An effective C-C double bond formation via Cu(I)-catalyzed dehydrogenation

Article abstract of DOI:10.1016/j.tetlet.2010.01.114

A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C-C double bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.

Full text of DOI:10.1016/j.tetlet.2010.01.114

Tetrahedron Letters 51 (2010) 1822–1825
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An effective C–C double bond formation via Cu(I)-catalyzed dehydrogenation
Thomas A. Ramirez, Baoguo Zhao, Yian Shi *
Department of Chemistry, Colorado State University, Fort Collins, CO 80523, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-
tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C–C double
bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 8 November 2009
Revised 28 January 2010
Accepted 29 January 2010
Available online 4 February 2010
Keywords:
Dehydrogenation
Diamination
N,N-Di-tert-butylthiadiaziridine 1,1-dioxide
N,N-Di-tert-butyldiaziridinone
1
. Introduction
Metal-mediated and metal-catalyzed diamination of olefins
dine 1,1-dioxide (2) (2.5 equiv) (Scheme 2). While an exact mech-
anism awaits further study, this dehydrogenative diamination is
likely to proceed through a radical pathway as previously proposed
8
,16–20
provides an attractive approach to vicinal diamines, and has been
extensively investigated. Various effective systems have been
developed.
(Scheme 3).
Reduction of the N–N bond of N,N-di-tert-butyl-
1
thiadiaziridine 1,1-dioxide (2) by CuCl affords radical species 10,
which abstracts a hydrogen from alkene 8 to form radical 11 and
copper complex 12. Upon homolysis of the N–Cu bond of 12, the
resulting nitrogen radical abstracts another hydrogen from 11 to
form diene 13 and di-tert-butyl sulfamide 14 and regenerate the
2
–6
In our studies, we have shown that conjugated
dienes and trienes can be effectively diaminated with complemen-
tary regioselectivity using Pd(0) or Cu(I)8 as catalyst and N,N-di-
7
tert-butyldiaziridinone (1)9
,10
as nitrogen source. It has been
shown that terminal olefins (3) can undergo dehydrogenative
1
1,12
diamination with Pd(0)
as catalyst using N,N-di-tert-butyldiaz-
O
1
3
O
O
iridinone (1) or N,N-di-tert-butylthiadiaziridine 1,1-dioxide (2) as
the nitrogen source (Scheme 1). These two dehydrogenative diam-
inations proceed via different mechanisms. In one mechanism,
diene 4 is generated in situ and is subsequently diaminated regio-
selectively at the internal double bond to form 5. In general, the
diene intermediate could neither be isolated nor be detected. In
the other mechanism, allyl sulfonamide 6 is initially formed and
subsequently undergoes a Pd(II)-catalyzed cyclization to give 7.
The Cu(I)-catalyzed diamination is also effective toward activated
S
N
N
N
N
R
1
2
tBuHN
t
N Bu
R
R
S
Pd(0)
Pd(0)
O
4
3
O
6
O
O
S
O
N
N
N
N
1
4–16
terminal olefins such as styrenes, enynes, and enol ethers.
R
R
5
7
Herein, we wish to report that the system of CuCl with three-mem-
bered ring compound 1 or 2 also provides a valuable dehydrogena-
tion method to introduce C–C double bonds.
Scheme 1.
In our efforts to expand the scope of our diamination methodol-
ogies, it was found that alkenes such as 1-phenyl-2-butene (8) un-
dergo a dehydrogenative diamination to form 9 in 38% yield when
O
S
N
10 mol%
O
O
O
N
CuCl-PPh (1:1)
treated with 10 mol% CuCl–PPh
3
and N,N-di-tert-butylthiadiaziri-
3
+
S
Ph
65 oC, 16.5 h
Ph
N
N
8
2
9
3
8%
*
Corresponding author. Tel.: +1 970 491 7424; fax: +1 970 491 1801.
E-mail address: yian@lamar.colostate.edu (Y. Shi).
Scheme 2.
