Ring opening of aziridines with silylated nucleophiles under neutral conditions

Article abstract of DOI:10.1002/ejoc.200500599

Ring-opening of aziridines with silylated nucleophiles in DMF without any catalysts afforded the corresponding products in good to excellent yields under extremely mild reaction conditions. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500599

SHORT COMMUNICATION
Ring Opening of Aziridines with Silylated Nucleophiles under Neutral
Conditions
Jie Wu,*[a] Xiaoyu Sun,[a] and Hong-Guang Xia[a]
Keywords: Aziridine / Ring-opening / DMF / Silylated nucleophiles
Ring-opening of aziridines with silylated nucleophiles in
DMF without any catalysts afforded the corresponding pro-
ducts in good to excellent yields under extremely mild reac-
tion conditions.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
The marked reactivity of aziridines toward ring opening presence of a catalytic amount of TMEDA to give the de-
and expansion is dependent upon their extremely strained sired compounds in good yields, strangely, ring opening of
ring structures. Among the procedures of ring opening of aziridines with the silyl chloride under the conditions did
aziridines, the nucleophilic ring-opening reaction is one of not proceed at all to recover the starting material.
the major routes to highly functionalized compounds.[1]
Meanwhile, Kobayashi et al. have reported that allyl-
Many ring-opening reactions of aziridines have been devel- trichlorosilanes are activated by neutral organic molecules
oped by using silylated nucleophiles.[2] Most of these meth- such as N,N-dimethylformamide (DMF) and hexameth-
ods are limited to the use of heavy and/or inexpensive me- ylphosphoramide (HMPA) to undergo allylation of alde-
tal-based catalysts such as a Lewis acid and frequently re- hydes[7] or N-acylhydrazones[8] without the use of any metal
sult in the formation of mixtures of regioisomers. Recently, catalyst. These organic molecules were proven to coordinate
we reported ring-opening reactions of aziridines with si- to allyltrichlorosilanes to form hypervalent silicon com-
lylated nucleophiles triggered by tetrabutylammonium fluo- pounds[9] that react with electrophiles in a stereospecific
ride (TBAF) gave the corresponding products regioselec- manner. Inspired by these results, we found that, without
tively in excellent yield.[3] It provides a facile and efficient any catalysts, the reaction of aziridine 1a with trimethylsilyl
procedure for the ring-opening reactions of aziridines and azide also proceeded smoothly in DMF to afford the corre-
affords a practical access to the synthesis of 1,2-bifunc- sponding product in high yield (95%) (Scheme 1). The anti-
tional compounds because of its efficiency and simplicity. stereochemistry of the product 2a was confirmed by the
Moreover, inspired by the results reported by Mukaiyama coupling constant for two cyclic methine hydrogen atoms in
and Kobayashi[4] that Lewis bases are good catalysts for the the trans-positions.[3] The resulting product has the poten-
silylcyanation of aldehydes with TMSCN, we found that tial for serving as good building blocks for the preparation
Lewis bases (tertiary amines and phosphanes) were also ef- of vicinal diamines.[3]
ficient as catalysts in the ring-opening reactions of azirid-
ines with silylated nucleophiles.[5] Very recently, another ex-
ample of using Lewis bases as catalysts in the ring openings
of aziridines with trimethylsilylated nucleophiles was re-
ported by Minakata.[6] The ring opening of N-tosylazirid-
ines with trimethylsilylated nucleophiles, catalyzed by
Scheme 1. Reaction of aziridine 1a with trimethylsilyl azide in
N,N,NЈ,NЈ-tetramethylethylenediamine (20 mol-%), led to
the production of β-functionalized sulfonamides in good
yields.[6] However, the catalyst loading is high (20 mol-%)
and reactions usually needed 24–100 hours for completion.
On the other hand, although this amine-catalyzed reaction
of aziridines with TMSX (X = CN, N3, Br, and I), was
readily opened by cyanide, azide, bromide, and iodide in the
DMF.
To demonstrate the generality of this method, without
optimization of the reaction conditions, we next investi-
gated the scope of this reaction and the results are summa-
rized in Table 1. The operation is simple: silylated nucleo-
phile (1.0 equiv.) was added to a solution of substrate 1
(0.25 mmol) in DMF (2.0 mL). The reaction mixture was
stirred at 40 °C for a period of time (3–10 hours). After the
reaction was completed monitored by TLC, the mixture was
washed with water and extracted with ethyl acetate. The
[a] Department of Chemistry, Fudan University,
220 Handan Road, Shanghai 200433, China
Fax: +86-21-6510-2412
E-mail: jie_wu@fudan.edu.cn
Eur. J. Org. Chem. 2005, 4769–4772
DOI: 10.1002/ejoc.200500599
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4769

