Heterodimerization of Olefins. 1. Hydrovinylation Reactions of Olefins That Are Amenable to Asymmetric Catalysis

Article abstract of DOI:10.1021/jo035171b

Through a systematic examination of ligand and counterion effects, new protocols for a nearly quantitative and highly selective codimerization of ethylene and various functionalized vinylarenes have been discovered. In a typical reaction, 4-bromostyrene and ethylene undergo codimerization in the presence of 0.0035 equiv each of [(allyl)NiBr]2, triphenylphosphine, and AgOTf in CH₂Cl₂ at -56 °C to give 3-(4-bromophenyl) -1-butene in >98% yield and selectivity. Corresponding reactions with [(allyl)PdX]₂ are much less efficient and less selective and may require further optimization before a viable system can be identified. Another useful protocol that gives comparable yield and selectivity involves the use of a single-component catalyst prepared from allyl 2-diphenylphosphinobenzoate, Ni(COD)₂, and (C₆F₅)₃B. Recognition of a synergistic relationship between a chiral hemilabile ligand (for example, (R)-2-methoxy-2′-diphenylphosphino-1,1′-binaphthyl, MOP) and a highly dissociated counteranion (BARF or SbF6) in an enantioselective version of the Ni-catalyzed reaction raises the prospects of developing a practical route for the synthesis of 3-arylbutenes. Several pharmaceutically relevant compounds, including widely used 2-arylpropionic acids, can be synthesized from these key intermediates. This reaction appears to be quite general. Synthesis of several new 2-diphenylphosphino-1,1-binaphthyl derivatives, prepared to probe the effect of hemilabile coordination on the efficiency and selectivity of the reaction, are also described.

Full text of DOI:10.1021/jo035171b

Heter od im er iza tion of Olefin s. 1. Hyd r ovin yla tion Rea ction s of
Olefin s Th a t Ar e Am en a ble to Asym m etr ic Ca ta lysis
T. V. RajanBabu,* Nobuyoshi Nomura, J ian J in, Malay Nandi, Haengsoon Park, and
Xiufeng Sun
Department of Chemistry, The Ohio State University, 100 W. 18th Avenue, Columbus, Ohio 43210
RajanBabu.1@osu.edu
Received August 9, 2003
Through a systematic examination of ligand and counterion effects, new protocols for a nearly
quantitative and highly selective codimerization of ethylene and various functionalized vinylarenes
have been discovered. In a typical reaction, 4-bromostyrene and ethylene undergo codimerization
in the presence of 0.0035 equiv each of [(allyl)NiBr]2, triphenylphosphine, and AgOTf in CH2Cl2 at
-56 °C to give 3-(4-bromophenyl)-1-butene in >98% yield and selectivity. Corresponding reactions
with [(allyl)PdX]2 are much less efficient and less selective and may require further optimization
before a viable system can be identified. Another useful protocol that gives comparable yield and
selectivity involves the use of a single-component catalyst prepared from allyl 2-diphenylphosphi-
nobenzoate, Ni(COD)2, and (C6F5)3B. Recognition of a synergistic relationship between a chiral
hemilabile ligand (for example, (R)-2-methoxy-2′-diphenylphosphino-1,1′-binaphthyl, MOP) and a
highly dissociated counteranion (BARF or SbF6) in an enantioselective version of the Ni-catalyzed
reaction raises the prospects of developing a practical route for the synthesis of 3-arylbutenes.
Several pharmaceutically relevant compounds, including widely used 2-arylpropionic acids, can be
synthesized from these key intermediates. This reaction appears to be quite general. Synthesis of
several new 2-diphenylphosphino-1,1-binaphthyl derivatives, prepared to probe the effect of
hemilabile coordination on the efficiency and selectivity of the reaction, are also described.