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.114

T. A. Ramirez et al. / Tetrahedron Letters 51 (2010) 1822–1825
1823
O
S
Table 1
tBuN
O
Cu(I)-catalyzed dehydrogenation
O
O
t
N Bu
S
R4
1
0 mol%
R4
Ph
tBuN N Bu
t
O
tBuN
O
NtBu
X
9
R1
CuCl-PPh3
R1
S
R3
+
N
N
R3
LCuCl
2
5 o
6
C
R2
R2
A: X = SO2
B: X = CO
LCu
Cl
1
0
Ph
L
O
S
O
tBuN
O
LCuCl
8
t
Bu
S
Aa Yieldc
(%)
Bb Yieldc
(%)
Cl Cu
t
Entry Substrate
Product
N
O
N Bu
N Bu
t
Ph
LCu
Cl
+
11
O
Ph
10
15
Ph
Ph
O
Ph
Ph
S
1
50
tBuN
LCu
Cl
NH Bu
t
Z/E = 8.4/1
Ph
13
12
+
2
3
4
63
43
50
62
69
O
O
tBuNH S NH Bu
t
1
4
Scheme 3.
O
O
O
O
O
CuCl catalyst. Diene 13 is subsequently diaminated at the terminal
double bond as previously described.16 Efforts to isolate the diene
by reducing the loading of 2 were unsuccessful, suggesting that the
diene was being rapidly diaminated as it was generated. Our pre-
vious studies showed that reactive substrates for the Cu(I)-cata-
lyzed diamination generally require the presence of a terminal
5
6
60
59
48
70
O
N
N
Ph
Ph
8
,14,16
double bond.
Therefore, it was envisioned that dehydrogena-
N
O
N
7
8
70
78
65
95
tion products could be isolated if they have no terminal double
bonds, thus providing a potentially useful method for the C–C dou-
ble bond formation. Toward this end, various substrates were sub-
jected to the dehydrogenation conditions.
Ph
Ph
O
Ph
Ph
Subjecting 1,4-diphenyl-2-butene to the reaction conditions
O
N
O
N
(
3
10 mol % CuCl–PPh , 2 equiv 2 at 65 °C without solvent) indeed
Ph
Ph
Ph
Ph
led to the formation of 1,4-diphenylbutadiene as a major product,
which was unreactive toward diamination under the reaction con-
ditions. (E,E)-1,4-Diphenyl-butadiene was isolated in 50% yield
Ph
Ph
9
0
73
62
68
80
O
N
O
N
(Table 1, entry 1, Method A). As shown in Table 1, dihydronaphtha-
lenes, tetralin, and dihydrocoumarin were effective substrates for
dehydrogenation (Table 1, entries 2–5). Further studies show that
various heterocycles were efficiently dehydrogenated (Table 1, en-
tries 6–10). The dehydrogenation provides a viable method to con-
vert oxazolines and thiazolines to their respective oxazoles and
thiazoles (Table 1, entries 8–10). N,N-Di-tert-butyldiaziridinone
Ph
Ph
1
S
N
S
N
a
Method A: The reactions were carried out with substrate (0.3 mmol), N,N-di-
tert-butylthiadiaziridine 1,1-dioxide (2) (0.6 mmol), and CuCl–PPh (1:1)
0.03 mmol) at 65 °C under argon for 20 h unless otherwise stated. For entry 5, the
3
(
(
1
1) can also be used for the dehydrogenation in most cases (Table
, Method B). A representative example for the plausible catalytic
cycle of the dehydrogenation using N,N-di-tert-butyldiaziridinone
reaction was run on 1/3 scale. For entry 9, the reaction was run on 1.5 scale. For
entry 4, N,N-di-tert-butylthiadiaziridine 1,1-dioxide (2) (1.2 mmol) was employed.
b
Method B: The reactions were carried out with substrate (1.0 mmol), N,N-di-
tert-butyldiaziridinone (1) (2.0 mmol), and CuCl–PPh
CD Cl at 65 °C under argon for 12 h unless otherwise stated. For entries 7 and 8, the
reaction was run on 1/2 scale. For entries 5 and 10, the reaction was run in CDCl
3
(1:1) (0.1 mmol) in 0.26 mL
(1) is shown in Scheme 4.
