Ring opening of cyclic sulfamidates with magnesiated heterocycles: Expedient synthesis of highly functionalised azaindolines and azatetrahydroquinolines

Article abstract of DOI:10.1055/S-0032-1317170

Magnesiated chloropyrimidine and chloropyridine derivatives, obtained by deprotonation with TMPMgCl·LiCl at room temperature, undergo facile ring-opening reactions with five- and six-membered N-Boc and N-Bn cyclic sulfamidates. After an acidic workup, the

Full text of DOI:10.1055/S-0032-1317170

2408▌
LETTER
lRettierng Opening of Cyclic Sulfamidates with Magnesiated Heterocycles:
Expedient Synthesis of Highly Functionalised Azaindolines and Azatetra-
hydroquinolines
Expedient Synthesis of Azaindolines and Azatetrahydroquinolines
Thomas A. Moss,* Barry R. Hayter, Ian A. Hollingsworth, Thorsten Nowak
AstraZeneca Mereside, Alderley Park, Cheshire, SK10 4TG, UK
E-mail: thomas.moss@astrazeneca.com
Received: 03.07.2012; Accepted after revision: 06.08.2012
hydropyrrolopyrimidines and tetrahydropyridopyrimi-
Abstract: Magnesiated chloropyrimidine and chloropyridine de-
dines are documented in the literature, their synthesis
rivatives, obtained by deprotonation with TMPMgClLiCl at room
typically involves either an amidation–intramolecular cy-
temperature, undergo facile ring-opening reactions with five- and
six-membered N-Boc and N-Bn cyclic sulfamidates. After an acidic
clisation strategy,5a which often requires multiple steps to
workup, the adducts undergo rapid intramolecular cyclisation on form the pyrimidine starting material, or reduction of the
aromatic system,5b which may not be compatible with
sensitive functional groups (Scheme 1). Examples of
basification to give highly functionalised stereodefined aza-
indolines and azatetrahydroquinolines in good yields.
Key words: cyclic sulfamidate, metalation, ring opening, pyrimi-
dine, azaindoline
these scaffolds with alkyl or aryl substituents in the satu-
rated rings are not well precedented, and furthermore the
known routes cannot reliably provide these molecules as
single enantiomers.
Recent studies have suggested that increasing the degree
of sp3 saturation in a drug candidate molecule improves its
probability of progressing from discovery phase to mar-
ket.1 In this respect, indolines are an important class of
molecule which are found in a number of biologically ac-
tive natural products and drug molecules.2 Accordingly, a
number of routes towards these molecules have been de-
veloped, including domino amination–alkylation process-
es,3 and recently an aziridine ring opening–intramolecular
cyclisation strategy.4 ‘Azaindolines’ on the other hand,
such as those derived from pyrimidines, pyridines and
pyrazines, are less well documented. This is also true for
the ring-expanded scaffold, where the partially saturated
five-membered ring is replaced by a six-membered ring
(Figure 1). Pyrimidines are a particularly privileged class
of heterocyclic scaffold, with tetrahydropyrrolopyrimi-
dines and tetrahydropyridopyridazines finding use as ki-
nase inhibitors.5
R2
R2
R2
R3NH2
Pd/C, H2
N
N
N
X
R1
N
Cl
Cl
R1
N
R1
N
N
R3
N
R3
R2
R2
R2
R3NH2
X
PtO2, H2
R1
N
N
N
R1
N
R1
N
N
R3
N
N
Scheme 1 Typical routes to tetrahydropyrrolopyrimidines and to tet-
rahydropyridopyrimidines
Requiring a more general method for the synthesis of
these molecules, we considered an alternative strategy
whereby the saturated carbon–nitrogen framework could
be derived from the ring-opening reaction of a suitably
protected cyclic sulfamidate with a metalated chloro-
pyrimidine derivative. Aryl metalation–ring-opening se-
quences are well documented using metals such as
lithium, magnesium, copper and zinc with N-protected
aziridines as electrophiles.3,6 Conversely, the analogous
reaction with their cyclic sulfamidate analogues are less
well documented.7,8 This is surprising since cyclic sul-
famidates as electrophiles have a number of advantages
over aziridines. Firstly, the ring-opening reaction is com-
pletely regioselective (at the oxygen-bearing position),
which is not always the case with N-protected aziridines.