In tr od u ction
Among transition-metal-catalyzed carbon-carbon bond-
forming processes, cationic nickel hydride-catalyzed ho-
modimerization of propene, which forms the basis of the
Dimersol technology (eq 1), is one of the most efficient
Since the branched product 1 is chiral, a regio- and
stereoselective version of this reaction could provide easy
access to variety of olefin-derived products, including
carboxylic acid derivatives. Thus hydrovinylation of
vinylarene derivatives that leads to 3-arylbutenes could
be used for the synthesis widely used antiinflammatory
2-arylpropionic acids (eq 3).4 One of the hydrovinylation
products of styrene, (R)-3-phenyl-1-butene, has been
reported to give a very high melting (>400 °C) isotactic
polymer under Ziegler conditions.2a
homogeneous catalyzed reactions.1 The active catalyst,
generated from [η3-(allyl)NiX]2, a trivalent phosphorus
ligand and a Lewis acid, produces a mixture of C6-olefins
from propene with rates in excess of 625 000 [propene]-
[Ni]-1[h]-1 2
. Applications of this and of other related
heterodimerization reactions for the synthesis of fine
chemicals have been the subject of much research since
its discovery.3 Among these, the hydrovinylation reaction,
viz., the addition of a vinyl group and a hydrogen across
a double bond (eq 2), has attracted the most attention.
(3) Reviews: (a) Bogdanovic´, B. Adv. Organomet. Chem. 1979, 17,
105. (b) J olly, P. W.; Wilke, G. Hydrovinylation. In Applied Homoge-
neous Catalysis with Organometallic Compounds; Cornils, B., Her-
rmann, W. A., Eds.; VCH: New York, 1996; Vol. 2, pp 1024-1048. (c)
RajanBabu, T. V.; Nomura, N.; J in, J .; Radetich, B.; Park, H.; Nandi,
M. Chem. Eur. J . 1999, 5, 1963. (d) Goossen, L. J . Angew. Chem., Int.
Ed. 2002, 41, 3775. (e) RajanBabu, T. V. Chem. Rev. 2003, 103, 2845.
(4) (a) Rieu, J .-P.; Boucherle, A.; Cousse, H.; Mouzin, G. Tetrahedron
1986, 42, 4095. (b) Sonawane, H. R.; Bellur, N. S.; Ahuja, J . R.;
Kulkarni, D. G. Tetrahedron: Asymmetry 1992, 3, 163. (c) Stahly, G.
P.; Starrett, R. M. In Chirality in Industry II; Collins, A. N., Sheldrake,
G. N., Crosby, J ., Eds.; Wiley: Chichester, 1997; p 19.
(1) (a) Wilke, G.; Bogdanovic´, B.; Hardt, P.; Heimbach, P.; Keim,
W.; Kro¨ner, M.; Oberkirch, W.; Tanaka, K.; Stienru¨cke, E.; Walter,
D.; Zimmermann, H. Angew. Chem., Int. Ed. Engl. 1966, 5, 151. (b)
Chauvin, Y.; Olivier, H. Dimerization and Codimerization. In Applied
Homogeneous Catalysis with Organometallic Compounds; Cornils, B.,
Herrmann, W. A., Eds.; VCH: New York, 1996; Vol. 1, pp 258-268.
(2) (a) Wilke, G. Angew. Chem., Int. Ed. 1988, 27, 185. (b) Bogdanovic´,
B.; Spliethoff, B.; Wilke, G. Angew. Chem., Int. Ed. 1980, 19, 622.
10.1021/jo035171b CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/02/2003
J . Org. Chem. 2003, 68, 8431-8446
8431

RajanBabu et al.
The hydrovinylation reaction has a long history dating
back to 1965, when Alderson, J enner, and Lindsey first
reported the use of hydrated Rh and Ru chlorides to effect
the codimerization of ethylene at high pressures (1000
psi) with a variety of olefins, including styrene and
butadiene.5a Styrene has served as a prototypical test
case for most investigations reported to date. In early
studies, in addition to Rh,5 other metals such as Ru,5a,6
Co,7 Pd,8 and Ni9 were also used, and in most instances,
the reactions were complicated by isomerization of the
initially formed 3-arylbutenes and oligomerization of the
starting olefins (eq 2). Notable among the early studies
are also the first examples of the asymmetric hydrovi-
nylation of 1,3-cyclooctadiene, norbornene, and norbor-
nadiene and a codimerization of propene and 2-butene
using a combination of [η3-C3H5)NiCl]2/Et3Al2Cl3 and a
monoterpene-derived chiral phosphine, even though the
selectivities were unacceptably poor.10
F IGURE 1. Assorted ligands used in hydrovinylation reac-
tions.
mostly linear products and/or extensive isomerization,
subsequent studies have shown that use of ligands such
as Cy3P,12 4,13 and 514 (Figure 1) and carefully chosen
reaction conditions permit the isolation of the branched
product. Acceptable yields and best selectivities are
achieved under low conversions, since isomerization of
the primary product is a persistent problem with many
of these reactions. Among these ligands, the phosphinite
4 is particularly noteworthy (eq 4).13 With the appropriate
counterion (SbF6-), 3-phenyl-1-butene can be synthesized
in a moderate yield and in ee’s up to 86% (S).
