Palladium-catalyzed N-arylation reactions with aziridine and azetidine

Article abstract of DOI:10.1055/s-2006-958947

Studies on the viability of palladium-catalyzed cross-coupling reactions of aryl- or hetaryl bromides with the parent aziridine or azetidine showed that a wide range of N-arylaziridines and N-arylazetidines are accessible by this method. Ring cleavage of the N-arylaziridines or -azetidines thus produced does not occur under the applied reaction conditions. The synthetic utility of the method is illustrated by examples of double N-arylations with either aziridine or azetidine. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-958947

PAPER
243
Palladium-Catalyzed N-Arylation Reactions with Aziridine and Azetidine
P
B
alladium-Cataly
e
ze
d
N
-Aryl
r
ation Re
n
actions
w
ith
h
A
ziridine an
a
d
A
zetidin er d Witulski,* Stefan Senft, Jordi Bonet, Oliver Jost
Johannes Gutenberg Universität-Mainz, Institut für Organische Chemie, Duesbergweg 10–14, 55099 Mainz, Germany
Fax +49(6131)3926777; E-mail: witulski@uni-mainz.de
Received 3 August 2006; revised 12 October 2006
may induce ring cleavage in aziridines. In general, aziri-
dine as well as N-arylaziridines undergo ring-opening re-
actions under relatively mild conditions.6
Abstract: Studies on the viability of palladium-catalyzed cross-
coupling reactions of aryl- or hetaryl bromides with the parent azir-
idine or azetidine showed that a wide range of N-arylaziridines and
N-arylazetidines are accessible by this method. Ring cleavage of the
N-arylaziridines or -azetidines thus produced does not occur under
the applied reaction conditions. The synthetic utility of the method
is illustrated by examples of double N-arylations with either aziri-
dine or azetidine.
Yudin et al. reported the use of substituted aziridines in
7
palladium- and copper-mediated N-arylations. However,
in this study only substituted and kinetically stabilized
aziridines such as cyclohexenimine and 2-benzoyl-3-tert-
butylaziridine have been investigated, and most of the ex-
amples were subsequently treated with tetrafluoroboric
acid in methanol to induce ring opening prior to isolation.
Hartwig reported on the stoichiometric reaction of the
lithium amide of aziridine with an arylpalladium bromide
Key words: aziridines, azetidines, N-arylations, cross-coupling,
palladium
The synthesis of N-aryl- or N-hetarylamines by transition-
metal-catalyzed cross-coupling reactions between aryl- or
hetaryl halides and nitrogen nucleophiles has emerged as
a highly valuable synthetic tool with many potential appli-
8
complex, but truly catalytic N-arylations with the parent
aziridine or azetidine have not been documented so far.
A few syntheses of N-arylaziridines and N-arylazetidines
have been carried out by conventional synthetic methods,
but most of them are rather limited in scope or are based
on multistep sequences.9 Furthermore, none of them al-
lows efficient access to aryl cores substituted with more
than one aziridine or azetidine moiety.
cations in medicinal or material-science-oriented chemis-
try.1 Especially the palladium-catalyzed N-arylation
,10
reaction, the so-called Buchwald–Hartwig reaction, has
recently evolved into one of the most powerful modern
methods for gaining access to a wide variety of aryl- or
hetarylamines for industrial use.1 A large range of nitro-
gen nucleophiles has been employed in these cross-
coupling reactions, and include primary and secondary
aliphatic amines, anilines, amides, carbamates, ureas, sul-
fonamides, sulfoximines, and aromatic NH-containing
heterocycles such as indoles, indazoles, carbazoles, and
,2
The feasibility of palladium-catalyzed cross-coupling of
aryl bromides with small-ring nitrogen heterocycles was
investigated through the reaction between bromoben-
zophenone 1a and aziridine (Scheme 1). The results of the
search for a suitable base and phosphine ligand to develop
an efficient protocol for the desired palladium-catalyzed
N-arylaziridination reaction are shown in Table 1. The
scope of this cross-coupling reaction was extended to oth-
er aryl- or hetaryl bromides, and the results of this are
shown in Table 2.
1
a
pyrroles.
As part of our ongoing program on the design, synthesis,
and photophysical evaluation of novel functionalized do-
3
nor–p-spacer–acceptor chromophores, and as part of our
efforts in multiple or sequential cross-coupling reactions,4
the use of small-ring secondary amines, e.g. the parent
aziridine (also known as ethylenimine) and azetidine, in
palladium-catalyzed N-arylation reactions is of interest to
us. The two key challenges in using aziridine as a cross-
O
O
HN
(2 equiv)
(i)
Ph
Ph
Br
N
coupling partner lie in its low basicity (the pK of the azir-
1a
2a (90%)
a
idinium ion is 8.0, whereas that of ordinary secondary
5
Scheme 1 Reagents and conditions: (i) 3 mol% Pd(OAc)
, 4 mol%
2
amines is ca. 11) and its inherent ring strain of approxi-
BINAP, Cs CO (2 equiv), toluene, 100 °C, 1 d (for other ligands and
–
1
2
3
mately 111 kJ·mol . The low basicity is considered to
make aziridine less prone to palladium-mediated N-aryla-
tions because of the weaker association of the amine to the
active palladium catalyst, whereas the ring strain makes
ring cleavage a risk. Either nucleophilic attack at the car-
bon atom or Lewis acid coordination at the nitrogen atom
bases, see Table 1).
Among the bases studied, cesium carbonate and, notably,
sodium tert-butoxide proved to be suitable, and in neither
case was a significant amount of a ring-opened product
observed (Table 1). The N-arylaziridination of 1a in the
presence of 3 mol% Pd/BINAP resulted in the formation
of N-arylaziridine 2a in 90% isolated yield when the reac-
tion was carried out in toluene at 100 °C (Table 1, entry
SYNTHESIS 2007, No. 2, pp 0243–0250
x
x
.
x
x
.2
0
0
7
Advanced online publication: 14.12.2006
DOI: 10.1055/s-2006-958947; Art ID: T12206SS
Georg Thieme Verlag Stuttgart · New York
3
). Several other mono- and bidentate ligands that have
©

2
44
B. Witulski et al.
PAPER
Table 1 N-Arylaziridination of 1a in the Presence of Different
er in this case (entry 8). In general, triphenylphosphine is
not a suitable ligand for cross-coupling reactions of aryl
bromides or iodides with secondary amines, but it has
been used by us and others as an efficient ligand in N-ar-
ylations of macrocyclic amines and aza-crown ethers with
electron-deficient aryl bromides.11 Furthermore, second-
ary cyclic alkylamines are amongst the easiest substrates
for palladium-catalyzed N-arylation reactions. Most like-
ly this is because they are less prone to b-hydrogen elimi-
nation, and the latter should be effectively suppressed
when aziridine is used as the amine component, for elec-
tronic reasons.
