Ethylzincation of monosubstituted alken es catalyzed by EtMgBr-Cl2ZrCp2 and palladium-catalyzed cross coupling of the resultant diisoalkylzinc derivatives

Article abstract of DOI:10.1021/om991004j

The reaction of monosubstituted alkenes with 0.5 molar equiv of EtZn in the presence of a catalyst generated in situ by treatment ofClzZrCpz with 2 molar equiv of EtMgBr produces regioselectively the corresponding diisoalkylzincs 1, generally in high yields. Their direct cross coupling with a variety of organic halides in the same reaction vessel can be achieved in good yields with a catalytic amount of a palladium complex.

Full text of DOI:10.1021/om991004j

Organometallics 2000, 19, 2417-2419
2417
Eth ylzin ca tion of Mon osu bstitu ted Alk en es Ca ta lyzed by
EtMgBr -Cl2Zr Cp 2 a n d P a lla d iu m -Ca ta lyzed Cr oss
Cou p lin g of th e Resu lta n t Diisoa lk ylzin c Der iva tives
Sebastien Gagneur,1 J ean-Luc Montchamp, and Ei-ichi Negishi*
H. C. Brown Laboratories of Chemistry, Purdue University,
West Lafayette, Indiana 47907-1393
Received December 17, 1999
Ta ble 1. Eth ylzin ca tion of Mon osu bstitu ted
Alk en es w ith Dieth ylzin c a n d EtMgBr -Cl2Zr Cp 2,
in Ca ta lytic Am ou n ts
Summary: The reaction of monosubstituted alkenes with
0.5 molar equiv of Et2Zn in the presence of a catalyst
generated in situ by treatment of Cl2ZrCp2 with 2 molar
equiv of EtMgBr produces regioselectively the corre-
sponding diisoalkylzincs 1, generally in high yields.
Their direct cross coupling with a variety of organic
halides in the same reaction vessel can be achieved in
good yields with a catalytic amount of a palladium
complex.
R of
reacn
product yield
unreacted starting
alkene, %b
RCHdCH2 time, ha RCH(Et)CH2I, %b
Herein reported is a novel ethylzincation of mono-
substituted alkenes with diethylzinc and a catalyst
generated in situ by the treatment of Cl2ZrCp2 with 2
molar equiv of EtMgBr. The reaction produces regiose-
lectively diisoalkylzincs 1, generally in high yields
(Table 1). Their cross coupling with a variety of organic
halides can be achieved in good yields with catalytic
amounts of palladium complexes. Although the allyl-
zincation of alkenes has been known for many decades
and is well-documented,2 this ethylzincation appears to
be novel. In contrast with the Zr-catalyzed carboalumi-
nation of 1-alkenes,3 all carbon groups bonded to Zn
undergo carbometalation. The carbozincation reaction
is also cleaner and higher yielding than the Dzhemilev
carbomagnesation.4 Unlike the latter, which generally
requires an excess of an ethylmagnesium derivative, all
Et groups are incorporated in the products in high
yields. Furthermore, the isoalkyl-Zn bonds readily
undergo Pd-catalyzed cross coupling with various or-
ganyl halides (Table 2). The corresponding reactions of
isoalkylmetals containing Mg are much more sluggish
and lower yielding, and isoalkylalanes fail to undergo
Pd-catalyzed cross coupling.
n-octyl
cyclohexyl
benzyl
4
4
4
95 (90)
74 (68)
84 (80)
58 (45)
5
20
14
10c
phenyl
12
a
All reactions were conducted at room temperature in THF.
Yields were calculated by GC using mesitylene as an internal
b
standard. Figures in parentheses are isolated yields (isolated by
distillation). c High-molecular-weight byproducts were observed.
cation of alkynes is generally sluggish and is of limited
scope.7c Although carbozincation of alkynes can be
achieved rather cleanly using catalytic amounts of
zirconocene diiodide,7a,b its scope also remains limited.
