Nickel-catalyzed carbonylative Negishi cross-coupling reactions

Article abstract of DOI:10.1016/j.tetlet.2008.03.035

Catalytic carbonylative Negishi cross-coupling reactions are described. This method readily provides various enones from enol triflates and diorganozinc reagents with catalytic amounts of nickel(II) chloride-4,4′-dimethoxyl-2,2′-bipyridyl under carbon mon

Full text of DOI:10.1016/j.tetlet.2008.03.035

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2916–2921
Nickel-catalyzed carbonylative Negishi cross-coupling reactions
Qiaoling Wang, Chuo Chen *
Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas,
5323 Harry Hines Boulevard, Dallas, TX 75390-9038, United States
Received 1 February 2008; revised 4 March 2008; accepted 5 March 2008
Available online 10 March 2008
Abstract
Catalytic carbonylative Negishi cross-coupling reactions are described. This method readily provides various enones from enol
triflates and diorganozinc reagents with catalytic amounts of nickel(II) chloride–4,40-dimethoxyl-2,20-bipyridyl under carbon monoxide
atmosphere. The rate of carbon monoxide insertion is increased by the addition of lithium or magnesium halides and the use of polar
solvents. Alkenyl iodides can also be used in place of enol triflates.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Carbonylative cross-coupling; Negishi reaction; Nickel catalysis; Enone
Enones are important structural motifs and versatile
functional groups for conjugate addition and cycloaddition
reactions. They are normally accessed by the oxidation of
ketones or olefins, aldol condensation reactions, cross-
metathesis reactions, Wittig-type reactions, and the acyl-
ation of organometallic reagents.1 They can also be synthe-
sized through catalytic carbonylative cross-coupling
reactions.2 This three-component coupling reaction can
be used for complementary strategic bond disconnection
in convergent total synthesis.
Compared to the recent advancement of cross-coupling
reactions,3,4 the catalytic carbonylative cross-coupling
reactions are relatively underexplored. The first example
of this type of transformation was reported by Heck in
1968, using arylmercuric chloride as the nucleophilic cou-
pling component.5 Tanaka6 and Stille7 subsequently devel-
oped the carbonylative coupling reactions using organotin
reagents. Since then, several methods have been developed
for the carbonylative Stille8 and Suzuki9 reactions.10 How-
ever, the carbonylative Negishi reactions are less studied.
Early development focuses on carbonylative aryl–alkyl,
aryl–alkenyl, and allyl–alkyl couplings using palladium–
triphenylphosphine catalyst systems.11 While the dialkyl-
nickel complexes are known to catalyze the carbonylative
aryl–aryl couplings, this protocol gives considerable
amounts of direct coupling and over-reaction side prod-
ucts.12 We report herein a facile nickel-catalyzed carbony-
lative Negishi coupling reaction for general enone
synthesis. This protocol avoids the use of toxic organotin
reagents and allows the direct preparation of the nucleo-
philic coupling components from the main-group organo-
metallic reagents or halides. We focus on the coupling of
enol triflates and organozinc reagents generated from the
Grignard reagents in this work (Scheme 1).
The development of carbonylative cross-coupling
reactions has been hindered by the intervention of direct
*
Corresponding author. Tel.: +1 214 648 5048; fax: +1 214 648 0320.
Scheme 1. Nickel-catalyzed carbonylative Negishi coupling reaction.
E-mail address: Chuo.Chen@UTSouthwestern.edu (C. Chen).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.035

Q. Wang, C. Chen / Tetrahedron Letters 49 (2008) 2916–2921
2917
coupling reactions. This problem is not seen in the alkoxy-
and amino-carbonylation reactions because the reductive
elimination of alkoxo and amino metal complexes is rather
slow.13 The nickel-catalyzed carbonylative Negishi reaction
described here is further challenged by the CO-deactivation
of nickel catalysts and organozinc reagents. Nevertheless,
we have found that the rate of reductive elimination, CO
insertion, and catalyst stability can be tuned with metal
ligands, additives,14 and solvents15 to achieve good results
for this transformation.
We used the carbonylative coupling between cyclohexe-
nyl triflate (2) and phenylzinc reagents (3) as the system for
catalyst optimization. Some of the results are presented in
Table 1. We first found that the palladium catalysts were
less reactive than the nickel catalysts. For example,
Pd(PPh3)4 gave the desired products only in the presence
of CuI (entry 1). Employing a more polar solvent improved
the yield; however, the conversion was still low (entry 2). In
contrast, good conversions were achieved with various
nickel catalysts (entries 3–5). We therefore focused our
efforts on the nickel catalyst systems.
magnesium halides improved the ratio of 4:5 and reaction
rate. For example, the reaction between 2 and Ph2Zn gen-
erated in situ from PhMgBr and ZnBr2 (1.8:1) in the pres-
ence of 2 mol % of NiCl2ꢀglyme gave 4 and 5 in a 3:1 ratio
with 100% conversion (entry 5).
