Nickel-catalyzed reactions of vinyl aziridines and aziridinylen-ynes

Article abstract of DOI:10.1016/j.tetlet.2008.09.056

Ni/NHC was found to catalyze the rearrangement of vinyl aziridines and aziridinylen-ynes under mild conditions.

Full text of DOI:10.1016/j.tetlet.2008.09.056

Tetrahedron Letters 49 (2008) 6797–6799
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Tetrahedron Letters
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Nickel-catalyzed reactions of vinyl aziridines and aziridinylen-ynes
*
Gang Zuo, Kainan Zhang, Janis Louie
University of Utah, Department of Chemistry, 315 South 1400 East, Salt Lake City, UT 84112, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Ni/NHC was found to catalyze the rearrangement of vinyl aziridines and aziridinylen-ynes under mild
conditions.
Received 27 August 2008
Accepted 10 September 2008
Available online 15 September 2008
Published by Elsevier Ltd.
Keywords:
Nickel catalyst
N-Heterocyclic carbene
Vinyl aziridine
Aziridinylen-ynes
Imines
Heterocycles
A primary interest of our group is the development of efficient
cycloadditions that afford heterocycles and carbocycles. We have
found that Ni/NHC complexes effectively catalyze the cycloaddi-
tion of diynes with CO2,1 isocyanates,2 carbonyls,3 and nitriles.4
These reactions afford pyrones, pyridones, pyrimidinones, pyrans,
and pyridines in high yields. In addition, the same Ni/NHC system
also mediates the rearrangement of vinyl cyclopropanes5 and
cyclopropylen-ynes.6 As part of our continuing effort in this field,7
we present our investigations involving the Ni-catalyzed reactions
of vinyl aziridines8,9 and aziridinylen-ynes.
It is known that the type of protecting group can have a large
influence on the product that is obtained.8,14–16 As such, a variety
of vinylaziridines containing different protecting groups were
investigated using Ni(COD)2/NHC as catalyst (Eq. 2, Table 2).17 Most
vinylaziridines underwent rearrangements at room temperature
except 1-tosyl vinylaziridine (1f),18 which destroyed the catalyst
(entry 7). The Ni/NHC-catalyzed rearrangements of vinylaziridines
were highly substrate-dependent. 1-Benzoyl vinylaziridine (1b),19
1-Boc vinylaziridine (1c),20 and 1-methoxycarbonyl vinylaziridine
(1d)21 were isomerized to the corresponding 5-vinyl-2-oxazoline
(entries 2–4).22,23 Interestingly, the Ni/IPr-catalyzed rearrangement
5 mol% Ni(COD)2
Tr
N
of 1-benzhydryl vinylaziridine (1e)24 did not afford an
a,b-unsatu-
10 mol% ligand
N
rated imine. Instead, a 1,3-butadienylamine (2e) was obtained
(entry 5). However, when IPr was replaced with its saturated ana-
ð1Þ
Tr
1a
log, SIPr, 1e was converted to the expected
a
,b-unsaturated imine
2e0 (entry 6).
The Ni-catalyzed rearrangement of 1-trityl-2-vinylaziridine
(1a)10 was investigated, and a variety of tertiary phosphines and
N-heterocyclic carbene ligands (NHCs)11 were explored as potential
ligands (Eq. 1, Table 1). In most cases, no reaction was observed (en-
tries 2–7). However, when IPr was employed, vinylaziridine 1a was
Table 1
Ni-catalyzed rearrangements of 1aa
Entry
Ligand
% Conv. of 1ab
smoothly converted to an
a
,b-unsaturated imine 2a12 (entry 1).13
1
2
3
4
5
6
7
8
IPr
100
Trace
No rearrangement was observed in the absence of ligand (entry 8).
SIPr
IMes
ItBu
PPh3
PCy3
PBu3
—
0
0
0
0
0
0
5 mol% Ni(COD)2
10 mol% NHC
R
N
Product
ð2Þ
1
a
Reaction conditions: 5 mol % Ni(COD)2, 10 mol % ligand, toluene, 60 °C,
overnight.
* Corresponding author. Tel.: +1 801 581 7309; fax: +1 801 581 8433.
E-mail address: louie@chem.utah.edu (J. Louie).
b
Determined by GC using naphthalene as an internal standard.
