Synthesis and rearrangement of 1,2,3-triheteroaryl(aryl)-substituted aziridines

Article abstract of DOI:10.1002/ejoc.200700462

Aziridines carrying three (or two) heteroaryl groups with electron-withdrawing effects were synthesised with sufficient diastereoselectivity. The cis aziridines are susceptible to ring opening and rearrangement when the formation of secondary enamines in

Full text of DOI:10.1002/ejoc.200700462

FULL PAPER
DOI: 10.1002/ejoc.200700462
Synthesis and Rearrangement of 1,2,3-Triheteroaryl(aryl)-Substituted Aziridines
Emanuela Pindinelli,[a] Tullio Pilati,[b] and Luigino Troisi*[a]
Keywords: Aziridines / Enamines / Rearrangement / Carbanions / Nitrogen heterocycles
Aziridines carrying three (or two) heteroaryl groups with
electron-withdrawing effects were synthesised with suf-
ficient diastereoselectivity. The cis aziridines are susceptible
to ring opening and rearrangement when the formation of
secondary enamines in stable hexacyclic structures with a N–
H···N hydrogen bond is possible.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
The great interest in the synthesis and reactivity of azirid-
ines, one of the most valuable three-membered ring systems
in modern synthetic chemistry, is due to their widely recog-
nised versatility as significant intermediates for the synthe-
sis of biologically and pharmacologically active com-
pounds.[1,2] Recently, a review on the ability of this small
heterocycle to undergo ring-opening reactions with a wide
variety of nucleophiles was reported.[3] The synthesis of
amino acids,[4] azasugars,[5] chiral ligands,[6] natural prod-
ucts[7] and more generally, nitrogen-containing organic
compounds are some of the main synthetic applications.
Moreover, further potential applications are possible with
aziridines containing heterocyclic substituents, which are
capable of freeing masked carbonyl functionalities.[8] Many
synthetic approaches for the synthesis of aziridines have
been reported in the literature, including reactions between
nitrenes and olefins[9] or between carbenes and imines.[10]
Those involving the cyclisation of β-amino alcohols seem
to be particularly interesting.[11] Preparative methodologies
for chiral aziridines have also been extensively re-
viewed.[1a,12] Our research group has recently developed
methodology for a simple, diasteroselective synthesis of sev-
eral heterocycle-substituted aziridines on the basis of the
Darzens reaction between α-chloroalkyl heterocycles and
imines[13] (Scheme 1).
Scheme 1.
that the presence of an electron-withdrawing group, such as
a para-tolylsulfonyl group, at the aziridine nitrogen atom is
crucial for the stabilisation of the developing negative
charge during the reaction and so for the ring-opening reac-
tion to occur. Aziridine and aziridinyl anion binding α-aza-
heterocycles (EWG groups) at C2 and/or C3 seem fairly
stable, particularly when one of these is the oxazoline.[2b,14]
In fact, the diastereoselective functionalisation of aziridines
by formation of aziridinyllithiums and quenching with elec-
trophiles has been reported (Scheme 2).
Scheme 2.
The functionalisation of these three-membered rings
through the generation of the aziridinyl anion at C2 or C3,
and then reaction with electrophilic groups to form more
complex aziridines is also very interesting. Many studies
have been reported concerning the stability and reactivity
of aziridines and aziridinyl anions.[14] It has been reported
In contrast, we think it would be interesting to study az-
iridines substituted with more electron-withdrawing groups,
such as a heteroaryl moiety, and particularly those carrying
a third azaheterocycle on the nitrogen atom. According to
the results of the literature,[15] the stability of such an azirid-
ine ring could change and, under basic conditions, result in
ring opening. Recently, we discovered that 1,2,3-triheterocy-
cle-substituted aziridines carrying the nonaromatic oxazol-
ine heterocycle at C2 were easily and stereoselectively ob-
tained and also functionalised by the formation, with strong
base, of stable aziridinyl anions and coupling with electro-
philes, as described in Scheme 2.[16] To further clarify the
[a] Dipartimento di Scienze e Tecnologie Biologiche ed Ambi-
entali, University of Lecce,
Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy
Fax: +39-0832-298-701
E-mail: luigino.troisi@unile.it
[b] C.N.R “Institute of Molecular Science and Technology”,
Via C. Golgi 19, 20133 Milan, Italy
5926
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Rearrangement of 1,2,3-Triheteroaryl(aryl)-Substituted Aziridines
possibility of synthesis and stability of this strained ring, we was isolated in good yield; the structure of which corre-
now report the notable and unexpected results we acquired
from the synthesis of 1,2,3-triheteroaryl- and 1-phenyl-2,3-
dietheroaryl-substituted aziridines.
sponded to a secondary enamine on the basis of spectro-
scopic data; whereas no trace amounts of aziridine were
found (Table 1, Entry 1). Stable enamine 14a was also iso-
lated as a pure product from the reaction of 2-chlorometh-
ylpyridinyllithium, derived from deprotonation of 9, with
imine 4 (Table 1, Entry 2), whereas enamine 15a was iso-
lated when α-chloromethyl-4-methylthiazolyllithium, de-
rived from 11, was treated with imine 5 (Table 1, Entry 3).
The configuration of the enamino moiety (Z) and the con-
formation (s-cis) of the obtained compounds were estab-
lished by NMR spectroscopic studies and by comparison
with 21a, which was obtained in the analogous reaction of
2-chloromethylpyridinyllithium with imine 7 (Table 1, En-
try 9), and whose X-ray data[20] also showed a hexacyclic
structure with a strong intramolecular N–H···N hydrogen
bond (Figure 1).
Results and Discussion
Darzens methodology was used for the construction of
the aziridine rings as summarised in Table 1. Already
known (E)-heteroarylimines 3, 5[17], 6, 7[18] and 8,[19] un-
known 1, 2 and 4 and chloromethyl heteroaryl compounds
9–12 were prepared as described in the Experimental Sec-
tion. 2-Chloromethyl pyridine 9 was lithiated with nBuLi in
THF at –78 °C under an atmosphere of nitrogen and added
to imine 3. The reaction mixture was gradually warmed to
room temperature and then stirred overnight (13–15 h). Af-
ter quenching with aqueous ammonium chloride, only 13a
Table 1. Coupling reaction between heteroarylimines 1–8 and chloromethyl heteroaryl compounds 9–12.
1
[a] Isolated yields. [b] Diastereomeric ratios evaluated by GC and H NMR spectroscopy.
Eur. J. Org. Chem. 2007, 5926–5933
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E. Pindinelli, T. Pilati, L. Troisi
FULL PAPER
structure. In any case, we think the presence of a nearby α-
aza functionality is important for rearrangement and for
stabilisation of the hexacyclic structure through the forma-
tion of an N–H···N hydrogen bond (Scheme 3). Indeed, ring
opening and rearrangement did not occur when it was pos-
sible for deprotonation to take place on the C atom bearing
Het3, which has an α-aza group with strong electron-with-
drawing effects: only a mixture of cis and trans aziridines
was isolated, and in the absence of an α-aza group on Het2,
enamine coordination through the construction of a hexa-
cyclic structure was impossible (Table 1, Entries 7, 12). At
last, under the conditions listed in Table 1, Entry 11, the
possibility for rearrangement did not exist, and the aziridine
was isolated in good yield; the lack of an α-aza group at
C2 and C3 did not favour deprotonation and the possible
Figure 1. Plot of one independent molecule of compound 21a with formation of the hexacyclic system with a strong N–H–N
numbering scheme. Ellipsoids at 50% probability level, H atoms
hydrogen bond.
not to scale.
