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J. Peng et al. / Tetrahedron Letters 52 (2011) 2172–2175
Li+
Ph Ni- Cl
X
depended on the Ni-catalysts; notably, (MeO)2Dipyr(H)2ꢀNiCl2 gave
the (Z,Z)-diene contaminated with only ꢁ5% of the (Z,E)-isomer,
but free from the (E,E)-diene.
LiCl
Ph NiII
X
Ph NiII Ph
eq. 3
eq. 4
A
B
The homocoupling of iodoalkenes was then studied with
(MeO)2Dipyr(H)2ꢀNiCl2 (Table 3). For di-substituted (E)- and
(Z)-1-iodohex-1-enes, the catalyst loading of 2 mol % (MeO)2Di-
pyr(H)2ꢀNiCl2 and 5 mol % Zr(cp)2Cl2 was sufficient to complete
the coupling within 1 and 5 h, respectively (entries 2 and 4). The
product obtained from (E)-1-iodohex-1-ene was the expected
(E,E)-diene free from (E,Z)- and (Z,Z)-isomers. For the coupling of
tri-substituted (E)-2-iodohex-2-ene, the catalyst loading of
4 mol % (MeO)2Dipyr(H)2ꢀNiCl2 and 10 mol % Zr(cp)2Cl2 was re-
quired to complete the homocoupling within 24 h, furnishing the
expected (E,E)-diene free from (E,Z)- and (Z,Z)-isomers (entry 3).
However, homocoupling of the corresponding tri-substituted
(Z)-iodoalkene was very sluggish; with 10 mol % (MeO)2Di-
pyr(H)2ꢀNiCl2 and 25 mol % Zr(cp)2Cl2 at room temperature for
24 h, the homocoupling progressed only up to 60% completion
and gave the diene (55% yield) composing of a 1.9:5.8:1.0 mixture
of (Z,Z)-, (Z,E)-, and (E,E)-isomers (entry 5).
ZrIV Cl
Ph NiII Cl
Cl
Ph ZrIV Cl
Cl
NiII
Cl
+
+
A
C
Li+
Ph Zr- Cl
Cl
LiCl
Ph ZrIV Cl
Cl ZrIV Cl
C
eq. 5
Ph NiII
X
Ph NiII Ph
A
B
Ph
Ph
Cl
Ni
Zr
Cl
Cl
Zr
Cl
E
Ni
Ph
Cl
D
Figure 5. Possible transformations involved in the homocoupling.21
For the Ni-mediated homocouplings, several different mecha-
nisms have been proposed.16 However, there appears to be a con-
sensus on two aspects. First, the coupling is initiated via oxidative
addition of aryl or alkenyl halide to Ni(0) to form an aryl- or alke-
nyl-Ni(II) halides, cf., Eq. 1 (Fig. 4). Second, the homodimer is
formed via reductive elimination from a diaryl- or dialkenyl-Ni(II)
species, cf., Eq. 2. Accepting these two steps, we speculate the ef-
fects of LiCl and Zr(cp)2Cl2 on the coupling.
It is generally agreed that the formation of a diaryl- or dialke-
nyl-Ni(II), cf., B, from aryl- or alkenyl-Ni(II) halide, cf., A, is slow
(Fig. 5). Related to this step, we observed that LiCl gives an accel-
eration effect for the catalytic Ni/Cr-mediated couplings and sug-
gested that it is due to an acceleration of the transmetallation
step from Ni to Cr, probably via the formation of an ate Ni-interme-
diate.2 Similarly, we expect that LiCl could accelerate this step via
the formation of an ate-complex, cf., Eq. 3. The observed small, but
definite effect of LiCl appears to support this notion.17
In conclusion, a new catalytic system (cat. (H)2Phen(Me)2ꢀNiCl2
or (MeO)2Dipyr(H)2ꢀNiCl2), cat. Zr(cp)2Cl2, 2 equiv Mn, and 2 equiv
LiCl) has been developed to facilitate the homocoupling of a wide
range of aryl, alkenyl, and alkynyl halides. With (MeO)2Dipyr(H)2
ꢀNiCl2, the stereochemistry of di-substituted (E)- and (Z)-iodoalk-
enes and tri-substituted (E)-iodoalkene is retained. As all reagents
required are air and moisture stable, this method offers experi-
mental convenience. Finally, we have speculated a mechanism to
explain the dramatic acceleration effect by the combined use of
Zr(cp)2Cl2 and LiCl.
Acknowledgment
We are grateful to Eisai USA Foundation for generous financial
support.