Bases and Ligandsa
c
Entry
Ligandb
Base
Yield (%)
1
2
3
4
5
6
7
rac-BINAP
rac-BINAP
rac-BINAP
rac-BINAP
Xantphos
dppf
K CO
17
54
90
88
91
90
86
2
3
K PO
3
4
Cs CO
2
3
t-BuONa
Cs CO
2
3
3
3
Cs CO
2
Next, the scope of the N-arylaziridination process was ex-
plored with other aryl and hetaryl bromides (Table 2). The
following optimized conditions were used for all the reac-
tions of this study: per bromine functionality two equiva-
lents aziridine,12 3 mol% palladium(II) acetate as
precatalyst, 4 mol% of either BINAP or Xantphos, and
two equivalents of cesium carbonate were used; the reac-
tions proceeded smoothly at 100 °C in toluene to give the
desired N-aryl- or N-hetarylaziridines 2a–f and 4a–f in
mostly very high yield (78–98%). However, the N-aryl-
aziridination reaction was low-yielding in the case of
2-(Dicyclohexylphosphino)bi- Cs CO
2
phenyl
8
PPh3
Cs CO
45
2
3
a
Reagents and conditions: 1 (1 equiv), aziridine (2 equiv), 3 mol%
Pd(OAc) , 4 mol% ligand, base (2 equiv), toluene, 100 °C, 1 d.
2
b
Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene;
dppf = 1,1¢-bis(diphenylphosphino)ferrocene.
c
Yield of isolated product after column chromatography.
been established in N-arylation reactions of aliphatic sec- paracyclophane 1f. The aziridinylparacyclophane 2f was
ondary amines were also tested. The reaction of 1a with obtained in only 17% yield and the parent paracyclophane
aziridine was high-yielding when rac-BINAP, 4,5- was the major reaction product.13 Dehydrobromination
bis(diphenylphosphino)-9,9-dimethylxanthene
phos), or 1,1¢-bis(diphenylphosphino)ferrocene (dppf) hindrance caused by the bulky aryl cross-coupling part-
Pd/ligand, 1:1.2) was used as the ligand (Table 1, entries ner. The increased steric hindrance in the key arylpalladi-
, 5, 6). Besides these bidentate ligands, the monophos- um–imido intermediate makes b-hydride elimination
(Xant- was favored in this example as a consequence of steric
(
3
phine ligand 2-(dicyclohexylphosphino)biphenyl turned more favorable than reductive elimination, and, as a con-
out to be equally suitable (entry 7). Notable is that the re- sequence, dehydrobrominated products are formed.14
action could also be performed with triphenylphosphine
(
Pd/PPh , 1:2). However, the yield was significantly low-
3
Table 2 Palladium-Catalyzed N-Arylaziridination Reactions of Aryl or Hetaryl Bromidesa
Ligandb
Time (d)
Product 2 or 4
Yield (%)
c
Entry
ArBr 1 or 3
Br
CN
N
2b
N
CN
1
rac-BINAP
1
86
1
b
Br
2
3
Xantphos
Xantphos
3
3
89
N
Ts
N
Ts
1
c
2
2
c
Br
N
88
88
1
d
d
4
Xantphos
1
N
Br
1
e
2
e
Synthesis 2007, No. 2, 243–250 © Thieme Stuttgart · New York

PAPER
Palladium-Catalyzed N-Arylation Reactions with Aziridine and Azetidine
245
a
Table 2 Palladium-Catalyzed N-Arylaziridination Reactions of Aryl or Hetaryl Bromides (continued)
c
Entry
5
ArBr 1 or 3
Ligandb
Time (d)
Product 2 or 4
Yield (%)
Br
N
Xantphos
3
17
1f
2f
O
O
6
7
Xantphos
1
98
N
N
Br
Br
3
a
4
a
CO2Me
CO2Me
Xantphos
Xantphos
2
3
82
87
N
N
N
N
Br
Br
3
b
4
4
b
c
8
9
Br
Br
X
3
c
X
Xantphos
Xantphos
3
1
N
N
93
95
3
d X = Br
4d
4d
1
1
0
1
3e X = I
Br
N
Xantphos
3
1
78
94
Br
N
N
3f
4
4
e
f
1
2
rac-BINAP
N
N
Br
N
Br
3g
a
Reagents and conditions: 1a–f (1 equiv) or 3a–g (0.5 equiv), aziridine (2 equiv), 3 mol% Pd(OAc) , 4 mol% ligand, Cs CO (2 equiv), toluene,
2
2
3
1
00 °C.
b
Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene.
Yield of isolated product after column chromatography.
c
The N-arylaziridines 2a–f and 4a–f could all be purified ample, the doubly N-aziridinated product 4d was obtained
efficiently by column chromatography with neutral alu- in 95% yield (Table 2, entry 10).
minum oxide and were sufficiently stable for neat isola-
All cross-couplings are truly catalytic, because omission
tion. Application of the optimized reaction conditions
of the palladium source resulted in no reaction. However,
allowed the synthesis of either mono- or doubly aziridi-
in the case of the rather electron-deficient 2,6-dibromopy-
nated aryl or hetaryl compounds, and possible ring-cleav-
ridine (3g) small amounts of a monoaziridinated product
age products were successfully suppressed. The N-
already formed by a noncatalytic S Ar process. Notably,
N
arylaziridination reaction was found to be tolerant of ke-
only the palladium-catalyzed cross-coupling reaction of
tone, cyano, and ester functionalities, and both electron-
aziridine with 3g provided a high-yielding access to the
doubly N-aziridinated pyridine 4f, previously shown to be
deficient as well as electron-rich aryl bromides could be
used. Furthermore, aryl iodides were applied as substrates
for N-arylaziridinations with equal efficiency, as evi-
denced by the use of 1,4-diiodobenzene (3e). For this ex-
an effective chemosterilant when evaluated as a fumigant
15
against the tobacco budworm Heliothis virescens (F.).