To the best of our knowledge, only two examples with
similar structures have been reported: (1) the [2+2] cycload-
dition reaction of an oxazolinyl alkylamide with dimethyl
fumarate[21] and (2) the reaction of azaenolates of 2-alkyl-
oxa(thia)zolines with imidoyl chlorides.[22] The 1H NMR
chemical shift (11.10–11.70 ppm) for the enamine hydrogen
of our compounds was in accordance with those from the
literature.
When 2-chloromethylpyridinyllithium was treated with
imine 2, under the same reaction conditions, stable aziridine
16 was isolated in two diastereomeric forms [(R*,S*)/
(R*,R*), 56:31] and the product of its own rearrangement
16a (13%; Table 1, Entry 4). 2-Chloromethylbenzothiaz-
olyllithium, derived from deprotonation of 10, was also
treated with imine 2, with the same reaction time and under
the same conditions, and produced aziridine 17 in two dia-
stereomeric forms [(R*,S*)/(R*,R*), 72:26] and enamine
17a (2%; Table 1, Entry 5). A greater quantity of enamine
was isolated when the same 2-chloromethylbenzothiazolyl-
lithium was coupled with imine 1 (Table 1, Entry 6). Apart
from aziridine 18 in the diastereomeric forms (R*,S*), two
enamines, 18a and 18b, were isolated in an equal ratio. Azir-
idine and enamine were also formed together when a phenyl
group was bound at the nitrogen atom of starting imine 6
or 7 (Table 1, Entries 8, 9). The complete analysis of the
results reported in Table 1 indicates that the aziridine, with
at least two heterocycles at C2 and C3, is not stable and,
under basic conditions, has a propensity to undergo depro-
Scheme 3.
tonation at C2 or at C3 because of the groups with stronger
As confirmation of our hypothesis, when 2-chlorometh-
electron-withdrawing capabilities that are connected to ylpyridinyllithium was treated with imine 7 (e.g., Table 1,
them. The stability of the aziridinyllithium that is formed is Entry 9) and the reaction was quenched after just 20 min,
linked to the possibility to coordinate the Li+ from the azir- only aziridines (R*,S*)-21 and (R*,R*)-21 were isolated
idine nitrogen atom. This occurs if the aziridinyl anion is (10:90 ratio, 50% yield) and no trace amounts of enamines
produced from the trans structure, and therefore, the ring 21a and 21b were observed. Aziridine (R*,S*)-21 was then
opening occurs with difficulty and does not rearrange; deprotonated with nBuLi at –78 °C in THF and quenched
moreover, in the presence of an electrophile, it can be cap- after 2 h with D2O. The starting material deuterated at C2
tured. Instead, the lack of coordination with the Li+ ion in and C3 was recovered, which points out the high stability
the aziridinyl anion produced from the cis structure causes of the trans aziridinyl anion. Under the same conditions,
ring opening and rearrangement in a very stable enamine aziridine (R*,R*)-21 was transformed completely into en-
5928
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5926–5933

Rearrangement of 1,2,3-Triheteroaryl(aryl)-Substituted Aziridines
appropriate amine (1 mmol) with the corresponding aldehyde
(1 mmol) in anhydrous Et2O, in the presence of molecular sieves
(Aldrich, 4 A°, 1.6 mm pellets, 7 g) for 7–16 h, following the proto-
col of Taguchi.[25]
amines 21a and 21b, which points out the tendency of the
cis aziridinyl anion to undergo rearrangement.
Conclusions
N-[(1E)-Pyridin-2-ylmethylene]pyridin-3-amine (1): Yield: 114 mg
(62.5%), oil. 1H NMR (400.13 MHz, CDCl3): δ = 7.36 (dd, J =
5.2, 8.0 Hz, 1 H), 7.39–7.42 (m, 1 H), 7.58–7.61 (m, 1 H), 7.83 (t,
J = 7.7 Hz, 1 H), 8.21 (d, J = 7.7 Hz, 1 H), 8.52 (d, J = 4.7 Hz, 1
H), 8.57 (d, J = 2.0 Hz, 1 H), 8.62 (s, 1 H), 8.74 (d, J = 4.7 Hz, 1
H) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 122.1, 123.7, 125.5,
127.7, 136.7, 143.0, 146.8, 147.8, 149.8, 154.0, 162.4 ppm. IR
We prepared aziridines with good diastereoselectivity
and carrying three (or two) heteroaryl groups with strong
electron-withdrawing effects. The cis aziridines are suscepti-
ble to ring opening and rearrangement when the formation
of secondary enamines in stable hexacyclic structures with a
N–H···N hydrogen bond is granted. The formation of these
compounds is unprecedented in organic synthesis and could
reveal a variety of interests.
(CHCl ): ν = 3059, 2984, 1632, 1588, 1476, 1438, 1418 cm–1. GC–
˜
3
MS (70 eV): m/z (%) = 183 (91) [M]+, 182 (100), 155 (86), 130 (21),
105 (25), 78 (70). HRMS (ESI): calcd. for C11H10N3 184.17130 [M
+ H]+; found 184.17129.
N-[(1E)-Pyridin-4-ylmethylene]pyridin-2-amine (2): Yield: 115 mg
(63%), yellow solid. M.p. 46–48 °C (petroleum ether). 1H NMR
(400.13 MHz, CDCl3): δ = 7.36 (dd, J = 4.8, 8.3 Hz, 1 H), 7.55–
7.58 (m, 1 H), 7.77 (d, J = 6.0 Hz, 2 H), 8.48 (s, 1 H), 8.52–8.55
(m, 2 H), 8.79 (d, J = 6.0 Hz, 2 H) ppm. 13C NMR (100.62 MHz,
CDCl3): δ = 122.2, 123.7, 127.8, 142.1, 142.5, 146.7, 148.1, 150.7,
Experimental Section
General Remarks: n-Butyllithium (nBuLi) was a commercial solu-
tion in hexanes (Aldrich) and was titrated with N-pivaloyl-o-tolu-
idine prior to use.[23] THF, triethylamine, 4-formylmorpholine, 2-
pyridinecarboxaldehyde, 3-pyridinecarboxaldehyde, 4-pyridinecar-
boxaldehyde, 4-methylthiazole, 2-aminothiazole, methanesulfonyl
chloride, 2-aminopyridine, 3-aminopyridine, 2-aminothiophenol,
glycolic acid, 2-(chloromethyl)pyridine hydrochloride and 4-(chlo-
romethyl)pyridine hydrochloride were of commercial grade (Ald-
rich) and used without further purification. Aniline and benzalde-
hyde were of commercial grade (Aldrich) and purified by distil-
lation prior to use. Substrate 10 was obtained by reaction of 2-
aminothiophenol with glycolic acid and subsequent halogena-
tion.[24] Compound 11 was prepared by formylation of 4-methylthi-
azole, reduction of the so-obtained 2-thiazolylaldehyde and subse-
quent halogenation, following reported synthetic protocols.[13b] Pe-
159.7 ppm. IR (CHCl ): ν = 3059, 2986, 1632, 1600, 1560, 1476,
˜
3
1417, 1320, 1229, 1185 cm–1. GC–MS (70 eV): m/z (%) = 183 (100)
[M]+, 182 (84), 155 (10), 105 (42), 78 (74). HRMS (ESI): calcd. for
C11H10N3 184.17130 [M + H]+; found 184.17127.