J. Wu, X. Sun, H.-G. Xia
SHORT COMMUNICATION
Table 1. Ring-opening of aziridines 1 with silylated nucleophiles in DMF.
[a] Isolated yield based on aziridine 1.
4770
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4769–4772

Ring Opening of Aziridines with Silylated Nucleophiles
SHORT COMMUNICATION
organic extracts were dried (MgSO4), filtered, and concen- general and convenient way to prepare a variety of 1,2-bi-
trated under reduced pressure. Purification by column functional compounds. The advantages of this method in-
chromatography column on silica gel afforded the corre- clude good substrate generality, extremely mild reaction
sponding product (Scheme 2).
conditions, and experimentally operational ease. Desymme-
trization of meso-aziridines with silylated nucleophiles by
using chiral DMF analogues is under investigation in our
laboratory.
Scheme 2. Ring-opening of aziridines 1 with various silylated nu- Experimental Section
cleophiles in DMF.
General Procedure for Reactions of Aziridines 1 with Silylated Nu-
cleophiles: The silylated nucleophile (1.0 equiv.) was added to a
solution of substrate 1 (0.25 mmol) in DMF (2.0 mL). The reaction
mixture was stirred at 40 °C for a period of time indicated in
Table 1. After the reaction was completed (monitoring was done
by TLC), the mixture was washed with water and extracted with
ethyl acetate. The organic extracts were dried (MgSO4), filtered,
and concentrated under reduced pressure. Purification by column
chromatography column on silica gel afforded the corresponding
product. The data of products was identical with the literature re-
ports.[3,5,6,10] Selected examples are given below.
This condition has proved to be useful for ring openings
of a range of aziridines 1 with electron-withdrawing groups
attached on the nitrogen atom (Table 1). In most of the
cases, the reactions proceeded very clean and the desired
products were afforded in good to excellent yields. Trimeth-
ylsilyl azide, as well as trimethylsilyl chloride and iodide are
all suitable partners. However, no product was detected at
all when trimethyl(trifluoromethyl)silane reacted with aziri-
dine 1a (Entry 4). In the case of unsymmetrically substi-
tuted aziridines 1c and 1d, completely regioselectivity with
the attack of nucleophile on the less substituted aziridine
carbon was observed. For the substrates 1f, as previously
reported, the attack of nucleophile was on the benzyl posi-
tion due to electron effect. And also, it is reasonable that
regioselectivity is not as specific as others when aziridine 1e
was employed as the substrate. Furthermore, the reactivity
N-(2-Azidocyclohexyl)-4-methylbenzenesulfonamide (2a):[3] Color-
less liquid. IR (film): ν = 3273, 2940, 2863, 2100, 1599 cm–1. 1H
˜
NMR (400 MHz, CDCl3): δ = 1.10–1.45 (m, 4 H), 1.60–1.80 (m, 2
H), 1.95–2.15 (m, 2 H), 2.45 (s, 3 H), 2.90–3.00 (m, 1 H), 3.00–3.10
(m, 1 H), 4.80 (br. d, J = 6.0 Hz, 1 H), 7.35 (d, J = 8.0 Hz, 2 H),
7.80 (d, J = 8.0 Hz, 2 H) ppm. MS: m/z = 295 [MH+]. HRMS:
C13H18NO2S [M – N3]+ 252.1058, found 252.1070.
of aziridine was reduced according to the decreased elec- N-(2-Chlorocyclohexyl)-4-methylbenzenesulfonamide (2b):[3] White
solid with m.p. 100–102 °C. IR (film): ν = 3255, 2947, 2869, 1922,
˜
tron-withdrawing ability of the substituent on the nitrogen
atom of aziridine. For example, no reaction took place
when compounds 1i and 1j were employed as substrates
(Entries 17 and 18). For the role of DMF in the reactions,
according to the precedent reports, we believe that DMF
coordinates to trimethylsilyl compounds to form hyperval-
ent silicon compounds,[8,9] which undergo further nucleo-
philic ring openings.
Further studies of solvent screening showed that only
DMF was the best choice of solvents. The reaction of aziri-
dine 1a with trimethylsilyl azide also proceeded smoothly
at room temperature although prolonged reaction time was
needed (93% yield, 16 h). Moreover, 1.0 equiv. of DMF
could push the reaction to go to completion (79% yield,
72 h, Scheme 3) when the solvent was changed to MeCN.
However, no product was detected when DMA was em-
ployed. Addition of HMPA retarded the reaction.
1
1596 cm–1. H NMR (400 M Hz, CDCl3): δ = 1.20–1.40 (m, 3 H),
1.55–1.75 (m, 3 H), 2.10–2.30 (m, 2 H), 2.40 (s, 3 H), 3.10–3.20 (m,
1 H), 3.60–3.70 (m, 1 H), 4.85 (br., 1 H), 7.30 (d, J = 8.0 Hz Hz, 2
H), 7.80 (d, J = 8.2 Hz Hz, 2 H) ppm. MS: 289 (M+, 37Cl), 287
(M+, 35Cl). C13H18ClNO2S (289.81): calcd. C 54.26, H 6.26, N 4.87;
found: C 54.55, H 6.26, N 4.71.
N-(2-Iodocyclohexyl)-4-methylbenzenesulfonamide (2c):[10] 1H NMR
(400 MHz, CDCl3): δ = 1.26–1.32 (m, 3 H), 1.61–1.71 (m, 3 H),
2.16–2.27 (m, 2 H), 2.43 (s, 3 H), 3.24–3.27 (m, 1 H), 3.99–4.01 (m,
1 H), 5.01–5.02 (d, J = 6.2 Hz, 1 H), 7.26–7.31 (m, 2 H), 7.8 (d, J
= 8.3 Hz, 2 H) ppm.
Acknowledgments
Financial support from National Natural Science Foundation of
China (NSFC) and Fudan University is gratefully acknowledged.
[1] A recent review, see: a) X. E. Hu, Tetrahedron 2004, 60, 2701–
2743 and references cited therein; b) L. G. Ma, J. X. Xu, Progr.
Chem. 2004, 16, 220–235.
[2] a) S. Matsubara, T. Kodama, K. Utimoto, Tetrahedron Lett.
1990, 31, 6379–6380; b) W. H. Leung, M. T. Yu, M. C. Wu,
L. L. Yeung, Tetrahedron Lett. 1996, 37, 891–892; c) D. Fer-
raris, W. J. Drury III, C. Cox, J. Lectka, J. Org. Chem. 1998,
63, 4568–4569; d) Z. Li, M. Fernandez, E. N. Jacobsen, Org.
Lett. 1999, 1, 1611–1613; e) M. Chandrasekhar, G. Sekar, V. K.
Singh, Tetrahedron Lett. 1990, 31, 6379–6380; f) S.-H. Shin,
E. Y. Han, C. S. Park, W. K. Lee, H.-J. Ha, Tetrahedron: Asym-
metry 2000, 11, 3293–3301; g) J. S. Yadav, B. V. S. Reddy, G. M.
Kumar, C. V. S. R. Murthy, Synth. Commun. 2000, 30, 1797–
1802; h) M. A. Reddy, L. R. Reddy, N. Bhanumathi, K. R.
Scheme 3.
In conclusion, we have discovered ring-opening reactions
of aziridines with silylated nucleophiles in DMF without
any catalysts proceeded highly efficient, which provided a
Eur. J. Org. Chem. 2005, 4769–4772
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4771

