PhI=NSes: A New Iminoiodinane Reagent for the Copper-Catalyzed Aziridination of Olefins

Full text of DOI:10.1021/jo990356x

5304
J . Org. Chem. 1999, 64, 5304-5307
Sch em e 1
Sch em e 2
P h IdNSes: A New Im in oiod in a n e Rea gen t
for th e Cop p er -Ca ta lyzed Azir id in a tion of
Olefin s
Philippe Dauban* and Robert H. Dodd*
Institut de Chimie des Substances Naturelles, CNRS,
F-91198 Gif-sur-Yvette, France
Received February 26, 1999
In tr od u ction
In addition to their incorporation in the structures of
natural and/or biologically active products, aziridines are
of paramount importance in organic synthesis since they
are valuable precursors of amino sugars, alkaloids, or
substituted R-amino acids.1 Among the numerous routes
to this heterocycle, the copper-catalyzed aziridination of
olefins developed by Evans2 has become a method of
choice, allowing the formation of aziridines directly by
reaction with a nitrene generated from an iminophe-
nyliodinane (Scheme 1). The value of this process has
recently been demonstrated in the total synthesis of
natural products and dipeptide isosteres.3
So far, only [N-(arenesulfonyl)imino]phenyliodinanes
1 have been used as nitrene sources, leading to N-
(arenesulfonyl)aziridines.4 Although several methods of
deprotection of sulfonamides have been reported in the
literature,5 their cleavage sometimes proves to be
troublesome.3a,6 Thus, it appeared to us that preparation
of N-[2-(trimethylsilyl)ethanesulfonyl]aziridines (N-(Ses)-
aziridines) would provide an interesting alternative to
the (arenesulfonyl)aziridines in terms of protection-
deprotection strategy.
prepare in rather modest yields N-(methylsulfonyl)-
aziridines from olefins9 but their deprotection would
require harsh conditions incompatible with many func-
tional groups.10
On the basis of this result, we next turned our
attention to the Ses group. This protecting group, orig-
inally developed by Weinreb,11 has found numerous
applications in total synthesis.12 More significantly,
N-(Ses)aziridines13a have been successfully used for the
preparation of substituted R-amino acids13b and oligo-
saccharides.13c In this context, we report herein the
preparation and the synthetic application of the [N-
((trimethylsilyl)ethanesulfonyl)imino]phenyliodinane
(PhIdNSes) 3, the first [N-(alkylsulfonyl)imino]phenyl-
iodinane, for the copper-catalyzed aziridination of olefins
leading to synthetically versatile Ses-protected aziridines.
Resu lts a n d Discu ssion
Following the protocol described for the isolation of the
iodinanes PhIdNSO2Ar,4,14 the reaction of sulfonamide
2 (prepared from the corresponding sulfonyl chloride
according to the recently published procedure)11b with
iodosobenzene diacetate in the presence of potassium
hydroxide gave the reagent 3 (Scheme 2). However, a
slight modification of the workup was needed because the
nitrene precursor 3 could not be crystallized from the
medium. Thus, despite the sensitivity of the phenyliodi-
nanes to water, dilution of the reaction mixture with
dichloromethane, followed by an aqueous wash with ice-
water, allowed the isolation of PhIdNSes 3 in quantita-
tive yield as a stable yellow solid of analytical purity,
which can be stored at -20 °C under argon.
Until now, no aziridinations using [N-(alkylsulfonyl)-
imino]phenyliodinanes have been described, probably
because the N-methylsulfonyl derivative has been claimed
to be unstable and explosive.7 To the best of our knowl-
edge, a single report deals with the attempt to generate
a nitrene species from this ylide.8 Despite this, prelimi-
nary experiments with this iodinane have allowed us to
* To whom correspondence should be addressed. Fax: Int. Code +
(1) 69077247. E-mail: robert.dodd@icsn.cnrs-gif.fr; philippe.dauban@
icsn.cnrs-gif.fr.
(1) For reviews, see: (a) Tanner, D. Angew. Chem., Int. Ed. Engl.
1994, 33, 599. (b) Osborn, H. M. I.; Sweeney, J . Tetrahedron: Asym-
metry 1997, 8, 1693.
(2) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J . Am. Chem. Soc.
1994, 116, 2742.