Secondly, almost any N-protecting group can be used (in-
cluding alkyl), whereas aziridines generally perform bet-
ter with highly activating groups such as N-tosyl. Finally,
six-membered cyclic sulfamidates (an azetidine analogue)
are still highly reactive electrophiles. Once the ring-open-
ing reaction had occurred, we anticipated that an intra-
N
N
N
N
N
N
H
H
tetrahydropyrollo-
pyrimdine
tetrahydropyrido-
pyrimdine
Figure 1 Generic tetrahydropyrrolopyrimidine and tetrahydropyri-
dopyrimidine scaffolds
During the course of our studies, we required a range of
functionalised tetrahydropyrrolopyrimidines and tetra-
hydropyridopyrimidines bearing orthogonal substituents
allowing for further manipulation. Although simple tetra-
SYNLETT 2012, 23, 2408–2412
Advanced online publication: 10.09.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317170; Art ID: ST-2012-D0563-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
Expedient Synthesis of Azaindolines and Azatetrahydroquinolines
2409
molecular cyclisation would then give the desired family Boc group was achieved with TFA, and on basification we
of products (Scheme 2).
noticed that cyclisation had already begun to occur. Com-
plete cyclisation could be achieved by addition of triethyl-
amine and warming to 80 °C for 30 minutes to give the
cyclised product 4 in a 94% yield from intermediate 3. As
both steps had proceeded cleanly (with the only other by-
product observed being a small amount of unreacted start-
ing material), we next attempted the reaction without iso-
lation of the intermediate ring-opened product. By
carrying through the intermediate stages without isola-
tion, the final product 4 could be obtained in an 85% over-
all yield (Scheme 3).
O
O
O
N
S
P
n
R2
N
R3
R2
N
R2
N
R3
ring
R3
M
cyclisation
R1
opening
N
N
N
n
n
NHP
N
R1
Cl
R1
Cl
P
Scheme 2 Proposed ring-opening–cyclisation sequence
Metalated α-chloro heteroaromatics can be readily formed
and reacted with electrophiles under cryogenic conditions
by insertion into a carbon–halogen bond with metals such
as lithium and magnesium.9 Anticipating that the metal in-
sertion pathway would require an additional step as the
5-iodinated or 5-brominated pyrimidine starting materials
would not be commercially available, we concentrated
our studies on the alternative deprotonation pathway. Al-
though chloropyrimidines have been directly lithiated
with classical lithium amide bases such as LDA and
LiTMP,10 low reaction temperatures are necessary (–78 °C
or below) due to sensitivity of the ring to organometallic
reagents. Recently, Knochel and co-workers have report-
ed that chloropyrimidines can be metalated at room tem-
perature with TMPMgClLiCl11 (TMP = 2,2,6,6-
tetramethylpiperidine). Further studies have shown that
sensitive chloro heterocycles such as pyrazines and pyrid-
azines, and aromatics bearing reactive functionality can
be metalated and reacted at room temperature with vari-
ous electrophiles using TMP2ZnCl2MgCl22LiCl and
TMPZnClLiCl as bases.12 In addition to the range of sen-
sitive functionality tolerated, these methods have the add-
ed convenience that they can be conducted at ambient
temperature.
Cl
Cl
O
O
O
N
TMPMgCl⋅LiCl
S
N
N
Boc
+
THF, r.t.
85%
NHBoc
MeS
N
Cl
MeS
N
Cl
1
2
3
TFA, evaporate
then Et3N
94%
i) TMPMgCl⋅LiCl, THF
ii) TFA
iii) Et3N, MeCN
Cl
N
85%
N
H
MeS
N
4
Scheme 3 Initial studies into the ring-opening–cyclisation sequence
We next investigated the scope of the reaction with re-
gards to the cyclic sulfamidate. The (S)-methyl cyclic sul-
famidate 5 could be used, thus giving access to both
enantiomers of the product, as could the ethyl-substituted
sulfamidate 6 and its unsubstituted analogue 8. When the
methyl function was moved to the oxygen-bearing posi-
tion of the electrophile (7), we found that reactivity was
greatly diminished presumably on steric grounds, with the
product 14 only being obtained in a moderate 43% yield
after extended stirring in the ring-opening reaction. None-
theless, as ring-opening reactions with aziridines general-
ly occur at the less hindered carbon, this substitution
pattern could not be easily obtained from the analogous
aziridine ring-opening reaction. N-Alkyl aziridines are
fairly unreactive to ring opening under basic conditions,
so it was pleasing that the N-Bn sulfamidate 9 was also
well tolerated in the reaction. In this case, the cyclised
product 16 bearing the N-Bn could be obtained directly
from acidic workup (2 M HCl) followed by basification
and stirring with triethylamine. The methodology also ex-
tended well to six-membered sulfamidates, with both the
unsubstituted electrophile 10, and the chlorophenyl-sub-
stituted sulfamidate 11 giving the tetrahydropyridopyrim-
idines 17 and 18, respectively in good yields. This was
particularly interesting as this motif could not be easily
obtained from the analogous azetidine ring-opening
reaction15 (Table 1).