J. Wu, X. Sun, H.-G. Xia
SHORT COMMUNICATION
Rao, Chem. Lett. 2001, 246–247; i) H. M. I. Osborn, J. B.
Sweeney, Synlett 1994, 145–147; j) M. Chandrasekhar, G. Se-
kar, V. K. Singh, Tetrahedron Lett. 2000, 41, 10079–10083.
[3] J. Wu, X.-L. Hou, L.-X. Dai, J. Org. Chem. 2000, 65, 1344–
1348.
6620–6628; c) C. Ogawa, M. Sugiura, S. Kobayashi, Chem.
Commun. 2003, 192–193.
[8] a) S. Kobayashi, R. Hirabayashi, J. Am. Chem. Soc. 1999, 121,
6942–6943; b) R. Hirabayashi, C. Ogawa, M. Sugiura, S. Ko-
bayashi, J. Am. Chem. Soc. 2001, 123, 9493–9499; c) C. Ogawa,
M. Sugiura, S. Kobayashi, J. Org. Chem. 2002, 67, 5359–5364.
[9] a) A review on pentacoordinate silicon chemistry: C. C. Chuit,
R. J. Corriu, C. Reye, J. C. Young, Chem. Rev. 1993, 93, 1371–
1448; b) H. Sakurai, Synlett 1989, 1–8.
[4] S. Kobayashi, Y. Tsuchiya, T. Mukaiyama, Chem. Lett. 1991,
537–540.
[5] J. Wu, Ph. D. Thesis, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 2000.
[6] S. Minakata, Y. Okada, Y. Oderaotoshi, M. Komatsu, Org.
Lett. 2005, 7, 3509–3512.
[7] a) S. Kobayashi, K. Nishio, Tetrahedron Lett. 1993, 34, 3453–
3456; b) S. Kobayashi, K. Nishio, J. Org. Chem. 1994, 59,
[10] G. Sabitha, S. R. Babu, M. Rajkumar, C. S. Reddy, J. S. Yadav,
Tetrahedron Lett. 2001, 42, 3955–3958.
Received: August 5, 2005
Published Online: September 26, 2005
4772
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4769–4772