(3) (a) Hudlicky, T.; Tian, X.; Ko¨nigsberger, K.; Maurya, R.; Rouden,
J .; Fan, B. J . Am. Chem. Soc. 1996, 118, 10752. (b) Masse, C. E.;
Knight, B. S.; Stavropoulos, P.; Panek, J . S. J . Am. Chem. Soc. 1997,
119, 6040.
In the presence of a catalytic amount of Cu(OTf)2, a
slight excess of the iodinane 3 reacted with olefins 4 (the
(4) For a representative survey of the [N-(arenesulfonyl)imino]-
phenyliodinanes that can be prepared, see: So¨dergren, M. J .; Alonso,
D. A.; Bedekar, A. V.; Andersson, P. G. Tetrahedron Lett. 1997, 38,
6897.
(5) (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Chemistry, 2nd ed.; Wiley-Interscience: New York, 1991. (b) Kocienski,
P. J . Protecting Groups; Thieme: Stuttgart, 1994. (c) Vedejs, E.; Lin,
S. J . Org. Chem. 1994, 59, 1602. (d) Fukuyama, T.; J ow, C.-K.; Cheung,
M. Tetrahedron Lett. 1995, 36, 6373. (e) Parsons, A. F.; Pettifer, R. M.
Tetrahedron Lett. 1996, 37, 1667. (f) Fleming, I.; Frackenpohl, J .; Ila,
H. J . Chem. Soc., Perkin Trans. 1 1998, 1229.
(9) Dauban, P.; Dodd, R. H. Unpublished results.
(10) Rudolph, J .; Sennhenn, P. C.; Vlaar, C. P.; Sharpless, K. B.
Angew. Chem., Int. Ed. Engl. 1996, 35, 2810.
(11) (a) Weinreb, S. M.; Demko, D. M.; Lessen, T. A.; Demers, J . P.
Tetrahedron Lett. 1986, 27, 2099. (b) Weinreb, S. M.; Chase, C. E.;
Wipf, P.; Venkatraman, S. Org. Synth. 1998, 75, 161.
(12) (a) J arowicki, K.; Kocienski, P. Contemp. Org. Synth. 1997, 4,
454. (b) Li, S.; Yamamura, S.; Hosomi, H.; Ohba, S. Tetrahedron Lett.
1998, 39, 2601. (c) Boger, D. L.; Schu¨le, G. J . Org. Chem. 1998, 63,
6421.
(13) (a) Aggarwal, V. K.; Thompson, A.; J ones, R. V. H.; Standen,
M. C. H. J . Org. Chem. 1996, 61, 8368. (b) Wipf, P.; Venkatraman, S.;
Miller, C. P. Tetrahedron Lett. 1995, 36, 3639. (c) Griffith, D. A.;
Danishefsky, S. J . J . Am. Chem. Soc. 1996, 118, 9526.
(14) Yamada, Y.; Yamamoto, T.; Okawara, M. Chem. Lett. 1975, 361.
(6) Wuts, P. G. M.; Northuis, J . M. Tetrahedron Lett. 1998, 39, 3889.
(7) Stang, P. J .; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123.
(8) Abramovitch, R. A.; Bailey, T. D.; Takaya, T.; Uma, V. J . Org.
Chem. 1974, 39, 340.
10.1021/jo990356x CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/17/1999

Notes
J . Org. Chem., Vol. 64, No. 14, 1999 5305
Ta ble 1. Cop p er -Ca ta lyzed Azir id in a tion of
Rep r esen ta tive Olefin s
Sch em e 3
Ta ble 2. Dep r otection of th e N-Ses Der iva tives
a
b
Isolated yield after flash chromatography. Value in paren-
theses for yield based on consumed starting olefin. c 2 equiv of
olefin was used. 5 equiv of olefin was used. e 63% (entry 5) and
d
53% (entry 6) of aziridines were, respectively, isolated when 1.7
equiv of PhIdNSes was used.
a
Key: (A) 3 equiv of CsF, DMF, 90 °C; (B) 4 equiv of TASF,
b
DMF, rt; (C) 4 equiv of TASF, acetonitrile, rt. Isolated yield after
flash chromatography.
stoichiometrically limiting component except in entries
3 and 4, Table 1) to form the N-(Ses)aziridines 5. The
yields were in the 35-60% range and are comparable to
those obtained with PhIdNTs.2,4,15 Moreover, the yields
could be substantially increased by the use of the copper-
(I) salt, CuOTf, instead of Cu(OTf)2 (Table 1, entries 1,
3, 5, 9, and 10), or by adding a larger quantity of the
nitrene precursor (Table 1, entries 5 and 6). The reaction
takes place with terminal, electron-rich, or electron-poor
olefins. It proceeds in a stereospecific manner with trans-
olefins since only trans-aziridines derived from methyl
cinnamate and methyl tiglate were isolated (Table 1,
entries 3 and 6). In the case of norbornene, as noted by
Evans,2 the exo-aziridine was the sole isomer produced.
