Aryl iodide mediated aziridination of alkenes

Article abstract of DOI:10.1021/ol052293c

(Chemical Equation Presented) Aryl iodide mediated aziridination of a variety of alkenes with N-aminophthalimide under mild conditions (m-CPBA, K ₂CO₃, CH₂Cl₂, 25°C) was achieved in moderate to good yields (up to 94%). By recovering the aryl iodide, a recyclable system is developed with product yield over 79% attained for the aziridination of trans-1,2-diphenylethylene.

Full text of DOI:10.1021/ol052293c

ORGANIC
LETTERS
2
005
Vol. 7, No. 26
801-5804
Aryl Iodide Mediated Aziridination of
Alkenes
5
†
‡
,†,‡
Jiayin Li, Philip Wai Hong Chan, and Chi-Ming Che*
Shanghai-Hong Kong Joint Laboratory on Chemical Synthesis, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai
200032, P. R. China, and Department of Chemistry and Open Laboratory of Chemical
Biology of the Institute of Molecular Technology for Drug DiscoVery and Synthesis,
The UniVersity of Hong Kong, Pokfulam Road, Hong Kong, P. R. China
cmche@hku.hk
Received September 22, 2005
ABSTRACT
2 3 2 2
Aryl iodide mediated aziridination of a variety of alkenes with N-aminophthalimide under mild conditions (m-CPBA, K CO , CH Cl , 25 °C) was
achieved in moderate to good yields (up to 94%). By recovering the aryl iodide, a recyclable system is developed with product yield over 79%
attained for the aziridination of trans-1,2-diphenylethylene.
3
Aryl-λ -iodane mediated organic transformations have at-
tracted a myriad of attention in recent years due to the useful
oxidative properties of hypervalent iodine(III) compounds
and the benign ecological character and commercial avail-
pounds such as PhIdNSO
PhI(OAc) have useful applications in transition metal
catalyzed C-N bond forming reactions. In this regard, we
2
R (usually R ) Ar), PhIdO, and
2
4
5
and Yudin et al. reported that a PhI(OAc)
2
mediated version
of the lead(IV) acetate catalyzed intermolecular aziridination
of alkenes using N-aminophthalimide (PthNH ) as a nitrogen
3
1
2
6
ability of aryl-λ -iodane precursors. Indeed, works by us
and others have shown that polyvalent iodine(III) com-
3
2
source could be accomplished in good to excellent yields.
Despite these advances, the challenge remains to develop
†
Shanghai Institute of Organic Chemistry.
The University of Hong Kong.
‡
(
1) (a) HyperValent Iodine Chemistry; Wirth, T., Ed.; Springer: Berlin,
003; Top. Curr. Chem. issue 224. (b) Zhdankin, V. V.; Stang, P. J. Chem.
ReV. 2002, 102, 2523.
2) (a) Zhang, J.; Chan, P. W. H.; Che, C.-M. Tetrahedron Lett. 2005,
6, 5403. (b) He, L.; Chan, P. W. H.; Tsui, W.-M.; Yu, W.-Y.; Che, C.-M.
2
Lett. 2005, 7, 2787. (e) Fruit, C.; M u¨ ller, P. HelV. Chim. Acta 2004, 87,
1607. (f) Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois, J. J. Am. Chem.
Soc. 2004, 126, 15378. (g) Levites-Agababa, E.; Menhaji, E.; Perlson, L.
N.; Rojas, C. M. Org. Lett. 2002, 4, 863. (h) Padwa, A.; Stengel, T. Org.
Lett. 2002, 4, 2137. (i) Guthikonda, K.; Du Bois J. J. Am. Chem. Soc. 2002,
124, 13672. (j) Espino, C. G.; Wehn, P. M.; Chow, J.; Du Bois, J. J. Am.
