aziridine nitrogen, treatment of dimer 1a with Wittig reagent
2 at room temperature in TFE furnished vinyl aziridine 3a
in 98% yield (Table 1, entry 1). Under optimized conditions,
a variety of R,ꢀ-unsaturated vinyl aziridines can be prepared
in one step from aziridine aldehyde dimers.
Table 1. One-Step Construction of Vinyl Aziridines from
Unprotected Aziridine Aldehydesa
Conditions that allow the use of Wittig salts were also
developed. Despite the fact that the dimeric amino aldehydes
do not readily dissociate at high pH (there is no crossover
between two structurally different dimeric amino aldehydes
in the presence of base), treatment of 1 with a variety of
Wittig salts 4 in the presence of t-BuOK at 0 °C afforded
the corresponding vinylaziridines 5a-g with high cis selec-
tivity with respect to olefin geometry (Table 2). As free
product
(trans/cis)
entry
R1
R2
R3
yieldb [%]
1
2
3
4
5
6
Ph
H
H
H
Me
Me
Me
OEt
OEt
OEt
OEt
OEt
OEt
3a (8/2)
3b (8/2)
3c (>95/5)
3d (>95/5)
3e (>95/5)
3f (>95/5)
98c
85
65
95
80
63
p-F-Ph
p-OMe-Ph
Ph
p-F-Ph
p-OMe-Ph
Table 2. Construction of Vinyl Aziridines Using Wittig Saltsa
a General conditions: reactions were performed on a 0.04 mmol scale
in TFE using a ratio of 1:2.2 for the amino aldehyde dimer/Wittig reagent.
b Isolated yields. c 1 mmol scale.
or azido alcohols10 or the treatment of R,ꢀ-unsaturated
oximes11 or hydrazones12 with Grignard reagents. Especially
noteworthy is the pioneering study by Brois, in which the
1,2-divinylaziridine, prepared by the low-temperature addi-
tion of hexafluoro-2-butyne to the parent vinylaziridine,
underwent ring expansion.9 Protecting groups allow easier
access to substituted C-vinyl aziridines, but their removal is
difficult since the respective acidic conditions promote rapid
and undesired SN2′ ring opening.13 The lack of a mild
approach prompted our investigation into olefination of
amphoteric amino aldehydes recently developed in our lab.14
These reagents can be prepared from simple starting materials
such as R-amino acids and exist as dimers with the monomer/
dimer equilibrium lying toward the latter in a variety of
solvents. 2,2,2-Trifluoroethanol (TFE) has been shown to
promote partial dissociation of the dimer. We happily noted
that the dissolution of aziridine aldehydes in TFE allowed
reactions with stabilized Wittig reagents to proceed smoothly
(Scheme 1, path A). Despite the presence of the nucleophilic
product
entry
R1
R2
R3
(cis/trans) yieldb [%]
1
2
3
4
5
6
7
Ph
Ph
Ph
Ph
H
H
Me
Pr
5a (-)
5b (8/2)
5c (8/2)
88c
85
80
70
80
70
65
H
H
H
H
H
(CH2)2C′CPh 5d (9/1)
p-F-Ph
p-OMe-Ph
Ph
Pr
Pr
5e (8/2)
5f (8/2)
Me (CH2)2C′CPh 5g (9/1)
a General conditions: reactions were performed on a 0.1 mmol scale
in THF using a reactant ratio of 1:4:4.5 for dimer/Wittig salt/t-BuOK.
b Isolated yields. c 2 mmol scale.
aldehyde is not observed in THF by NMR, we contend that
t-BuOK promotes the reaction of the partially dissociated
dimer (Scheme 1, path B). The latter has been implicated in
(7) (a) For a recent example of strain-release rearrangement of N-vinyl
aziridines, see: Eckelbarger, J. D.; Wilmot, J. T.; Gin, D. Y. J. Am. Chem.
Soc. 2006, 128, 10370–10371. (b) For an excellent synthesis of seven-
membered lactams from vinyl aziridines, see: Lindstro¨m, U. M.; Somfai,
P. J. Am. Chem. Soc. 1997, 119, 8385–8386. (c) Lewis acid-catalyzed
rearrangements of vinyl aziridines: Brichacek, M.; Lee, D.; Njardarson, J. T.
Org. Lett. 2008, 10, 5023–5026. (d) Dynamic kinetic resolution of vinyl
aziridines: Trost, B. M.; Fandrick, D. R.; Brodmann, T.; Stiles, D. T. Angew.
Chem., Int. Ed. 2007, 46, 6123–6125.
Scheme 1. Vinyl Aziridine Synthesis: The Two Pathways
(8) See Ohno, H. Aziridines and Epoxides in Organic Synthesis; Yudin,
A. K., Ed.; John Wiley & Sons: New York, 2006.
(9) Stogryn, E. L.; Brois, S. J. J. Am. Chem. Soc. 1967, 89, 605–609.
(10) (a) Zamboni, R.; Rokach, J. Tetrahedron Lett. 1983, 24, 331–334.
(b) Lindstro¨m, U. M.; Somfai, P. Synthesis 1998, 109–117. (c) Olofsson,
B.; Wijtmans, R.; Somfai, P. Tetrahedron 2002, 58, 5979–5982.
(11) Ferrero, L.; Rouillard, M.; Decouzon, M.; Azzaro, M. Tetrahedron
Lett. 1974, 15, 131–134.
(12) Chaabouni, R.; Laurent, A. Synthesis 1975, 464–467.
(13) (a) Ohno, H.; Anzai, M.; Toda, A.; Ohishi, S.; Fujii, N.; Tanaka,
T.; Takemoto, Y.; Ibuka, T. J. Org. Chem. 2001, 66, 4904–4914. (b) Zhou,
J.; Magomedov, N. A. J. Org. Chem. 2007, 72, 3808–3815. (c) Morton,
D.; Pearson, D.; Field, R. A.; Stockman, R. A. Org. Lett. 2004, 6, 2377–
2380.
(14) (a) Yudin, A. K.; Hili, R. Chem.sEur. J. 2007, 13, 6538–6542.
(b) Hili, R.; Yudin, A. K. J. Am. Chem. Soc. 2006, 128, 14772–14773. (c)
Li, X.; Yudin, A. K. J. Am. Chem. Soc. 2007, 129, 14152–14153.
Org. Lett., Vol. 12, No. 2, 2010
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