N-[(1E)-Pyridin-2-ylmethylene]thiazol-2-amine (4): Yield: 110 mg
(58.3%), yellow solid. M.p. 71.6–73.1 °C (petroleum ether). 1H
NMR (400.13 MHz, CDCl3): δ = 7.29 (d, J = 3.4 Hz, 1 H), 7.39–
7.43 (m, 1 H), 7.74 (d, J = 3.4 Hz, 1 H), 7.83 (t, J = 6.8 Hz, 1 H),
8.26 (d, J = 7.8 Hz, 1 H), 8.75 (d, J = 4.3 Hz, 1 H), 9.08 (s, 1 H)
ppm. 13C NMR (100.62 MHz, CDCl3): δ = 119.0, 122.9, 125.8,
136.6, 141.8, 150.0, 153.4, 163.6, 172.0 ppm. IR (CHCl ): ν = 3059,
˜
3
1
2994, 1625, 1609, 1499, 1470, 1215, 1138 cm–1. GC–MS (70 eV):
m/z (%) = 189 (100) [M]+, 188 (55), 162 (35), 105 (24), 78 (20).
HRMS (ESI): calcd. for C9H8N3S 190.12774 [M + H]+; found
190.12771.
troleum ether refers to the 40–60 °C boiling fraction. The H and
the 13C NMR spectra were recorded with a Bruker Avance 400
apparatus (400.13 and 100.62 MHz, for 1H and 13C, respectively)
with CDCl3 as the solvent and TMS as an internal standard (δ =
7.24 ppm for 1H spectra; δ = 77.0 ppm for 13C spectra). The IR
spectra were recorded with an FTIR spectrophotometer Digilab
Scimitar Series FTS 2000. GC–MS analyses were performed with
an Agilent Technologies 6850 series II gas chromatograph (5%
phenylpolymethylsiloxane capillary column, 30 m, 0.25 mm i.d.),
equipped with a 5973 Network mass-selective detector operating at
70 eV. The electrospray ionisation [HRMS (ESI)] experiments were
carried out in a hybrid QqTOF mass spectrometer (PE SCIEX-
QSTAR) equipped with an ion-spray ionisation source. MS (+)
spectra were acquired by direct infusion (5 µLmin–1) of a solution
containing the appropriate sample (10 pmolµL–1) dissolved in a
solution 0.1% acetic acid, methanol/water (50:50) at the optimum
ion voltage of 4800 V. The nitrogen gas flow was set at 30 psi
(pounds per square inch) and the potentials of the orifice, the fo-
cusing ring and the skimmer were kept at 30, 50 and 25 V relative
to ground, respectively. Melting points were determined with an
Electrothermal melting point apparatus and are uncorrected. TLC
was performed on Merck silica gel plates with F-254 indicator;
viewing was by UV light (254 nm). Flash chromatography was per-
formed with Merck 230–400 mesh silica gel by using petroleum
ether/diethyl ether (Et2O) or ethyl acetate (AcOEt) mixtures as elu-
ants. All reactions involving air-sensitive reagents were performed
under an atmosphere of nitrogen in oven-dried glassware by using
syringe/septum cap techniques.
General Procedure for the Preparation of Compounds 13–24: To a
stirred mixture of imine 1–8 (1.0 mmol) and 9–12 (1.0 mmol) in
THF (10 mL) was added dropwise nBuLi (2.5  in hexane, 0.6 mL,
1.5 mmol) at –78 °C under an atmosphere of nitrogen. After 20 min
the resulting mixture was warmed slowly to room temperature and
then, after overnight, quenched with a saturated aqueous solution
of NH4Cl. The aqueous layer was extracted with Et2O (3ϫ20 mL),
and the combined organic layer was dried with anhydrous Na2SO4
and concentrated in vacuo. The crude mixture was flash-chromato-
graphed (silica gel, petroleum ether/Et2O, 2:8 for 13a; 4:6 for 15a,
20–24; 1:9 for 16–19; petroleum ether/AcOEt, 4:6 for 14a) to afford
pure products 13–24 (41–90%).
[1-(4-Methylthiazol-2-yl)-2-pyridin-2-ylvinyl]pyridin-2-ylamine
1
(13a): Yield: mg 191 (65%), oil. H NMR (400.13 MHz, CDCl3):
δ = 2.43 (s, 3 H), 638–6.40 (m, 2 H), 6.65–6.68 (m, 1 H), 6.83 (s, 1
H), 6.97–7.00 (m, 1 H), 7.16–7.19 (m, 1 H), 7.31 (td, J = 2.0,
8.2 Hz, 1 H), 7.54 (td, J = 1.0, 7.7 Hz, 1 H), 8.11 (d, J = 4.0 Hz, 1
H), 8.51 (d, J = 4.0 Hz, 1 H), 11.31 (br. s, exchanges with D2O, 1
H) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 17.3, 110.1, 112.7,
115.1, 116.2, 120.4, 124.6, 136.3, 137.0, 137.8, 148.1, 148.3, 153.1,
155.5, 156.7, 166.1 ppm. IR (CHCl ): ν = 3350 (br.), 3058, 2965,
˜
3
2828, 2806, 1621, 1593, 1499, 1472, 1437, 1305, 1257, 1151 cm–1.
GC–MS (70 eV): m/z (%) = 294 (18) [M]+, 293 (10), 216 (100), 144
(9), 78 (25). HRMS (ESI): calcd. for C16H15N4S 295.10195 [M +
H]+; found 295.10190.
General Procedure for the Preparation of Heteroarylimines 1–8: Het-
eroarylimines 1–8 were prepared by dehydration reaction of the
Eur. J. Org. Chem. 2007, 5926–5933
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E. Pindinelli, T. Pilati, L. Troisi
FULL PAPER
(1,2-Dipyridin-2-ylvinyl)thiazol-2-ylamine (14a): Yield: 115 mg
(41%), oil. 1H NMR (400.13 MHz, CDCl3): δ = 6.17 (s, 1 H), 6.58
(d, J = 3.6 Hz, 1 H), 7.08 (dd, J = 6.0, 7.4 Hz, 1 H), 7.18–7.23 (m,
2 H), 7.30 (dd, J = 6.0, 7.4 Hz, 1 H), 7.58 (d, J = 7.9 Hz, 1 H),
7.64 (td, J = 1.8, 7.9 Hz, 1 H), 7.69 (td, J = 1.9, 7.9 Hz, 1 H), 8.60
(d, J = 4.5 Hz, 1 H), 8.70 (d, J = 4.6 Hz, 1 H), 11.18 (br. s, ex-
changes with D2O, 1 H) ppm. 13C NMR (100.62 MHz, CDCl3): δ
= 108.7, 111.1, 120.3, 123.4, 123.9, 124.2, 136.3, 136.5, 138.8, 144.3,
7.06–7.13 (m, 2 H), 7.23 (d, J = 5.5 Hz, 2 H), 7.39 (t, J = 7.5 Hz,
1 H), 7.47 (t, J = 7.5 Hz, 1 H), 7.87 (d, J = 7.9 Hz, 1 H), 7.90 (d,
J = 8.1 Hz, 1 H), 8.21–8.28 (m, 2 H), 8.59 (d, J = 5.5 Hz, 2 H)
ppm. 13C NMR (100.62 MHz, CDCl3): δ = 47.2, 48.3, 121.6, 121.9,
123.2, 123.4, 125.6, 126.5, 127.8, 134.8, 142.7, 143.1, 143.9, 144.5,
150.0, 153.1, 164.4 ppm. IR (CHCl ): ν = 3064, 3037, 2987, 1602,
˜
3
1480, 1426, 1245 cm–1. GC–MS (70 eV): m/z (%) = 330 (37) [M]+,
252 (100), 148 (11), 78 (10). HRMS (ESI): calcd. for C19H15N4S
147.8, 149.7, 154.2, 156.9, 165.2 ppm. IR (CHCl ): ν = 3297 (br.), 331.10195 [M + H]+; found 331.10191.