We therefore sought alternative metal-catalyzed proce-
dures for carbozincation of alkenes and have found that
the reaction of monosubstituted alkenes with diethylzinc
can indeed be catalyzed by zirconium. Without a cata-
lyst, no reaction was observed. Furthermore, it was
necessary to treat zirconocene dichloride with 2 molar
equiv of EtMgBr before the reaction. Specifically, the
best results were obtained for 1-decene with the follow-
ing procedure. A solution of EtMgBr (20 mol %) in Et2O
was added dropwise at -78 °C to a solution of zir-
conocene dichloride (10 mol %) in THF. After 5 min, 1
molar equiv of alkene was added. The reaction mixture
was then brought to 23 °C over 20 min. Finally, a
solution of 0.5 molar equiv of a 1 M solution of Et2Zn in
hexanes was added at 23 °C, and the reaction mixture
was stirred at this temperature. Quenching with iodine
in Et2O or THF afforded 1-iodo-2-ethyldecane in 95%
yield. Using this procedure, the scope of the ethylzin-
cation was examined. As the results summarized in
Table 1 indicate, the reaction appears to be reasonably
general with respect to the R group of monosubstituted
The intramolecular nickel-catalyzed carbozincation of
alkynes5a and the intramolecular palladium-catalyzed
carbozincation of alkenes5b are very effective.6 However,
the corresponding Ni-catalyzed intermolecular carbozin-
(1) Purdue Research Foundation Graduate Research Fellow (1999-
2000).
(2) (a) Frangin, Y.; Gaudemar, M. C.R. Acad. Sci., Ser. C 1974,
278(12), 885. (b) Frangin, Y.; Gaudemar, M. J . Organomet. Chem. 1977,
142(1), 9. (c) Negishi, E.; Miller, J . A. J . Am. Chem. Soc. 1983, 105,
6761.
(3) (a) Kondakov, D. Y.; Negishi, E. J . Am. Chem. Soc. 1995, 117,
10771. (b) Kondakov, D. Y.; Negishi, E. J . Am. Chem. Soc. 1996, 118,
1577.
(4) (a) Dzhemilev, U. M.; Vostrikova, O. S.; Sultanov, R. M. Izv.
Akad. Nauk SSSR, Ser. Khim. 1983, 219. (b) Takahashi, T.; Seki, T.;
Nitto, Y.; Saburi, M.; Rousset, C.; Negishi, E. J . Am. Chem. Soc. 1991,
113, 6266. (c) Waymouth, R. M. J . Am. Chem. Soc. 1991, 113, 6268.
(d) Houri, A. F.; Didiuk, M. T.; Xu, Z. M.; Horan, N. R.; Hoveyda, A.
H. J . Am. Chem. Soc. 1993, 115, 6614. Visser, M. S.; Heron, N. M.;
Didiuk, M. T.; Sagal, J . F.; Hoveyda, A. H. J . Am. Chem. Soc. 1996,
118, 4291. (e) Bell, L.; Brookings, D. C.; Dawson, G. J .; Whitby, R. J .
Tetrahedron 1998, 54, 14617 and pertinent references therein.
(5) (a) Studemann, T.; Knochel, P. Angew. Chem., Int. Ed. Engl.
1997, 36, 93. (b) Stadtmuller, H.; Lentz, R.; Tucker, C. E.; Studemann,
T.; Dorner, W.; Knochel, P. J . Am. Chem. Soc. 1993, 115, 7027.
(6) Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117.
(7) (a) Negishi, E.; Yoshida, T. Tetrahedron Lett. 1980, 21, 1501.
(b) Negishi, E.; Van Horn, D.; Yoshida, T.; Rand, C. L. Organometallics
1983, 2, 563. (c) Studemann, T.; Ibrahim-Ouali, M.; Knochel, P.
Tetrahedron 1998, 54, 1299.