In more recent studies, the yield and selectivity of the
Pd- and Ni-catalyzed hydrovinylation reactions have been
improved considerably by varying the ligands and reac-
tion conditions. Even though some initial reports8,11
seemed to indicate that the Pd-catalyzed reactions gave
Recent improvements in the Ni-catalyzed heterodimer-
ization reaction includes the use of [ArNi(PR3)(MeCN)]+
(5) (a) Alderson, T.; J enner, E. L.; Lindsey, R. V. J . Am. Chem. Soc.
1965, 87, 5638. (b) Umezaki, H.; Fujiwara, Y.; Sawara, K.; Teranishi,
S. Bull. Chem. Soc., J pn. 1973, 46, 2230. (c) Dzhemilev, U. M.;
Gubaidullin, L. Y.; Tolstikov, G. A. Bull. Acad. Sci. U.S.S.R. 1976,
2009.
-
BF4 (Ar ) mesityl, R ) benzyl), which served as an
efficient catalyst for hydrovinylation of styrene (eq 5).15
(6) Use of Ru: (a) see ref 5(a). (b) Umezaki, H.; Fujiwara, Y.; Sawara,
K.; Teranishi, S. Bull. Chem. Soc., J pn. 1973, 46, 2230.
(7) Use of Co: (a) Pillai, S. M.; Tembe, G. L.; Ravindranathan, M.
J . Mol. Catal. 1993, 84, 77. (b) A more recent related example: Hilt,
G.; Lu¨ers, S. Synthesis 2002, 609.
(8) Early studies with Pd catalysts: (a) Barlow, M. G.; Bryant, M.
J .; Haszeldine, R. N.; Mackie, A. G. J . Organomet. Chem. 1970, 21,
215. (b) Kawamoto, K.; Tatani, A.; Imanaka, T.; Teranishi, S. Bull.
Chem. Soc., J pn. 1971, 44, 1239. For related studies see also: Drent,
E. US Patent 5,227,561, 1993. [Chem. Abstr. 1994, 120, 31520]. (c)
Nozima, H.; Kawata, N.; Nakamura, Y.; Maruya, K.; Mizoroki, T.;
Ozaki, A. Chem. Lett. 1973, 1163.
(9) Ni (a) Kawata, N.; Maruya, K.; Mizoroki, T.; Ozaki, A. Bull.
Chem. Soc. J pn. 1971, 44, 3217. (b) Kawata, N.; Maruya, K.; Mizoroki,
T.; Ozaki, A. Bull. Chem. Soc., J pn. 1974, 47, 413. (c) See also:
Kawakami, K.; Kawata, N.; Maruya, K.; Mizoroki, T.; Ozaki, A. J .
Catal. 1975, 39, 134. (d) Dzhemilev, U. M.; Gubaidullin, L. Y.;
Tolstikov, G. A. Bull. Acad. Sci. U.S.S.R. 1976, 2009. (e) Azizov, A.
G.; Mamedaliev, G. A.; Aliev, S. M.; Aliev, V. S. Azerb. Khim. Zh 1978,
3. Chem. Abstr. 1979, 90, 6002. (f) Azizov, A. G.; Mamedaliev, G. A.;
Aliev, S. M.; Aliev, V. S. Azerb. Khim. Zh 1979, 3. [Chem. Abstr. 1980,
93, 203573.]. (g) Mamedaliev, G. A.; Azizov, A. G.; Yu, G. Pol. J . (J pn.)
1985, 17, 1075.
(10) (a) Bogdanovic´, B.; Henc, B.; Meister, B.; Pauling, H.; Wilke,
G. Angew. Chem., Int. Ed. 1972, 11, 1023. (b) Bogdanovic´, B.; Henc,
B.; Lo¨ser, A.; Meister, B.; Pauling, H.; Wilke, G. Angew. Chem., Int.