2
2
In summary, various substrates such as carbocycles and hetero-
3
.
cycles can be effectively dehydrogenated under mild conditions
using CuCl–PPh and 1 or 2 to allow the introduction of C–C double
bond(s). This can be particularly useful in the generation of oxaz-
For entry 9, the reaction was run on 4.48 mmol scale in 3 mL CHCl
3
for 14 h.
c
Isolated yield based on substrate.
3
2
1
2
2
oles and thiazoles from oxazolines and thiazolines, respectively.
O
O
O
As indicated in Scheme 3, this dehydrogenation involves a radical
process, and as a result, effective substrates require one or more
radical-stabilizing groups such as aromatic groups, alkenyl groups,
and/or hetero atoms to facilitate radical generation.
Ph
N
+
t
t
t
t
Bu HN NH Bu
Bu N N Bu
LCuCl
1
O
O
O
t
t
2
2
. Experimental section
Ph
N
+ Bu N
NH Bu
t
t
Bu N
N Bu
L Cu
L Cu
Cl
Cl
.1. Dehydrogenative diamination of 1-phenyl-2-butene (8)
(Scheme 2)
O
N
To an oven-dried 1.5-mL vial equipped with a magnetic stir bar
Ph
were added CuCl (0.0015 g, 0.015 mmol) and PPh
.015 mmol). The vial was sealed with a rubber septum, evacuated,
and then filled with argon. This process was repeated three times.
3
(0.004 g,
0
Scheme 4.

1
824
T. A. Ramirez et al. / Tetrahedron Letters 51 (2010) 1822–1825
1
(
-Phenyl-2-butene (8) (0.0198 g, 0.15 mmol) and dry
0.060 mL) were then added. The vial was then immersed in an oil
bath set at 65 °C. A solution of N,N-di-tert-butylthiadiaziridine
,1-dioxide (2) (0.078 g, 0.375 mmol) in dry C (0.14 mL) was
added to the reaction mixture dropwise with a syringe pump over
.5 h. After the addition was complete, the reaction mixture was
C
6
D
6
Supplementary data
Supplementary data (the preparation of N,N-di-tert-butylthi-
adiaziridine 1,1-dioxide (2), the characterization of dehydrogenation
products, and the NMR spectra) associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2010.01.114.
1
6 6
D
2
stirred for an additional 14 h. At this point, the crude reaction mix-
ture was concentrated and then purified by flash column chroma-
References and notes
tography (SiO
0:1 hexanes/ether, v/v) to give the diamination product 9 as a
white solid (0.019 g, 38%). mp 157–160 °C; IR (film): 1282,
2
, hexanes, 50:1 hexanes/ether, 25:1 hexanes/ether,
1
1. For leading reviews, see: (a) Lucet, D.; Gall, T. L.; Mioskowski, C. Angew. Chem.,
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À1
1
1
6
3
3
139 cm ; H NMR (300 MHz, CDCl ) d 7.43–7.24 (m, 5H), 6.62–
2006, 67, 101; (d) de Figueiredo, R. M. Angew. Chem., Int. Ed. 2009, 48, 1190; (e)
.40 (m, 2H), 4.24–4.16 (m, 1H), 3.55 (dd, J = 8.6, 6.5 Hz, 1H),
Cardona, F.; Goti, A. Nat. Chem. 2009, 1, 269.
.09 (dd, J = 8.6, 3.6 Hz, 1H), 1.46 (s, 9H), 1.41 (s, 9H); 13C NMR
2. For examples of metal-mediated diaminations, see: Tl (a) Aranda, V. G.;
Barluenga, J.; Aznar, F. Synthesis 1974, 504; Os: (b) Chong, A. O.; Oshima, K.;
Sharpless, K. B. J. Am. Chem. Soc. 1977, 99, 3420; (c) Muñiz, K. Eur. J. Org. Chem.
(
3
75 MHz, CDCl ) d 136.3, 131.7, 130.6, 128.9, 128.3, 126.8, 57.9,
5
6.5, 55.7, 47.5, 28.8, 27.6.
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Barluenga, J.; Alonso-Cires, L.; Asensio, G. Synthesis 1979, 962; Co: (f) Becker, P.
N.; White, M. A.; Bergman, R. G. J. Am. Chem. Soc. 1980, 102, 5676; Mn: (g)
Fristad, W. E.; Brandvold, T. A.; Peterson, J. R.; Thompson, S. R. J. Org. Chem.
