The first example of catalytic aziridination mediated by arsonium ylides: Preparation of trans-pentafluorophenyl-containing aziridines

Article abstract of DOI:10.1055/s-2005-868498

Triphenylarsine catalyzes the formation of aziridines from tosyl imines and aromatic diazo compounds in a one-pot reaction. It is the first example of catalytic aziridination mediated by arsonium ylides. It gave aziridines in excellent diastereoselectivity with pentafluorophenyl diazomethane as the substrate. This catalytic reaction is complementary with the reaction mediated by sulfur ylides. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-868498

LETTER
1429
The First Example of Catalytic Aziridination Mediated by Arsonium Ylides:
Preparation of trans-Pentafluorophenyl-Containing Aziridines
Catalytic
Azirh
if
a
ium
Y
lide
s
Zhu,a Yuanxi Liao,a Shizheng Zhu*a,b
a
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 20032, P. R. China
b
College of Chemical Environmental, South China Normal University, Guangzhou, 510631, P. R. China
Fax +86(21)64166128; E-mail: zhusz@mail.sioc.ac.cn
Received 25 February 2005
more than 95% yield and 97% purity. The crude products
aryl diazomethanes 1 could be used without further puri-
fication after general work-up. This procedure reduces the
potential hazard significantly by avoiding heating the
Abstract: Triphenylarsine catalyzes the formation of aziridines
from tosyl imines and aromatic diazo compounds in a one-pot reac-
tion. It is the first example of catalytic aziridination mediated by
arsonium ylides. It gave aziridines in excellent diastereoselectivity
with pentafluorophenyl diazomethane as the substrate. This catalyt- tosyl salt in vacuo.
ic reaction is complementary with the reaction mediated by sulfur
ylides.
The introduction of fluorine into organic molecules may
profoundly influence their physical and biological proper-
ties. Recently, there has been growing interest in fluorine-
containing aromatic compounds due to the unique physi-
cal properties of the fluorine atom. Herein, we report our
attempts to prepare fluorine-containing aziridines catalyt-
ically from diazo compounds, mediated by arsonium
ylides.
Key words: diazocompound, ylide, fluorine, aziridine, catalyze
Aziridines are synthetic intermediates that can be convert-
ed into important nitrogen containing functional groups.1
Although several efficient synthesis of aziridines from
olefins or imines have been reported, most methods are
non-catalytic and result in low diastereoselectivities.2 Ag-
garwal reported a novel catalytic and asymmetric process
for aziridination mediated by sulfur ylides, however, the
diastereoselectivities are low.3 Moreover, the relative low
reactivity of sulfur ylides limits the scope of their further
applications. For example, sulfur ylides substituted with
electron-withdrawing groups cannot react with imines to
give the aziridines (see the details in this paper). Arsoni-
um ylides have high reactivity with carbonyl compounds
or electron-deficient alkenes and produce alkenes, ep-
oxides, and cylcopropanes in high diastereoselectivity.4
However, in the field of catalytic aziridination mediated
by arsonium ylides, to the best of our knowledge, no
examples have been reported.
As we all know, sulfur ylides are well known for their
abilities to react with aldehydes, electron-poor alkenes,
and imines to form epoxides, cyclopropanes, and aziri-
dines, respectively. Initially, to make sure that the sulfur
ylide generated from pentafluorophenyl diazomethane
(1a) could react with tosyl imines to give the corres-
ponding aziridines, we used Rh2(OAc)4 to catalyze the
decomposition of diazo compound 1a, and tetra-
hydrothiophene to trap the metal carbenenoid. To our dis-
appointment, no aziridine was isolated after several
attempts (Equation 1). The imine was recycled in almost
quantitative yield. The strong electron-withdrawing
properties of fluorine atoms on the phenyl rings may be
attributed to the failure of this transformation.
Previously, we reported a catalytic procedure for the di-
rect coupling of aldehydes with pentafluorophenyl ben-
zaldehyde tosylhydrazone salts to give the trans-alkenes
exclusively.5 The reaction temperature (ca. 40 °C) and
low yields (ca. 50%) severely limit its further applica-
tions. The inefficient decomposition of the sodium salt of
pentafluorobenzaldehyde tosylhydrazone may account
for the low yields. Therefore, development of an efficient
method to generate the potentially hazardous diazo
compound is necessary. Reese et al. reported that 2,4,6-
triisopropylbenzenesulfonyl hydrazones are better inter-
mediates than tosyl hydrazones in the preparation of aryl-
diazoalkanes.6 Aryl diazomethane 1a (Ar = C6F5 ) and 1b
(Ar = Ph), by using Reese’s method, can be synthesized in
Ts
Rh2(OAc)4,
N
R2S
ArCHN2
Ar'CH=NTs
+
Ar
Ar'
1
2
Equation 1
To resolve this problem, ylides with higher activity should
be used. We know that tellurium ylides have similar
chemical properties to sulfur ylides because they are situ-
ated in the same main group in the periodic table. More-
over, telluronium ylides are more reactive than the
corresponding sulfur ylides. We assumed that the
telluronium ylides generated in situ from the reaction of
telluride and pentafluorophenyl diazomethane could react
with tosyl imines to give aziridines. The reaction was
carried out at room temperature by adding the diazo
compound 1a dissolved in THF dropwise to a solution of
SYNLETT 2005, No. 9, pp 1429–1432
0
1.
0
6.
2
0
0
5
Advanced online publication: 27.04.2005
DOI: 10.1055/s-2005-868498; Art ID: U05105ST
© Georg Thieme Verlag Stuttgart · New York