Ed. 1973, 12, 954. As an asymmetric metal-catalyzed carbon-carbon
bond-forming reaction, only Nozaki’s Cu(II)-catalyzed cyclopropanation
of styrene with ethyl diazoacetate predates this discovery. See: Nozaki,
H.; Moriuti, S.; Takaya, H.; Noyori, R. Tetrahedron Lett. 1966, 5239.
(11) (a) Britovsek, G. J . P.; Keim, W.; Mecking, S.; Sainz, D.; Wagner,
T. J . Chem. Soc., Chem. Commun. 1993, 1632. (b) Britovsek, G. J . P.;
Cavell, K. J .; Keim, W. J . Mol. Catal. A, Chem. 1996, 110, 77. (c) For
a related dendrimeric Pd-catalyst, see: Hovestad, N. J .; Eggeling, E.
B.; Heidbu¨chel, H. J .; J astrzebski, J . T. B. H.; Kragl, U.; Keim, W.;
Vogt, D.; van Koten, G. Angew. Chem., Int. Ed. 1999, 38, 1655. For a
full report, see: Eggeling, E. B.; Hovestad, N. J .; J astrzebski, T. B.
H.; Vogt, D.; van Kotten, G. J . Org. Chem. 2000, 65, 8857.
High turnover numbers (up to 1915 h-1) and selectivities
for the 3-arylbutenes can be achieved for a variety of
styrenes at 15 bar ethylene pressure. Heteroatom sub-
stituents are tolerated, but ring-alkylated styrenes give
poor yields. The reaction rates fall unacceptably low
below 20 °C, and as the temperature is increased,
isomerization of the initially formed product is seen.
Substitution of tribenzylphosphine with cis-myrtanyl-
diphenylphosphine gives high selectivity toward 3-phen-
ylbutene, albeit with a disappointing enantioselectivity
(12) DiRenzo, G. M Mechanistic Studies of Catalytic Olefin Dimer-
ization Reactions Using Electrophilic η3-allyl-Palladium(II) Complexes,
Ph.D. Thesis; University of North Carolina, 1997. We thank Prof.
Brookhart and Dr. DiRenzo for a copy of this dissertation.
(13) Bayersdo¨rfer, R.; Ganter, B.; Englert, U.; Keim, W.; Vogt, D.
J . Organomet. Chem. 1998, 552, 187.
(14) (a) Albert, J .; Cadena, M.; Granell, J .; Muller, G.; Ordinas, J .
I.; Panyella, D.; Puerta, C.; Sanudo, C.; Valerga, P. Organometallics
1999, 18, 3511. For use of other highly basic phosphines, see also: (c)
Albert, J .; Bosque, R.; Cadena, J . M.; Delgado, S.; Granell, J .; Muller,
G.; Ordinas, J . I.; Bardia, M. F.; Solans, X. Chem. Eu. J . 2002, 8, 2279.
(d) Englert, U.; Haerter, R.; Vasen, D.; Salzer, A.; Eggeling, E. B.; Vogt,
D. Organometallics 1999, 18, 4390.
(15) (a) Ceder, R.; Muller, G.; Ordinas, J . I. J . Mol. Catal. 1994, 92,
127. (b) Muller, G.; Ordinas, J . I. J . Mol. Catal., A: Chem. 1997, 125,
97. See also ref 9a,b.
8432 J . Org. Chem., Vol. 68, No. 22, 2003

Heterodimerization of Olefins
(∼7% ee). Since there is an exothermic polymerization
of ethylene at the end of the relatively more facile
heterodimerization, control of temperature is crucial to
get good selectivities under these reaction conditions.
Monteiro et al.16 reported the use of dicationic nickel
complexes ([Ni(CH3CN)6]2+‚2[BF4]-/Ph3P/Et2AlCl) at room
temperature and 10 bar pressure of ethylene to get yields
of 68-87% of various hydrovinylation products. Isomer-
ization of the primary product can be prevented by
maintaining a high pressure of ethylene (>10 bar). A
unique feature of this catalyst system that is not seen in
any other Ni-catalyzed reactions is that chelating
phosphines [e.g., diphenylphosphinoethane (dppe) or
N,N-dimethyl-1-[2-(diphenylphosphino)ferrocen-yl]eth-
ylamine (dppfa)] do not inhibit the reaction.