Synthesis 2007, No. 2, 243–250 © Thieme Stuttgart · New York

2
46
B. Witulski et al.
PAPER
Table 3 N-Arylations with Azetidine
a
Entry
1
ArBr 1
Time (h)
10
Product 5
Yield (%)
O
O
Ph
Ph
95
N
Br
1
a
5
a
2
3
Br
CN
15
15
N
CN
86
85
1
b
d
5b
Br
N
1
1
5
5
c
Br
N
4
5
15
95
g
d
Br
CN
N
CN
24
24
95
89
1
1
h
5e
Br
Br
N
N
6
i
5
f
a
Yield of isolated product after column chromatography.
Finally, this cross-coupling protocol was extended to the with Xantphos or BINAP as suitable ligands and either ce-
use of azetidine as cross-coupling partner (Table 3). Aze- sium carbonate or sodium tert-butoxide as a suitable base.
tidine is more basic (pK = 11.3), and due to lower angle The process allows the introduction of several aziridines
a
strain considerably less reactive than its three-membered or azetidines within the same aromatic or heteroaromatic
counterpart, but nonetheless azetidines are capable of un- core, and the amination products thus obtained are stable
1
6
dergoing similar ring-opening reactions. This small-ring enough to allow their isolation by column chromatogra-
secondary amine has not yet been investigated in palladi- phy over neutral aluminum oxide. Further studies on mul-
1
7
um-catalyzed N-arylation reactions, and the thus formed tiple ring-opening reactions as well as application of this
N-arylazetidines are considered to be equally useful as protocol for the construction of novel donor–p-spacer–
synthetic building blocks as the corresponding aziridines. acceptor molecular probes are underway in our laborato-
Cross-coupling reactions of aryl bromides with azetidines ries.
in the presence of 3 mol% palladium(II) acetate, 4 mol%
Xantphos, and sodium tert-butoxide as base gave N-aryl-
azetidines 5a–f in high yields (Table 3). Again, besides
single N-arylation reactions, double N-azetidination is under argon; vacuum lines, Schlenk tubes, and oven-dried glass-
All reagents were analytical grade and all solvents were purified by
standard methods and distilled prior to use. All reactions were run
possible, as exemplified by the transformation of 1i into 5f ware were used. Reaction mixtures were stirred magnetically and
were monitored by TLC using neutral aluminum oxide plates from
without loss of overall efficiency (Table 3, entry 6).
Macherey-Nagel & Co. (Düren, Germany). Column chromatogra-
In conclusion, we have demonstrated that both N-arylazir-
idines and N-arylazetidines can be prepared in very good
1
phy was performed on alumina N activity grade III from ICN. H
1
3
and C NMR spectra were recorded on Bruker AC200 and Bruker
yields by palladium-catalyzed N-arylamination reactions AMX400 spectrometers, and were referenced against TMS
Synthesis 2007, No. 2, 243–250 © Thieme Stuttgart · New York

PAPER
Palladium-Catalyzed N-Arylation Reactions with Aziridine and Azetidine
247
d = 0.00, H) and CDCl (d = 77.0, 13C) as internal standards. 13
1
C
1
H NMR (400 MHz, CDCl ): d = 7.85 (d, J = 8.8 Hz, 1 H), 7.75 (d,
(
3
3
NMR assignments were made on the basis of DEPT experiments.
Mass spectra were obtained on a Finnigan MAT 90 spectrometer
J = 8.4 Hz, 2 H), 7.52 (d, J = 3.7 Hz, 1 H), 7.22 (d, J = 8.4 Hz, 2 H),
7.05 (d, J = 8.8 Hz, 1 H), 6.56 (d, J = 3.6 Hz, 1 H), 2.34 (s, 3 H),
(EI, 70 eV) and on a Quattro-LCZ spectrometer from Waters-Mi-
2.12 (s, 4 H).
cromass (ESI). IR spectra were recorded of solid samples in KBr
pellets or of films on NaCl plates on a Perkin-Elmer FT-IR spec-
trometer. Melting points were recorded on a Büchi apparatus, and
are uncorrected. Microanalysis was performed on a Perkin-Elmer
Elementaranalyzer EA 240 and a Perkin-Elmer Elementaranalyzer
13
C NMR (100 MHz, CDCl ): d = 151.3 (s), 144.9 (s), 135.3 (s),
3
1
31.4 (s), 130.8 (s), 129.9 (d), 127.1 (d), 126.8 (d), 119.1 (d), 113.9
(
d), 112.2 (d), 108.9 (d), 28.0 (t), 21.6 (q).
+
MS (EI, 70 eV); m/z (%) = 312 (26) [M ], 284 (13), 157 (70), 130
(18), 115 (12), 91 (17), 32 (16), 28 (100).
1
8
19
2
400 CHN. PE (bp 40–60 °C) was used. Aziridine, azetidine, 4-
2
0
bromo[2.2]paracyclophane (1f), and 9-bromo-10-cyanoanthra-
Anal. Calcd for C H N (312.39): C, 65.36; H, 5.16; N, 8.97.
Found: C, 65.25; H, 5.20; N, 8.58.
1
5
13
cene (1h)21 were prepared according to literature procedures.
N-Arylaziridines 2a–f; General Procedure
1
-(2-Naphthyl)aziridine (2d)
Into a Schlenk tube with a screw cap under argon were introduced
an aryl bromide 1a–f (0.5 mmol), Cs CO (131 mg, 1.0 mmol),
Yield: 88%; colorless solid; mp 67–68 °C.
2
3
IR (KBr): 3059, 2993, 1626, 1595, 1503, 1468, 1389, 1304, 1293,
1
1H NMR (400 MHz, CDCl
4 H), 2.19 (s, 4 H).
Pd(OAc) (4 mg, 3 mol%) and Xantphos (12 mg, 4 mol%). The
2
–1
060, 957, 919, 856, 821 cm .
Schlenk tube was evacuated and flushed with argon. Then anhyd
toluene (10 mL) and aziridine (43 mg, 0.05 mL, 1.0 mmol) were
added by syringe through a septum. The Schlenk tube was sealed
with a screw cap and the mixture was stirred at 100 °C for the time
period given in Table 2. The mixture was filtered through a plug of
Celite 545, which was washed several times with CH Cl . The sol-
vent was evaporated and the resulting crude product was purified by
column chromatography (alumina III/N, PE–EtOAc); this gave N-
arylaziridines 2a–f.