1985, 50, 3647.
For recent Cu(II)-mediated intramolecular diamination, see: (a) Zabawa, T. P.;
Kasi, D.; Chemler, S. R. J. Am. Chem. Soc. 2005, 127, 11250; (b) Zabawa, T. P.;
Chemler, S. R. Org. Lett. 2007, 9, 2035.
2
1
.2. Representative dehydrogenation procedure using 2 (Table
, entry 9, Method A)
3.
To an oven-dried 1.5-mL vial equipped with a magnetic stir bar
were added CuCl (0.0045 g, 0.045 mmol) and PPh
3
(0.012 g,
4. For recent Pd(II)- and Ni(II)-catalyzed intramolecular diamination of olefins,
see: (a) Streuff, J.; Hövelmann, C. H.; Nieger, M.; Muñiz, K. J. Am. Chem. Soc.
0
.045 mmol). (Note: In cases where the substrate was a solid, it
2005, 127, 14586; (b) Muñiz, K.; Streuff, J.; Hövelmann, C. H.; Núñez, A. Angew.
was added at this point.) The vial was sealed with a rubber septum,
evacuated, and then filled with argon. This process was repeated
three times. 2-Phenyl oxazoline (0.066 g, 0.45 mmol) was then
added with a syringe. The reaction mixture was then stirred for
Chem., Int. Ed. 2007, 46, 7125; (c) Muñiz, K. J. Am. Chem. Soc. 2007, 129, 14542;
(d) Muñiz, K.; Hövelmann, C. H.; Streuff, J. J. Am. Chem. Soc. 2008, 130, 763; (e)
Sibbald, P. A.; Michael, F. E. Org. Lett. 2009, 11, 1147.
5
.
.
2
For Rh(II)- and Fe(III)-catalyzed diamination with TsNCl , see: (a) Li, G.; Wei,
H.-X.; Kim, S. H.; Carducci, M. D. Angew. Chem., Int. Ed. 2001, 40, 4277; (b) Wei,
H.-X.; Kim, S. H.; Li, G. J. Org. Chem. 2002, 67, 4777.
2
min, and N,N-di-tert-butylthiadiaziridine 1,1-dioxide (2)
6
For
a recent example of Pd(II)-catalyzed intermolecular diamination of
(
0.186 g, 0.90 mmol) was added via a syringe. The vial was then
conjugated dienes, see: Bar, G. L. J.; Lloyd-Jones, G. C.; Booker-Milburn, K. I. J.
Am. Chem. Soc. 2005, 127, 7308.
7. For Pd(0)-catalyzed intermolecular diamination of conjugated dienes and
trienes using N,N-di-tert-butyldiaziridinone, see: (a) Du, H.; Zhao, B.; Shi, Y. J.
Am. Chem. Soc. 2007, 129, 762; (b) Xu, L.; Du, H.; Shi, Y. J. Org. Chem. 2007, 72,
immersed into an oil bath set at 65 °C and stirred for 20 h. The vial
was cooled to room temperature and the residue was purified by
flash column chromatography (SiO
0:1 hexanes/ether, 12:1 hexanes/ether, v/v) to afford 2-phenyl
oxazole as a colorless oil (0.0475 g, 73%). IR (film): 1587, 1557,
2
, hexanes, 50:1 hexanes/ether,
2
7038; (c) Du, H.; Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 11688;
(
d) Xu, L.; Shi, Y. J. Org. Chem. 2008, 73, 749; (e) Du, H.; Zhao, B.; Shi, Y. Org.
À1
1
1
483 cm
;
H NMR (300 MHz, CDCl
3
) d 8.08–8.02 (m, 2H), 7.72
Synth. 2009, 86, 315.
1
3
8. For Cu(I)-catalyzed intermolecular diamination of conjugated dienes and
trienes using N,N-di-tert-butyldiaziridinone, see: (a) Yuan, W.; Du, H.; Zhao,
B.; Shi, Y. Org. Lett. 2007, 9, 2589; (b) Du, H.; Zhao, B.; Yuan, W.; Shi, Y. Org. Lett.