˜
3
3061, 2958, 1632, 1590, 1521, 1469, 1373, 1159 cm–1. GC–MS
(R*,R*)-17: Yield: 56 mg (17%), oil. 1H NMR (400.13 MHz,
(70 eV): m/z (%) = 280 (35) [M]+, 247 (90), 202 (100), 78 (38) cm–1.
HRMS (ESI): calcd. for C15H13N4S: 281.08629, [M + H]+; found
281.08627
CDCl3): δ = 3.90 (d, J = 6.5 Hz, 1 H), 4.19 (d, J = 6.5 Hz, 1 H),
7.25–7.29 (m, 1 H), 7.33 (t, J = 8.0 Hz, 1 H), 7.41–7.47 (m, 4 H),
7.66 (d, J = 7.9 Hz, 1 H), 7.93 (d, J = 8.1 Hz, 1 H), 8.40 (dd, J =
1.1, 4.6 Hz, 1 H), 8.50–8.52 (m, 3 H) ppm. 13C NMR (100.62 MHz,
CDCl3): δ = 46.9, 48.2, 121.5, 122.7, 122.8, 123.7, 125.2, 126.1,
127.0, 134.6, 142.1, 142.4, 145.4, 147.8, 149.6, 153.3, 166.1 ppm.
[1,2-Bis(4-methylthiazol-2-yl)vinyl]thiazol-2-ylamine (15a): Yield:
1
211 mg (66%), oil. H NMR (400.13 MHz, CDCl3): δ = 2.49 (s, 3
H), 2.50 (s, 3 H), 6.46 (s, 1 H), 6.70 (d, J = 3.5 Hz, 1 H), 6.78 (s,
1 H), 7.00 (s, 1 H), 7.28 (d, J = 3.5 Hz, 1 H), 11.21 (br. s, exchanges
with D2O, 1 H) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 17.2,
103.47, 103.50, 112.3, 116.1, 136.7, 139.0, 153.3, 153.8, 162.2,
IR (CHCl ): ν = 3065, 3039, 2966, 1605, 1585, 1479, 1427,
˜
3
1241 cm–1.GC–MS (70 eV): m/z (%) = 330 (30) [M]+, 252 (100),
148 (12), 78 (9). HRMS (ESI): calcd. for C19H15N4S 331.10195 [M
+ H]+; found 331.10189.
163.9, 164.5 ppm. IR (CHCl ): ν = 3225 (br.), 3116, 2980, 2927,
˜
3
2863, 1617, 1522, 1443, 1263, 1156, 1112 cm–1. GC–MS (70 eV):
m/z (%) = 320 (94) [M]+, 319 (47), 287 (100), 222 (96). HRMS
(ESI): calcd. for C13H13N4S 321.03049 [M + H]+; found 321.03048.
(2-Benzothiazol-2-yl-1-pyridin-4-yl-vinyl)pyridin-3-yl-amine
17a:
Yield: 1.0%. GC–MS (70 eV): m/z (%) = 330 (60) [M]+, 329 (55),
252 (100), 196 (50), 78 (40).
2-(1-Pyridin-3-yl-3-pyridin-4-ylaziridin-2-yl)pyridine (16)
2-(3-Pyridin-2-yl-1-pyridin-3-ylaziridin-2-yl)benzothiazole [(R*,S*)-
18]: Yield: 212 mg (64%), oil. 1H NMR (400.13 MHz, CDCl3): δ
= 4.16 (d, J = 2.6 Hz, 1 H), 4.70 (d, J = 2.6 Hz, 1 H), 7.03–7.06
(m, 1 H), 7.13–7.16 (m, 2 H), 7.38 (t, J = 7.4 Hz, 1 H), 7.48 (t, J
= 8.5 Hz, 2 H), 7.67 (td, J = 1.5, 7.6 Hz, 1 H), 7.86 (d, J = 8.0 Hz,
1 H), 7.97 (d, J = 8.0 Hz, 1 H), 8.12–8.16 (m, 2 H), 8.40 (d, J =
4.5 Hz, 1 H) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 45.4, 51.0,
121.7, 122.9, 123.0, 123.1, 123.9, 125.3, 126.3, 127.7, 134.8, 136.5,
(R*,S*)-16: Yield: 100 mg (36.4%), oil. 1H NMR (400.13 MHz,
CDCl3): δ = 3.81 (d, J = 2.6 Hz, 1 H), 4.18 (d, J = 2.6 Hz, 1 H),
6.99–7.05 (m, 2 H), 7.13–7.16 (m, 1 H), 7.29 (d, J = 5.9 Hz, 2 H),
7.43 (d, J = 7.8 Hz, 1 H), 7.67 (td, J = 1.7, 7.8 Hz, 1 H), 8.03–8.04
(m, 1 H), 8.14 (dd, J = 1.7, 4.4 Hz, 1 H), 8.37 (d, J = 4.4 Hz, 1 H),
8.58 (d, J = 5.9 Hz, 2 H) ppm. 13C NMR (100.62 MHz, CDCl3): δ
= 45.9, 50.7, 121.9, 122.7, 123.1, 124.1, 127.6, 136.5, 142.7, 143.4,
144.2, 145.9, 149.2, 149.8, 152.8 ppm. IR (CHCl ): ν = 3079, 3036,
˜
3
142.9, 143.7, 143.8, 149.4, 152.4, 153.5, 167.9 ppm. IR (CHCl ): ν
˜
3
2967, 2929, 2856, 1602, 1590, 1479, 1424 cm–1. GC–MS (70 eV):
m/z (%) = 274 (11) [M]+, 273 (7), 196 (100), 181 (21), 169 (16), 78
(35). HRMS (ESI): calcd. for C17H15N4 275.12985 [M + H]+; found
275.12981.
= 3063, 2988, 2857, 1591, 1480, 1425, 1241 cm–1. GC–MS (70 eV):
m/z (%) = 330 (80) [M]+, 329 (90), 297 (17), 281 (15), 252 (52), 196
(100), 182 (45). HRMS (ESI): calcd. for C19H15N4S 331.10195 [M
+ H]+; found 331.10190.