0040-4039/$ - see front matter Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2008.09.056

6798
G. Zuo et al. / Tetrahedron Letters 49 (2008) 6797–6799
Table 2
Table 3
Ni-catalyzed rearrangements of vinylaziridinesa
Ni-catalyzed rearrangements of 4aa
Entry
1
R
NHC
IPr
Productb
Entry
L
time (h)
Ratiob 5a:6a:7a
% Conversion of 4a
1
2
3
4
5
6
7
None
PPh3
PBu3
IMes
IPr
12
12
12
6
2
6
—
—
—
0
0
0
100
100
100
100
N
Tr (1a)
2a
Tr
1:2:trace
1:1:trace
4:1:trace
Trace:trace:1
R'
2
3
4
Bz (1b)
Boc (1c)
MeO2C (1d)
IPr
IPr
IPr
R' = Ph (2b)
O
R' = OBut (2c)
R' = OMe (2d)
SIPr
ItBu
N
2
a
H
N
Reaction conditions: 5 mol % Ni(COD)2, 10 mol % ligand, C6D6, 60 °C.
5
6
CHPh2 (1e)
IPr
Determined by 1H NMR.
2e
b
Ph2HC
N
CHPh2 (1e)
Ts (1f)
SIPr
IPr
2e'
Ph2HC
7
N.R.
O
O
a
Reaction conditions: 5 mol % Ni(COD)2, 10 mol % NHC, toluene, overnight.
Determined by 1H NMR.
b
N
N
tBu
CHPh2
The rearrangement of vinylaziridines to imines or 1,3-butadie-
4b
4c
nylamines can be rationalized by the formation of a key
Ni complex (Scheme 1). Due to the difficulty of reductive elimina-
tion of C(sp3)–N bond,25 this
-allyl/Ni complex undergoes
p-allyl/
Figure 1. Aziridinylen-ynes.
p
b-hydride elimination followed by reductive elimination. 1,3-Buta-
dienylamine or imine arises from metallazetidine intermediate
(3e0) or metallapiperidine intermediate (3e), respectively.
tween these two azepines even at lower catalyst loading and less
reaction time. In contrast, the Ni/ItBu-catalyzed rearrangement of
aziridinylen-yne 4a gave a conjugated unsaturated imine (7a)
selectively, which is consistent with the Ni/ItBu-catalyzed rear-
rangement of cyclopropyen-yne.6
In an effort to block competing b-hydride elimination pathways,
the cycloaddition of a vinyl aziridine possessing a tethered alkyne
was evaluated. 1-Trityl-2-(3-(2-butynyloxy)-1-propenyl)-aziridine
(4a)26 was subjected to the standard cycloaddition conditions in
the presence of a variety of ligands (Table 3). No rearrangement
was observed in the absence of ligand or when tertiary phosphines
were used as ligands (entries 1–3). However, aziridinylen-yne 4a
did react when NHCs were employed (entries 4–7). Interestingly,
the rearrangement of aziridinylen-yne 4a afforded three different
products whose ratios were dependent on which NHC ligand was
employed. NHCs possessing an aromatic side chain (IPr, SIPr, and
IMes) afforded two different azepines (5a and 6a). IMes favored
the formation of azepine 6a (entry 4), whereas SIPr favored the for-
mation of azepine 5a (entry 6).27 IPr showed no selectivity be-
O
O
O
O
5 mol% Ni(COD)2
10 mol% ligand
+
+
ð3Þ
N
Tr
N
N
Tr
Tr
TrN
4a
5a
6a
7a
Other aziridinylen-ynes possessing a bulky protecting group
(i.e., t-butyl (4b)28 and benzhydryl (4c),29 Fig. 1) also underwent
Ni-catalyzed rearrangement reactions. Conjugated imine products
(7b,c) were again observed exclusively, when ItBu was employed.
Similarly, a mixture of bicyclic azepines (i.e., 5b,c and 6b,c) was ob-
served, when N-aryl NHCs (i.e., IMes, IPr, SIPr) were employed.
Interestingly, azepines 5 and 6 appear to arise from C–C cleavage,
rather than C–N cleavage, of the aziridine ring. It is possible that
the steric hindrance of N-protecting groups prevents the nitrogen
atom from coordinating to nickel center and disfavors C–N bond
cleavage.
In summary, the combination of Ni(COD)2 and a bulky NHC
ligand serves as a catalyst for the rearrangement of vinyl aziridines
and aziridinylen-ynes. Vinyl aziridines were typically converted to
straight chain products. Aziridinylen-ynes afforded a mixture of
heterocyclic products. Mechanistic investigations are ongoing.