2008, 10, 4231.
(
d, J = 0.9 Hz, 1H), 7.50–7.44 (m, 3H), 7.24 (d, J = 0.9 Hz, 1H);
C
3
NMR (75 MHz, CDCl ) 162.2, 138.8, 130.6, 129.0, 128.6, 127.7,
1
26.6.
9. Greene, F. D.; Stowell, J. C.; Bergmark, W. R. J. Org. Chem. 1969, 34, 2254.
1
0. For a leading review on diaziridinones, see: Heine, H. W. In The Chemistry of
Heterocyclic Compounds; Hassner, A., Ed.; John Wiley & Sons, Inc.: Hoboken, NJ,
1983; p 547.
2
1
.3. Representative dehydrogenation procedure using 1 (Table
, entry 9, Method B)
1
1. For Pd(0)-catalyzed intermolecular allylic and homoallylic C-H diamination of
terminal olefins using N,N-di-tert-butyldiaziridinone, see: (a) Du, H.; Yuan, W.;
Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 7496; (b) Du, H.; Zhao, B.; Shi, Y. J.
Am. Chem. Soc. 2008, 130, 8590.
To an oven-dried 25 mL-round bottomed flask equipped with a
magnetic stir bar were added CuCl (0.045 g, 0.45 mmol) and PPh
0.12 g, 0.45 mmol) (Note: In cases where the substrate was a solid,
3
1
2. For Pd(0)-catalyzed dehydrogenative diamination of terminal olefins using
N,N-di-tert-butylthiadiaziridine 1,1-dioxide, see: Wang, B.; Du, H.; Shi, Y.
Angew. Chem., Int. Ed. 2008, 47, 8224.
(
it was added at this point). The flask was sealed with a rubber sep-
tum, evacuated, and then filled with argon. This process was re-
peated three times. CHCl (3 mL) was then added with a syringe,
3
followed by 2-phenyl oxazoline (0.66 g, 4.48 mmol). The reaction
mixture was then immersed in an oil bath set at 65 °C, stirred for
13. For a leading reference on N,N-di-tert-butylthiadiaziridine 1,1-dioxide, see:
Timberlake, J. W.; Alender, J.; Garner, A. W.; Hodges, M. L.; Özmeral, C.;
Szilagyi, S.; Jacobus, J. O. J. Org. Chem. 1981, 46, 2082.
1
4. For Cu(I)-catalyzed intermolecular diamination of conjugated dienes, trienes,
and activated terminal olefins using diaziridinimine, see Zhao, B.; Du, H.; Shi, Y.
Org. Lett. 2008, 10, 1087.
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2
9
min, and then N,N-di-tert-butyldiaziridinone (1) (1.63 g,
.58 mmol) was added with a syringe pump over 10 h. After the
1
addition was complete, the reaction mixture was stirred for an
additional 4 h. At this point, the crude reaction mixture was con-
centrated and then purified by flash column chromatography
16. For Cu(I)-catalyzed intermolecular diamination of activated terminal olefins
using N,N-di-tert-butylthiadiaziridine 1,1-dioxide and N,N-di-tert-
butyldiaziridinone, see: (a) Zhao, B.; Yuan, W.; Du, H.; Shi, Y. Org. Lett. 2007,
, 4943; (b) Wen, Y.; Zhao, B.; Shi, Y. Org. Lett. 2009, 11, 2365.
(
SiO
anes/ether, v/v) to afford 2-phenyl oxazole as a colorless oil (0.45 g,
8%).
2
, hexanes, 50:1 hexanes/ether, 25:1 hexanes/ether, 10:1 hex-
9
17. For a leading review on metal-promoted radical reactions, see: Iqbal, J.; Bhatia,
B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519.
6
1
8. For leading reviews on CuX-catalyzed atom transfer reactions see: (a) Patten, T.
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Acknowledgments
1
We are grateful for the generous financial support from the
General Medical Sciences of the National Institutes of Health
2
(
GM083944-02) and are also grateful to Bristol-Myers Squibb for
the Minority Chemist Fellowship awarded to T.A.R.

T. A. Ramirez et al. / Tetrahedron Letters 51 (2010) 1822–1825
1825
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