10.1021/om991004j CCC: $19.00 © 2000 American Chemical Society
Publication on Web 05/23/2000

2418 Organometallics, Vol. 19, No. 13, 2000
Communications
Ta ble 2. P d -Ca ta lyzed Cr oss Cou p lin g of th e Diisoa lk ylzin c Gen er a ted by Eth ylzin ca tion of 1-Decen e w ith
Va r iou s Or ga n ic Ha lid es
a
All yields were calculated by GC using mesitylene as an internal standard. Figures in parentheses are isolated yields (isolated by
distillation). All reactions were carried using 4 molar equiv of RX, unless otherwise noted. c 1 molar equiv of PhI was used. 2 molar
b
d
equiv of PhI was used.
high yields.10 In the presence of 1 molar equiv of
Sch em e 1
Et2Zn, transmetalation evidently occurs regioselectively
to give the bimetallic intermediate 4. The observed
regioselectivity may be due to the relief of steric hin-
drance to a greater extent, since the zirconocene unit
ends up at the less crowded site. The dialkylzirconocene
intermediate 4 would then undergo a chemoselective
â-hydrogen abstraction involving selective abstraction
of a â-H atom of the Et group9 to give 5 and regenerate
the zirconocene-ethylene complex. A similar reaction
of 5 involving the second ethyl-zinc bond will give
ultimately the diorganylzinc 1.11 To support this mech-
anism, the following experiments were conducted. The
ethylene-zirconocene complex 6 stabilized by 1 molar
equiv of methyldiphenylphosphine was generated ac-
cording to a reported procedure12 and used in catalytic
alkenes. It should be mentioned, however, that allyl
quantities in the reaction of 1-decene with Et2Zn
(Scheme 2, eq a). Ethylzincation took place and afforded
the expected 2-ethyldecane in 60% yield after 12 h.
Similarly, the use of the â-substituted zirconacyclopen-
tane 7 generated from zirconocene dichloride and
benzyl ether and allyl phenyl ether do not yield detect-
able amounts of ethylzincated products.
In light of the previous mechanistic studies on car-
boalumination8 and carbomagnesation,4b the mecha-
nism of this carbozincation can be thought to proceed
as depicted in Scheme 1. Treating zirconocene dichloride
with 2 molar equiv of EtMgBr has been shown to gen-
erate diethylzirconocene, which undergoes â-hydrogen
abstraction to give the zirconocene-ethylene complex
2.9 This zirconocene-ethylene complex thus prepared
in situ can react with 1 molar equiv of alkenes to give
regioselectively â-substituted zirconacyclopentanes 3 in
(9) Negishi, E.; Nguyen, T.; Maye, J . P.; Choueiri, D.; Suzuki, N.;
Takahashi, T. Chem. Lett. 1992, 114, 10091.
(10) (a) Swanson, D. R.; Rousset, C. J .; Negishi, E.; Takahashi, T.;
Seki, T.; Saburi, M.; Uchida, Y. J . Org. Chem. 1989, 54, 3521. (b)
Negishi, E.; Miller, S. R. J . Org. Chem. 1989, 54, 601. (c) Takahashi,
T.; Seki, T.; Nitto, Y.; Saburi, M.; Rousset, C. J .; Negishi, E. J . Am.
Chem. Soc. 1991, 113, 6266.
(11) With 1-decene as a substrate, in hexanes and with higher loads
of Et2Zn (1-2 molar equiv with respect to the alkene), the formation
of 1-iodo-2-(2-iodoethyl)decane after quenching with iodine was ob-
served, suggesting that a second transmetalation had occurred before
the â-hydrogen abstraction took place.
(8) (a) Van Horn, D. E.; Negishi, E. J . Am. Chem. Soc. 1978, 100,
2252. (b) Yoshida, T.; Negishi, E. J . Am. Chem. Soc. 1981, 103, 4985.
(c) Negishi, E.; Van Horn, D. E.; Yoshida, T. J . Am. Chem. Soc. 1985,
107, 6639.
(12) Takahashi, T.; Suzuki, N.; Hasegawa, M.; Nitto, Y.; Aoyagi, K.
I.; Saburi, M. Chem. Lett. 1992, 331.

Communications
Organometallics, Vol. 19, No. 13, 2000 2419
Sch em e 2
a
All yields were calculated using mesitylene as an internal standard.