We next examined the effects of ligand on this reaction.
We have found that dialkylamine ligands and N-heterocy-
clic carbene ligands completely deactivated the nickel cata-
lysts. While tri-tert-butylphosphine provided good results
in the initial testing (entry 6), it gave irreproducible results
when reactions were performed on a larger scale. Attempts
to increase the catalyst stability by employing diphosphine
ligands or P,N-ligands also resulted in catalyst deactivation
(entries 7 and 8).
Eventually, we found that 2,20-bipyridyl (7) increased
the catalyst lifetime considerably while it still maintained
good catalyst activity and carbonylation rate (entry 9).
Further stabilization of the catalyst with tripyridyl (8)
ligand led to the catalyst deactivation (entry 10). We have
also found that the introduction of electron-withdrawing
or electron-donating groups to the bipyridyl ligands
decreased the rate of the reaction (entries 11 and 12). How-
ever, the ratio of 4:5 was significantly improved. The best
results were obtained when the reaction was conducted
with 2 mol % of NiCl2–1 at 50 °C in DMSO. The desired
product 4 was isolated in 89% yield (entry 12).
We found several important factors that influence the
efficiency of this reaction. First, replacing the air-sensitive
Ni(COD)2 with air-stable NiCl2ꢀglyme greatly improved
the reproducibility. Second, the yield of this reaction was
further increased by using diorganozinc reagents. Third,
the reaction rate was substantially enhanced when con-
ducted in polar solvents. The highest reaction rate was
observed in DMSO. Fourth, the addition of lithium or
To confirm that diphenylzinc was the active nucleophilic
coupling component, we independently prepared the salt-
free diphenylzinc16 and allowed it to react with 2 in the
Table 1
Optimization of the reaction conditions
Entry Catalyst–ligand (loading) Ph–[Zn]a Additive
Solvent
THF
THF–DMSO (1:1) 23
THF–DMSO (1:1) 23
Temp (°C) Ratiob (4:5) Conversion (isolated yield) (%)
1
2
3
4
5
6
7
8
9
10
11
12
a
Pd(PPh3)4 (5 mol %)
Pd(PPh3)4 (5 mol %)
Ni(COD)2 (5 mol %)
NiCl2 (5 mol %)
PhZnI
PhZnI
PhZnI
PhZnBr
Ph2Zn
Ph2Zn
Ph2Zn
Ph2Zn
Ph2Zn
Ph2Zn
Ph2Zn
Ph2Zn
CuI (16 mol %)
CuI (16 mol %)
—
23
6:1
1:2
3:1
7:1
3:1
4:1
—
15
27
75
70
100
72
0
MgBr2 (1.0 equiv) THF–DMSO (1:1) 23
NiCl2 (2 mol %)
MgBr2 (1.8 equiv) DMSO
MgBr2 (1.8 equiv) DMSO
MgBr2 (1.8 equiv) DMSO
MgBr2 (1.8 equiv) DMSO
MgBr2 (1.8 equiv) DMSO
MgBr2 (1.8 equiv) DMSO
MgBr2 (1.8 equiv) DMSO
MgBr2 (1.8 equiv) DMSO
23
23
23
23
23
23
50
50
NiCl2–PtBu3 (2 mol %)
NiCl2–DPPE (2 mol %)
NiCl2–6 (2 mol %)
NiCl2–7 (2 mol %)
NiCl2–8 (2 mol %)
NiCl2–9 (2 mol %)
NiCl2–1 (2 mol %)
—
0
5:1
—
81
0
11:1
11:1
66
100 (89)
1.3 equiv Ph–[Zn] was used. PhZnBr/MgBr2 was generated in situ from mixing PhMgBr and ZnBr2 (1:1). Ph2Zn/MgBr2 was generated in situ from
mixing PhMgBr and ZnBr2 (1:0.55).
b
Determined by GC (uncalibrated).

2918
Q. Wang, C. Chen / Tetrahedron Letters 49 (2008) 2916–2921
presence of 2 mol % of NiCl2–1 and 1.8 equiv of MgBr2.
Identical results were obtained as the in situ method. The
desired product 4 was isolated in 87% yield and the ratio
of 4:5 was found to be 12:1.
zinc (entry 5). It should also be noted that the nature of
the additive (MgBr2, MgCl2, or LiCl) does not significantly
affect the reaction. The diorganozinc can be generated
in situ from RMgBr/ZnBr2 (entries 1–4), RMgCl/ZnCl2
(entry 5), or RLi/ZnCl2 (entry 6).