Finally, as recently described by us for nitrene precursors
of type 1, the 2-substituted acrylates show higher reac-
tivity than methyl acrylate itself (Table 1, entries 5-7
vs entry 4).15
resulting sulfonamides by use of cesium fluoride in
DMF.11 Thus, under these conditions, compound 6 could
be efficiently transformed into the amino derivative 9 in
95% yield (Table 2).
More significantly, the N-(Ses)aziridines themselves
could be deprotected without provoking opening of the
aziridine ring. Except for a few isolated examples, no
general procedure exists for this type of transforma-
tion.5c,16,17 While the above conditions (CsF in DMF)
applied to aziridines 5 unexpectedly failed to give the
corresponding deprotected three-membered ring, it was
found that use at room temperature of tris(dimethylami-
no)sulfonium difluorotrimethylsilicate (TASF), a reagent
recently found by Roush to cleave silicon protecting
groups under mild conditions,18 provided the NH aziri-
dine products 10, 11, 12, and 13, respectively, in good
yields (nonoptimized, Table 2). To the best of our knowl-
edge, TASF has never been employed before to cleave the
Ses protecting group.19 However, we observed that this
procedure failed with the acrylate-derived aziridines 5d -
f. Nevertheless, it should be pointed out that the condi-
tions developed by Andersson17 for deprotection of cyclo-
As previously demonstrated by Wipf,13b N-(Ses)aziri-
dines are sufficiently activated to allow ring opening by
nucleophiles. Thus, the 3-phenylaziridine derivative 5c
reacted with sodium borohydride/nickel chloride to give
exclusively the N-Ses-protected phenylalanine 6 in 90%
yield, while aziridine 5f reacted with a soft nucleophile
such as o-methoxythiophenol under mild conditions to
give mainly the C-3 aziridine ring-opened product 7
together with a minor quantity of the product of C-2
attack 8 (Scheme 3).
(16) (a) Bellos, K.; Stamm, H.; Speth, D. J . Org. Chem. 1991, 56,
6846. (b) Katoh, T.; Itoh, E.; Yoshino, T.; Terashima, S. Tetrahedron
Lett. 1996, 37, 3471.
(17) During the preparation of this manuscript, a convenient general
procedure was reported for the deprotection of N-(arenesulfonyl)-
aziridines: Alonso, D. A.; Andersson, P. G. J . Org. Chem. 1998, 63,
9455.
From a synthetic point of view, the N-(Ses) protecting
group offers the opportunity of mild deprotection of the
(18) Scheidt, K. A.; Chen, H.; Follows, B. C.; Chemler, S. R.; Coffey,
D. S.; Roush, W. R. J . Org. Chem. 1998, 63, 6436.
(15) Dauban, P.; Dodd, R. H. Tetrahedron Lett. 1998, 39, 5739.

5306 J . Org. Chem., Vol. 64, No. 14, 1999
Notes
SSi: C, 55.08; H, 7.47; N, 4.94; S, 11.31. Found: C, 54.87; H, 7.27;
N, 4.96; S, 11.36.
hexyl N-(tosyl)aziridine-2-carboxylates (i.e., reduction
with magnesium in methanol) were recently found to give
aziridine ring-opened product when applied to methyl
aziridine-2-carboxylates.20
N-(2-(Tr im eth ylsilyl)eth a n esu lfon yl)-2-(2-p h en yleth yl)-
a zir id in e (5b). Starting from 150 µL (1 mmol) of 4-phenyl-1-
butene, 0.125 g (0.40 mmol, 40%) of aziridine was isolated as a
colorless oil after flash chromatography on silica gel (heptane-
ethyl acetate 6:1): 1H NMR (250 MHz, CDCl3) δ 0.06 (s, 9H),
1.13 (m, 2H), 1.86 (m, 2H), 2.06 (d, 1H, J ) 4.6 Hz), 2.57 (d, 1H,
J ) 7 Hz), 2.78 (m, 3H), 3.05 (m, 2H), 7.19-7.29 (m, 5H); 13C
NMR (62.5 MHz, CDCl3) δ -1.9, 9.8, 33.1, 33.4, 33.8, 38.3, 48.9,
126.3, 128.4, 128.7; mass spectrum (CI) m/z 312 (M + H)+. Anal.