(R*,R*)-16: Yield: 55 mg (20%), oil. 1H NMR (400.13 MHz,
CDCl3): δ = 3.75 (d, J = 6.7 Hz, 1 H), 3.94 (d, J = 6.7 Hz, 1 H),
7.03 (t, J = 7 Hz, 1 H), 7.17–7.24 (m, 4 H), 7.35 (d, J = 7.5 Hz, 1
H), 7.47 (t, J = 7.5 Hz, 1 H), 8.29 (d, J = 4.2 Hz, 1 H), 8.36–8.42
(m, 4 H) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 47.6, 49.7,
121.9, 122.6, 122.7, 123.7, 127.1, 136.2, 142.5, 143.8, 144.9, 149.0,
(2-Benzothiazol-2-yl-1-pyridin-2-yl-vinyl)pyridin-3-yl-amine (18a):
Yield: 45 mg (14%), oil. H NMR (400.13 MHz, CDCl3): δ = 6.31
1
(s, 1 H), 6.96–6.98 (m, 1 H), 7.04–7.07 (m, 1 H), 7.26–7.34 (m, 2
H), 7.40 (d, J = 7.8 Hz, 1 H), 7.46 (td, J = 1.1, 7.4 Hz, 1 H), 7.64
(td, J = 1.7, 7.8 Hz, 1 H), 7.82 (d, J = 8.0 Hz, 1 H), 7.94 (d, J =
8.2 Hz, 1 H), 8.17 (dd, J = 1.1, 4.6 Hz, 1 H), 8.22 (d, J = 2.6 Hz,
1 H), 8.68 (dd, J = 1.1, 4.8 Hz, 1 H) 11.18 (br. s, exchanges with
D2O, 1 H) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 100.3, 121.3,
121.7, 123.2, 123.7, 123.8, 124.3, 126.2, 127.7, 133.4, 136.6, 138.3,
149.38, 149.45, 154.1 ppm. IR (CHCl ): ν = 3061, 3038, 2972, 1601,
˜
3
1587, 1479, 1405, 1275 cm–1. GC–MS (70 eV): m/z (%) = 274 (21)
[M]+, 196 (100), 181 (15), 169 (12), 92 (17), 78 (15). HRMS (ESI):
calcd. for C17H15N4 275.12985 [M + H]+; found 275.12980.
143.0, 143.3, 147.2, 150.8, 153.4, 153.7, 166.3 ppm. IR (CHCl ): ν
˜
3
= 3249 (br.), 3064, 2964, 1621, 1584, 1470, 1435, 1292, 1121 cm–1.
GC–MS (70 eV): m/z (%) = 330 (43) [M]+, 329 (58), 281 (9), 252
(100), 238 (33), 207 (16) cm–1. HRMS (ESI): calcd. for C19H15N4S
331.10195 [M + H]+; found 331.10197.
Pyridin-3-yl-(2-pyridin-2-yl-1-pyridin-4-yl-vinyl)amine (16a): Yield:
1
23 mg (8.5%), oil. H NMR (400.13 MHz, CDCl3): δ = 5.81 (s, 1
H), 6.80 (d, J = 8.2 Hz, 1 H), 6.98 (dd, J = 4.7, 8.1 Hz, 1 H), 7.06
(dd, J = 5.2, 6.6 Hz, 1 H), 7.18 (d, J = 8.1 Hz, 1 H), 7.37 (d, J =
5.9 Hz, 2 H), 7.64 (td, J = 1.7, 7.9 Hz, 1 H), 8.10 (d, J = 3.6 Hz, 1
H), 8.20 (d, J = 2.6 Hz, 1 H), 8.54 (d, J = 4.2 Hz, 1 H), 8.58 (d, J
= 5.9 Hz, 2 H), 11.72 (br. s, exchanges with D2O, 1 H) ppm. 13C
NMR (100.62 MHz, CDCl3): δ = 107.3, 119.9, 122.2, 123.1, 123.8,
127.1, 136.4, 138.5, 142.3, 142.5, 144.5, 145.2, 147.6, 150.1,
(1-Benzothiazol-2-yl-2-pyridin-2-yl-vinyl)pyridin-3-yl-amine (18b):
1
Yield: 45 mg (14%), oil. H NMR (400.13 MHz, CDCl3): δ = 6.59
(s, 1 H), 7.02–7.12 (m, 3 H), 7.30 (d, J = 8.0 Hz, 1 H), 7.39 (t, J =
7.2 Hz, 1 H), 7.50 (t, J = 8.0 Hz, 1 H), 7.67 (td, J = 1.8, 7.8 Hz, 1
H), 7.81 (d, J = 8.0 Hz, 1 H), 8.06 (d, J = 8.0 Hz, 1 H), 8.13 (dd,
J = 1.4, 4.0 Hz, 1 H), 8.31 (d, J = 2.6 Hz, 1 H), 8.56 (d, J = 4.6 Hz,
1 H), 11.37 (br. s, exchanges with D2O, 1 H) ppm. 13C NMR
(100.62 MHz, CDCl3): δ = 110.4, 120.8, 121.7, 123.3, 123.6, 124.7,
125.6, 126.4, 127.0, 135.6, 136.6, 139.3, 139.4, 142.5, 142.8, 147.9,
157.3 ppm. IR (CHCl ): ν = 3250 (br.), 3060, 2965, 2929, 1626,
˜
3
1594, 1471, 1414, 1262 cm–1. GC–MS (70 eV): m/z (%) = 274 (19)
[M]+, 273 (30), 196 (100), 182 (15), 169 (22), 78 (43). HRMS (ESI):
calcd. for C17H15N4 275.12985 [M + H]+; found 275.12987.
2-(3-Pyridin-4-yl-1-pyridin-3-ylaziridin-2-yl)benzothiazole (17)
(R*,S*)-17: Yield: 155 mg (47%), oil. 1H NMR (400.13 MHz,
CDCl3): δ = 4.10 (d, J = 2.2 Hz, 1 H), 4.18 (d, J = 2.2 Hz, 1 H),
153.2, 156.6, 165.8 ppm. IR (CHCl ): ν = 3243 (br.), 3063, 2990,
˜
3
1622, 1588, 1499, 1470, 1434, 1257 cm–1. GC–MS (70 eV): m/z (%)
= 330 (45) [M]+, 329 (57), 281 (30), 252 (100), 238 (38), 207
5930
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5926–5933

Rearrangement of 1,2,3-Triheteroaryl(aryl)-Substituted Aziridines
(55) cm–1. HRMS (ESI): calcd. for C19H15N4S 331.10195
[M + H]+; found 331.10196.
(100), 167 (18), 92 (27), 77 (48), 51 (26). HRMS (ESI): calcd. for
C20H16N3S 330.10668 [M + H]+; found 330.10666.