We have also explored the scope of the enol triflate
(Table 3). Cyclopentenyl triflate coupled with diarylzincs
equally well (entries 1 and 2). Increasing the steric hin-
drance of the enol triflate did not significantly affect the
reaction. The carbonylative coupling of 5-methylcyclo-
pentenyl triflate with diarylzinc or dialkylzinc reagents
gave comparable results (entries 3 and 4). As expected,
the reaction of 2,6-dimethylcyclohexenyl triflate with di-
(2-tolyl)zinc was slower. It required the addition of more
diarylzinc reagent to complete the reaction (entry 5).
After obtaining the optimal reaction conditions,17 we
explored the scope of this nickel-catalyzed carbonylative
Negishi coupling reaction of 2 with various diorganozinc
reagents (Table 2). Substitution at the 2-position of the
diarylzinc reagent resulted in lower reaction rate. A slight
elevation of the reaction temperature was required to
ensure good conversion (entry 1). Electron-deficient diaryl-
zinc reagents reacted equally well as diphenylzinc (entry 2),
and electron-rich diarylzinc reagents provided an excellent
ratio of carbonylative to direct coupling product (entry 3).
We have also demonstrated that dialkenylzinc and di-
alkylzinc can be used as the nucleophilic coupling
component. The carbonylative coupling of 2 with di(iso-
propenyl)zinc provided the corresponding dienone in good
yield (entry 4). Dienones are valuable substrates for the
Nazarov reaction.18 The carbonylative alkenyl–alkyl cou-
pling also required slightly higher reaction temperature.
Both primary and secondary dialkylzinc reagents reacted
well with 2 (entries 5 and 6). Notably, no direct coupling
product was observed when reacting 2 with dicyclohexyl-
Table 3
Exploration of the scope of the vinyl triflatea
Entry
1
Triflate
R4
Temp
(°C)
Ratiob
21:1
Yield
(°C)
Table 2
Exploration of the scope of the nucleophilic coupling componenta
80
50
50
95
86
87
2
3
12:1
16:1
Entry
1
R
Temp (°C)
Ratiob
15:1
Yield (%)
92
80
4c
5d
6e
80
80
15:1
22:1
72
88
2
3
50
50
12:1
89
85
>100:1
4c
50
5:1
79
50
50
>100:1
8:1
92%
85%
5d
80
80
—
91
78
e
6f
18:1
7
a
Reaction conditions: 1 mmol enol triflate, 1.3 mmol diorganozinc
reagent generated from RMgBr and ZnBr2.
Ratios of the carbonylative to direct coupling products determined by
GC (uncalibrated).
a
Reaction conditions: 1 mmol enol triflate, 1.3 mmol diorganozinc
reagent generated from RMgBr and ZnBr2.
b
b
Ratios of the carbonylative to direct coupling products determined by
c
GC (uncalibrated).
c
Reaction time: 32 min.
CyMgCl and ZnCl2 were used.
Direct coupling product not detected by GC.
n-Hex–Li and ZnCl2 were used.
d
Reaction time: 12 min.
With 2.6 mmol diorganozinc; reaction time: 40 min.
With 2 mol % catalyst; reaction time: 32 min.
d
e
e
f

Q. Wang, C. Chen / Tetrahedron Letters 49 (2008) 2916–2921
2919
P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and
Applications of Organotransition Metal Chemistry; University Science
Books: Mill Valley, 1987.
4. For reviews of recent advancements, see: (a) Netherton, M. R.; Fu, G.
C. In Topics in Organometallic Chemistry: Palladium in Organic
Synthesis; Tsuji, J., Ed.; Springer: New York, 2005; (b) Netherton, M.
R.; Fu, G. C. Adv. Synth. Catal. 2004, 346, 1525–1532; (c) Frisch, A.
C.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674–688; (d) Ca´rdenas,
D. J. Angew. Chem., Int. Ed. 2003, 42, 384–387; (e) Luh, T.-Y.; Leung,
M.-k.; Wong, K.-T. Chem. Rev. 2000, 100, 3187–3204; (f) Littke, A.
F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176–4211; (g)
Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275–286.
5. Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5546–5548.
Scheme 2. Nickel-catalyzed carbonylative Negishi coupling reaction of
alkenyl iodide.
6. Tanaka, M. Tetrahedron Lett. 1979, 20, 2601–2602.
7. (a) Sheffy, F. K.; Godschalx, J. P.; Stille, J. K. J. Am. Chem. Soc.
1984, 106, 4833–4840; (b) Baillargeon, V. P.; Stille, J. K. J. Am. Chem.
Soc. 1983, 105, 7175–7176; (c) Goure, W. F.; Wright, M. E.; Davis, P.