Calcd for C15H25NO2SSi‚0.25H2O: C, 57.01; H, 8.13; N, 4.43; S,
10.14. Found: C, 57.03; H, 7.97; N, 4.29; S, 10.21.
N-(2-(Tr im eth ylsilyl)eth a n esu lfon yl)-2-(m eth oxyca r bo-
n yl)-3-p h en yla zir id in e (5c). Starting from 146 mg (0.9 mmol)
of trans-methyl cinnamate and in the presence of 50 mg of
(CuOTf)2‚C6H6, 120 mg (0.35 mmol, 39%) of aziridine together
with 65 mg (0.39 mmol, 44%) of unreacted cinnamate were
isolated as a colorless oil after flash chromatography on silica
gel (heptane-ethyl acetate 9:1 then 8/1): 1H NMR (250 MHz,
CDCl3) δ 0.04 (s, 9H), 1.12 (m, 2H), 3.18 (m, 2H), 3.45 (d, 1H, J
) 3.8 Hz), 3.87 (s, 3H), 4.40 (d, 1H, J ) 3.8 Hz), 7.36 (m, 5H);
13C NMR (62.5 MHz, CDCl3) δ -2.0, 9.9, 47.0, 47.2, 52.0, 53.2,
127.0, 128.8, 129.1, 133.3, 166.3; mass spectrum (CI) m/z 342
(M + H)+. Anal. Calcd for C15H23NO4SSi‚0.25H2O: C, 52.07; H,
6.85; N, 4.05. Found: C, 51.73; H, 6.66; N, 4.22.
N-(2-(Tr im eth ylsilyl)eth a n esu lfon yl)-2-(m eth oxyca r bo-
n yl)a zir id in e (5d ). Starting from 360 µL (4.0 mmol) of methyl
acrylate dissolved in acetonitrile (2 mL) and 310 mg (0.8 mmol)
of PhIdNSes, 0.105 g (0.395 mmol, 49%) of aziridine was isolated
as a colorless oil after flash chromatography on silica gel
(heptane-ethyl acetate 4:1): 1H NMR (300 MHz, CDCl3) δ 0.07
(s, 9H), 1.13 (m, 2H), 2.60 (d, 1H, J ) 4.1 Hz), 2.75 (d, 1H, J )
7.0 Hz), 3.16 (m, 2H), 3.30 (dd, 1H, J ) 4.1, 7.0 Hz), 3.80 (s,
3H); 13C NMR (75 MHz, CDCl3) δ -2.0, 9.5, 31.6, 34.8, 49.3, 53.0,
167.5; mass spectrum (CI) m/z 266 (M + H)+. Anal. Calcd for
C9H19NO4SSi: C, 40.73; H, 7.22; N, 5.28; S, 12.08. Found: C,
40.81; H, 7.04; N, 5.21; S, 11.89.
N-(2-(Tr im eth ylsilyl)eth a n esu lfon yl)-2-(m eth oxyca r bo-
n yl)-2-m eth yla zir id in e (5e). Starting from 128 µL (1.2 mmol)
of methyl methacrylate, 0.175 g (0.63 mmol, 52%) of aziridine
was isolated as a colorless oil after flash chromatography on
silica gel (heptane-ethyl acetate 4:1): 1H NMR (250 MHz,
CDCl3) δ 0.07 (s, 9H), 1.12 (m, 2H), 1.84 (s, 3H), 2.65 (s, 1H),
2.86 (s, 1H), 3.14 (m, 2H), 3.77 (s, 3H); 13C NMR (62.5 MHz,
CDCl3) δ -1.9, 9.7, 15.7, 39.2, 45.2, 51.5, 53.1, 169.1; mass
spectrum (CI) m/z 280 (M + H)+. Anal. Calcd for C10H21NO4-
SSi: C, 42.98; H, 7.58; N, 5.01; S, 11.47. Found: C, 42.93; H, 7.43;
N, 4.87; S, 11.51.