): d = 7.76–7.67 (m, 3 H), 7.45–7.24 (m,
3
13
C NMR (100 MHz, CDCl ): d = 152.7 (s), 134.1 (s), 130.0 (s),
3
1
28.8 (d), 127.6 (d), 126.7 (d), 126.3 (d), 124.1 (d), 122.4 (d), 116.2
2
2
(
d), 27.8 (t).
MS (EI, 70 eV): m/z (%) = 169 (91) [M ], 154 (26), 141 (100), 140
20), 127 (83), 115 (25).
Anal. Calcd for C H N (169.22): C, 85.17; H, 6.55; N, 8.28.
+
(
1
2
11
4
-Aziridin-1-ylbenzophenone (2a)
Found: C, 85.02; H, 6.55; N, 8.18.
Yield: 91%; colorless crystals; mp 108–109 °C (CHCl –pentane);
3
Rf = 0.2 (alumina III/N, PE–EtOAc, 4:1).
1-(9-Phenanthryl)aziridine (2e)
Yield: 88%; colorless solid; mp 98–100 °C; R = 0.5 (alumina III/N,
PE–EtOAc, 9:1).
IR (KBr): 3053, 2992, 1643, 1600, 1505, 1446, 1416, 1309, 1279,
f
–
1
1
166, 1148, 938, 905, 857, 740, 700 cm .
1
IR (KBr): 3051, 2924, 1596, 1493, 1448, 1387, 1330, 1238, 1055,
H NMR (400 MHz, CDCl ): d = 7.68 (d, J = 8.8 Hz, 4 H), 7.48–
3
–
1
1
036, 871, 772, 752, 729 cm .
7
1
.38 (m, 3 H), 7.00 (d, J = 8.8 Hz, 2 H), 2.12 (s, 4 H).
1
3
H NMR (400 MHz, CDCl ): d = 8.75–8.72 (m, 1 H), 8.65–8.63 (m,
3
C NMR (100 MHz, CDCl ): d = 195.6 (s), 159.3 (s), 138.2 (s),
3
1
7
H), 8.54–8.52 (m, 1 H), 7–82–7.79 (m, 1 H), 7.74–7.72 (m, 2 H),
.60–7.55 (m, 2 H), 7.20 (s, 1 H), 2.36 (s, 4 H).
1
(
31.9 (d), 131.7 (d), 131.5 (s), 129.7 (d), 128.1 (d), 120.6 (d), 27.8
t).
1
3
+
C NMR (100 MHz, CDCl ): d = 148.2 (s), 132.5 (s), 131.1 (s),
MS (EI, 70 eV): m/z (%) = 223 (86) [M ], 195 (52), 169 (52), 167
(
(
3
1
28.7 (s), 127.8 (s), 127.5 (d), 126.9 (d), 126.8 (d), 126.6 (d), 125.0
69), 154 (13), 146 (32), 141 (100), 127 (47), 115 (16), 105 (27), 91
12), 77 (56).
(
d), 123.4 (d), 123.0 (d), 122.5 (d), 113.5 (d), 28.4 (t).
+
MS (EI, 70 eV): m/z (%) = 219 (100) [M ], 204 (30), 191 (48), 177
Anal. Calcd for C H NO (223.27): C, 80.69; H, 5.87; N, 6.27.
Found: C, 80.43; H, 5.85; N, 6.23.
1
5
13
(25), 176 (26), 165 (10), 108 (7).
HRMS (EI): m/z calcd for C H N: 219.1048; found: 219.1043.
1
6
13
4
-Aziridin-1-ylbenzonitrile (2b)
Yield: 86%; colorless crystals; mp 91–92 °C (CHCl –pentane);
Rf = 0.2 (alumina III/N, PE–EtOAc, 4:1).
4-Aziridin-1-yl[2.2]paracyclophane (2f)
Yield: 17%; colorless solid; mp 136–137 °C (CHCl –pentane).
3
3
IR (KBr): 3063, 2964, 2219, 1602, 1560, 1500, 1459, 1341, 1262,
IR (KBr): 2925, 2851, 1590, 1560, 1489, 1307, 1262, 1033, 889,
797 cm .
–
1
–1
1
159, 1109, 906, 846, 804m, 558 cm .
1
1
H NMR (400 MHz, CDCl ) d = 7.51 (d, J = 8.8 Hz, 2 H), 7.04 (d,
H NMR (400 MHz, CDCl ): d = 7.10 (dd, J = 7.8, 1.7 Hz, 1 H),
3
3
J = 8.8 Hz, 2 H), 2.19 (s, 4 H).
1
6.55 (dd, J = 7.8, 1.7 Hz, 1 H), 6.45–6.42 (m, 2 H), 6.31 (d, J = 7.6
Hz, 1 H), 6.25 (dd, J = 7.6, 1.6 Hz, 1 H), 5.79 (d, J = 1.4 Hz, 1 H),
3
2
3
C NMR (100 MHz, CDCl ) d = 159.2 (s), 133.2 (d), 121.6 (d),
3
.48–3.41 (m, 1 H), 3.22–3.15 (m, 1 H), 3.09–3.00 (m, 4 H), 2.91–
.86 (m, 1 H), 2.74–2.67 (m, 1 H), 2.06 (s, 2 H), 1.90 (s, 2 H).
1
19.3 (s), 105.2 (s), 27.9 (t).
+
MS (EI, 70 eV): m/z (%) = 144 (22) [M ], 129 (6), 117 (9), 116
(
1
3
C NMR (100 MHz, CDCl ): d = 153.8 (s), 141.1 (s), 139.7 (s),
100), 102 (23), 89 (14), 75 (11).
3
1
(
38.8 (s), 134.6 (d), 133.1 (d), 132.5 (s), 132.3 (d), 131.8 (d), 129.1
Anal. Calcd for C H N (144.17): C, 74.98; H, 5.59; N, 19.43.
Found: C, 74.98; H, 5.51; N, 19.40.
9
8
2
d), 126.6 (d), 126.2 (d), 35.4 (t), 35.0 (t), 33.8 (t), 32.7 (t), 27.4 (t).
+
MS (EI, 70 eV): m/z (%) = 249 (49) [M ], 145 (100), 144 (23), 130
(
10), 117 (6), 104 (20).
5
-Aziridin-1-yl-1-(p-toluenesulfonyl)-1H-indole (2c)
Yield: 89%; colorless solid; mp 129–130 °C (CHCl –pentane);
Rf = 0.2 (alumina III/N, PE–EtOAc, 3:2).