D.; Labadie, S. S.; Stille, J. K. J. Am. Chem. Soc. 1984, 106, 6417–
6422; (d) Crisp, G. T.; Scott, W. J.; Stille, J. K. J. Am. Chem. Soc.
1984, 106, 7500–7506; (e) Merrifield, J. H.; Godschalx, J. P.; Stille, J.
K. Organometallics 1984, 3, 1108–1112; (f) Echavarren, A. M.; Stille,
J. K. J. Am. Chem. Soc. 1988, 110, 1557–1565.
8. (a) Beletskaya, I. P. J. Organomet. Chem. 1983, 250, 551–564; (b)
Angle, S. R.; Fevig, J. M.; Knight, S. D.; Marquis, R. W.; Overman,
L. E. J. Am. Chem. Soc. 1993, 115, 3966–3976; (c) Kang, S.-K.; Ryu,
H.-C.; Lee, S.-W. J. Chem. Soc., Perkin Trans. 1 1999, 2661–2663; (d)
Ceccarelli, S.; Piarulli, U.; Gennari, C. J. Org. Chem. 2000, 65, 6254–
6256.
9. (a) Wakita, Y.; Yasunaga, T.; Akita, M.; Kojima, M. J. Organomet.
Chem. 1986, 301, C17–C20; (b) Kondo, T.; Tsuji, Y.; Watanabe, Y. J.
Organomet. Chem. 1988, 345, 397–403; (c) Suzuki, A. Pure Appl.
Chem. 1994, 66, 213–222; (d) Ishikura, M.; Terashima, M. J. Org.
Chem. 1994, 59, 2634–2637; (e) Ishiyama, T.; Kizaki, H.; Hayashi, T.;
Suzuki, A.; Miyaura, N. J. Org. Chem. 1998, 63, 4726–4731; (f)
Andrus, M. B.; Ma, Y.; Zang, Y.; Song, C. Tetrahedron Lett. 2002,
43, 9137–9140; (g) Mingji, D.; Liang, B.; Wang, C.; You, Z.; Xiang,
J.; Dong, G.; Chen, J.; Yang, Z. Adv. Synth. Catal. 2004, 346, 1669–
Finally, cycloheptenyl triflate was also shown to be a good
substrate for this reaction (entries 6 and 7).
As acyclic enol triflates cannot be obtained easily from
the corresponding ketones with a well-defined olefin geom-
etry, we turned our attention to acyclic alkenyl iodides.
Alkenyl iodides are readily available from hydrozircona-
tion–halogenation of the alkynes with excellent regioselec-
tivity and stereoselectivity.19 We have found that alkenyl
iodides showed higher reactivity than enol triflates. For
example, the carbonylative coupling of 10 with dialkenyl-
zinc in the presence of 2 mol % NiCl2–1 at room tempera-
ture gave the desired dienone 12 in 71% yield (Scheme 2).
However, the ratio of carbonylative to direct coupling
product was diminished (3:1).
In summary, we have developed an efficient nickel cata-
lyst system for the carbonylative Negishi coupling reac-
tions. The reaction of enol triflates or alkenyl iodides
with diorganozinc reagents under 1 atm CO atmosphere
in the presence of NiCl2–1 catalyst and lithium or magne-
sium halides gave enones in good yield. Carbonylative
alkenyl–aryl, alkenyl–alkenyl, and alkenyl–alkyl coupling
can all be achieved.
´
´
´
1673; (h) Petz, A.; Peczely, G.; Pinter, Z.; Kollar, L. J. Mol. Catal. A:
Chem. 2006, 255, 97–102; (i) Larini, P.; Guarna, A.; Occhiato, E. G.
Org. Lett. 2006, 8, 781–784; (j) Maerten, E.; Sauthier, M.; Mortreux,
A.; Castanet, Y. Tetrahedron 2007, 63, 682–689.
10. For other types of carbonylative coupling reactions, see: (a) Tanaka,
M. Bull. Chem. Soc. Jpn. 1981, 54, 637–638; (b) Kobayashi, T.;
Tanaka, M. J. Chem. Soc., Chem. Commun. 1981, 333–334; (c)
Hiyama, T.; Hatanakat, Y. Pure Appl. Chem. 1994, 66, 1471–1478; (d)
Kang, S.-K.; Yamaguchi, T.; Hong, R.-K.; Kim, T.-H.; Pyun, S.-J.
Tetrahedron 1997, 53, 3027–3034; (e) Ahmed, M. S. M.; Mori, A. Org.
Lett. 2003, 5, 3057–3060; (f) Sans, V.; Trzeciak, A. M.; Luis, S.;
Acknowledgments
We thank the UT Southwestern and Welch foundation
for financial supports. C.C. is Southwestern Medical Foun-
dation Scholar in Biomedical Research.