Chem. Soc. 2001, 123, 6935. (k) Dauban, P.; Sani e` re, L.; Tarrade, A.; Dodd,
R. H. J. Am. Chem. Soc. 2001, 123, 7707. (l) M u¨ ller, P.; Baud, C.; Jacquier,
Y. Can. J. Chem. 1998, 76, 738. (m) Evans, D. A.; Faul, M. M.; Bilodeau,
M. T. J. Am. Chem. Soc. 1994, 116, 2742. (n) Li, Z.; Conser, K. R.;
Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326. (o) Mahy, J. P.; Bedi,
G.; Battioni, P.; Mansuy, D. Tetrahedron Lett. 1988, 29, 1927. (p) Breslow,
R.; Gellman, S. H. Chem. Commun. 1982, 1400.
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2004, 45, 2685.
(5) Krasnova, L. B.; Hili, R. M.; Chernoloz, O. V.; Yudin A. K.
ARKIVOC 2005, 4, 26.
(6) (a) Yang, K.-S.; Chen, K. Org. Lett. 2002, 4, 1107. (b) Atkinson, R.
S. Tetrahedron 1999, 55, 1519. (c) Kapron, J. T.; Santarsiero, B. D.;
Vederas, J. C. Chem. Commun. 1993, 1074. (d) Atkinson, R. S.; Jones, D.
W.; Kelly, B. J. J. Chem. Soc., Perkin Trans. 1 1991, 1344.
(
4
Org. Lett. 2004, 6, 2405. (c) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Che,
C.-M. J. Org. Chem. 2004, 69, 3610. (d) Liang, J.-L.; Yuan, S.-X.; Chan,
P. W. H.; Che, C.-M. Tetrahedron Lett. 2003, 44, 5917. (e) Liang, J.-L.;
Huang, J.-S.; Yu, X.-Q.; Zhu, N.; Che, C.-M. Chem. Eur. J. 2002, 8, 1563.
f) Liang, J.-L.; Yu, X.-Q.; Che, C.-M. Chem. Commun. 2002, 124. (g)
Zhang, J.-L.; Che, C.-M. Org. Lett. 2002, 4, 1911. (h) Liang, J.-L.; Yuan,
S.-X.; Huang, J.-S.; Yu, W.-Y.; Che, C.-M. Angew. Chem., Int. Ed. 2002,
(
4
1, 3465. (i) Liang, J.-L.; Yuan, S.-X.; Chan, P. W. H.; Che, C.-M. Org.
Lett. 2002, 4, 4507. (j) Yu, X.-Q.; Huang, J.-S.; Zhou, X.-G.; Che, C.-M.
Org. Lett. 2000, 2, 2233. (k) Au, S.-M.; Huang, J.-S.; Yu, W.-Y.; Fung,
W.-H.; Che, C.-M. J. Am. Chem. Soc. 1999, 121, 9120. (l) Au, S.-M.; Zhang,
S.-B.; Fung, W.-H.; Yu, W.-Y.; Che, C.-M.; Cheung, K.-K. Chem. Commun.
1
998, 2677.
3) For recent reviews, see: (a) Davies, H. M. L.; Long, M. S. Angew.
Chem., Int. Ed. 2005, 44, 3518. (b) M u¨ ller, P.; Fruit, C. Chem. ReV. 2003,
03, 2905. (c) Katsuki, T. Synlett 2003, 281. For selected works by others,
see: (d) Catino, A. J.; Nichols, J. M.; Forslund, R. E.; Doyle, M. P. Org.
(
1
1
0.1021/ol052293c CCC: $30.25
© 2005 American Chemical Society
Published on Web 11/18/2005

3
less toxic and inexpensive alternatives to aryl-λ -iodane
reagents such as PhI(OAc) . Such reagents would be desir-
2
able in view of the growing interest and needs of the
chemical industry to develop nontoxic and inexpensive
catalysts that can mediate a wide variety of chemical
processes.
