
C6H4CH3
None
72
Noa
n-Bu
CH2CH2SiMe3
None
63
Yes
Cy
CH2CH2SiMe3
None
70
Yes
Data in agreement with lit.[Ref. 4]
General Procedure4
5
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A mixture of aldehyde (10 mmol), arenesulfonamide (10 mmol) and sodium ptoluenesulfinate (1.78 g, 10 mmol) or sodium benzenesulfinate (1.82 g, 11 mmol) in formic
acid (15 ml) and H2O (15 ml) was stirred for 12 h at RT. The resulting white precipitate was
filtered, washed with H2O (2  10 ml), then pentane (10 ml), and dissolved in CH2Cl2 (100
ml). Saturated (aq.) NaHCO3 or Na2CO3 (70 ml) was added and the solution was stirred for 2
h at RT. The organic phase was separated, the aqueous phase extracted with CH2Cl2 (70 ml)
and the combined organic layers dried with NaHCO3, filtered and the solvent removed in
vacuo to yield the corresponding sulfonylimine.
N-(n-Pentylidene)--trimethylsilylethanesulfonamide
Colourless oil (1.57 g, 63%); max/cm-1 (CDCl3) 1633 (N=C); H(250 MHz; C6D6) -0.95
(9H, s, Si(CH3)3), 0.75 (3H, t, J 7, CH3), 1.05-1.50 (6H, m, CH2), 2.05 (2H, m, CH2), 3.05
(2H, m, SO2CH2), 8.60 (1H, t, J 5, CH=N); C(63 MHz; CDCl3) -2.4, 9.9, 13.7, 22.2, 26.4,
35.4, 48.7, 179.5; m/z (CI, NH3) 267 (MNH4+, 50%), 250 (MH+, 86) 73 (Si(CH3)3), 69)
(Found M+, 249.1227. C10H23NO2SSi requires 249.1219).
N- Cyclohexylidene --trimethylsilylethanesulfonamide
Colourless oil (1.93 g, 70 %); max/cm-1 (CDCl3) 1631 (N=C); H(250 MHz; C6D6) -0.90
(9H, s, Si(CH3)3), 1.00-1.75 (12H, m), 2.00 (1H, m, CHCHN), 3.15 (2H, m, SO2CH2), 8.60
(1H, d, J 4.3,CH=N);C(63 MHz; CDCl3) -2.4, 9.9, 25.2, 25.7, 28.2, 43.5, 48.7, 182.2; m/z
(EI) 275 (M+, 3%), 73 (Si(CH3)3), 100), (Found M+, 275.1371. C12H25NO2SSi requires
275.1375).
Preparation of N-(Alkoxycarbonyl) Imines
Imines bearing alkoxycarbonyls groups (except of Boc) were prepared from a reaction of the
trimethylsilylbenzaldimine5 with the corresponding chloroformate (Scheme 3, Table 3).6 All
these imines including the silyl imine were purified by distillation under high vacuum, except
the N-CO2CMe2CCl3 imine, which was washed with dry hexane and used.
6
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N
O
SiMe3
O
OR 1
Cl
N
OR 1
CHCl 3
o
0 C-Reflux
Scheme 3: Preparation of N-(Alkoxycarbonyl) Imines.
Table 3 N-(Alkoxycarbonyl) Imines
R1
Purification
Yield(%)
New Imine
Me
Vacuum Distillation
70
Noa
Bn
Vacuum Distillation
75
Nob
CH2CH2TMS
Vacuum Distillation
68
Yes
Washed with dry hexane
98
Yes
CMe2CCl3
a
Data in agreement with lit.[Ref. 6] bData in agreement with lit.[Ref. 7]
All of the chloroformates were commercially available (Aldrich) except for the 2(trimethylsilyl)ethyl chloroformate which was prepared following a literature procedure.8
General Procedure6
A solution of methyl chloroformate (0.44 ml, 5.65 mmol) in anhydrous chloroform (filtered
through basic alumina immediately before use, 8 ml) was added dropwise over 15-30
minutes, to a solution of N-(trimethylsilyl)benzaldimine5 (1 g, 5.65 mmol) in anhydrous
chloroform (filtered through basic alumina immediately before use, 8 ml) at 0 oC. The
reaction mixture was refluxed for 3 hours before the solvent was removed in vacuo and
distillation yielded the imine (vacuum must be below 0.15 mmHg otherwise decomposition of
product will occur).
N- -Trimethylsilylethoxycarbonyl-benzaldimine
A colourless oil (0.95 g, 68%); max/cm-1 (C6D6) 1714 (C=O) 1629 (N=C); H(250 MHz;
C6D6) 0.00 (9H, s, Si(CH3)3), 1.05-1.20 (2H, m, CH2Si), 4.30-4.50 (2H, m, CH2O), 7.00-7.20
(3H, m, Ar), 7.60-7.80 (2H, m, Ar), 8.75 (1H, s, CH=N);C(63 MHz; C6D6) (selection of
7
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signals) –1.7, 17.6, 65.0, 128.3, 129.0, 133.1, 169.4; m/z (EI) 249 (M+, 10%) 73 (Si(CH3)3),
100), (Found M+, 249.1192. C13H19NO2Si requires 249.1185).
N-Trichloro-tert-butoxycarbonyl-benzaldimine
A white solid (1.70 g, 98%); max/cm-1 (C6D6) 1739 (C=O) 1629 (N=C); H(250 MHz;
C6D6) 1.95 (6H, s, C(CH3)2CCl3), 6.80-7.00 (3H, m, Ar), 7.45-7.50 (2H, m, Ar), 8.55 (1H, s,
CH=N);C(63 MHz; C6D6) 21.19 128.8, 130.4, 133.5, 170.0; m/z (EI) 308 (M+, 10%) 132 (M
– OC(CH3)2CCl3, 100), (Found, MH+ 308.0010. C12H13NO2Cl3 requires 308.0020).