´
Ziołlkowskib, J. J. Catal. Lett. 2006, 109, 37–41; (g) Kakusawa, N.;
References and notes
Kurita, J. Chem. Pharm. Bull. 2006, 54, 699–702; (h) Tour, J. M.;
Negishi, E.-i. J. Am. Chem. Soc. 1985, 107, 8289–8291; (i) Satoh, T.;
Itaya, T.; Okuro, K.; Miura, M.; Nomura, M. J. Org. Chem. 1995, 60,
7267–7271; (j) Gagnier, S. V.; Larock, R. C. J. Am. Chem. Soc. 2003,
125, 4804–4807.
1. For reviews, see: (a) Marsden, S. P. In Science of Synthesis; Cossy, J.,
Ed.; Georg Thieme: Stuttgart, 2004; Vol. 26, pp 1045–1121; (b)
Buckle, D. R.; Pinto, I. L. In Comprehensive Organic Synthesis; Trost,
B. M., Ed.; Pergamon: Oxford, 1991; Vol. 7, pp 119–146. See also: (c)
Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. J. Am. Chem. Soc. 2000,
122, 7596–7597; (d) Chatterjee, A. K.; Morgan, J. P.; Scholl, M.;
Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 3783–3784.
2. For a review of the carbonylative cross-coupling for diaryl ketone
synthesis, see: Brunet, J.-J.; Chauvin, R. Chem. Soc. Rev. 1995, 24,
89–95.
3. For reviews, see: (a) Tsuji, J. Transition Metal Reagents and Catalysts:
Innovations in Organic Synthesis; Wiley: Chichester, 2000; (b) Leong,
W. W.; Larock, R. C. In Comprehensive Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford,
1995; Vol. 12, pp 131–160; (c) Farina, V. In Comprehensive Organo-
metallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G.,
Eds.; Pergamon: Oxford, 1995; Vol. 12, pp 161–240; (d) Collman, J.
11. (a) Tamaru, Y.; Ochiai, H.; Yamada, Y.; Yoshida, Z.-i. Tetrahedron
Lett. 1983, 24, 3869–3872; (b) Tamaru, Y.; Ochiai, H.; Yoshida, Z.-i.
Tetrahedron Lett. 1984, 25, 3861–3864; (c) Yasui, K.; Fugami, K.;
Tanaka, S.; Tamaru, Y. J. Org. Chem. 1995, 60, 1365–1380; (d)
Jackson, R. F. W.; Turner, D.; Block, M. H. J. Chem. Soc., Perkin
Trans. 1 1997, 865–870.
12. Yamamoto, T.; Kohara, T.; Yamamoto, A. Chem. Lett. 1976, 1217–
1220.
13. For reviews, see: (a) Hartwig, J. F. Synlett 2006, 1283–1294; (b) Muci,
A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131–209; (c) Ley,
S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400–5449.
For a recent example of aminocarbonylation reaction, see: (d)
Martinelli, J. R.; Clark, T. P.; Watson, D. A.; Munday, R. H.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2007, 46, 8460–8463.

2920
Q. Wang, C. Chen / Tetrahedron Letters 49 (2008) 2916–2921
14. Butts, S. B.; Strauss, S. H.; Holt, E. M.; Stimson, R. E.; Alcock, N.
W.; Shriver, D. F. J. Am. Chem. Soc. 1980, 102, 5093–5100.
15. Wax, M. J.; Bergman, R. G. J. Am. Chem. Soc. 1981, 103, 7028–
7030.
16. Lee, K.-s.; Brown, M. K.; Hird, A. W.; Hoveyda, A. H. J. Am. Chem.
Soc. 2006, 128, 7182–7184.
1H), 5.56 (m, 1H), 5.41 (m, 1H), 2.27–2.43 (m, 4H), 1.93 (s, 3H), 1.70–
1.58 (m, 4H); 13C NMR (75 MHz, CDCl3) d 200.0, 143.7, 141.8,
138.1, 122.3, 25.9, 23.7, 22.0, 21.6, 19.2; MS(EI) 150 [M]+.
Table 2, entry 5: Rf = 0.43 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2930, 2855, 1663, 1449, 1196; 1H NMR (400 MHz, CDCl3) d 6.89 (m,
1H), 2.97 (dddd, J = 11.4, 11.4, 3.2, 3.2 Hz, 1H), 2.25–2.21 (m, 4H),
1.80–1.58 (m, 9H), 1.43–1.17 (m, 5H); 13C NMR (75 MHz, CDCl3) d
205.1, 138.9, 138.1, 44.1, 29.8 (2C), 26.1, 25.9 (2C), 25.7, 23.3, 22.0,
21.6; MS(EI) 192 [M]+.