As part of an ongoing program aimed at developing
polyvalent iodine(III) reagents for C-N bond formation, we
examined the potential applications of aryl iodides for
stereoselective nitrogen atom transfer reactions such as alkene
aziridination. Herein we describe the realization of a “ArI
+
2
PthNH ” protocol that is useful for the construction of
7
aziridines under mild conditions (Scheme 1). Notable
Scheme 1
Figure 1. Aryl iodides used in this work.
was obtained in 81% yield. Slightly lower product yields
(66-70%) were obtained upon lowering the loading of 1
from 1.4 to 1 equiv or in the absence of K CO . A markedly
2
3
lower product yield (31%) was found when the reaction was
conducted with 0.6 equiv of 1 (entries 2-4). In contrast, on
2 2 3
changing the oxidant from m-CPBA to either Na O , NaBO ,
t
1
observations we have made for this intermolecular C-N
bond formation process are: (1) in the absence of ArI,
complete chemo-switching occurs and the epoxide product
BuO H, or oxone no reaction was found on the basis of H
2
NMR analysis.
Inspection of entries 5-7, 9-11, and 13 in Table 1 reveals
that the intermolecular aziridinations of 11a with other aryl
iodides are slightly less effective. Under the conditions of 1
2
is furnished with quantitative recovery of PthNH , and (2)
it is possible to recover and recycle the ArI systems we have
employed. Since the completion of this work, the groups of
equiv of 11a, PthNH (1.4 equiv), and m-CPBA (2 equiv)
2
8
9
Kita and Ochiai have reported the use of a variety of aryl
iodides as recyclable catalysts for various organic oxidations
that proceeded in moderate to good yield.
in CH Cl at 25 °C for 12 h, aziridination with 1 equiv of
2
2
2-4, 6-8, or 10 as the ArI source gave 12a in 49-65%
At the outset of this study, we examined the effect of
several substituted aryl iodides 1-10 (Figure 1) on the
outcome of various intermolecular alkene aziridination
reactions. The aryl iodide reagents 1-10 were prepared
Table 1. Optimization of Reaction Conditionsa
8
following literature methods or purchased from commercial
sources.10 With styrene 11a as our initial probe substrate, a
survey of different reaction conditions revealed that aziri-
dination of 11a was best performed in the presence of
yield (%)b
entry
1c
ArI
PthNH
in CH
1) as aryl iodide source (Table 1, entry 1). Under these
conditions, 2-(2-phenyl-aziridin-1-yl)-isoindole-1,3-dione 12a
2
2 3
(1.4 equiv), m-CPBA (2 equiv), and K CO (3 equiv)
1
1
1
1
2
3
4
5
6
7
8
9
10
81
70
66
31
64
65
49
26
51
55
60
27
65
2
Cl at 25 °C for 12 h with 1.4 equiv of p-MeOC
2
6 4
H I
d
2
(
3
e
4
5
6
7
8
9
1
1
1
(7) For some applications of aziridines in organic and natural product
synthesis, see: (a) Hale, K. J.; Domostoj, M. M.; Tocher, D. A.; Irving, E.;
Scheinmann, F. Org. Lett. 2003, 5, 2927. (b) Sweeney, J. B. Chem. Soc.
ReV. 2002, 31, 247. (c) McCoull, W.; Davis, F. A. Synthesis 2000, 10,
1
1
347. (d) Roth. P.; Andersson, P. G.; Somfai, P. Chem. Commun. 2002,
752. (e) Dodd, R. H. Molecules 2000, 5, 293. (f) Atkinson, R. S.
0
1
2
Tetrahedron 1999, 55, 1519. (g) Stamm, H. J. Prakt. Chem. 1999, 341,
3
19. (h) Cantrill, A. A.; Osborn, H. M. I.; Sweeney, J. Tetrahedron 1998,
5
4, 2181. (i) Tanner, D. Angew. Chem., Int. Ed. 1994, 33, 599. (j) Tanner,
D.; He, H. M. Tetrahedron 1992, 48, 6079. (k) Tanner, D.; He, H. M.;
Somfai. P. Tetrahedron 1992, 48, 6069.