A careful examination of the work prior to our first
initial report17 on a new protocol for the Ni-catalyzed
hydrovinylation of vinylarenes shows that the best
catalyst reported for this reaction is also the one that
gives the best enantioselectivity. This is the Wilke system
that uses [η3-allyl)NiCl]2/[(RR)-6]/Et3Al2Cl3].3b,18,19 With
this catalyst, varying ee’s are obtained, depending on the
reaction conditions. The azaphospholene (RR)-6 is a very
special ligand for the hydrovinylation of vinylarenes and
1,3-dienes, and the Ni complexes derived from this ligand
have been claimed18 to give the highest ee recorded to
date for many of these substrates (eqs 6 and 7). A variety
an attempt to simplify the synthesis, and it has been
found that catalytic activity and enantioselectivity in-
variably fall below useful levels. These reports suggest
that the azaphospholene ligand class has a narrow scope
and are possibly of limited value for the development of
a broadly applicable hydrovinylation reaction, especially
for a practical enantioselective version. The use of
pyrophoric aluminum alkyl Lewis acids is another major
distraction of this protocol. We have since found that
sodium tetrakis[3,5-bis(trifluoromethyl)phenylborate] (Na-
BARF) is a suitable replacement for the Lewis acids in
the hydrovinylation reaction run in CH2Cl2 (vide infra).
Leitner has extended the use of this salt for reactions in
supercooled CO2 with the ligand (RR)-6.19
In a very important recent development, Leitner et al.
reported21 that Feringa’s phosphoramidite ligand 7 gave
very high enantioselectivities in the hydrovinylation of
a number of styrene derivatives (eq 8). Another signifi-
cant result in this area is the use of (PCy3)2(CO)Ru(Cl)H
in conjunction with HBF4‚Et2O.22a Use of silver salts in
place of the acid gives a more active hydrovinylation
catalyst (vide infra).
In this paper we report the details of our investigations
from which emerged a versatile and generally useful
protocol for the hydrovinylation of vinylarenes. As a
result, very high yields (>95%) and selectivities (>99%
for the 3-arylbutenes) for several vinylarenes at one
atmosphere of ethylene pressure and -55 °C have been
achieved. In addition, the protocol is amenable to asym-
metric catalysis by chiral phosphines. Two preliminary
reports dealing with the early parts of this investigation
have appeared.17,23
Resu lts a n d Discu ssion
Mech an ism of Ni-Catalyzed Hydr ovin ylation . Even
though much of the early studies of hydrovinylation of
styrene are characterized by a lack of any selectivity,
many of them provide significant mechanistic insights
into the reaction. For example, kinetic and solvent effect
of vinylarenes, including 4-chlorostyrene, 4-isobutylsty-
rene, 2-methylstyrene, and 6-methoxy-2-vinylnaphtha-
lene, gave very high ee’s in the hydrovinylation reaction.
The ligand (RR)-6 is prepared from (-)(R)-myrtenal and
(+)(R)-1-phenylethylamine in a multistep process.3b One
other congener of this compound, the diastereomer (RS)-6
(prepared from (-)(R)-myrtenal and (-)(S)-1-phenyleth-
ylamine), is much less active and selective for the
hydrovinylation of styrene. Monomeric and structurally
related versions of this ligand have been prepared3b,20 in
studies of hydrovinylation with NiX2/AlEt3/BF3‚OEt2/
9e-g
P(OPh)3
provided some early indications of the [Ni-
H]+ coordination to a styrene and subsequent addition.
The deactivating effect of a solvent was found to increase
in the order CH2Cl2, PhF, PhCl, PhMe, PhNO2, Et2O,
consistent with an inhibitory effect of a coordinating
Lewis base. Studies of D-distribution in the product when
the hydrovinylation was carried out with D2CdCD2
provide further evidence for the involvement of a cationic
nickel hydride intermediate.9f Even though a catalytically
active Ln[Ni-H]+ has not been isolated, its generation
(16) (a) Monteiro, A. L.; Seferin, M.; Dupont, J .; Souza, R. F.
Tetrahedron Lett. 1996, 37, 1157. (b) Fassina, V.; Ramminger, C.;
Seferin, M.; Monteiro, A. L. Tetrahedron 2000, 56, 7403.