17. General procedure: A round-bottom flask equipped with magnetic
stirbar was charged with ZnBr2 (1.48 g, 6.6 mmol) or ZnCl2 (0.90 g,
6.6 mmol) and flame-dried under vacuum. Anhydrous THF (12 mL)
was then introduced followed by a THF or Et2O solution of the
Grignard or organolithium reagent (12 mmol) at room temperature.
After stirring overnight, the solvents were removed under vacuum
(0.1 mmHg) or by distillation under ambient pressure at 100 °C. The
diorganozinc reagents and MgBr2 generated in situ were then
dissolved in DMSO (40 mL), leaving 25% of MgBr2 undissolved.
In a separate flask, carbon monoxide was bubbled through a solution
of enol triflate (1.0 mmol) in degassed DMSO (1 mL) for 2 min before
a solution of diorganozinc reagent (0.165 M in DMSO, 1.3 mmol,
8 mL) was added via syringe pump (25 mL/h) at 50 °C with
continuous carbon monoxide bubbling (54 mL/min). The amount of
dissolved MgBr2 was calculated to be 1.8 equiv (1.3 ꢁ 12/
6.6 ꢁ 0.75 = 1.8). After 30 sec, a solution of NiCl2–1 (0.2 M in
THF, 0.02 mmol, 0.1 mL) was introduced. The reaction mixture
turned deep red, which faded to pale yellow upon the completion of
the reaction. CAUTION: The catalyst deactivation leads to the
generation of Ni(CO)4, which is toxic and volatile. It may be released
from the reaction vessel through carbon monoxide bubbling. This
reaction should be performed in a well-ventilated fume hood. After
cooling to room temperature, the solution was passed through a short
pad of silica gel to remove DMSO and inorganic salts. The silica gel
was washed with 10% Et2O–pentane solution. The filtrate was
concentrated and purified by flash column chromatography.
5-Methylcyclopent-1-enyltrifluoromethanesulfonate: Rf = 0.35 (pen-
tane); 1H NMR (400 MHz, CDCl3) d 5.61 (m, 1H), 2.90 (m, 1H),
Table 2, entry 6: Rf = 0.30 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2930, 1667, 1229; 1H NMR (400 MHz, CDCl3) d 6.89 (m, 1H), 2.61 (t,
J = 7.4 Hz, 2H), 2.24 (m, 4H), 1.62–1.55 (m, 6H), 1.29 (m, 6H), 0.89
(t, J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 212.2, 139.5, 139.2,
37.0, 31.7, 29.1, 26.0, 24.9, 23.1, 22.5, 22.0, 21.6, 14.1; MS(EI) 194
[M]+.
Table 3, entry 1: Rf = 0.39 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2955, 1643, 1608, 1355, 734; 1H NMR (400 MHz, CDCl3) d 7.33–7.17
(m, 4H), 6.37 (m, 1H), 2.72 (m, 2H), 2.57 (m, 2H), 2.32 (s, 3H), 2.02
(m, 2H); 13C NMR (75 MHz, CDCl3) d 196.7, 149.1, 146.3, 139.8,
135.7, 130.8, 129.6, 127.6, 124.9, 34.2, 30.6, 23.0, 19.6; MS(EI) 186
[M]+.
Table 3, entry 2: Rf = 0.26 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2956, 1644, 1585, 1439, 1355, 1270, 779, 736; 1H NMR (400 MHz,
CDCl3) d 7.50 (m, 1H), 7.43–7.38 (m, 2H), 7.21 (dt, J = 8.3, 7.9,
2.2 Hz, 1H), 6.57 (m, 1H), 2.74 (m, 2H), 2.63 (m, 2H), 2.01 (m, 2H);
13C NMR (75 MHz, CDCl3) d 192.6, 162.4 (d, J = 246 Hz), 147.6,
144.3, 141.0 (d, J = 6.5 Hz), 129.8 (d, J = 7.8 Hz), 124.5 (d,
J = 3.0 Hz), 118.7 (d, J = 21.3 Hz), 115.6 (d, J = 22.5 Hz), 34.4,
31.7, 22.7; MS(EI) 190 [M]+.
Table 3, entry 3:Rf = 0.34 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2956, 1646, 1585, 1439, 1349, 1269, 748; 1H NMR (400 MHz, CDCl3)
d 7.52 (m, 1H), 7.44–7.37 (m, 2H), 7.22 (dt, J = 8.2, 8.2, 2.5 Hz, 1H),
6.46 (m, 1H), 3.26 (m, 1H), 2.65 (m, 1H), 2.47 (m, 1H), 2.24 (m, 1H),
1.59 (m, 1H), 1.17 (d, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) d
192.8, 162.4 (d, J = 247.5 Hz), 148.5, 146.5, 141.2 (d, J = 6.2 Hz),
129.8 (d, J = 7.8 Hz), 124.6 (d, J = 3.0 Hz), 118.7 (d, J = 21.4 Hz),
115.7 (d, J = 22.4 Hz), 39.5, 32.5, 31.9, 19.4. MS(EI) 204 [M]+.