2-[2-(4-Methyl-1,3-thiazol-2-yl)-3-pyridin-4-ylaziridin-1-yl]pyridine (R*,R*)-21: Yield: 161 mg (49%), oil. 1H NMR (400.13 MHz): δ =
(19)
4.04 (d, J = 6.5 Hz, 1 H), 4.16 (d, J = 6.5 Hz, 1 H), 7.06–7.12 (m,
2 H), 7.15–7.18 (m, 2 H), 7.27–7.33 (m, 3 H), 7.38–7.42 (m, 1 H),
7.57–7.65 (m, 2 H), 7.74 (d, J = 7.7 Hz, 1 H), 7.94 (d, J = 8.3 Hz,
1 H), 8.49 (dd, J = 0.9, 1.5 Hz, 1 H) ppm. 13C NMR (100.62 MHz):
δ = 47.2, 50.7, 119.8, 121.4, 122.6, 122.7, 122.8, 123.8, 124.8, 125.8,
129.4, 135.0, 136.1, 149.4, 152.0, 153.5, 154.4, 167.9 ppm. IR
(R*,S*)-19: Yield: 93 mg (31.5%), oil. 1H NMR (400.13 MHz,
CDCl3): δ = 2.35 (s, 3 H), 4.17 (d, J = 2.8 Hz, 1 H), 4.27 (d, J =
2.8 Hz, 1 H), 6.64 (d, J = 8.1 Hz, 1 H), 6.78 (s, 1 H), 6.90 (dd, J =
5.3, 6.4 Hz, 1 H), 7.19 (d, J = 5.8 Hz, 2 H), 7.43 (td, J = 1.7,
9.1 Hz, 1 H), 8.28 (d, J = 5.0 Hz, 1 H), 8.52 (d, J = 5.8 Hz, 2 H)
ppm. 13C NMR (100.62 MHz, CDCl3): δ = 16.9, 46.9, 48.1, 114.0,
116.6, 118.9, 122.0, 137.3, 144.7, 148.4, 149.7, 153.2, 158.8,
(CHCl ): ν = 3067, 2982, 1595, 1490, 1437, 1409 cm–1. GC–MS
˜
3
(70 eV): m/z (%) = 329 (15) [M]+, 251 (74), 195 (100), 167 (17), 92
(22), 77 (47), 51 (26). HRMS (ESI): calcd. for C20H16N3S
330.10668 [M + H]+; found 330.10665.
163.9 ppm. IR (film): ν = 3077, 2924, 1591, 1468, 1431, 1300, 797,
˜
735 cm–1. GC–MS (70 eV): m/z (%) = 294 (24) [M]+, 293 (14), 216
(100), 201 (44), 196 (61), 78 (60), 51 (27). HRMS (ESI): calcd. for (1-Benzothiazol-2-yl-2-pyridin-2-ylvinyl)phenylamine (21a): Yield
C16H14N4S 295.09392 [M + H]+; found 295.09392.
65.8 mg (20%), yellow solid. M.p. 128.6–130.8 °C (petroleum
ether). H NMR (400.13 MHz): δ = 6.48 (s, 1 H), 6.80–6.84 (m, 3
1
(R*,R*)-19: Yield: 201 mg (68.5%), oil. 1H NMR (400.13 MHz,
CDCl3): δ = 2.34 (s, 3 H), 4.08 (d, J = 6.4 Hz, 1 H), 4.27 (d, J =
6.4 Hz, 1 H), 6.68 (s, 1 H), 7.05 (dd, J = 5.1, 7.0 Hz, 1 H), 7.12 (d,
J = 8.1 Hz, 1 H), 7.39 (d, J = 4.7 Hz, 2 H), 7.64 (td, J = 1.8, 7.9 Hz,
1 H), 8.33 (d, J = 4.7 Hz, 1 H), 8.49 (d, J = 5.7 Hz, 2 H) ppm. 13C
NMR (100.62 MHz, CDCl3): δ = 16.8, 46.4, 47.5, 113.8, 115.6,
119.8, 123.1, 138.1, 143.2, 148.5, 149.2, 153.1, 162.6, 164.6 ppm.
H), 6.98 (dd, J = 0.8, 5.0 Hz, 1 H), 7.08 (dd, J = 2.2, 7.2 Hz, 2 H),
7.20 (d, J = 7.9 Hz, 1 H), 7.28 (t, J = 7.1 Hz, 1 H), 7.41 (t, J =
7.1 Hz, 1 H), 7.55 (td, J = 1.8, 7.7 Hz, 1 H), 7.70 (d, J = 8.0 Hz, 1
H), 8.01 (d, J = 8.0 Hz, 1 H), 8.46 (d, J = 4.4 Hz, 1 H), 11.13 (br.
s, 1 H) ppm. 13C NMR (100.62 MHz): δ = 109.2, 111.2, 117.2,
119.5, 121.9, 123.4, 124.5, 125.3, 126.1, 128.9, 135.9, 136.3, 140.2,
142.8, 147.9, 153.0, 157.0, 167.2 ppm. IR (CHCl ): ν = 3238, 3062,
˜
3
IR (CHCl ): ν = 3072, 3030, 2923, 1592, 1469, 1433, 1285, 1147,
˜
3
3009, 2960, 2928, 1620, 1591, 1498, 1470, 1262 cm–1. GC–MS
(70 eV): m/z (%) = 329 (35) [M]+, 328 (21), 251 (56), 237 (100), 194
(29), 135 (17), 77 (79), 51 (30). HRMS (ESI): calcd. for C20H16N3S
330.10668 [M + H]+; found 330.10663.
823, 789, 743 cm–1. GC–MS (70 eV): m/z (%) = 294 (22) [M]+, 293
(12), 216 (100), 201 (35), 196 (56), 78 (40), 51 (14). HRMS (ESI):
calcd. for C16H14N4S 295.09392 [M + H]+; found 295.09392.
2-(1-Phenyl-3-pyridin-2-ylaziridin-2-yl)pyridine [(R*,R*)-20]: Yield:
51 mg (18.7%), yellow solid. M.p. 109.5–110.3 °C (petroleum
(2-Benzothiazol-2-yl-1-pyridin-2-ylvinyl)phenylamine (21b): Com-
pound characterized only by 1H NMR as it was isolated in low
quantity containing an inseparable mixture of the two isomers
(21a+21b). Yield: 2.4%. 1H NMR (400.13 MHz): δ = 6.19 (s, 1 H),
6.73 (d, J = 7.5 Hz, 2 H), 6.83–6.87 (m, 2 H), 7.09 (t, J = 7.5 Hz,
2 H), 7.17–7.21 (m, 2 H), 7.35 (td, J = 0.9, 7.1 Hz, 1 H), 7.50 (td,
J = 1.6, 7.6 Hz, 1 H), 7.73 (t, J = 7.6 Hz, 1 H), 7.83 (d, J = 8.0 Hz,
1 H), 8.60 (d, J = 4.9 Hz, 1 H), 11.05 (br. s, 1 H) ppm.
1
ether). H NMR (400.13 MHz, CDCl3): δ = 4.17 (s, 2 H), 6.75 (d,
J = 7.6 Hz, 2 H), 6.86 (t, J = 7.4 Hz, 1 H), 7.07 (t, J = 7.6 Hz, 2
H), 7.12–7.16 (m, 2 H), 7.31 (d, J = 7.6 Hz, 2 H), 7.61 (td, J = 1.7,
7.7 Hz, 2 H), 8.49 (d, J = 4.4 Hz, 2 H) ppm. 13C NMR
(100.62 MHz, CDCl3): δ = 49.4, 120.7, 121.9, 122.3, 122.6, 128.5,
136.2, 148.3, 149.2, 155.7 ppm. IR (CHCl ): ν = 3063, 2970, 1592,
˜
3
1490, 1474, 1437 cm–1. GC–MS (70 eV): m/z (%) = 273 (4) [M]+,
195 (100), 167 (17), 92 (27). HRMS (ESI): calcd. for C18H16N3
274.13458 [M + H]+; found 274.13455.