R
R
N
R
Ni(COD)2
NHC
N
N
Ni
R = CHPh2, 1e
R
N
R
H
Ni
N
Ni
H
3e
β -H
elim.
3e'
β
-H
elim.
Acknowledgments
H
Ni
N
N
R
H
R
Ni
We gratefully acknowledge Merck, the Alfred P. Sloan Founda-
tion, and the NIGMS for support of this research.
R
R
References and notes
H
N
N
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Louie, J. Tetrahedron 2006, 62, 7547.
2e'
2e
Scheme 1. Proposed mechanism of rearrangements of vinylaziridines.

G. Zuo et al. / Tetrahedron Letters 49 (2008) 6797–6799
6799
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20. Compound 1c: 1H NMR (300 MHz, C6D6, ppm): d 5.35 (ddd, 17.1 Hz, 9.9 Hz,
7.2 Hz, 1H), 5.20 (dd, 17.1 Hz, 1.8 Hz, 1H), 4.95 (dd, 9.9 Hz, 1.8 Hz, 1H), 2.62–
2.68 (m, 1H), 2.10 (d, 6.3 Hz, 1H), 1.80 (d, 3.6 Hz, 1H), 1.35 (s, 9H); 13C{1H} NMR
(75 MHz, C6D6, ppm): d 161.8, 135.9, 117.8, 80.4, 39.2, 32.6, 27.9.
21. Aumann, R.; Froehlich, K.; Ring, H. Angew. Chem. 1974, 86, 309.
22. (a) Heine, H. W.; Proctor, Z. J. Org. Chem. 1958, 23, 1554; (b) Heine, H. W.;
Fetter, M. E.; Nicholson, E. M. J. Am. Chem. Soc. 1959, 81, 2202; (c) Heine, H. W.;
Kenyon, W. G.; Johnson, E. M. J. Am. Chem. Soc. 1961, 83, 2570; (d) Nishiguchi,
T.; Tochio, H.; Nabeya, A.; Iwakura, Y. J. Am. Chem. Soc. 1969, 91, 5835;
Nishiguchi, T.; Tochio, H.; Nabeya, A.; Iwakura, Y. J. Am. Chem. Soc. 1969, 91,
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6. Zuo, G.; Louie, J. J. Am. Chem. Soc. 2005, 127, 5798.
7. Zhang, K.; Chopade, P. R.; Louie, J. Tetrahedron Lett. 2008, 27, 4306.
8. Thermal or nucleophile-promoted rearrangements of vinylaziridines generally
lead to two different tautomers of pyrroline (a) Atkinson, R. S.; Rees, C. W.
Chem. Commun. 1967, 1232; (b) Gilchrist, T. L.; Rees, C. W.; Stanton, E. J. Chem.
Soc (C) 1971, 3036; (c) Hudlicky, T.; Frazier, J. O.; Seoane, G.; Tiedje, M.; Seoane,
A.; Kwart, L. D.; Beal, C. J. Am. Chem. Soc. 1986, 108, 3755; (d) Hudlicky, T.;
Seoane, G.; Lovelace, T. C. J. Org. Chem. 1988, 53, 2094; (e) Hudlicky, T.; Sinai-
Zingde, G.; Seoane, G. Synth. Commun. 1987, 17, 1155; (f) Hirner, S.; Somfai, P.
Synlett 2005, 3099.
23. A similar reaction has been observed in the Ni-catalyzed rearrangement of
acylvinylcyclopropanes to dihydrofurans: Bowman, R. K.; Johnson, J. S. Org.
Lett. 2006, 8, 573.
24. Compound 1e: 1H NMR (300 MHz, CDCl3, ppm): d 7.15–7.83 (m, 11H), 5.68 (m,
1H), 5.26 (dd, 17.1 Hz, 1.2 Hz, 1H), 5.11 (dd, 10.2 Hz, 1.2 Hz, 1H), 3.59 (s, 1H),
2.11 (m, 1H), 1.88 (d, 3.3 Hz, 1H), 1.73 (d, 6.6 Hz, 1H).
9.
A rare Pd(PPh3)4-catalyzed rearrangement of vinyl aziridines has been
reported: (a) Fugami, K.; Morizawa, Y.; Oshima, K.; Nozaki, H. Tetrahedron
Lett. 1985, 26, 857; (b) Fugami, K.; Miura, K.; Morizawa, Y.; Oshima, K.;
Utimoto, K.; Nozaki, H. Tetrahedron. 1989, 45, 3089.