2.36 (m, 2H), 2.24 (m, 1H), 1.56 (m, 1H), 1.14 (d, J = 6.8 Hz, 3H); 13
C
NMR (100 MHz, CDCl3) d 153.2, 118.9 (q, J = 318.6 Hz), 116.1,
37.7, 29.9, 26.4, 18.0; MS(EI) 230 [M]+.
(5E)-5-Iodo-dec-5-ene Rf = 0.67 (pentane); 1H NMR (400 MHz,
CDCl3) d 6.17 (t, J = 7.6 Hz, 1H), 2.35 (t, J = 7.3 Hz, 2H), 2.04 (m,
2H), 1.43 (m, 2H), 1.35 (m, 6H), 0.91 (m, 6H); 13C NMR (125 MHz,
CDCl3) d 141.4, 103.5, 38.2, 31.4, 31.3, 30.6, 22.2, 21.5, 14.0, 13.9;
MS(EI) 266 [M]+.
Table 3, entry 4: Rf = 0.35 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2954, 2930, 2865, 1666, 1376; 1H NMR (400 MHz, CDCl3) d 6.66 (m,
1H), 3.04 (m, 1H), 2.62 (t, J = 7.5 Hz, 2H), 2.42 (m, 1H), 2.47 (m,
1H), 2.17 (m, 1H), 1.61–1.49 (m, 3H), 1.29 (m, 5H), 1.07 (d,
J = 6.9 Hz, 3H), 0.88 (t, J = 6.3 Hz, 3H); 13C NMR (75 MHz,
CDCl3) d 199.5, 150.0, 142.5, 39.3, 38.2, 32.0, 31.8, 31.6, 29.0, 24.8,
22.5, 19.7, 14.0; MS(EI) 194 [M]+.
Table 1, entry 11: Rf = 0.39 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
1
2933, 1644, 1276, 1255, 702; H NMR (400 MHz, CDCl3) d 7.63 (m,
2H), 7.51 (m, 1H), 7.42 (m, 2H), 6.58 (m, 1H), 2.44 (m, 2H), 2.29 (m,
2H), 1.77 (m, 4H); 13C NMR (75 MHz, CDCl3) d 198.3, 144.1, 138.7,
131.2, 129.1, 128.0, 26.1, 23.9, 22.0, 21.6; MS(EI) 186 [M]+.
Table 3, entry 5: Rf = 0.29 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2928, 2867, 1649, 1453, 1243, 911, 740; 1H NMR (400 MHz, CDCl3) d
7.56 (dd, J = 7.7, 1.1 Hz, 1H), 7.35 (dt, J = 7.5, 7.5, 1.4 Hz, 1H), 7.23
(m, 2H), 2.66 (m, 2H), 2.55 (s, 3H), 2.07 (m, 2H), 1.74 (m, 2H), 1.65 (m,
1H), 1.55 (s, 3H), 1.46 (m, 1H), 0.94 (d, J = 7.0 Hz, 3H); 13C NMR
(75 MHz, CDCl3) d 203.2, 138.9, 138.5, 138.4, 137.6, 131.8, 131.1,
130.4, 125.6, 32.3, 30.8, 30.4, 21.3, 20.9, 19.9, 19.4; MS(EI) 228 [M]+.
Table 2, entry 1: Rf = 0.39 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2928, 1649, 1252, 730; 1H NMR (400 MHz, CDCl3) d 7.29 (m, 2H),
7.20 (m, 1H), 6.49 (m, 1H), 2.40 (m, 1H), 2.44 (m, 2H), 2.26 (s, 3H),
2.24 (m, 2H), 1.75 (m, 4H); 13C NMR (75 MHz, CDCl3) d 200.3,
146.4, 140.0, 139.7, 135.5, 130.5, 129.1, 127.4, 124.9, 26.3, 22.9, 21.9,
21.6, 19.5; MS(EI) 200 [M]+.
Table 3, entry 6: Rf = 0.11 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2920, 2849, 1638, 1600, 1251, 1170, 754; 1H NMR (400 MHz, CDCl3)
d 7.68 (m, 2H), 6.91 (m, 2H), 6.59 (t, J = 6.8 Hz, 1H), 3.85 (s, 3H), 2.59
(m, 2H), 2.33 (m, 2H), 1.83 (m, 2H), 1.59 (m, 4H); 13C NMR (75 MHz,
CDCl3) d 197.8, 162.4, 145.7, 145.2, 131.8, 130.9, 113.2, 55.4, 32.3,
29.2, 28.5, 26.6, 26.1; MS(EI) 230 [M]+.