13
a
(
8) Tohma, H.; Maruyama, A.; Maeda, A.; Maegawa, T.; Dohi, T.; Shiro,
M.; Morita, T.; Kita, Y. Angew. Chem., Int. Ed. 2004, 43, 3595.
9) Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.; Miyamoto, K.
J. Am. Chem. Soc. 2005, 127, 12244.
10) ArI 1-9 are commercially available from Sigma-Aldrich.
All reactions were performed in CH2Cl2 at 25 °C for 12 h with styrene/
ArI/PthNH2/m-CPBA ratio of 1:1:1.4:2d. Isolated yield. c Conducted with
1.4 equiv of 1 and 3 equiv of K2CO3. Conducted with 1 equiv of 1 and
3 equiv of K2CO3. e Conducted with 0.6 equiv of 1.
b
(
(
5802
Org. Lett., Vol. 7, No. 26, 2005

yield. Reactions of 11a with either 5 or 9 as ArI source are
the only instances where markedly lower yields of 26% and
Table 2. Intermolecular 1-Mediated Aziridination with PthNH
as Nitrogen Source and Comparison with the Analogous
PhI(OAc) -Mediated Reactions
2
2
27%, respectively, were obtained (entries 8 and 12).
At this juncture, we would like to highlight that employ-
ment of aryl iodide for the aziridination reaction is essential.
As depicted in Scheme 2, under our experimental conditions,
Scheme 2
the reaction of 1 equiv of 11a, 1.4 equiv of PthNH
2
, and 3
equiv of m-CPBA in CH Cl at 25 °C for 12 h gave styrene
2
2
oxide in 40% yield; the absence of ArI seemed to act as a
trigger for chemo-switching from C-N to C-O bond
formation (see later section).
To define the scope of 1-mediated aziridination reactions,
we applied this process on a series of terminal and internal
alkenes 11b-l (Table 2). These reactions afforded the
corresponding aziridines 12b-l in moderate to good yields
(up to 94%) (entries 2-12). The highest product yield of
94% attained in this work was for the intermolecular
aziridination of 1,3-diphenyl-propen-3-one 11h (entry 8). To
our knowledge, this represents the highest product yield so
far achieved for 1-mediated aziridination of alkenes using
2
PthNH as the nitrogen source under mild oxidizing condi-
tions. Notably, the electron-rich or -deficient nature of Cd
C bond was found to have a marked effect on reaction yield.
In general, electron-deficient alkenes were found to proceed
in g11% higher product yields than those with electron-
donating substituents (cf. entries 2-4 and 8 vs 5, 6, and 9).
Conformationally restricted alkenes, such as 2,2-dimethyl-
2H-chromene 11k and 1H-indene 11l, were also found to
undergo intermolecular aziridination, to give aziridines 12k
and 12l in 60 and 50% yield, respectively (entries 11 and
1
2).
As shown in Table 2, a comparison of the 1-mediated
aziridinations of 11a-l with the analogous reactions using
PhI(OAc) as aryl iodide source revealed that in the latter,
comparable product yields of 84-93% were obtained for
reactions of 11a and 11g-h (entries 1, 7, and 8), but g9%
lower product yields were found for reactions of 11b-d,
a Isolated yield. b All reactions were performed in CH Cl at 25 °C for
2 2
2 h with alkene/1/PthNH2/m-CPBA/K2CO3 ratio of 1:1.4:1.4:2:3. All
2
c
1
reactions were performed in CH2Cl2 at 25 °C for 12 h with alkene/
PhI(OAc)2/PthNH2/K2CO3 ratio of 1:1.5:1.4:2.8. d No reaction.
11f, and 11l (entries 2-4, 6, and 12). In addition, PhI(OAc)
2
was found in this work to be unable to mediate the
aziridination of 11i and 11j; in both instances, the alkene
starting material was recovered in quantitative yield (entries
3, entry 1). The aryl iodide 10 was recovered and subjected
to another five consecutive reactions under the same condi-
tions mentioned above (see Supporting Information for
details). As shown in entries 2-6 in Table 3, product yields
of 80%, 82%, 89%, 84%, and 79% were achieved for each
consecutive reaction and no apparent loss of activity was
observed.