25. (a) Koo, K.; Hillhouse, G. L. Organometallics 1996, 15, 2669; (b) Lin, B. L.; Clough,
C. R.; Hillhouse, G. L. J. Am. Chem. Soc. 2002, 124, 2890; (c) Macgregor, S. A.;
Neave, G. W.; Smith, C. Faraday Discuss. 2003, 124, 111.
10. Compound 1a: 1H NMR (300 MHz, CDCl3, ppm): d 7.48 (d, 7.2 Hz, 6H), 7.20–
7.30 (m, 9H), 5.83 (ddd, 7.8 Hz, 10.2 Hz, 17.4 Hz, 1H), 5.25 (d, 17.4 Hz, 1H), 5.16
(d, 10.2 Hz, 1H), 1.81 (d, 3.0 Hz, 1H), 1.69–1.73 (m, 1H), 1.35 (d, 6.0 Hz, 1H);
13C{1H} NMR (75 MHz, CDCl3, ppm): d 144.6, 139.4, 129.8, 127.6, 126.8, 116.5,
74.5, 35.0, 29.2.
26. 1-Trityl-2-(3-(2-butynyloxy)-1-propenyl)-aziridine (4a): 1H NMR (300 MHz,
CDCl3, ppm): d 7.28 (d, 7.2 Hz, 6H), 7.20–7.29 (m, 9H), 5.75–5.77 (m, 2H),
4.11–4.13 (m, 2H), 4.06–4.08 (m, 2H), 1.88 (t, 1.8 Hz, 3H), 1.80–1.81 (m, 1H),
1.75–1.78 (m, 1H), 1.24 (d, 6.3 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3, ppm): d
144.6, 135.6, 129.7, 128.0, 127.6, 126.9, 82.6, 74.5, 69.7, 58.4, 57.4, 33.9, 29.3,
3.8.
11. IPr = 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene; SIPr
diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene; IMes
=
1,3-bis(2,5-
1,3-bis(2,4,6-
=
trimethylphenyl)-imidazol-2-ylidene; ItBu
=
1,3-di-tert-butylimidazol-2-
27. Azepine 5a could be isolated in 66% yield. Unfortunately, azepine 6a
decomposed upon all purification attempts.
ylidene.
12. Compound 2a: 1H NMR (300 MHz, CDCl3, ppm): d 7.61 (d, 1H), 7.49 (d, 6H),
7.09-7.20 (m, 9H), 6.60 (dd, 1H), 5.53 (dq, 1H), 1.45 (d, 3H).
General procedure: In a glove box, 2-(3-(2-butynyloxy)-1-propenyl)-1-
triphenylmethyl-aziridine (4a, 50 mg, 0.13 mmol) was added to an oven
13. 1,5-H shifts of vinyl aziridines to conjugated imines have been observed: (a)
Borel, D.; Gelas-Mialhe, Y.; Vessière, R. Can. J. Chem. 1976, 54, 1590; (b)
Hudlicky, T.; Frazier, J. O.; Kwart, L. D. Tetrahedron Lett. 1985, 26, 3523; (c)
Pearson, W. H. Tetrahedron Lett. 1985, 26, 3527.
14. Hudlicky, T.; Reed, J. W. In Comprehensive Organic Synthesis; Trost, B., Fleming,
I., Paquette, L. A., Eds.; Pergamon: Oxford, 1992; Vol. 5, p 899.
15. (a) Scheiner, P. J. Org. Chem. 1967, 32, 2628; (b) Pommelet, J. C.; Chuche, J. Can. J.
Chem. 1976, 54, 1571; (c) Figeys, H. P.; Jammar, R. Tetrahedron Lett. 1980, 21,
2995; (d) Figeys, H. P.; Jammar, R. Tetrahedron Lett. 1981, 22, 637.
16. (a) Mente, P. G.; Heine, H. W.; Scharoubim, G. R. J. Org. Chem. 1968, 33, 4547;
(b) Heine, H. W.; Mente, P. G. J. Org. Chem. 1971, 36, 3076.