Table 2, entry 2: Rf = 0.39 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2935, 1649, 1584, 1436, 1260, 792, 745; 1H NMR (400 MHz, CDCl3) d
7.40 (m, 2H), 7.32 (m, 1H), 7.18 (m, 1H), 6.61 (m, 1H), 2.40 (m, 2H),
2.29 (m, 2H), 1.76–1.64 (m, 4H); 13C NMR (75 MHz, CDCl3) d 196.6,
162.3 (d, J = 247.5 Hz), 144.8, 140.8 (d, J = 6.3 Hz), 138.5, 129.7 (d,
J = 7.8 Hz), 124.8 (d, J = 3.0 Hz), 118.1 (d, J = 21.3 Hz), 116.0 (d,
J = 22.4 Hz), 26.2, 23.8, 21.9, 21.5; MS(EI) 204 [M]+.
Table 3, entry 7: Rf = 0.43 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
1
2922, 2851, 1642, 1448, 1129; H NMR (400 MHz, CDCl3) d 6.77 (t,
J = 6.8 Hz, 1H), 5.56 (m, 1H), 5.42 (m, 1H), 2.46 (m, 2H), 2.32 (m,
2H), 1.93 (s, 3H), 1.78 (m, 2H), 1.57–1.49 (m, 4H); 13C NMR
(75 MHz, CDCl3) d 200.4, 146.0, 144.7, 143.9, 122.8, 32.3, 29.1, 27.5,
26.4, 26.0, 19.2; MS(EI) 164 [M]+.
Table 2, entry 3: Rf = 0.07 (10% Et2O–pentane); FTIR (neat, cmꢂ1
)
2933, 1638, 1600, 1251, 1170, 839, 756; 1H NMR (400 MHz, CDCl3) d
7.70 (d, J = 8.5 Hz, 2H), 6.92 (d, J = 8.5 Hz, 2H), 6.49 (m, 1H), 3.86
(s, 3H), 2.40 (m, 2H), 2.26 (m, 2H), 1.76–1.66 (m, 4H); 13C NMR
(75 MHz, CDCl3) d 197.2, 162.4, 141.6, 138.6, 131.6, 131.0, 113.3,
55.4, 25.9, 24.3, 22.1, 21.7; MS(EI) 216 [M]+.
(Z)-4-Butyl-2-methylnona-1,4-dien-3-one (12): Rf = 0.47 (10% Et2O–
pentane); FTIR (neat, cmꢂ1) 2957, 2927, 1643, 1100; 1H NMR
(400 MHz, CDCl3) d 6.27 (t, J = 7.4 Hz, 1H), 5.59 (m, 1H), 5.44 (m,
1H), 2.35 (m, 2H), 2.24 (m, 2H), 1.96 (s, 3H), 1.55–1.29 (m, 8H), 0.94–
0.88 (m, 6H); 13C NMR (75 MHz, CDCl3) d 200.8, 144.5, 143.7, 140.6,
Table 2, entry 4: Rf = 0.27 (10% Et2O–pentane); FTIR (neat, cmꢂ1
2931, 1641, 1168, 926, 779; 1H NMR (400 MHz, CDCl3) d 6.68 (m,
)

Q. Wang, C. Chen / Tetrahedron Letters 49 (2008) 2916–2921
2921
123.2, 31.2, 31.1, 28.3, 26.3, 22.8, 22.5, 19.1, 14.0, 13.9; MS(EI) 208
[M]+.
18. For reviews, see: (a) Frontier, A. J.; Collison, C. Tetrahedron 2005, 61,
7577–7606; (b) Pellissier, H. Tetrahedron 2005, 61, 6479–6517; (c)
Tius, M. A. Eur. J. Org. Chem. 2005, 2193–2206; (d) Habermas, K.
L.; Denmark, S. E.; Jones, T. K. Org. React. 1994, 45, 1–158.
19. For reviews, see: Reviews: (a) Schwartz, J.; Labinger, J. A. Angew.
Chem., Int. Ed. Engl. 1976, 88, 402–409; (b) Negishi, E.; Takahashi, T.
Synthesis 1988, 1–19; (c) Wipf, P.; Jahn, H. Tetrahedron 1996, 52,
12853–12910; (d) Wipf, P.; Kendall, C. Top. Organomet. Chem. 2005,
8, 1–25. For directed-hydrozirconation, see: (e) Zhang, D.; Ready, J.
M. J. Am. Chem. Soc. 2007, 129, 12088–12089.