We began our studies by synthesising a range of five- and
six-membered cyclic sulfamidates. To achieve this, the
corresponding N-protected amino alcohols were treated
with thionyl chloride and imidazole with triethylamine as
base, to give the cyclic sulfamidite intermediates. These
were then oxidised with NaIO4 and catalyst RuCl3 in
acetonitrile–water to give the cyclic sulfamidate electro-
philes in good overall yields.13 In cases where the cyclisa-
tion was slow or significant O-dimerisation was observed,
an acetonitrile–pyridine mixture in the absence of imidaz-
ole was used.14 With these reagents in hand, we began our
investigations into the ring-opening–cyclisation process.
We initially selected 4,6-dichloro-2-(methylthio)pyrimi-
dine (1) as the aromatic partner as the target product
would have two orthogonal substituents for further elabo-
ration. Treatment of 1 with TMPMgClLiCl in THF at
room temperature for 30 minutes, followed by addition of
the (R)-methyl N-Boc sulfamidate 2 led to rapid consump-
tion of the starting material, which after an aqueous citric
acid workup gave the ring-opened product 3 as a mixture
of rotamers in a pleasing 85% yield. Cleavage of the N-
We next explored the scope of the reaction with respect to
the aryl component. The relative positions of the thio-
methyl and chloride atoms could be switched in pyrimi-
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2408–2412

2410
T. A. Moss et al.
LETTER
Table 1 Reaction of 4,6-Dichloro-2-(thiomethyl)pyrimidine (1)
dine 19 to give the products 26 and 27 from sulfamidates
5 and 10, respectively in comparable yields to pyrimidine
1. Pleasingly, other relatively electron-rich aromatics
were also well tolerated, with 4-methoxy (20) and 2-meth-
ylaniline (21) substituted dichloropyrimidines working
well. Interestingly, when the N-methylaniline was moved
to the 4-position of the pyrimidine, reactivity almost com-
pletely diminished, with only ca 5% product detected by
LCMS. Significant decomposition of the pyrimidine was
not observed until the reaction was warmed to 50 °C, sug-
gesting that the increased steric hindrance around the
available proton was inhibiting the metallation step. p-Chloro-
phenoxy was also tolerated in the 2-position with N-Bn
sulfamidate 9, although when the N-Boc sulfamidate 2
was used, some displacement of the chlorophenoxy by
chloride was seen in the cyclisation step (giving product
32). 2,4,6-Trichloropyrimidine (24) turned out to the less
stable in the metallation step than the other examples sur-
veyed, which was generally the case with less electron-
rich systems (sensitive chloro heterocycles such as 2,6-di-
chloropyrazine and 3,6-dichloropyridazine failed to give
any ring-opened product under these conditions). In this
case, the dichloropyrimidine product 32 could be obtained
in a slightly reduced yield by conducting the metallation
step at –10 °C and for a shorter period of time. Finally, the
method could also be extended to pyridines, with 2,6-di-
chloro-4-(thiomethyl)pyridine (25) giving the tetrahydro-
pyrrolopyridine 33 in reasonable yield after reacting with
sulfamidate 2. In this case, the metallation step required
stirring at 30 °C for 1.5 hours. In addition, the final cycli-
sation step was much less facile than with the chloro-
pyrimidines surveyed, requiring heating to 130 °C in a
microwave vial to effect cyclisation (Table 2).