HRMS (EI): m/z calcd for C H N: 249.1517; found: 249.1516.
3
18 19
N-Arylaziridines 4a–f; General Procedure
Into a Schlenk tube with a screw cap under argon were introduced
IR (KBr): 3065, 2927, 2851, 1615, 1590, 1560, 1455, 1367, 1260,
–
1
1
091, 1035, 888 cm .
an aryl dihalide 3a–g (0.5 mmol), Cs CO (489 mg, 1.5 mmol),
2
3
Synthesis 2007, No. 2, 243–250 © Thieme Stuttgart · New York

2
48
B. Witulski et al.
PAPER
Pd(OAc) (7 mg, 0.03 mmol, 6 mol%), and Xantphos (23 mg, 8
Anal. Calcd for C H N : C, 74.97; H, 7.55; N, 17.48. Found: C,
2
10 12
2
mol%). The Schlenk tube was evacuated and flushed with argon.
Then anhyd toluene (10 mL) and aziridine (86 mg, 0.1 mL, 2.0
mmol) were added by syringe through a septum. The Schlenk tube
was sealed with a screw cap and the mixture was stirred at 100 °C
for the time period given in Table 2. The mixture was filtered
through a plug of Celite 545 which was washed several times with
CH Cl . The solvent was evaporated and the resulting crude product
74.82; H, 7.37; N, 17.42.
2,6-Bis(aziridin-1-yl)naphthalene (4e)
Yield: 78%; colorless solid; mp 180–181 °C; R = 0.1 (alumina III/
N, PE–EtOAc, 4:1).
f
IR (KBr): 3051, 2925, 2855, 1600, 1500, 1384, 1293, 1184, 1141,
2
2
–1
1
111, 944, 875, 814, 791, 528 cm .
was purified by column chromatography (alumina III/N, PE–
EtOAc).
1
H NMR (400 MHz, CDCl ): d = 7.59 (d, J = 8.5 Hz, 2 H), 7.25–
3
7
.23 (m, 4 H), 2.16 (s, 8 H).
4
,4¢-Bis(aziridin-1-yl)benzophenone (4a)
13
C NMR (100 MHz, CDCl ): d = 151.4 (s), 130.5 (s), 127.6 (d),
3
Yield: 98%; colorless solid; mp 163–164 °C (CHCl –pentane);
Rf = 0.3 (alumina III/N, PE–EtOAc, 1:4).
3
122.8 (d), 116.2 (d), 27.8 (t).
+
MS (EI, 70 eV): m/z (%) = 210 (100) [M ], 195 (13), 182 (51), 168
IR (KBr): 3055, 2994, 1642, 1602, 1505, 1414, 1312, 1280, 1161,
1
(45), 167 (17), 149 (22), 154 (18), 140 (14).
–
1
113, 929, 903, 858, 770, 685, 565 cm .
HRMS (EI): m/z calcd for C H N : 210.1157; found: 210.1159.
1
4
14
2
1
H NMR (400 MHz, CDCl ): d = 7.70 (d, J = 8.5 Hz, 4 H), 7.06 (d,
3
J = 8.4 Hz, 4 H), 2.19 (s, 8 H).
2
,6-Bis(aziridin-1-yl)pyridine (4f)
1
3
Yield: 94%; yellow solid; mp 106–107 °C; R = 0.1 (alumina III/N,
C NMR (100 MHz, CDCl ): d = 194.6 (s), 158.9 (s), 132.1 (d),
f
3
EtOAc).
1
31.3 (s), 120.5 (d), 27.7 (t).
+
IR (KBr): 3068, 2994, 1566, 1439, 1313, 1190, 1167, 1144, 1087,
MS (EI, 70 eV): m/z (%) = 264 (100) [M ], 236 (23), 209 (11), 208
(
(
–
1
1
030, 988, 904, 818, 779, 747 cm .
64), 166 (7), 165 (10), 146 (47), 118 (33), 117 (23), 104 (22), 91
25), 90 (24), 77 (11), 76 (13).
1
H NMR (400 MHz, CDCl ): d = 7.43 (t, J = 7.8 Hz, 1 H), 6.58 (d,
3
J = 7.8 Hz, 2 H), 2.25 (s, 8 H).
HRMS (EI): m/z calcd for C H N O: 264.1263; found: 264.1267.
1
7
16
2
1
3
C NMR (100 MHz, CDCl ): d = 164.8 (s), 139.1 (d), 110.0 (d),
3
Methyl 3,5-Bis(aziridin-1-yl)benzoate (4b)
Yield: 82%; yellow solid; mp 109–110 °C (CHCl –pentane);
Rf = 0.4 (alumina III/N, PE–EtOAc, 4:1).
2
7.4 (t).
3
+
MS (EI, 70 eV): m/z (%) = 161 (100) [M ], 146 (7), 134 (7), 133
(
(
16), 119 (6), 119 (7), 107 (6), 106 (14), 93 (8), 91 (14), 79 (7), 78
6).
IR (KBr): 3061, 2992, 1718, 1593, 1436, 1367, 1253, 1195, 1121,
–1
1
002, 883, 774 cm .
Anal. Calcd for C H N : C, 67.06; H, 6.88; N, 26.07. Found: C,
9
11
3
1
H NMR (400 MHz, CDCl ): d = 7.27 (s, 2 H), 6.87 (s, 1 H), 3.87
3
66.83; H, 6.93; N, 25.96.
(
s, 3 H), 2.11 (s, 8 H).
1
3
N-Arylazetidines 5a–e; General Procedure
Into a Schlenk tube with a screw cap under argon were introduced
an aryl bromide 1a,b,d,g, or h (1.0 mmol), t-BuONa (144 mg, 1.50
C NMR (100 MHz, CDCl ): d = 166.8 (s), 155.9 (s), 131.4 (s),
3
1
18.2 (d), 116.2 (d), 52.1 (q), 27.8 (t).
+
MS (EI, 70 eV): m/z (%) = 218 (100) [M ], 190 (18), 187 (13), 163
40), 160 (15), 159 (12), 131 (24), 130 (16).
mmol), Pd(OAc) (8 mg, 3 mol%), and Xantphos (24 mg, 4 mol%).
