Synthesis of Functionalized Styrenes and Aliphatic Alkenes
9
arsenic, and tellurium ylides. Although in these cases the
formation of stabilized phosphonium ylides was shown to be
inefficient, we believed that optimization of reaction conditions
using trimethylsilyldiazomethane could lead to the formation
of methylenetriphenylphosphorane. In addition to the cost of
rhodium complexes, the rhodium-catalyzed methylenation reac-
tion proved problematic with aromatic nitro-containing sub-
strates, leading to degradation reactions.7 As the nitro group
appeared to react with the metal center, we hypothesized that
the replacement of phosphine ligands with stronger σ-donor
e
1
0
ligands, such as N-heterocyclic carbenes (NHC), would
overcome this functional group compatibility problem. Further-
more, (NHC)-copper complexes have been reported to catalyze
FIGURE 1. (NHC)-copper complexes.
11,12
a number of reactions,
including cyclopropanation reactions
TABLE 1. Copper-Catalyzed Methylenation of Cinnamaldehyde
with diazo carbonyl compounds.1 Here, we disclose the use of
copper salts and (NHC)-copper complexes as catalysts for the
methylenation of aldehydes and ketones with trimethylsilyldia-
zomethane, triphenylphosphine, and 2-propanol. The transfor-
mation of substrates containing nitro, trifluoromethyl, amino,
ester, pyridine, pyrrole, and indole groups with aromatic
3
a
entry
CuX
conditions
conversion, %
(
NHC)-copper complexes (IPr and IMes, see Figure 1) is also
1
2
3
4
5
6
7
8
9
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuBr
CuBr
CuBr
CuI
THF, 25 °C, 16 h
ether, 25 °C, 24 h
DCM, 25 °C, 24 h
THF, 60 °C, 1 h
80
e5
e5
g95 (74)
70
85
g95
60
presented.
Results and Discussion
DCE, 60 °C, 3 h
dioxane, 60 °C, 24 h
dioxane, 80 °C, 3 h
toluene, 80 °C, 3 h
THF, 25 °C, 16 h
THF, 60 °C, 2 h
dioxane, 60 °C, 16 h
THF, 25 °C, 16 h
THF, 60 °C, 3 h
dioxane, 60 °C, 16 h
THF, 25 °C, 24 h
THF, 25 °C, 16 h
dioxane, 60 °C, 16 h
THF, 25 °C, 24 h
dioxane, 60 °C, 24 h
THF, 25 °C, 16 h
dioxane, 60°C , 16 h
THF, 25°C , 24 h
The mechanistic studies of the rhodium-catalyzed methyl-
enation reaction with trimethylsilyldiazomethane, triphenylphos-
phine, and 2-propanol showed the in situ formation of meth-
90
10
11
12
13
14
15
16
17
18
19
g95 (68)
g95
70
g95 (67)
g95
e5
60
75
80
70
(9) (a) Liao, Y.; Huang, Y. Z. Tetrahedron Lett. 1990, 31, 5897-5900.
(
6
b) Zhou, Z. L.; Huang, Y. Z.; Shi, L. L. Tetrahedron 1993, 49, 6821-
CuI
CuI
830.
(10) (a) Herrmann, W. A.; Kocher, C. Angew. Chem, Int. Ed. 1997, 36,
[Cu(MeCN)4]PF6
CuCl2
CuCl2
Cu(OAc)2
Cu(OAc)2
Cu(OTf)2
2
163-2187. (b) Arduengo, A. J., III Acc. Chem. Res. 1999, 32, 913-921.
(c) Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G. Chem. ReV. 2000,
1
4
1
2
2
00, 39-91. (d) Jafarpour, L.; Nolan, S. P. AdV. Organomet. Chem. 2001,
6, 181-222. (e) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290-
309. (f) Yong, B. S.; Nolan, S. P. Chemtracts: Org. Chem. 2003, 16, 205-
27. (g) Crudden, C. M.; Allen, D. P. Coord. Chem. ReV. 2004, 248, 2247-
273. (h) Crabtree, R. H. J. Organomet. Chem. 2005, 690, 5451-5457.
20
21
22
e5
50
e5
Cu(OTf)2
Cu(BF4)2‚6H2O
(
11) For structural studies of NHC-Cu complexes, see: (a) Arduengo,
A. J., III; Dias, H. V. R.; Calabrese, J. C.; Davidson, F. Organometallics
993, 12, 3405-3409. (b) Arnold, P. L.; Scarisbrick, A. C.; Blake, A. J.;
a
Conversion by GC-MS; isolated yields in parentheses.
1
Wilson, C. Chem. Commun. 2001, 2340-2341. (c) Arnold, P. L. Heteroat.