with Various Cyclic Sulfamidatesa (continued)
Cl
R1
TMPMgCl⋅LiCl
Cl
O
O
then
H+, basify
S
Boc
R2
N
N
O
N
n
+
MeS
N
N
H
R2
R1
MeS
N
Cl
n
1
2, 5–11
4, 12–18
Entry Sulfamidate
Product
Yield
(%)b
Cl
O
O
O
S
NBoc
Et
N
Et
3
79
N
H
MeS
N
6
13
Cl
O
O
O
S
NBoc
N
4c
43
83
83
81
N
H
MeS
N
7
14
Cl
O
O
O
S
S
N
NBoc
5
N
H
MeS
N
8
15
Cl
O
O
O
N
NBn
6d
N
MeS
N
Bn
9
16
Table 1 Reaction of 4,6-Dichloro-2-(thiomethyl)pyrimidine (1)
Cl
with Various Cyclic Sulfamidatesa
O
O
S
S
N
O
NBoc
TMPMgCl⋅LiCl
then
Cl
R1
Cl
7
O
O
MeS
N
N
H
H+, basify
S
Boc
R2
N
N
O
N
n
+
10
17
R1
MeS
N
N
H
R2
MeS
N
Cl
n
Cl
O
O
O
1
2, 5–11
4, 12–18
N
NBoc
8
78
Entry Sulfamidate
Product
Yield
(%)b
MeS
N
N
H
C6H4-4-Cl
C6H4-4-Cl
11
18
Cl
O
O
O
a Reaction conditions: (i) 2-mmol scale, chloropyrimidine (1.0 equiv),
TMPMgClLiCl (1.1 equiv), THF (7.5 mL), r.t., 30 min, then sulfami-
date (1.1 equiv), r.t., 1 h; (ii) TFA, r.t., 15 min; (iii) Et3N (4.0 equiv),
MeCN, 80 °C, 30 min.
S
NBoc
N
1
2
85
82
N
N
MeS
H
b Isolated yields after silica gel chromatography.
c Ring-opening step was stirred for 16 h at r.t.
d TFA step was not required. Acidic workup was carried out with aq
2 M HCl.
2
4
Cl
O
O
O
S
N
NBoc
N
N
MeS
H
In conclusion, we have developed an efficient route to
variously substituted azaindolines and azatetrahydroquin-
olines in a stereo-predictable manner via ring opening of
cyclic sulfamidates with metallated chloro heterocycles,
5
12
Synlett 2012, 23, 2408–2412
© Georg Thieme Verlag Stuttgart · New York

LETTER
Expedient Synthesis of Azaindolines and Azatetrahydroquinolines
2411
followed by intramolecular cyclisation.16 The fragment- tile building blocks. As such, this method should find
sized products, which otherwise would be difficult or te- particular use in medicinal chemistry campaigns.
dious to synthesise, represent extremely useful and versa-
Table 2 Ring-Opening of Sulfamidates with Various Magnesiated Chloropyrimidines and Chloropyridinesa
Entry
1
Aryl chloride
Sulfamidate
Product
Yield (%)b
SMe
Cl
N
O
O
O
S
N
NBoc
77
N
Cl
N
Cl
N
SMe
SMe
OMe
H
5
19
26
SMe
Cl
O
O
S
N
O
NBoc
N
2
3
75
80
Cl
N
N
Cl
N
H
10
19
27
OMe
Cl
O
O
O
S
N
NBoc
N
N
Cl
N
Cl
N
N
H
5
20
28
Cl
N
Cl
O
O
O
S
N
NBoc
Ph
Ph
4
5
74
<5
N
N
Cl
N
N
H
Me
Me
2
21
29
Cl
N
Me
Ph
O
O
O
N
N
S
N
NBoc
N
Ph
Cl
N
N
H
Cl
Me
2
30
22
Cl
N
Cl
N
O
O
O
S
S
S
Cl
Cl
NBn
N
N
6
75
71
55
N
O
O
Cl
Bn
9
23
31
Cl
N
Cl
N
O
O
O
N
NBoc
N
7c
N
H
Cl
Cl
Cl
2
24
32
SMe
N
SMe
N
O
O
O
NBoc
8
N
H
Cl
Cl
Cl
2
25
33
a Reaction conditions: (i) 2-mmol scale, chloropyrimidine (1.0 equiv), TMPMgClLiCl (1.1 equiv), THF (7.5 mL), r.t., 30 min, then sulfamidate
(1.1 equiv), r.t., 1 h; (ii) TFA, r.t., 15 min; (iii) Et3N (4.0 equiv), MeCN, 80 °C, 30 min.
b Isolated yield after silica gel chromatography.
c Metallation step was conducted at –10 °C for 15 min.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2408–2412

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T. A. Moss et al.