2
(
The Schlenk tube was evacuated and flushed with argon. Then an-
hyd toluene (10 mL) and azetidine (114 mg, 2.0 mmol) were added
by syringe through a septum. The Schlenk tube was sealed with a
screw cap and the mixture was stirred at 100 °C for the time period
given in Table 3. The mixture was filtered through a plug of Celite
545 which was washed several times with CH Cl . The solvent was
Anal. Calcd for C H N O : C, 66.04; H, 6.47; N, 12.84. Found: C,
6
1
2
14
2
2
6.05; H, 6.53; N, 12.69.
1
,3-Bis(aziridin-1-yl)benzene (4c)
Yield: 87%; colorless solid; mp 41–42 °C; R = 0.2 (alumina III/N,
f
2
2
PE–EtOAc, 3:2).
evaporated and the resulting crude product was purified by column
chromatography (alumina III/N, PE–EtOAc); this gave N-arylaze-
tidines 5a–e.
IR (KBr): 3063, 2959, 1596, 1482, 1441, 1340, 1299, 1152, 968,
–1
8
60, 746 cm .
1
H NMR (400 MHz, CDCl ): d = 7.02 (t, J = 7.7 Hz, 1 H), 6.63 (t,
3
4-Azetidin-1-ylbenzophenone (5a)
Yield: 95%; colorless crystals; mp 118–119 °C (CHCl –pentane);
Rf = 0.7 (alumina III/N, PE–EtOAc, 4:1).
J = 2.2 Hz, 1 H), 6.56 (dd, J = 7.7, 2.1 Hz, 2 H), 2.02 (s, 8 H).
1
3
3
C NMR (100 MHz, CDCl ): d = 155.8 (s), 129.3 (d), 115.2 (d),
3
1
13.8 (d), 27.6 (t).
IR (KBr): 3082, 3051, 2992, 2896, 1644, 1598, 1504, 1473, 1446,
1418, 1338, 1312, 1318, 1283, 1168, 1148, 938, 904 cm .
–
1
+
MS (EI, 70 eV): m/z (%) = 160 (100) [M ], 132 (29), 117 (21), 105
(
42), 91 (27), 77 (35).
1
H NMR (400 MHz, CDCl ): d = 7.79 (d, J = 8.6 Hz, 2 H), 7.73 (d,
3
J = 7.3 Hz, 2 H), 7.54 (t, J = 7.4 Hz, 1 H), 7.47 (dd, J = 7.5, 7.3 Hz,
HRMS (EI): m/z calcd for C H N : 160.1000; found: 160.1004.
1
0
12
2
2
H), 6.40 (d, J = 8.6 Hz, 2 H), 4.04 (t, J = 7.4 Hz, 4 H), 2.46 (quin,
J = 7.4 Hz, 2 H).
1
,4-Bis(aziridin-1-yl)benzene (4d)
Yield: 93%; colorless solid; mp 93–94 °C; R = 0.2 (alumina III/N,
PE–EtOAc, 4:1).
13
f
C NMR (100 MHz, CDCl ): d = 195.3 (s), 154.3 (s), 139.3 (s),
3
1
32.6 (d), 131.1 (s), 129.5 (d), 128.0 (d), 125.5 (s), 109.4 (d), 51.6
1
(t), 16.6 (t).
MS (EI, 70 eV): m/z (%) = 237 (28) [M ], 209 (12), 181 (6), 152 (4),
32 (43), 77 (32), 28 (100).
H NMR (400 MHz, CDCl ): d = 6.87 (s, 4 H); 2.09 (s, 8 H).
3
+
1
3
C NMR (100 MHz, CDCl ): d = 149.8 (s), 221.2 (d), 27.60 (t).
3
1
+
MS (EI, 70 eV): m/z (%) = 160 (100) [M ], 132 (78), 118 (39), 104
(
32), 91 (48), 77 (30).
Synthesis 2007, No. 2, 243–250 © Thieme Stuttgart · New York

PAPER
-Azetidin-1-ylbenzonitrile (5b)
Palladium-Catalyzed N-Arylation Reactions with Aziridine and Azetidine
249
4
Anal. Calcd for C H N : C, 83.69; H, 5.46, N, 10.84. Found: C,
1
8
14
2
Yield: 86%; colorless solid; mp 108–109 °C (CHCl –pentane);
83.54; H, 5.48; N, 10.86.
3
Rf = 0.8 (alumina III/N, PE–EtOAc, 4:1).
1
,2-Bis(azetidin-1-yl)benzene (5f)
Into a Schlenk tube with a screw cap under argon were introduced
,2-dibromobenzene (1i; 118 mg, 0.50 mmol), t-BuONa (125 mg,
1.30 mmol), Pd(OAc) (7 mg, 0.03 mmol), and Xantphos (23 mg,
IR (KBr): 3068, 2928, 2856, 2215, 1609, 1521, 1480, 1168, 827
cm .
–
1
1
1
H NMR (400 MHz, CDCl ): d = 7.41 (d, J = 8.8 Hz, 2 H), 6.32 (d,
3
2
J = 8.8 Hz, 2 H), 3.96 (t, J = 7.3 Hz, 4 H), 2.42 (quin, J = 7.3 Hz, 2
0
.04 mmol). The Schlenk tube was evacuated and flushed with ar-
H).
gon. Then anhyd toluene (10 mL) and azetidine (114 mg, 0.13 mL,
2 mmol) were introduced by syringe through a septum. The Schlenk
tube was sealed with a screw cap and the mixture was stirred 10 h
at 100 °C. The mixture was filtered through a plug of Celite 545
which was washed several times with CH Cl . The solvent was
1
3
C NMR (100 MHz, CDCl ): d = 153.3 (s), 133.3 (d), 120.7 (s),
3
1
10.3 (s), 98.0 (s), 51.5 (t), 16.5 (t).
+
MS (EI, 70 eV): m/z (%) = 158 (44) [M ], 131 (8), 130 (100), 129
(
2
2
54), 57 (26), 42 (61).
evaporated and the crude product was purified by column chroma-
tography (alumina III/N, PE–CH Cl , 1:1).
+
HRMS (ESI): m/z calcd for C H N [M + Na] : 181.0747; found:
1
0
10
2
2
2
1
81.0747.
Yield: 84 mg (89%); colorless solid; mp 50–51 °C.
1
H NMR (400 MHz, CDCl ): d = 6.85 (m, 2 H), 6.61 (m, 2 H), 3.73
2
-Azetidin-1-ylnaphthalene (5c)
3
(
13
t, J = 7.2 Hz, 4 H), 2.21 (quin, J = 7.2 Hz, 2 H).