In conclusion, PhIdNSes 3 represents the first [(N-
(alkylsulfonyl)imino]phenyliodinane useful for the cop-
per-catalyzed aziridination of olefins. In comparison to
PhIdNTs, its isolation is much easier while their reac-
tivities are comparable. Moreover, this new iodinane
allows the formation of N-(Ses)aziridines that can, in
turn, be opened by nucleophiles under mild conditions
and/or deprotected at the nitrogen position without side
reactions. In the latter case, use of the hypervalent silicon
reagent TASF for deprotection of the Ses group is very
convenient. These N-(Ses)aziridines are thus of high
synthetic interest. Extension of this work to the asym-
metric copper-catalyzed aziridination of olefins is cur-
rently under investigation.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. IR spec-
tra of samples were obtained as films (i.e., by application of a
CHCl3 solution to an NaCl plate followed by evaporation of the
1
solvent). H and 13C NMR chemical shifts are given as δ values
with reference to Me4Si as internal standard. Thin-layer chro-
matography was performed on Merck silica gel 60 plates with a
fluorescent indicator. The plates were visualized with UV light
(254 nm) and with a 3.5% solution of phosphomolybdic acid in
ethanol. All column chromatography was conducted on Merck
60 silica gel (230-240 mesh) at medium pressure (200 mbar).
All solvents were distilled and stored over 4 Å molecular sieves
before use. Elemental analyses were performed at the ICSN,
CNRS, Gif-sur-Yvette, France.
[N -(2-(Tr im e t h ylsilyl)e t h a n e su lfon yl)im in o]p h e n yl-
iod in a n e (3). To a stirred solution of 2-(trimethylsilyl)ethane-
sulfonamide (2, 1.19 g, 6.56 mmol, 1.00 equiv) and potassium
hydroxide pellets (0.92 g, 16.4 mmol, 2.50 equiv) in dry methanol
(20 mL) held at 0 °C under argon was added iodosobenzene
diacetate (2.12 g, 6.56 mmol, 1.00 equiv). The reaction mixture
was kept at 0 °C for 30 min and then allowed to warm to 20 °C.
After being stirred for 3 h, the homogeneous yellow solution was
cooled before being diluted with dichloromethane (30 mL) and
washed with ice-water (20 mL). The organic phase was dried
with MgSO4 and then evaporated to dryness to give a pale yellow
solid (2.50 g, 6.52 mmol, 99%): mp 84-85.5 °C; IR (film) 2953,
1441, 1330, 1245, 1225, 1165, 1145, 1115, 885, 860, 735 cm-1
;
N-(2-(Tr im eth ylsilyl)eth a n esu lfon yl)-2-(m eth oxyca r bo-
n yl)-2,3-d im eth yla zir id in e (5f). Starting from 96 µL (0.8
mmol) of methyl tiglate, 0.110 g (0.37 mmol, 47%) of aziridine
was isolated as a colorless oil after flash chromatography on
silica gel (heptane-ethyl acetate 5:1): 1H NMR (250 MHz,
CDCl3) δ 0.04 (s, 9H), 1.08 (m, 2H), 1.31 (d, 3H, J ) 5.8 Hz),
1.48 (s, 3H), 3.08 (m, 2H), 3.63 (q, 1H, J ) 5.8 Hz), 3.75 (s, 3H);
13C NMR (62.5 MHz, CDCl3) δ -2.0, 9.7, 12.8, 15.3, 43.6, 51.1,
53.0, 168.8; mass spectrum (CI) m/z 294 (M + H)+. Anal. Calcd
for C11H23NO4SSi‚0.03C7H16: C, 45.42; H, 7.98; N, 4.72; S, 10.81.
Found: C, 45.46; H, 7.71; N, 4.67; S, 11.02.
1H NMR (250 MHz, CDCl3) δ -0.06 (s, 9H), 0.92 (m, 2H), 2.84
(m, 2H), 7.40 (t, 2H, J ) 7.7 Hz), 7.52 (d, 1H, J ) 7.4 Hz), 7.96
(d, 2H, J ) 7.9 Hz). Anal. Calcd for C11H18INO2SSi: C, 34.47; H,
4.73; N, 3.65; S, 8.36. Found: C, 34.61; H, 4.74; N, 3.75; S, 8.51.
Typ ica l Azir id in a t ion P r oced u r e (u n less Ot h er w ise
Noted ). PhIdNSes 3 (1.3 equiv) was added portionwise, over a
period of 3 h, to a mixture held under argon of 4 Å molecular
sieves (∼150 mg), Cu(OTf)2 (10 mol %), and olefin (1 equiv) in
acetonitrile (1.6 mL). The green reaction mixture was stirred
at room temperature for 24 h and then purified directly by flash
chromatography on silica gel, affording aziridines 5.