1430
S. Zhu et al.
LETTER
tosyl imine, dibutyl telluride, and a catalytic amount of When a stoichiometric amount of triphenyl arsine was
Rh2(OAc)4 (1 mol%) in the same solvent. The reaction, used instead of dibutyl telluride under the same reaction
which was monitored by TLC, was complete in four conditions, the starting material tosyl imine derived from
hours. The aziridines were isolated in moderate yields and benzaldehyde disappeared completely after four hours.
diastereoselectivities after general work-up (Table 1, en- The aziridine 2a was obtained in almost quantitative yield
tries 1, 2). The tosyl imine of trans-cinnamaldehyde gave and with complete trans stereoselectivity, which was in
the aziridine 2c in lower yield and diastereoselectivity line with our prediction (Table 1, entry 4). Extension of
than the saturated imines (Table 1, entry 3). The unpleas- the substrates showed that the yields of the aziridines are
ant odor and ready oxidation by air of TeBu2 made this good to excellent for the imines of electron poor or neutral
procedure very inconvenient.
aromatic aldehydes (Table 1, entries 4–8), while moderate
yields for those imines derived from electron rich alde-
hydes (Table 1, entries 9, 10). In particular, the low solu-
bility of the tosyl imine derived from 4-nitrobenzaldehyde
in THF resulted in moderate yield of aziridine (Table 1,
entry 11). The reactions gave almost exclusive trans
diastereoselectivities for all tosyl imines of aromatic
aldehydes except trans-cinnamaldehyde. The trans
stereoselectivities of aziridines were further confirmed by
X-ray analysis (Figure 1).
Rh2(OAc)4
X = CHAr
Ar'CH = NTs
ArCHN2
Ts
N
N2
Rh = CHAr
X
Ar
Ar'
Ar
X = TeBu2, AsPh3
Ts
N
1 mol% Rh2(OAc)4AsPh3
or TeBu2
ArCHN2
Ar'CH = NTs
+
THF, r.t.
Ar'
trans:cis = >99:1
Scheme 1 Catalytic cycle for the preparations of aziridines.
Discouraged by the above results, we turned our attention
to the arsonium ylides. Arsonium ylides are known for
their high reactivity and high diastereoselectivity in alk-
ene, epoxide, and cyclopropane formation.4 They have
similar reactivity to the telluronium ylides, and in general
exhibit higher diastereoselectivities than the latter. More-
over, the stability of triphenyl arsine in air may facilitate
the experimental operations. Based on the above, we
believed that arsonium ylides would produce the aziri-
dines in higher yields and diastereoselectivities.
Figure 1
Table 1 Preparation of Aziridines from the Reaction of Tosyl Imines and Diazo Compound 1a
Entry
Ar¢CH=NTs (Ar¢ = )
Ph
TeBu2 or Ph3As (mol%)
TeBu2 (100)
TeBu2 (100)
TeBu2 (100)
Ph3As (100)
Ph3As (100)
Ph3As (100)
Ph3As (100)
Ph3As (100)
Ph3As (100)
Ph3As (100)
Ph3As (100)
Products
2a
Yield (%)a
trans/cisb
18:1
1
64
49
40
98
76
90
73
82
55
63
54
2
p-ClC6H4
2b
9:1
3
trans-PhCH=CH
Ph
2c
5:2
4
2a
>99:1
>99:1
25:2
5
p-ClC6H4
2b
6
trans-PhCH=CH
p-BrC6H4
2c
7
2d
>99:1
>99:1
>99:1
>99:1
>99:1
8
o-NO2C6H4
p-CH3C6H4
p-CH3OC6H4
p-NO2C6H4
2e
9
2f
10
2g
11
2h
a Isolated yield.
b Determined by 1H NMR.
Synlett 2005, No. 9, 1429–1432 © Thieme Stuttgart · New York