1-decene10 in place of 6 afforded the expected 2-ethyl-
decane in >98% yield after 4 h (Scheme 2, eq b). The
â-substituted zirconacyclopentane 7 was also treated
with 2 molar equiv of Et2Zn. Iodination gave 1-iodo-2-
ethyldecane in more than 98% yield (Scheme 2, eq c).
cross coupling, and it has to be removed by evaporation
under vacuum before cross coupling. It is noteworthy
that the cross-coupling reactions of the carbomag-
nesation and carboalumination products of 1-decene
with phenyl iodide using Cl2Pd(dppp) or Cl2Pd(dppf) as
a catalyst were unsuccessful. Carbomagnesation of
1-decene, addition of ZnBr2 or ZnCl2, evaporation of the
solvents, and cross coupling with phenyl iodide under
the conditions used in Table 2 did provide the desired
cross-coupled product in moderate yield. However, the
carbozincation reaction itself is significantly higher
yielding and cleaner than the corresponding carbomag-
nesation reaction, as is the carbozincation-cross coup-
ling tandem process. Using 5 mol % of Cl2Pd(dppp) in
DMF at 23 °C, the scope of the Pd-catalyzed cross
coupling was examined. As the results summarized in
Table 2 indicate, a variety of electrophiles can be cross-
coupled satisfactorily. However, 2-ethyl-1-decene is the
major product when the cross coupling is very slow.14
1
The H NMR spectrum of the â-substituted zirconacy-
clopentane 7 showed two Cp signals at 6.010 and 6.014
ppm. After treatment with 1 molar equiv each of Et2Zn
and PMe3, the 1H NMR spectrum of the reaction
mixture 8 showed two Cp signals at 5.019 and 5.025
ppm (Scheme 2, eq d).
The Pd-catalyzed cross coupling of the diisoalkylzincs
1a generated by ethylzincation of 1-decene can be
achieved in good yields with a variety of electrophiles.
The optimal conditions were sought for the case of cross-
coupling with phenyl iodide, and the results are sum-
marized in Table 2. The use of Pd(PPh3)4 as a catalyst
does not yield any cross-coupling product in detectable
amounts. Derivatives of PdCl2 appear to be much more
preferable. The major byproducts are 2-ethyldecane due
to the unreacted organozinc reagent and 2-ethyl-1-
decene due to dehydropalladation.13 The latter can be
considerably reduced by the use of chelating ligands on
palladium such as dppf, dppp, and dppb. Indeed, the
dehydropalladation occurs after the isoalkylpalladium
intermediate is formed by transmetalation from the iso-
alkylzinc. On the other hand, Cl2Pd(TFP)2, where TFP
is tris(2-furyl)phosphine, Cl2Pd(PPh3)2, and Pd(dba)2 +
2 TFP give poor yields of cross-coupling products in
either THF or DMF. With Cl2Pd(dppf), Cl2Pd(dppp), and
Cl2Pd(dppb), high yields of cross coupling products are
obtained in DMF. THF seems to be detrimental to the
Ack n ow led gm en t. We thank the National Science
Foundation (Grant No. CHE-9704994), the National
Institutes of Health (Grant No. GM36792), and Purdue
Research Foundation (Graduate Research Fellowship to
S.G.) for support of this research.
Su p p or tin g In for m a tion Ava ila ble: Text giving details
of the synthesis and characterization data for the compounds
discussed in the paper and figures giving NMR spectra of these
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
OM991004J
(14) When a large excess of electrophile was used, homocoupling of
the electrophile was observed in fair amount (with 4 molar equiv of
PhI, about 40% of PhPh was formed).
(15) 1-Cyclohexenyl triflate was generated according to a reported
procedure: (a) Scott, W. J .; Stille, J . K. J . Am. Chem. Soc. 1986, 108,
3033. (b) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299.
(13) (a) When 1 or 2 molar equiv of Et2Zn was used to perform the
ethylzincation, the organozinc generated was an (ethyl)(isoalkyl)zinc
species and byproducts from the cross coupling between the ethyl
moiety and the electrophile were observed but remained minor. (b)
Traces of biphenyl byproduct were observed.