N-(2-(Tr im eth ylsilyl)eth a n esu lfon yl)-2-(ter t-bu toxyca r -
bon yl)-2-p h en yla zir id in e (5g). Starting from 184 mg (0.9
mmol) of tert-butyl atropate, 165 mg (0.43 mmol, 48%) of
aziridine together with 50 mg (0.24 mmol, 27%) of unreacted
starting material were isolated as a colorless oil after flash
chromatography on silica gel (heptane-ethyl acetate 8:1): 1H
NMR (300 MHz, CDCl3) δ 0.07 (s, 9H), 1.23 (m, 2H), 1.46 (s,
9H), 2.56 (s, 1H), 3.28 (m, 2H), 3.43 (s, 3H), 7.35-7.44 (m, 5H);
13C NMR (62.5 MHz, CDCl3) δ -2.0, 9.7, 27.6, 37.6, 50.1, 53.8,
83.6, 127.2, 128.5, 128.7, 135.1, 165.2; mass spectrum (CI) m/z
384 (M + H)+. Anal. Calcd for C18H29NO4SSi: C, 56.36; H, 7.62;
N, 3.65; S, 8.36. Found: C, 56.58; H, 7.62; N, 3.63; S, 8.32.
N-(2-(Tr im eth ylsilyl)eth a n esu lfon yl)-7-a za bicyclo[4.1.0]-
h ep ta n e (5h ). Starting from 81 µL (0.8 mmol) of cyclohexene,
72 mg (0.275 mmol, 34%) of aziridine was isolated as a white
solid after flash chromatography on silica gel (heptane-ethyl
N -(2-(Tr im e t h ylsilyl)e t h a n e su lfon yl)-2-p h e n yla zir i-
d in e (5a ). Starting from 69 µL (0.6 mmol) of styrene, 0.100 g
(0.35 mmol, 58%) of aziridine was isolated as a colorless oil after
flash chromatography on silica gel (heptane-ethyl acetate 8:1):
1H NMR (250 MHz, CDCl3) δ 0.03 (s, 9H), 1.14 (m, 2H), 2.42 (d,
1H, J ) 4.4 Hz), 2.98 (d, 1H, J ) 7.1 Hz), 3.13 (m, 2H), 3.71 (dd,
1H, J ) 4.4, 7.1 Hz), 7.34 (m, 5H); 13C NMR (75 MHz, CDCl3) δ
-2.1, 9.7, 35.1, 40.4, 49.1, 126.5, 128.4, 128.7, 135.1; mass
spectrum (CI) m/z 284 (M + H)+. Anal. Calcd for C13H21NO2-
(19) This could be an interesting alternative to the classical reagent
(i.e., CsF in DMF) since cases have been reported in which the N-(Ses)
protecting group could not be removed under the standard conditions.
For example, see: Ward, D. E.; Gai, Y.; Kaller, B. F. J . Org. Chem.
1996, 61, 5498.
1
(20) Pak, C. S.; Kim, T. H.; Ha, S. J . J . Org. Chem. 1998, 63, 10006.
acetate 6:1): mp 57-58 °C; H NMR (250 MHz, CDCl3) δ 0.06

Notes
J . Org. Chem., Vol. 64, No. 14, 1999 5307
1
(s, 9H), 1.08-1.15 (m, 2H), 1.23-1.35 (m, 2H), 1.39-1.51 (m,
2H), 1.89 (m, 4H), 2.95 (m, 2H), 3.00-3.07 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ -2.0, 9.8, 19.5, 23.0, 39.1, 49.0; mass
spectrum (CI) m/z 262 (M + H)+. Anal. Calcd for C11H23NO2-
SSi: C, 50.53; H, 8.87; N, 5.36; S, 12.26. Found: C, 50.62; H, 8.61;
N, 5.15; S, 12.26.
gave compound 7 (75 mg, 67%) as a colorless oil; H NMR (250
MHz, CDCl3) δ 0.04 (s, 9H), 1.04-1.12 (m, 2H), 1.33 (d, 3H, J )
7.1 Hz), 1.72 (s, 3H), 2.95-3.08 (m, 2H), 3.32 (q, 1H, J ) 7.1
Hz), 3.72 (s, 3H), 3.92 (s, 3H), 5.73 (s, 1H), 6.92 (2d, 2H, J ) 7.9
Hz), 7.33 (dd, 1H), 7.45 (dd, 1H); mass spectrum (CI) m/z 434
(M + H)+.