2-(1-Phenyl-3-pyridin-3-ylaziridin-2-yl)pyridine (22)
1
(R*,S*)-22: Yield: 26 mg (9.5%), oil. H NMR (400.13 MHz): δ =
(1,2-Dipyridin-2-yl-vinyl)phenylamine (20a): Yield: 153 mg (56.2%),
yellow solid. M.p. 110.8–112.0 °C (petroleum ether). 1H NMR
(400.13 MHz, CDCl3): δ = 6.17 (s, 1 H), 6.70 (dd, J = 3.7, 8.7 Hz,
2 H), 6.82 (t, J = 7.4 Hz, 1 H), 6.96–7.00 (m, 1 H), 7.07–7.11 (m,
2 H), 7.17–7.22 (m, 2 H), 7.37 (dd, J = 1.0, 8.9 Hz, 1 H), 7.51–7.59
(m, 2 H), 8.51 (dd, J = 4.1, 4.9 Hz, 1 H), 8.66–8.67 (m, 1 H), 11.48
(br. s, 1 H) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 106.6, 119.2,
120.7, 121.0, 122.7, 123.5, 123.9, 128.7, 136.0, 142.9, 146.1, 147.5,
3.77 (d, J = 2.7 Hz, 1 H), 3.94 (d, J = 2.7 Hz, 1 H), 6.67 (dd, J =
0.8, 7.4 Hz, 2 H), 6.82 (t, J = 7.4 Hz, 1 H), 7.03 (t, J = 7.8 Hz, 2 H),
7.08–7.12 (m, 2 H), 7.27–7.30 (m, 2 H), 7.58 (td, J = 1.7, 7.8 Hz, 1
H), 8.41 (td, J = 0.8, 7.4 Hz, 2 H), 8.55 (d, J = 1.8 Hz, 1 H) ppm.
13C NMR (100.62 MHz): δ = 46.3, 50.2, 120.7, 122.3, 122.4, 122.5,
123.0, 128.7, 131.9, 134.2, 136.4, 147.6, 148.8, 149.2, 149.5,
155.3 ppm. IR (film): ν = 3056, 2925, 1592, 1489, 1435, 1025 cm–1.
˜
GC–MS (70 eV): m/z (%) = 273 (15) [M]+, 272 (21), 195 (30), 181
(100), 167 (20), 77 (41), 51 (23). HRMS (ESI): calcd. for C18H16N3
274.13458 [M + H]+; found 274.13455.
149.5, 155.7, 158.1 ppm. IR (CHCl ): ν = 3190 (br.), 3085, 3058,
˜
3
2962, 2928, 1628, 1590, 1498, 1467, 1388 cm–1. GC–MS (70 eV):
m/z (%) = 273 (20) [M]+, 272 (20), 195 (100), 181 (57), 77 (41), 51
(25). HRMS (ESI): calcd. for C18H16N3 [M + H]+ 274.13458; found
274.13454.
1
(R*,R*)-22: Yield: 190 mg (69.5%), oil. H NMR (400.13 MHz): δ
= 3.65 (d, J = 6.5 Hz, 1 H), 3.79 (d, J = 6.5 Hz, 1 H), 6.94–7.05
(m, 5 H), 7.19–7.23 (m, 3 H), 7.39 (td, J = 1.5, 7.7 Hz, 1 H), 7.52
(dt, J = 1.6, 7.8 Hz, 1 H), 8.29 (dd, J = 1.3, 4.7 Hz, 1 H), 8.35
(d, J = 4.9 Hz, 1 H), 8.53 (d, J = 1.8 Hz, 1 H) ppm. 13C NMR
(100.62 MHz): δ = 46.4, 49.4, 119.7, 121.7, 122.1, 122.6, 123.2,
129.2, 131.0, 135.2, 135.9, 148.3, 149.0, 149.3, 153.0, 155.1 ppm.
2-(1-Phenyl-3-pyridin-2-ylaziridin-2-yl)benzothiazole (21)
(R*,S*)-21: Yield: 29.6 mg (9%), yellow solid. M.p. 93.7–95.6 °C.
1H NMR (400.13 MHz): δ = 4.10 (d, J = 2.3 Hz, 1 H), 4.60 (d, J
= 2.3 Hz, 1 H), 6.84 (d, J = 7.8 Hz, 2 H), 6.91 (t, J = 7.2 Hz, 1 H),
7.10–7.18 (m, 3 H), 7.31–7.38 (m, 2 H), 7.46 (t, J = 7.8 Hz, 1 H),
7.63 (td, J = 1.5, 7.8 Hz, 1 H), 7.83 (d, J = 7.8 Hz, 1 H), 7.98
(d, J = 7.8 Hz, 1 H), 8.45 (d, J = 4.4 Hz, 1 H) ppm. 13C NMR
(100.62 MHz): δ = 46.2, 51.7, 120.7, 121.0, 121.7, 122.7, 122.9,
123.0, 125.1, 126.1, 128.7, 135.0, 136.3, 147.2, 149.3, 153.68, 153.7,
IR (CHCl ): ν = 3058, 2926, 1593, 1489, 1436, 1266, 1026 cm–1.
˜
3
GC–MS (70 eV): m/z (%) = 273 (23) [M]+, 272 (16), 195 (100), 181
(38), 167 (20), 168 (20), 92 (21), 77 (21), 51 (11). HRMS (ESI):
calcd. for C18H16N3 274.13458 [M + H]+; found 274.13452.
3-(1-Phenyl-3-pyridin-4-ylaziridin-2-yl)pyridine [(R*,R*)-23]: Yield:
257 mg (94%), yellow solid. M.p. 172.2–173.8. 1H NMR
168.8 ppm. IR (CHCl ): ν = 3065, 2990, 2928, 1597, 1490,
˜
3
1437 cm–1. GC–MS (70 eV): m/z (%) = 329 (11) [M]+, 251 (63), 195 (400.13 MHz): δ = 3.59 (d, J = 6.5 Hz, 1 H), 3.65 (d, J = 6.5 Hz,
Eur. J. Org. Chem. 2007, 5926–5933
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5931

E. Pindinelli, T. Pilati, L. Troisi
FULL PAPER
[7]
B. Zwanenburg, P. T. Holte, Top. Curr. Chem. 2001, 216, 93–
124.
A. Dondoni in Modern Synthetic Methods (Ed.: R. Sheffold),
Helvetica Chimica Acta, Basel, 1992, pp. 377–473.
D. A. Evans, M. M. Faul, M. T. Bilodeau, J. Am. Chem. Soc.
1994, 116, 2742–2753.
K. B. Hansen, N. S. Finney, E. N. Jacobsen, Angew. Chem. Int.
Ed. Engl. 1995, 34, 676–678.
a) H. M. I. Osborn, A. A. Cantrill, B. Sweeney, W. Howson,
Tetrahedron Lett. 1994, 35, 3159–3162; b) J. E. Baldwin, C. N.
Farthing, A. T. Russell, C. J. Schofield, A. C. Spivey, Tetrahe-
dron Lett. 1996, 37, 3761–3764; c) H. M. I. Osborn, J. B.
Sweeney, W. Howson, Synlett 1994, 145–146.
1 H), 7.00–7.06 (m, 4 H), 7.13 (dd, J = 1.3, 4.6 Hz, 2 H), 7.25 (td,
J = 2.0, 7.4 Hz 2 H), 7.46 (dt, J = 1.7, 7.9 Hz, 1 H), 8.33–8.36 (m,
3 H), 8.52 (d, J = 2.1 Hz, 1 H) ppm. 13C NMR (100.62 MHz): δ =
46.7, 47.5, 119.8, 122.6, 122.9, 123.5, 129.4, 130.6, 135.0, 144.3,
[8]
[9]
148.9, 149.4, 149.5, 153.0 ppm. IR (CHCl ): ν = 3078, 2986, 2973,
˜
3
1600, 1489, 1404, 1275 cm–1. GC–MS (70 eV): m/z (%) = 273 (63)
[M]+, 272 (93), 195 (23), 181 (28), 168 (100), 77 (100), 51 (57).