9
2
and 10). PhI(OAc) -mediated aziridinations of 11e and 11k
are the only examples where higher product yields of 70%
were obtained (entries 5 and 11).
In this work, a recyclable aryl iodide system for aziridi-
nation of alkenes was developed. Addition of 11g (1 equiv)
The proposed mechanism for the 1-mediated aziridination
1
1
to a CH
2
Cl
2
solution containing 10 (1.4 equiv), PthNH
2
(1.4
of alkenes is depicted in Scheme 3. We postulate that
1
2
1
equiv), and m-CPBA (2 equiv) at 25 °C followed by
subsequent stirring for 12 h gave 12g in 87% yield (Table
PthNH
Ar ) m-ClC
2
is oxidized by Ar I(OCOAr )
2
6 4
(Ar ) p-MeOC H ,
2
H
6 4
), the latter is produced in situ from
Org. Lett., Vol. 7, No. 26, 2005
5803

Table 3. Recyclable Aryl Iodide 10 for Alkene Aziridination
Reactiona
Scheme 3
entry
yield (%)b
1
2
3
4
5
6
87
80
82
89
84
79
aziridine product for reactions conducted with oxidants other
than m-CPBA.
In summary, we have developed an efficient and recyclable
method for mediating alkene aziridination that is practical,
nontoxic, and inexpensive. The method probably involves
a
All reactions were performed in CH2Cl2 at 25 °C for 12 h with 11g/
0/PthNH2/m-CPBA/K2CO3 ratio of 1:1.4:1.4:2:3. Isolated yield.
b
1
3
in situ generation of an aryl-λ -iodane species from oxidation
1
of the aryl iodide with m-CPBA. Reaction of this intermedi-
ate with PthNH produces the active species of the alkene
2
aziridination step. Efforts are currently underway to develop
an asymmetric aryl iodide mediated version of the present
reaction and its application to the total synthesis of natural
products.
oxidation of 1 by m-CPBA. Dissociation of Ar I from the
1
2
newly formed Ar I(OCOAr )(NHPth) intermediate results in
the generation of N-benzoyloxyaminophthalimide, the active
species that undergoes CdC bond addition and cyclization
to give the aziridine 12. The role of 1 seems to facilitate
formation of the aryl-λ -iodane species. As mentioned in an
12
3
earlier section, this is supported by the reaction of 11a in
the absence of 1, which gave styrene oxide (without
competitive formation of 12a) and quantitative recovery of
Acknowledgment. This work is supported by the Area
of Excellence Scheme (AoE/P-10-01) established under the
University Grants Committee (HKSAR), the Hong Kong
Research Grants Council (HKU7011/04P), CAS-Croucher
Foundation and the University Development Fund of The
University of Hong Kong. P.W.H.C. wishes to thank The
University of Hong Kong (Small Project Funding Pro-
gramme) for funding.
2
PthNH . The involvement of such polyvalent iodine(III)
intermediates is further supported by the systematic decrease
in product yields from 81% to 31% with a decrease in aryl
iodide loading from 1.4 to 0.6 equiv and detection of no
(
11) A similar mechanism has been proposed for the analogous PhI-
(
OAc)2- and Pb(OAc)4-mediated aziridinations. For PhI(OAc)2-mediated
reaction; see ref 5. For Pb(OAc)4-mediated reactions, see ref 6c,d and (a)
Supporting Information Available: Detailed experi-
mental procedures and characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
Atkinson, R. S.; Grimshire, M. J.; Kelly, B. J. Tetrahedron 1989, 45, 2875.
(
2
b) Atkinson, R. S.; Malpass, J. R. J. Chem. Soc., Perkin Trans. 1 1977,
242.
12) It is possible that the N-benzoyloxyaminophthalimide intermediate
(
2
may eliminate Ar CO2H to give a nitrene species.
OL052293C
5804
Org. Lett., Vol. 7, No. 26, 2005