LETTER
Rottländer, M.; Knochel, P. J. Org. Chem. 2000, 65, 4618;
and references therein.
References and Notes
(1) For a discussion on the link between sp3 saturation and the
probability of clinical success, see: Lovering, F.; Bikker, J.;
Humblet, C. J. Med. Chem. 2009, 52, 6752.
(2) (a) For a review, see: Zhang, D.; Song, H.; Qin, Y. Acc.
Chem. Res. 2011, 44, 447. (b) The Alkaloids: Chemistry and
Biology; Vol. 50; Cordell, G. A., Ed.; Academic Press: San
Diego, 1998.
(3) (a) Minatti, A.; Buchwald, S. L. Org. Lett. 2008, 10, 2721.
(b) Li, K.-J.; Mei, T.-S.; Yu, J.-Q. Angew. Chem. Int. Ed.
2008, 47, 6452. (c) Thansandote, P.; Raemy, M.; Rudolph,
A.; Lautens, M. Org. Lett. 2007, 9, 5255.
(4) Michaelis, D. J.; Dineen, T. A. Tetrahedron Lett. 2009, 50,
1920.
(5) (a) Ohwada, J.; Ebiike, H.; Kawada, H.; Tsukazaki, M.;
Nakamura, M.; Miyazaki, T.; Morikami, K.; Yoshinari, K.;
Yoshida, M.; Kondoh, O.; Kuramoto, S.; Ogawa, K.; Aoki,
Y.; Shimma, N. Bioorg. Med. Chem. Lett. 2011, 21, 1767.
(b) Choi, H.-S.; Wang, Z.; Richmond, W.; He, X.; Yang, K.;
Jiang, T.; Sim, T.; Karanewsky, D.; Gu, X.-J.; Zhou, V.; Liu,
Y.; Ohmori, O.; Caldwell, J.; Gray, N.; He, Y. Bioorg. Med.
Chem. Lett. 2006, 16, 2173. (c) Nagashima, S.; Hondo, T.;
Nagata, H.; Ogiyama, T.; Maeda, J.; Hoshii, H.; Kontani, T.;
Kuromitsu, S.; Ohga, K.; Orita, M.; Ohno, K.; Moritomo, A.;
Shiozuka, K.; Furutani, M.; Takeuchi, M.; Ohta, M.;
Tsukamoto, S. Bioorg. Med. Chem. Lett. 2009, 17, 6926.
(d) Sabbatini, F. M.; Di Fabio, R.; St-Denis, Y.; Capelli,
A.-M.; Castiglioni, E.; Contini, S.; Donati, D.; Fazzolari, E.;
Gentile, G.; Micheli, F.; Pavone, F.; Rinaldi, M.;
(10) (a) Turck, A.; Plé, N.; Quéguiner, G. Heterocycles 1994, 37,
2149. (b) Radinov, R.; Chanev, C.; Haimova, M. J. Org.
Chem. 1991, 56, 4793. (c) Wada, A.; Yamamoto, J.;
Hamaoka, Y.; Okhi, K.; Nagai, S.; Kanatomo, S.
J. Heterocycl. Chem. 1990, 27, 1831.
(11) Mosrin, M.; Knochel, P. Chem.–Eur. J. 2009, 15, 1468; and
references therein.
(12) (a) Mosrin, M.; Knochel, P. Org. Lett. 2009, 11, 1837.
(b) Bresser, T.; Mosrin, M.; Monzon, G.; Knochel, P. J. Org.
Chem. 2010, 75, 4686.
(13) Bower, J. F.; Rujirawanich, J.; Gallagher, T. Org. Biomol.
Chem. 2010, 8, 1505.
(14) Moss, T. A.; Alonso, B.; Fenwick, D. R.; Dixon, D. J.
Angew. Chem. Int. Ed. 2010, 49, 568.
(15) Generally, activation by strong Lewis acids or formation of
the azetidinium ion is necessary: Couty, F.; Evano, G.
Synlett 2009, 3053.