N -(2-(Tr im e t h ylsilyl)e t h a n e su lfon yl)-3-a za t r icyclo-
[3.2.1.0.2,4exo]octa n e (5i). Starting from 94 mg (1.0 mmol) of
norbornene, 0.150 g (0.55 mmol, 55%) of aziridine was isolated
as a white solid after flash chromatography on silica gel
(heptane-ethyl acetate 5:1): mp 59.5-61 °C; 1H NMR (250
MHz, CDCl3) δ 0.06 (s, 9H), 0.81 (d, 1H, J ) 10 Hz), 1.06-1.14
(m, 2H), 1.26-1.30 (m, 2H), 1.47-1.54 (m, 3H), 2.52 (s, 2H), 2.90
(s, 2H), 2.99-3.06 (m, 2H); 13C NMR (50 MHz, CDCl3) δ -2.0,
9.8, 25.7, 28.3, 35.9, 41.0, 49.2; mass spectrum (CI) m/z 274 (M
+ H)+. Anal. Calcd for C12H23NO2SSi: C, 52.71; H, 8.48; N, 5.12;
S, 11.72. Found: C, 52.43; H, 8.16; N, 5.02; S, 11.65.
Continued elution of the column with ethyl acetate-heptane
(1:4) gave compound 8 (20 mg, 18%) as a colorless oil: 1H NMR
(250 MHz, CDCl3) δ 0.01 (s, 9H), 1.04-1.15 (m, 2H), 1.22 (s,
3H), 1.38 (d, 3H, J ) 6.6 Hz), 2.98-3.20 (m, 2H), 3.73 (s, 3H),
3.78 (m, 1H), 3.84 (s, 3H), 5.25 (d, 1H, J ) 8.9 Hz), 6.92 (m,
2H), 7.31-7.48 (m, 2H); mass spectrum (CI) m/z 434 (M + H)+.
Typ ica l P r oced u r e for th e Dep r otection of th e N-(Ses)-
a zir id in es. Meth od B: 2-P h en yla zir id in e (10). A solution of
the N-(Ses)aziridine 5a (58 mg, 0.205 mmol) and TASF (225 mg,
4 equiv) in DMF (0.7 mL) was stirred at room temperature. After
completion of the reaction as indicated by TLC, the mixture was
purified by flash chromatography on silica gel (heptane-ethyl
acetate 1:2), affording the deprotected aziridine 10 (15 mg, 0.126
mmol, 62%) as a yellow oil whose spectroscopic data were
identical to those previously reported:17 1H NMR (300 MHz,
CDCl3) δ 1.15 (br s, 1H), 1.80 (d, 1H, J ) 3.4 Hz), 2.21 (d, 1H,
J ) 6.0 Hz), 3.02 (dd, 1H, J ) 3.4 and 6.0 Hz), 7.22-7.34 (m,
5H); mass spectrum (CI) m/z 120 (M + H)+.
N-(2-(Tr im et h ylsilyl)et h a n esu lfon yl)-2-n on yla zir id in e
(5j). Starting from 205 µL (1.0 mmol) of 1-undecene, 0.110 g
(0.33 mmol, 33%) of aziridine was isolated as a colorless oil after
flash chromatography on silica gel (heptane-ethyl acetate 15:
1): 1H NMR (250 MHz, CDCl3) δ 0.07 (s, 9H), 0.88 (t, 3H, J )
6.9 Hz), 1.11-1.19 (m, 2H), 1.23-1.57 (m, 16H), 2.08 (d, 1H, J
) 4.6 Hz), 2.59 (d, 1H, J ) 7.0 Hz), 2.70 (m, 1H), 3.03-3.10 (m,
2H); 13C NMR (62.5 MHz, CDCl3) δ -1.9, 9.8, 14.1, 22.7, 26.9,
29.3, 29.4, 29.6, 31.6, 32.0, 33.4, 39.3, 48.9; mass spectrum (EI)
m/z 333 (M)+. Anal. Calcd for C16H35NO2SSi: C, 57.61; H, 10.57;
N, 4.20; S, 9.61. Found: C, 57.38; H, 10.48; N, 4.11; S, 9.76.