The Boc imine was prepared via Boc-N3 as described by Vidal.7 The diphenylphosphinyl
benzaldimine was prepared by the method of Jennings.9
8
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HPLC Conditions
Determination of Enantiomeric Excesses of trans-N-trimethylsilylethylsulfonylaziridines.
Column
:
25 cm , 4.6 mm diameter, stainless steel column packed with
Chiralcel OD stationary phase.
Mobile phase :
95:5 petrol:propan-2-ol
Flow rate
2 ml min-1
:
Temperature :
Ambient
Detection
254 nm
:
Aziridine
Minor enantiomer
Major enantiomer
N-Tosyl-2,3-diphenylaziridine.
9.8 min.(S, S)
11.7 min. (R,R)
N--trimethylsilylethylsulfonyl
9.89 min. (S,S)
15.88 min. (R,R)
7.5 min. (S,S)
10.8 min. (R,R)
7.5 min. (S,S)
12.8 min. (R,R)
1.69 min. (S,S)
5.33 min. (R,R)
Short column
Short column
-2,3-diphenylaziridine.
N--trimethylsilylethylsulfonyl
-2-p-methylphenyl-3phenylaziridine.
N--trimethylsilylethylsulfonyl
-2-p-chlorophenyl-3phenylaziridine.
(E)-N-trimethylsilylethylsulfonyl
-2-(-3-phenylprop-2-enylidene)3-phenylaziridine.
9
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Determination of Enantiomeric Excess of trans-N-(Alkoxycarbonyl)aziridines.
Column
:
25 cm, 4.6 mm diameter, stainless steel column packed with
Chiralcel OD stationary phase.
Detection
:
Diode array
Aziridine
N-(methoxycarbonyl)-2,3diphenylaziridine
N-(benzylcarbonyl)-2,3diphenylaziridine
N--trimethylsilylethanyl
carbonyl-2,3-
Temperature :
Minor
Major
enantiomer
enantiomer
4.32 min.
6.31 min.
(S,S)
(R,R)
15.20 min.
25.72 min.
(S,S)
(R,R)
7.93 min.
13.51 min.
(S,S)
(R,R)
3.52 min.
4.27 min.
(S,S)
(R,R)
6.18 min.
5.68 min.
(S,S)
(R,R)
17.90 min.
18.69 min.
(S,S)
(R,R)
Ambient
Hexane:IPA
ml min-1
97:3
2
98:2
1
98:2
1
98:2
1
98:2
1
99:1
1
diphenylaziridine
N-(tert-butoxycarbonyl)2,3-diphenylaziridine
N-(trichloro-tertbutoxycarbonyl)-2,3diphenylaziridine
N-(trichloro-tertbutoxycarbonyl)-2-(4chlorophenyl)-3phenylaziridine
10
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Determination of Enantiomeric Excess of cis-N-Tosyl-2-Ethoxycarbonyl-3arylaziridines.
Column
:
25 cm, 4.6 mm diameter, stainless steel column packed with
Chiralcel OD stationary phase.
Detection
:
Diode array
Aziridine
N-tosyl-2-
Temperature :
Ambient
Hexane:IPA
ml min-1
17.62 min.
95:5
1
11.29 min.
15.75 min.
90:10
1
9.07 min.
12.20 min.
90:10
1
19.92 min.
24.62 min.
90:10
1
4.55 min.
6.26 min.
95:5
1
Minor
Major
enantiomer
enantiomer
11.65 min.
ethoxycarbonyl-3phenylaziridine
N-tosyl-2ethoxycarbonyl-3-(4methoxyphenyl)aziridine
N-tosyl-2ethoxycarbonyl-3-(4chlorophenyl)-aziridine
N-tosyl-2ethoxycarbonyl-3-(4nitrophenyl)-aziridine
N-tosyl-2ethoxycarbonyl-3cyclohexylaziridine
11
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Determination of Enantiomeric Excess of cis-N-tosyl-2-carboxyl-Diethylamine-3-Phenyl
Aziridine.
Column
:
25 cm, 4.6 mm diameter, stainless steel column packed with
Chiralcel OD stationary phase.
Detection
:
Diode array
Aziridine
N-tosyl-2-carboxyl-
Temperature :
Minor
Major
enantiomer
enantiomer
7.09 min.
8.48 min.
diethylamine-3-phenyl
aziridine.
12
Ambient
Hexane:IPA
ml min-1
90:10
1
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References
†
Current address: School of Chemistry, Cantock’s Close, Bristol University, Bristol
BS8 1TS, UK. Email: V.Aggarwal@Bristol.ac.uk.
1
W. R. McKay and G. R. Proctor, J. Chem. Soc., Perkin Trans. I, 1981, 2435.
2
S. M. Weinreb, D. M. Demko and T. A. Lessen, Tetrahedron Lett., 1986, 27, 2099.
3
S. M. Weinreb, E. C. Charles, P. Wipf and S. Venkatraman, Org. Synth., 1998, 75,
161.
4
F. Chemla, V. Hebbe and J.-F. Normant, Synthesis, 2000, 75.
5
D. J. Hart and D. G. Thomas, J. Org. Chem., 1983, 48, 289.
6
E.-U. Wurthwein and S. Meier, Synthesis, 1984, 689.
7
J. Vidal, S. Damestoy, L. Guy, J.-C. Hannachi, A. Aubry and A. Collet, Chem. Eur. J.,
1997, 3, 1691.
8
R. E. Shute and D. H. Rich, Synthesis, 1987, 346.
9
W. B. Jennings and C. J. Lovely, Tetrahedron, 1991, 47, 5561.
13