(16) Representative Procedure for the Synthesis of
Azaindoline 12: To an oven-dried three-necked flask
containing 4,6-dichloro-2-(thiomethyl)pyrimidine (1; 390
mg, 2.0 mmol) in anhyd THF (7.5 mL) was added
TMPMgClLiCl (1 M in THF, 2.4 mL, 2.4 mmol) at r.t. After
stirring for 30 min, tert-butyl (4S)-4-methyl-1,2,3-
oxathiazolidine-3-carboxylate 2,2-dioxide (5; 498 mg, 2.10
mmol) was added and the reaction was stirred for a further 1
h at r.t. 1 N Citric acid (7.5 mL) and EtOAc (7.5 mL) were
added, and the reaction was stirred vigorously for 5 min
before separation of the layers. The organic layer was
concentrated, then the residue was stirred in TFA (5 mL)
for 15 min before again being concentrated. [Note:
Alternatively, TFA (7.5 mL) and H2O (1 mL) can be added
directly to the reaction mixture to cleave the sulfamic acid
intermediate and N-Boc group in one process.] The residue
was dissolved in MeCN (20 mL) and Et3N (1.12 mL, 8.0
mmol) was added. The reaction was warmed to 80 °C for 30
min to effect cyclisation. The volatiles were removed under
vacuum and the residue was purified by silica gel chroma-
tography [heptane–EtOAc, 95:5 → 80:20] to give (R)-4-
chloro-6-methyl-2-(methylthio)-6,7-dihydro-5H-
pyrollo[2,3-d]pyrimidine (12) as a colourless solid (354.5
mg, 82%); mp 192–193 °C. IR: 3350 (w), 2985 (m), 1180
(s), 1045 (s), 885 (m) cm–1. 1H NMR (400 MHz, CDCl3):
δ = 6.83 (s, 1 H, NH), 4.16 (m, 1 H, CHMe), 3.19 (dd, 1 H,
J = 9.5, 16.8 Hz, CHaHb), 2.59 (dd, 1 H, J = 5.8, 16.8 Hz,
CHaHb), 2.49 (s, 3 H, SMe), 1.37 (d, 3 H, J = 6.3 Hz, Me).
13C NMR (100 MHz, CDCl3): δ = 170.76, 167.86, 151.43,
112.20, 51.86, 33.17, 23.11, 14.14. MS (EI): m/z = 216 (100)
[M + H]+. HRMS (EI): m/z [M + H]+ calcd for C8H11N3ClS:
216.03567; found: 216.03557
Pasquarello, A.; Zampori, M. G.; Felice, P. D.; Zarantonello,
P.; Arban, R.; Perini, B.; Vitulli, G.; Benedetti, R.; Oliosi,
B.; Worby, A. ChemMedChem 2008, 3, 226.
(6) For reviews on aziridine ring-opening reactions with
organometallic reagents, see: (a) Pineschi, M. Eur. J. Org.
Chem. 2006, 4979. (b) Hu, X. E. Tetrahedron 2004, 60,
2701. (c) McCoull, W.; Davis, F. A. Synthesis 2000, 1347.
(7) For seminal work, see: (a) Alker, D.; Doyle, K. J.; Harwood,
L. M.; McGregor, A. Tetrahedron: Asymmetry 1990, 1, 877.
(b) Baldwin, J. E.; Spivey, A. C.; Schofield, C. J.
Tetrahedron: Asymmetry 1990, 1, 881. (c) Lowe, G.; Reed,
M. A. Tetrahedron: Asymmetry 1990, 1, 885. (d) White,
G. J.; Garst, M. E. J. Org. Chem. 1991, 56, 3177.
(8) (a) For a review, see: Meléndez, R. E.; Lubell, W. D.
Tetrahedron 2003, 59, 2581. (b) For a recent application,
including a comparison with N-protected aziridines, see:
Hebeisen, P.; Weiss, U.; Alker, A.; Staempfli, A.
Tetrahedron Lett. 2011, 52, 5229.
(9) (a) Piller, F. M.; Appukkuttan, P.; Gavryushin, A.; Helm,
M.; Knochel, P. Angew. Chem. Int. Ed. 2008, 47, 6802.
(b) Abarbri, M.; Thibonnet, J.; Bérillon, L.; Dehmel, F.;
Synlett 2012, 23, 2408–2412
© Georg Thieme Verlag Stuttgart · New York