Red u ctive Rin g Op en in g of th e N-(Ses)a zir id in e 5c. A
solution of the N-(Ses)aziridine 5c (80 mg, 0.234 mmol) in
methanol (4 mL) was treated at 0 °C under argon with nickel
chloride hexahydrate (55 mg, 0.234 mmol), and after the mixture
had stirred for 5 min, sodium borohydride (88 mg, 2.34 mmol)
was added in small portions. The reaction mixture was stirred
for 1 h at 0 °C before saturated aqueous NH4Cl (5 mL) was
added. The mixture was extracted with dichloromethane (3 ×
10 mL), the combined organic phases were dried over MgSO4,
and the solvents were evaporated under vacuum. The residue
was purified by column chromatography on silica gel (ethyl
acetate-heptane 1:3), providing N-(Ses)-phenylalanine methyl
ester 6 (72 mg, 80%) as a colorless oil: 1H NMR (250 MHz,
CDCl3) δ 0.07 (s, 9H), 0.92 (m, 2H), 2.67-2.84 (m, 2H), 3.08 (dd,
1H, J ) 7.9, 13.8 Hz), 3.26 (dd, 1H, J ) 5.1, 13.8 Hz), 3.88 (s,
3H), 4.44 (ddd, 1H, J ) 9.4 Hz), 7.30-7.42 (m, 5H); mass
spectrum (CI) m/z 344 (M + H)+.
Meth od C: 3-Aza tr icyclo[3.2.1.0.2,4exo]octa n e (12). A solu-
tion of the N-(Ses)aziridine 5i (74 mg, 0.270 mmol) and TASF
(230 mg, 3 equiv) in acetonitrile (1 mL) was stirred at room
temperature. After completion of the reaction as indicated by
TLC, the mixture was purified by flash chromatography on silica
gel (dichloromethane-ethanol 9:1), affording the deprotected
aziridine 12 (18 mg, 0.164 mmol, 60%) as a colorless oil whose
spectroscopic data were identical to those previously reported:
21
1H NMR (250 MHz, CDCl3) δ 0.70 (d, 1H, J ) 10.7 Hz), 0.99
(br s, 1H), 1.11-1.17 (m, 1H), 1.23-1.29 (m, 2H), 1.46-1.50 (m,
2H), 1.98 (s, 2H), 2.34 (s, 2H); mass spectrum (CI) m/z 110 (M
+ H)+.
2-P h en yleth yla zir id in e (11). Starting from 80 mg (0.257
mmol) of N-(Ses)aziridine 5b, 23 mg (0.156 mmol, 60%) of the
deprotected aziridine 11 was isolated as a yellow oil after flash
chromatography on silica gel (dichloromethane-ethanol 9:1): 1H
NMR (300 MHz, CDCl3) δ 1.25 (br s, 1H), 1.35 (d, 1H, J ) 3.5
Hz), 1.69-1.78 (m, 3H), 1.94 (m, 1H), 2.77 (m, 2H), 7.17-7.28
(m, 5H); mass spectrum (CI) m/z 148 (M + H)+.
2-Non yla zir id in e (13). Starting from 110 mg (0.33 mmol)
of N-(Ses)aziridine 5j, 38 mg (0.224 mmol, 68%) of the depro-
tected aziridine 13 was isolated as a yellow oil after flash
chromatography on silica gel (dichloromethane-ethanol 9:1): 1H
NMR (250 MHz, CDCl3) δ 0.88 (t, 3H, J ) 6.9 Hz), 1.19-1.50
(m, 18H), 1.77 (d, 1H), 1.95 (m, 1H); mass spectrum (CI) m/z
170 (M + H)+.
Acid -Ca ta lyzed Rin g Op en in g of th e N-(Ses)a zir id in e 5f.
To a solution of the N-(Ses)aziridine 5f (76 mg, 0.260 mmol) and
2-methoxythiophenol (95 µL, 0.780 mmol) in CH2Cl2 (1.2 mL)
was added at -20 °C under argon boron trifluoride etherate (64
µL, 0.520 mmol). The reaction mixture was then allowed to come
to 0 °C and stirred for 2 h before saturated aqueous NaHCO3 (2
mL) was added. The mixture was extracted with ethyl acetate
(2 × 5 mL), the combined organic phases were dried over MgSO4,
and the solvents were evaporated under vacuum. Elution of the
chromatography column with ethyl acetate-heptane (1:5) first
J O990356X
(21) Hermes, M. E.; Marsh, F. D. J . Org. Chem. 1972, 37, 2969.