dried scintillation vial equipped with a magnetic stir bar and was dissolved in
toluene (0.5 mL). To the stirring solution,
a solution of Ni(COD)2 (2 mg,
0.007 mmol) and SIPr (5 mg, 0.013 mmol) was added. The reaction mixture
was stirred at room temperature overnight (or until complete consumption of
starting material was observed as judged by GC or TLC). The mixture was
concentrated in vacuo and purified by silica gel column chromatography (10%
Et2O/pentanes) to afford 3-(1,3-butadienyl)-4-ethylidenetetrahydrofuran (5a,
33 mg, 66%) as a colorless oil. 1H NMR (300 MHz, C6D6, ppm): d 7.48 (d, 7.2 Hz,
6H), 6.97–7.14 (m, 9H), 6.47 (d, 9.3 Hz, 1H), 4.70–4.90 (m, 4H), 4.59 (d, 9.3 Hz,
1H), 3.34 (dd, 1.5 Hz, 12.9 Hz, 1H), 2.76–2.83 (m, 1H), 2.41 (dd, 7.8 Hz, 12.9 Hz,
1H), 0.60 (d, 7.2 Hz, 3H); 13C{1H} NMR (75 MHz, C6D6, ppm): d 144.8, 141.3,
133.6, 130.0, 129.0, 127.2, 94.9, 80.1, 79.4, 56.0, 36.0, 17.5.
17. Compound 2b: 1H NMR (300 MHz, CDCl3, ppm): d 8.09 (d, 2H), 7.04–7.10 (m,
3H), 5.26 (ddd, 1H), 5.10 (dd, 1H), 4.90 (dd, 1H), 4.89 (dt, 1H), 3.83 (dd, 1H),
3.59 (dd, 1H). Compound 2c: 1H NMR (300 MHz, CDCl3, ppm): d 5.60 (ddd, 1H),
5.03 (dd, 1H), 4.83 (dd, 1H), 4.50 (dt, 1H), 3.72 (dd, 1H), 3.40 (dd, 1H), 1.50 (s,
9H). Compound 2e: 1H NMR (300 MHz, CDCl3, ppm): d 7.42–7.54 (m, 4H), 7.10–
7.20 (m, 6H), 6.32 (dt, 1H), 6.08 (dd, 1H), 5.24 (dd, 1H), 5.18 (d, 1H), 4.92 (dd,
1H), 4.78 (dd, 1H), 3.25 (br, 1H) ppm. Compound 2e0: 1H NMR (300 MHz, CDCl3,
ppm): d 7.79 (d, 1H), 7.49 (d, 4H), 7.09–7.20 (m, 6H), 6.43 (dd, 1H), 5.76 (dq,
1H), 5.32 (s, 1H), 1.45 (d, 3H).
28. 1-tert-Butyl-2-(3-(2-butynyloxy)-1-propenyl)-aziridine (4b): 1H NMR (300 MHz,
CDCl3, ppm): d 5.81 (dt, 6.6 Hz, 15.6 Hz, 1H), 5.48 (dd, 7.8 Hz, 15.6 Hz, 1H),
4.05–4.07 (m, 2H), 3.99 (d, 6.6 Hz, 2H), 2.11–2.15 (m, 1H), 1.8 (t, 1.8 Hz, 3H),
1.69 (d, 6.6 Hz, 1H), 1.50 (d, 3.0 Hz, 1H), 0.97 (s, 9H); 13C{1H} NMR (75 MHz,
CDCl3, ppm): d 136.2, 127.2, 82.6, 75.3, 69.9, 57.7, 53.3, 32.8, 28.4, 26.7, 3.8.
29. 1-Benzhydryl-2-(3-(2-butynyloxy)-1-propenyl)-aziridine (4c): 1H NMR (300
MHz, C6D6, ppm): d 7.43–7.56 (m, 4H), 7.04–7.16 (m, 6H), 5.75 (dt, 5.4 Hz,
15.3 Hz, 1H), 5.62 (dd, 7.2 Hz, 15.3 Hz, 1H), 4.02 (q, 2.1 Hz, 2H), 3.94 (d, 5.4 Hz,
2H), 3.33 (s, 1H), 1.80–1.84 (m, 1H), 1.62 (d, 3.3 Hz, 1H), 1.47 (t, 2.1 Hz, 3H),
1.33 (d, 6.6 Hz, 1H); 13C{1H} NMR (75 MHz, C6D6, ppm): d 144.2, 144.0, 133.5,
127.2, 127.0, 82.0, 78.4, 76.1, 69.3, 57.5, 40.7, 35.8, 3.2.
18. (a) Trost, B. M.; Fandrick, D. R. J. Am. Chem. Soc. 2003, 125, 11836; (b) Ali, S. I.;
Nikalje, M. D.; Sudalai, A. Org. Lett. 1999, 1, 705.
19. Charrier, N.; Gravestock, D.; Zard, S. Z. Angew. Chem., Int. Ed. 2006, 45, 6520.