HRMS (ESI): calcd. for C18H16N3 274.13458 [M + H]+; found
274.13453.
[10]
[11]
2-(1-Phenyl-3-pyridin-4-ylaziridin-2-yl)pyridine (24)
(R*,S*)-24: Yield: 116 mg (42.5%), yellow solid. M.p. 113.8–
115.2 °C (petroleum ether). 1H NMR (400.13 MHz, CDCl3): δ =
3.74 (d, J = 2.5 Hz, 1 H), 3.93 (d, J = 2.5 Hz, 1 H), 6.64 (d, J =
7.5 Hz, 2 H), 6.83 (t, J = 7.3 Hz, 1 H), 7.01–7.11 (m, 5 H), 7.26 (d,
J = 7.8 Hz, 1 H), 7.57 (td, J = 1.6, 7.7 Hz, 1 H), 8.37 (d, J = 4.0 Hz,
1 H), 8.44 (d, J = 5.9 Hz, 2 H) ppm. 13C NMR (100.62 MHz,
CDCl3): δ = 46.9, 50.9, 120.5, 122.2, 122.3, 122.5, 122.8, 128.7,
[12]
[13]
H. M. I. Osborn, J. Sweeney, Tetrahedron: Asymmetry 1997, 8,
1693–1715.
a) L. Troisi, C. Granito, C. Carlucci, F. Bona, S. Florio, Eur.
J. Org. Chem. 2006, 775–781; b) F. Bona, L. De Vitis, S. Florio,
L. Ronzini, L. Troisi, Tetrahedron 2003, 59, 1381–1387; c) L.
De Vitis, S. Florio, C. Granito, L. Ronzini, L. Troisi, V. Capri-
ati, R. Luisi, T. Pilati, Tetrahedron 2004, 60, 1175–1182; d) S.
Florio, L. Troisi, V. Capriati, G. Suppa, Eur. J. Org. Chem.
2000, 22, 3793–3797; e) S. Florio, L. Troisi, V. Capriati, Tetra-
hedron Lett. 1998, 39, 7951–7954; f) S. Florio, L. Troisi, Tetra-
hedron Lett. 1996, 37, 4777–4780; g) S. Florio, L. Troisi, V.
Capriati, G. Ingrosso, Tetrahedron Lett. 1999, 40, 6101–6104.
136.3, 145.9, 147.5, 149.2, 149.5, 154.6 ppm. IR (CHCl ): ν = 3063,
˜
3
2973, 2930, 1598, 1491, 1437, 1277 cm–1. GC–MS (70 eV): m/z (%)
= 273 (11) [M]+, 272(7), 195 (100), 181 (24), 167 (20), 92 (29), 77
(34), 51 (24). HRMS (ESI): calcd. for C18H16N3 274.13458 [M +
H]+; found 274.13455.
[14]
a) E. Vedejs, J. O. Moss, J. Am. Chem. Soc. 1993, 115, 1607–
1608; b) E. Vedejs, J. T. Kendall, J. Am. Chem. Soc. 1997, 119,
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L. Troisi, C. Granito, E. Pindinelli, L. Ronzini, Heterocycles
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L. Troisi, L. Ronzini, C. Granito, E. Pindinelli, A. Troisi, T.
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E. Denecke, K. Muller, T. Bluhm, Org. Magn. Reson. 1982, 18,
68–70.
(R*,R*)-24: Yield: 116 mg (42.5%), yellow solid. M.p. 108.3–
109.5 °C (petroleum ether). 1H NMR (400.13 MHz, CDCl3): δ =
3.63 (d, J = 6.7 Hz, 1 H), 3.83 (d, J = 6.7 Hz, 1 H), 6.99–7.06 (m,
4 H), 7.19–7.27 (m, 5 H), 7.45 (td, J = 1.6, 7.7 Hz, 1 H), 8.33 (dd,
J = 1.2, 4.8 Hz, 2 H), 8.36 (d, J = 4.9 Hz, 1 H) ppm. 13C NMR
(100.62 MHz, CDCl3): δ = 47.7, 49.9, 119.8, 121.9, 122.4, 122.8,
123.4, 129.3, 136.1, 144.7, 149.3, 149.4, 152.9, 154.9 ppm. IR
[15]
[16]
[17]
[18]
[19]
[20]
(CHCl ): ν = 3064, 2987, 2967, 1599, 1489, 1419, 1268, 1148 cm–1.
˜
3
GC–MS (70 eV): m/z (%) = 273 (11) [M]+, 195 (100), 181 (29), 167
(22), 92 (32), 77 (42), 51 (31). HRMS (ESI): calcd. for C18H16N3
274.13458 [M + H]+; found 274.13455.
Acknowledgments
X-ray crystallographic data for 21a: C20H15N3S, T = 123 K,
0.22ϫ0.16ϫ0.13 mm3, yellow, prismatic crystal, triclinic,
This work was carried out under the framework of the National
Project “Stereoselezione in Sintesi Organica. Metodologie ed Ap-
plicazioni” supported by the Ministero dellЈIstruzione, dellЈUniver-
sità e della Ricerca (MIUR, Rome). We would like to thank also
the University of Lecce and the CINMPIS (Consorzio Interuni-
versitario Nazionale Metodologie e Processi Innovativi di Sintesi)
for their financial support.
¯
space group P1, a = 11.155(2) Å, b = 11.671(2) Å, c =
13.575(2) Å, α = 82.32(2)°, β = 74.05(2)°, γ = 75.25(2)°, V =
1639.4(5) Å3, Z = 4, Dcalcd. = 1.335 gcm–3, λ (Mo-Kα) =
0.71073 Å, µ (Mo-Kα) = 0.203 mm–1. Data collection: Bruker
SMART APEX diffractometer, Oxford low temperature device,
data collection blow 2θ = 55°, 16357 data collected, 7519 inde-
pendent, 4549 observed [IϾ2σ(I)]. The structure was solved by
SIR2002 (M. C. Burla, M. Camalli, B. Carrozzini, G. L. Cas-
carano, C. Giacovazzo, G. Polidori, R. Spagna, J. Appl. Cryst.
2003, 36, 1103), and refined on F2 by SHELX97 (G. M. Sheld-
rick, Program for the Refinement of Crystal Structures, Univer-
sity of Göttingen, Germany, 1997). Final R = 0.0484, wR
[1] For reviews on aziridines, see: a) D. Tanner, Angew. Chem. Int.
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=
0.0867, on observed data, goodness-of-fit = 0.950,
–0.29Ͻ∆ρϽ0.24 eÅ–3. The crystal structure of 21a contains
two independent molecules; their conformations are similar, in
spite of some geometrical parameters differing significantly. In
particular, the intramolecular distance N18···N13 (hydrogen
bonded) is 2.804(2) Å and 2.741(2) Å in the two independent
molecules. Other quite significant differences are, for example,
the torsion angles S1–C2–C10–N18 and C2–C10–N18–C19,
whose values are 37.5(2), 23.4(2) and 47.9(3), 57.1(3)°, respec-
tively, for the two independent molecules. CCDC-638681 con-
tains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: May 22, 2007
Published Online: October 11, 2007
Eur. J. Org. Chem. 2007, 5926–5933
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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