Yield: 85%; colorless solid; mp 58–60 °C; R = 0.2 (alumina III/N,
PE–EtOAc, 9:1).
f
C NMR (100 MHz, CDCl ): d = 143.0 (s), 120.2 (d), 113.9 (d),
3
5
3.3 (d), 17.8 (d).
IR (KBr): 3050, 2960, 2840, 1600, 1472, 1389, 1361, 1324, 1189,
1
–1
088, 960 cm .
+
MS (EI, 70 eV): m/z (%) = 188 (34) [M ], 131 (38), 104 (100), 91
(64).
1
H NMR (400 MHz, CDCl ): d = 7.72–7.63 (m, 3 H), 7.38 (m, 1 H),
3
7
.22 (m, 1 H), 6.82 (dd, J = 8.8, 2.4 Hz, 1 H), 6.69 (d, J = 2.2 Hz, 1
Anal. Calcd for C H N : C, 76.55; H, 8.57; N, 14.88. Found: C,
7
1
2
16
2
H), 3.99 (t, J = 7.2 Hz, 4 H), 2.41 (quin, J = 7.3 Hz, 2 H).
6.63; H, 8.56; N, 14.86.
1
3
C NMR (100 MHz, CDCl ): d = 150.4 (s), 135.1 (s), 131.1 (d),
3
1
29.2 (d), 128.2 (s), 126.7 (d), 126.3 (d), 122.4 (d), 114.9 (d), 105.3
Acknowledgement
(
d), 52.9 (t), 17.4 (t).
MS (EI, 70 eV): m/z (%) = 183 (79) [M ], 155 (100), 127 (31), 126
12), 77 (12).
Anal. Calcd for C H N: C, 85.21; H, 7.15. Found: C, 85.13; H,
+
Financial support of this work by the Fonds der Chemischen Indu-
strie and the Dr. Otto-Röhm-Gedächtnisstiftung is gratefully ack-
nowledged.
(
1
3
13
7
.27.
References
1
-Azetidin-1-ylnaphthalene (5d)
Yield: 95%; colorless oil; R = 0.2 (alumina III/N, PE–EtOAc, 9:1).
(1) For reviews, see: (a) Jiang, L.; Buchwald, S. L. In Metal-
f
nd
Catalyzed Cross-Coupling Reactions – 2 Completely
IR (KBr): 3048, 2960, 2853, 1574, 1460, 1407, 1303, 1123, 768
Revised and Enlarged Edition; de Meijere, A.; Diederich, F.,
Eds.; Wiley-VCH: Weinheim, 2004, 699–760. (b) Muci, A.
R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131.
(c) Hartwig, J. F. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E.; de Meijere,
A., Eds.; Wiley-Interscience: New York, 2002, 1051–1096.
–
1
cm .
1
H NMR (400 MHz, CDCl ): d = 7.99 (d, J = 8.3 Hz, 1 H), 7.81 (d,
3
J = 8.1 Hz, 1 H), 7.47–7.35 (m, 4 H), 6.57 (dd, J = 6.3, 2.0 Hz, 1 H),
4
.18 (t, J = 7.4 Hz, 4 H), 2.42 (quin, J = 7.3 Hz, 2 H).
1
3
C NMR (100 MHz, CDCl ): d = 148.9 (s), 134.9 (s), 129.9 (s),
3
(
d) Hartwig, J. F. In Modern Arene Chemistry; Astruc, D.,
1
28.4 (d), 125.9 (d), 125.6 (d), 124.1 (d), 123.7 (d), 119.5 (d), 107.9
Ed.; Wiley-VCH: Weinheim, 2002, 107–168. (e) Hartwig,
J. F. In Modern Amination Methods; Ricci, A., Ed.; Wiley-
VCH: Weinheim, 2000, 195–262. (f) Hartwig, J. F. Angew.
Chem. Int. Ed. 1998, 37, 2046; Angew. Chem. 1998, 110,
2154. (g) Wolfe, J. P.; Wagaw, S.; Marcoux, J. F.;
Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805.
(
d), 55.3 (t), 17.5 (t).
MS (EI, 70 eV): m/z (%) = 183 (100) [M ], 155 (82), 127 (53), 77
12), 44 (17).
Anal. Calcd for C H N: C, 85.21; H, 7.15; N, 7.64. Found: C,
+
(
1
3
13
8
4.79; H, 7.13; N, 7.76.
(
2) (a) Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz, U.
Adv. Synth. Catal. 2006, 348, 23. (b) Schlummer, B.;
Scholz, U. Adv. Synth. Catal. 2004, 346, 1599.
1
0-Azetidin-1-ylanthracene-9-carbonitrile (5e)
Yield: 95%; red solid; mp 217–218 °C (CHCl –pentane); R = 0.2
3
f
(
alumina III/N, PE–CH Cl = 1:1).
(3) (a) Witulski, B.; Weber, M.; Bergsträßer, U.; Desvergne, J.-
P.; Bassani, D. M.; Bouas-Laurent, H. Org. Lett. 2001, 3,
1467. (b) Witulski, B.; Zimmermann, Y.; Darcos, V.;
Desvergne, J.-P.; Bassani, D. M.; Bouas-Laurent, H.
Tetrahedron Lett. 1998, 39, 4807.
2
2
IR (KBr): 3059, 2975, 2945, 2868, 2179, 1611, 1556, 1492, 1464,
1
–
1
442, 1298, 1174, 1193, 1032, 900 cm .
1
H NMR (400 MHz, CDCl ): d = 8.24 (d, J = 8.4 Hz, 2 H), 7.89 (d,
3
J = 8.5 Hz, 2 H), 7.54 (ddd, J = 8.4, 6.7, 1.1 Hz, 2 H), 7.20 (ddd,
J = 8.4, 6.7, 1.1 Hz, 2 H), 4.76 (t, J = 7.8 Hz, 4 H), 2.46 (m, 2 H).
(
4) (a) Witulski, B.; Azcon, J. R.; Alayrac, C.; Arnautu, A.;
Collot, V.; Rault, S. Synthesis 2005, 771. (b) Arnautu, A.;
Collot, V.; Calvo Ros, J.; Alayrac, C.; Witulski, B.; Rault, S.
Tetrahedron Lett. 2002, 43, 2695. (c) Witulski, B.; Senft,
S.; Thum, A. Synlett 1998, 504.