Chem. 2002, 13, 534-539. (d) Hu, X. L.; Castro-Rodriguez, I.; Meyer, K.
J. Am. Chem. Soc. 2003, 125, 12237-12245. (d) N-Heterocyclic Carbenes
in Synthesis; Nolan, S. P., Ed.; Wiley and Sons: New York, 2006.
7
e
ylenetriphenylphosphorane at room temperature. Under similar
reaction conditions with copper(I) chloride or (IMes)CuCl, we
observed the appearance of methylenetriphenylphosphorane by
(
12) (a) Guillen, F.; Winn, C. L.; Alexakis, A. Tetrahedron: Asymmetry
2
001, 12, 2083-2086. (b) Alexakis, A.; Winn, C. L.; Guillen, F.; Pytkowicz,
1
H NMR (C6D6). At room temperature, the formation of the
J.; Roland, S.; Mangeney, P. AdV. Synth. Catal. 2003, 345, 345-348. (c)
Jurkauskas, V.; Sadighi, J. P.; Buchwald, S. L. Org. Lett. 2003, 5, 2417-
phosphorus ylide was slow and did not reach completion,
whereas at 60 °C, the conversion was complete after 3 h. When
copper(I) chloride was tested in the methylenation of cinnama-
ldehyde in the presence of trimethylsilyldiazomethane, triph-
enylphosphine, and 2 propanol, good yields were obtained when
the reaction was carried out at 60 °C (Table 1, entry 4).
Numerous copper(I) complexes were found to be active in
this process, including copper(I) salts and (NHC)-copper(I)
complexes (Tables 1 and 2). Copper(II) salts also led to the
formation of the corresponding alkene, but reaction times proved
longer (Table 1, entries 16-22). More dissociative ligands led
to less active catalyst, as no conversion was observed at room
temperature with Cu(OTf)2 and Cu(BF4)2‚6H2O compared to
2
420. (d) Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. Organometallics
2
004, 23, 1157-1160. (e) Tominaga, S.; Oi, Y.; Kato, T.; An, D. K.;
Okamoto, S. Tetrahedron Lett. 2004, 45, 5585-5588. (f) Arnold, P. L.;
Rodden, M.; Davis, K. M.; Scarisbrick, A. C.; Blake, A. J.; Wilson, C.
Chem. Commun. 2004, 1612-1613. (g) Larsen, A. O.; Leu, W.; Nieto-
Oberhuber, C.; Campbell, J. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2004,
1
26, 11130-11131. (h) Clavier, H.; Coutable, L.; Guillemin, J. C.; Mauduit,
M. Tetrahedron: Asymmetry 2005, 16, 921-924. (i) D ´ı ez-Gonz a´ lez, S.;
Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. J. Org. Chem. 2005, 70,
4
5
784-4796. (j) Yun, J.; Kim, D.; Yun, H. Chem. Commun. 2005, 5181-
183. (k) Clavier, H.; Coutable, L.; Toupet, L.; Guillemin, J. C.; Mauduit,
M. J. Organomet. Chem. 2005, 690, 5237-5254. (l) Bantu, B.; Wang, D.
R.; Wurst, K.; Buchmeiser, M. R. Tetrahedron 2005, 61, 12145-12152.
(m) Okamoto, S.; Tominaga, S.; Saino, N.; Kase, K.; Shimoda, K. J.
Organomet. Chem. 2005, 690, 6001-6007. (n) Winn, C. L.; Guillen, F.;
Pytkowicz, J.; Roland, S.; Mangeney, P.; Alexakis, A. J. Organomet. Chem.
2
005, 690, 5672-5695. (o) Laitar, D. S.; Muller, P.; Sadighi, J. P. J. Am.
Chem. Soc. 2005, 127, 17196-17197. (p) Munro-Leighton, C.; Blue, E.
D.; Gunnoe, T. B. J. Am. Chem. Soc. 2006, 128, 1446-1447. (q) D ´ı ez-
Gonz a´ lez, S.; Scott, N. M.; Nolan, S. P. Organometallics 2006, 25, 2355-
(13) (a) Fructos, M. R.; Belderrain, T. R.; Nicasio, M. C.; Nolan, S. P.;
Kaur, H.; D ´ı az-Requejo, M. M.; P e´ rez, P. J. J. Am. Chem. Soc. 2004, 126,
10846-10847. (b) Diaz-Requejo, M. M.; Perez, P. J. J. Organomet. Chem.
2005, 690, 5441-5450. (c) Gawley, R. E.; Narayan, S. Chem. Commun.
2005, 5109-5111.
2
358. (r) D ´ı ez-Gonz a´ lez, S.; Correa, A.; Cavallo, L.; Nolan, S. P. Chem.
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J. Org. Chem, Vol. 72, No. 1, 2007 145