LETTER
Catalytic Aziridination Mediated by Arsonium Ylides
1431
When a substoichiometric amount of AsPh3 (20 mol%) dine will form without reversible reaction. This means
was used to catalyze the reaction, the aziridines were that the reaction gives mainly the thermodynamic stable
obtained in similar diastereoselectivity, but with a slightly isomers 2 diastereoselectively. As for the intermediates b
reduced yield (Table 2).
and b¢, due to the high activity of triphenyl arsin-phenyl-
methylene, the rate constant k5 is much greater than k–5 (k5
>> k–5), as a result a mixture of trans- and cis-aziridines
are formed.
Table 2 Preparation of the Aziridines from the Reaction of Tosyl
Imines and Diazo Compound 1a Using a Catalytic Amount of AsPh3
(20%)
Ts
N
Yield (%)a
2a (61)
2b (49)
2c (59)
2d (45)
2e (61)
2g (51)
trans/cisb
>99:1
>99:1
12:1
C6F5
Entry
Ar¢CH=NTs (Ar¢ = )
Ph
Ph3As
H
1
2
3
4
5
6
k3
k1
p-ClC6H4
N
C6F5
H
C6F5
Ar
trans-PhCH=CH
p-BrC6H4
AsPh3
k-1
Ts
Ar
2
a
H
H
>99:1
>99:1
>99:1
+
H
Ts
Ts
o-NO2C6H4
p-CH3OC6H4
Ph3As
k2
C6F5
N
N
k4
k–2
Ar
a Isolated yield.
b Determined by 1H NMR spectroscopy.
N
C6F5
Ar
H
Ts
Ar
2'
a'
C6H5
Encouraged by the above results, we then tried to extend
this method to the preparation of non-fluoroaziridines.
The corresponding non-fluoroaziridine 3a was prepared
in quantitative yield under the same reaction conditions by
using a stoichiometric amount of Ph3As and diazo com-
pound 1b (Table 3, entry 1), unfortunately with complete
loss of diastereoselectivity. Reducing the amount of
AsPh3 to a substoichiometric amount (20 mol%), it gave
the aziridines in excellent yields but again no diastereo-
selectivity resulted (Table 3, entries 2, 3).
Ph3As
H
N
H
Ts
N
C6H5
Ts
Ar
b
AsPh3
k5
k6
+
H
H
k–5
H
Ts
Ph3As
C6H5
C6H5
Ar
N
Table 3 Preparation of Aziridines from the Reaction of Tosyl
Imines and Diazo Compound (1b)
3
Ar
N
H
Entry
Ar¢CH=NTs Ph3As
Yield
(%)a
trans/cisb
Ts
Ar
(Ar¢ = )
(mol%)
100
20
b'
1
2
3
Ph
3a (100)
3a (97)
3b (83)
51:49
53:47
1:1
Scheme 2 Probable mechanisms of the reaction to prepare
aziridines.
Ph
p-ClC6H4
20
In summary, we have reported that arsonium ylides, gen-
erated in situ from the reaction of triphenyl arsine with ar-
omatic diazomethane catalyzed by Rh2(OAc)4, mediated
aziridination of the tosyl imine. It could give, selectively,
completely trans-perfluorophenyl-containing aziridines
starting from the tosyl imines of saturated aromatic alde-
hydes. Due to the high reactivity, the diastereoselectivity
disappeared completely when using phenyl diazomethane
as the substrate, although the yield is excellent. To the best
of our knowledge, it is the first report that arsonium ylide
mediated aziridination from imines. It is complementary
to the sulfur ylides which have lower reactivity for the
preparation of aziridines. This base-free, catalytic, dia-
stereoselective and mild reaction will be the method of
choice in many instances.
a Isolated yield.
b Determined by 1H NMR spectroscopy.
To account for the different diastereoselectivities between
these two types of arsonium ylides, possible reaction
mechanisms were proposed (Scheme 2). The reaction of
the arsonium ylides with the tosyl imines to form the azir-
idines should be stepwise, and the first step giving the in-
termediates should be reversible. Due to the strong
electronegativity of the fluorine atom, the negative charge
on the intermediate species can be efficiently stabilized by
the pentafluorophenyl. The thermodynamically unstable
intermediate a¢ would then convert back to the starting
materials ylide and imine. As for the thermodynamically
stable intermediate a, k1>>k–1, therefore the trans-aziri-
Synlett 2005, No. 9, 1429–1432 © Thieme Stuttgart · New York

1432
S. Zhu et al.
LETTER
(7) (a) Ramachandran, P. V. In Asymmetric Fluoroorganic
Acknowledgment
Chemistry: Synthesis Applications and Future Directions,
ACS Symposium Series 746; American Chemical Society:
Washington DC, 2000. (b) Ojima, I.; McCarthy, J. R.;
Welch, J. T. In Biomedical Frontiers of Fluorine Chemistry,
ACS Symposium Series 639; American Chemical Society:
Washington DC, 1996. (c) Kukhar’, V. P.; Soloshonok, V.
A. In Fluorine-containing Amino Acids: Synthesis and
Properties; Wiley: New York, 1995. (d) Welch, J. T. In
Selective Fluorination in Organic and Bioorganic
Chemistry, ACS Symposium Series 456; American Chemical
Society: Washington DC, 1991. (e) Welch, J. T.;
Eswarakrishnan, S. In Fluorine in Bioorganic Chemistry;
Wiley & Sons: New York, 1991.
The authors thank the National Natural Science Foundation of
China (NNSFC) (No. 20372077 and 20472106).
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Synlett 2005, No. 9, 1429–1432 © Thieme Stuttgart · New York