1
3
C NMR (100 MHz, CDCl ): d = 153.7 (s), 135.5 (s), 128.4 (d),
3
1
1
25.1 (d), 124.7 (d), 121.1 (d), 119.8 (s), 116.0 (s), 90.1 (s), 61.9 (t),
7.9 (t).
(
5) (a) Searles, S.; Tamres, M.; Block, F.; Quarterman, L. A. J.
Am. Chem. Soc. 1956, 78, 4917. (b) Barb, W. G. J. Chem.
Soc. 1955, 2564. (c) Kallies, B.; Mitzner, R. J. Phys. Chem.
B 1997, 101, 2959.
+
MS (EI, 70 eV): m/z (%) = 258 (100) [M ], 229 (70), 203 (21), 175
(
6), 151 (10).
Synthesis 2007, No. 2, 243–250 © Thieme Stuttgart · New York

2
50
B. Witulski et al.
PAPER
(
6) For reviews on the chemistry of aziridines, see: (a) Watson,
(11) (a) Witulski, B. Synlett 1999, 1223. (b) Subat, M.; König,
B. Synthesis 2001, 1818.
I. D. G.; Yu, L.; Yudin, A. K. Acc. Chem. Res. 2006, 39,
1
94. (b) Hu, E. X. Tetrahedron 2004, 60, 2701.
(12) No efforts were undertaken to optimize the reaction
regarding the amount of aziridine, because of its high
volatility (bp 57 °C/780 Torr).
(13) For other examples on the use of 4-bromo[2.2]paracyclo-
phane in the Buchwald–Hartwig amination reaction, see:
(a) Rossen, K.; Pye, P. J.; Maliakal, A.; Volante, R. P. J.
Org. Chem. 1977, 62, 6462. (b) Löber, S.; Ortner, B.;
Bettinetti, L.; Hübner, H.; Gmeiner, P. Tetrahedron:
Asymmetry 2002, 13, 2303. (c) Kreis, M.; Friedmann, C. J.;
Bräse, S. Chem. Eur. J. 2005, 11, 7387.
(14) For recent contributions on the mechanism of the
Buchwald–Hartwig amination reaction, see: (a) Shekar, S.;
Ryberg, P.; Hartwig, J. F. Org. Lett. 2006, 8, 851.
(b) Shekhar, S.; Ryberg, P.; Hartwig, J. F.; Mathew, J. S.;
Blackmond, D. G.; Strieter, E. R.; Buchwald, S. L. J. Am.
Chem. Soc. 2006, 128, 3584.
(15) (a) Pomonis, J. G.; North, D. T.; Zaylskie, R. G. J. Med.
Chem. 1970, 13, 989. (b) Wolfenbarger, D. A.; Cantu, E.;
Robinson, S. H.; Anwar, M.; Woods, C. W.; Pomonis, J. G.
Fla. Entomol. 1975, 58, 207. (c) Wolfenbarger, D. A.;
Cantu, E.; Guerra, A. A.; Pomonis, J. G.; Robinson, S. H.;
Garcia, R. D. Fla. Entomol. 1974, 57, 287.
(
(
(
(
c) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247.
d) McCoull, W.; Davies, F. A. Synthesis 2000, 1347.
e) Tanner, D. Angew. Chem. Int. Ed. Engl. 1994, 33, 599.
f) Ibuka, T. Chem. Soc. Rev. 1998, 27, 145. (g) Dermer, O.
C.; Ham, G. E. Ethylenimine and other Aziridines –
Chemistry and Application; Academic Press: New York,
1
963.
7) Sasaki, M.; Dalili, S.; Yudin, A. K. J. Org. Chem. 2003, 68,
045.
8) Louie, J.; Paul, F.; Hartwig, J. F. Organometallics 1996, 15,
794.
9) (a) Murugan, E.; Siva, A. Synthesis 2005, 2022.
b) Krumper, J. R.; Gerisch, M.; Suh, J. M.; Bergman, R. G.;
(
(
(
2
2
(
Tilley, T. D. J. Org. Chem. 2003, 68, 9705. (c) Aggarwal,
V. K.; Stenson, R. A.; Jones, R. V. H.; Fieldhouse, R.;
Blacker, J. Tetrahedron Lett. 2002, 42, 1587. (d) Aires-de-
Sousa, J.; Prabhakar, S.; Lobo, A. M.; Rosa, A. M.; Gomes,
M. J. S.; Corvo, M. C.; Williams, D. J.; White, A. J. P.
Tetrahedron: Asymmetry 2001, 12, 3349. (e) Sriraghavan,
K.; Ramakrishnan, V. T. Synth. Commun. 2001, 31, 1105.
(
f) Casarrubios, L.; Pérez, J. A.; Brookhart, M.; Templeton,
J. L. J. Org. Chem. 1996, 61, 8358. (g) Pereira, M. M.;
Santos, P. P. O.; Reis, L. V.; Lobo, A. M.; Prabhakar, S.
Chem. Commun. 1993, 38. (h) Brown, H. C.; Midland, M.
M.; Levy, A. B.; Suzuki, A.; Sono, S.; Itoh, M. Tetrahedron
(16) For examples of ring-opening reactions with azetidines, see:
(a) Couty, F.; David, O.; Durrat, F.; Evano, G.; Lakhdar, S.;
Marrot, J.; Vargas-Sanchez, M. Eur. J. Org. Chem. 2006,
3479. (b) Ghorai, M. K.; Das, K.; Kumar, A.; Das, A.
Tetrahedron Lett. 2006, 47, 5393. (c) Cospito, G.;
Illuminati, G.; Lilloci, C.; Petride, H. J. Org. Chem. 1981,
46, 2944. (d) Van der Plas, H. C. Ring Transformations of
Heterocycles, Vol. 1; Academic Press: London, 1973.
(17) For a single example of a palladium-mediated C–N bond
formation with (N-azetidino)trimethyltin, see: Koza, D. J.;
Nsiah, Y. A. J. Org. Chem. 2002, 67, 5025.
1
987, 43, 4079. (i) Rudesill, J.; Severson, R. F.; Pomonis, J.
G. J. Org. Chem. 1971, 36, 3071. (j) Heine, H. W.; Kapur,
B. L.; Bove, J. L.; Greiner, R. W.; Klinger, K. H.; Mitch, C.
J. Am. Chem. Soc. 1954, 76, 2503. (k) Heine, H. W.; Kapur,
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