Related to the effect of Zr(cp)2Cl2, the Ni-catalyzed cross-
coupling reactions of alkenylzirconium derivatives with aryl
halides, reported by Negishi,18 Suginome,19 and Fu20 are instruc-
tive; these works demonstrate that the alkenyl transfer from Zr
to Ni is a facile process. Then, we would suggest that the initially
formed aryl- or alkenyl-Ni(II) halide, cf., A, transfers an aryl or
alkenyl group to Zr(cp)2Cl2, to form an aryl- or alkenyl-Zr(IV)
halide, cf., Eq. 4.21 C might transfer the aryl- or alkenyl-group back
to the initially formed aryl- or alkenyl-Ni(II) halide via an ate-
complex, cf., Eq. 5.22 Assuming that the process represented by
Eq. 5 is faster than that by Eq. 3, we could explain the observed
accelerating effect of Zr(cp)2Cl2. Overall, Zr(cp)2Cl2 might serve as
the aryl- or alkenyl-group acceptor as well as donor in the presence
of LiCl. Perhaps, a simplistic view is that transmetallation takes
place through four-centered, bridged Ni–Zr bimetallic transition
states, such as D and E.
References and notes
1. For the discovery of Ni/Cr-mediated coupling reactions, see: (a) Jin, H.; Uenishi,
J.; Christ, W. J.; Kishi, Y. J. Am. Chem. Soc. 1986, 108, 5644; (b) Takai, K.;
Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki, H. J. Am. Chem. Soc.
1986, 108, 6048.
2. For cataytic non-asymmetric Cr-mediated coupling reactions, see: (a) Namba,
K.; Wang, J.; Cui, S.; Kishi, Y. Org. Lett. 2005, 7, 5421; For catalytic asymmetric
Cr-mediated coupling reactions, see: (b) Guo, H.; Dong, C.-G.; Kim, D.-S.; Urabe,
D.; Wang, J.; Kim, J. T.; Liu, X.; Sasaki, T.; Kishi, Y. J. Am. Chem. Soc. 2009, 131,
15387. and references cited therein.
3. (a) Semmelhack, M. F.; Helquist, P. M.; Jones, L. D. J. Am. Chem. Soc. 1971, 93,
5908; (b) Semmelhack, M. F.; Helquist, P. M.; Gorzynski, J. D. J. Am. Chem. Soc.
1972, 94, 9234.
4. Zembayashi, M.; Tamao, K.; Yoshida, J.; Kumada, M. Tetrahedron Lett. 1977, 47,
4089.
5. Iyoda, M.; Otsuka, H.; Sato, K.; Nisato, N.; Oda, M. Bull. Chem. Soc. Jpn. 1990, 63,
80.
6. For preparation of Ni-catalysts, see Ref. 2.
7. For abbreviation of ligands, see Figure 2.
8. This test was done with (H)2Phen(Me)2ꢀNiCl2 fixed at 2 mol %, thereby
revealing that the effect of Zr(cp)2Cl2 reaches the saturation at 4 mol %.
9. For the couplings summarized in Tables 1–3, the following procedure is used.
To a suspension of a NiCl2-complex (0.01 mmol, 0.02 equiv), Zr(cp)2Cl2 (Strem,
99%; 7.3 mg, 0.025 mmol, 0.05 equiv), Mn powder (Aldrich, 99.99%; 54.9 mg,
1.0 mmol, 2.0 equiv) and LiCl (Aldrich, anhydrous, ground powder; 42.4 mg,
1.0 mmol, 2.0 equiv) in DME (Aldrich, anhydrous, 99.5%; 1.0 mL) was added an
iodide (0.5 mmol) under nitrogen. The mixture was stirred at rt under nitrogen
until the reaction completed (TLC). Except for the dipyridyls, the mixture was
loaded on silica gel directly, and the flash chromatography on silica gel gave the
homo-coupling product. For dipyridyls, the reaction was quenched with aq.
NH4OH (27% w/w, 0.6 mL), stirred for 10 min, extracted with CH2Cl2
(10 mL ꢂ 3), washed with brine (15 mL), dried over Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by flash
chromatography on silica gel to give the homocoupling product. For alkenyl
halide substrates (Fig. 3 and Table 3), the reaction was done in 0.2 mmol scale
Ni- or Pd-catalyst
+
2 x
+
Ph Ph
MX2
Ph
X
M = Zn or Mn
6
5
eq. 1
eq. 2
Ph
X
Ni(0)
Ph Ni
X
5
A
+
Ph Ni Ph
Ni(0)
Ph Ph
B
6
Figure 4. Two transformations generally accepted for the Ni-mediated
homocoupling.
(C: 0.5 M) with added toluene (42 ll, 0.4 mmol, 2.0 equiv) as an internal