(17) Nomura, N.; J in, J .; Park, H.; RajanBabu, T. V. J . Am. Chem.
Soc. 1998, 120, 459.
(18) Wilke, G.; Monkiewicz, J .; Kuhn, H. Preparation of optically
active azaphospholenes and their use in catalysis for asymmetric
codimerization of olefins; US Patent, 4912274, 1990 [Chem. Abstr.
1991, 114, 43172].
(19) Use of the Wilke catalyst system in scCO2 has since been
reported. See: (a) Wegner, A.; Leitner, W. J . Chem. Soc., Chem.
Commun. 1999, 1583. (b) Bo¨smann, A.; Francio`, G.; J anssen, E.;
Solinas, M.; Leitner, W.; Wasserscheid, P. Angew. Chem., Int. Ed. 2001,
40, 2697.
(20) Angermund, K.; Eckerle, A.; Lutz, F. Z. Naturforsch., B: Chem.
Sci. 1995, 50, 488.
(21) Francio´, G.; Faraone, F.; Leitner, W. J . Am. Chem. Soc. 2002,
124, 736.
(22) (a) Yi, C. S.; He, Z.; Lee, D. W. Organometallics 2001, 20, 802.
(b) He, Z.; Yi, C. S.; Donaldson, W. A. Org. Lett. 2003, 5, 1567.
(23) Nandi, M.; J in, J .; RajanBabu, T. V. J . Am. Chem. Soc. 1999,
121, 9899.
J . Org. Chem, Vol. 68, No. 22, 2003 8433

RajanBabu et al.
SCHEME 1. P r op osed Mech a n ism for th e
Heter od im er iza tion of Eth ylen e a n d Styr en e
dotal observations reported in the literature and some
made during this study can be accommodated by this
mechanism.
(a) The diminished reactivity of electron-deficient vi-
nylarenes might arise from the low rate of metal hydride
addition (11 f 13).
(b) The apparent poor reactivity of substrates carrying
heteroatoms when R2AlX-type Lewis acids are employed
could be the result of the coordination of these atoms to
aluminum.
(c) The coordinating solvents show deactivating effects.
(d) The isomerization of the initially formed 3-aryl-1-
butene to 2-aryl-2-butens (1 f 2) could be mediated by
the metal hydride via sequential addition-elimination
reactions.
(e) Chelating phosphines totally inhibit the reaction
(vide infra).
An Im p r oved P r otocol for th e Hyd r ovin yla tion
of Vin yla r en es. We have already alluded to the fact that
when we started this work the only ligand that gave a
satisfactory yield and selectivity for this reaction was
Wilke’s azaphospholene ligand 6 (eq 6). Several struc-
tural modifications of this ligand lead to inferior ligands.
We concluded that the scope and selectivity of hydrovi-
nylation could be significantly expanded by a careful
study of the reaction in the presence of other phosphine
ligands and what appeared to be the other important
component of the catalyst, viz., the counteranion Y (see
11, in Scheme 1). In this connection, we wondered
whether with appropriately chosen counteranions of
other metal salts could serve as an effective replacement
for the troublesome Lewis acid in the traditional Wilke
dimerization catalyst. In this context, readily available
silver salts, with anions of varying donor abilities, could
be explored. Previous studies had indicated that while
the counteranion (Y in Scheme 1) played a significant
role in various olefin dimerization and related reactions,3a
the catalytic activity and selectivity varied considerably
with the ligand used. For example, while weakly coor-
dinating anions (Et2AlCl2-, OTf-, BF4-) give best selec-
tivities with ligand (RR)-6,3b for other ligands such as
and inter-2a and intramolecular24 additions have been
documented. Since these early studies, Brookhart and
DiRenzo have provided more details of their mechanistic
study of the closely related Pd-catalyzed codimerization
of styrene and ethylene.12 On the basis of all the available
evidence and our own initial observations, a hypothetical
mechanism, shown in Scheme 1, can be proposed for this
reaction. The functional equivalent of a catalyst can be
represented by 11, a cationic metal hydride intermediate
associated with a weakly coordinated counteranion and
a phosphine. This species is formed by the Lewis acid-
assisted dissociation of the Ni-X bond from the 16-
electron phosphine complex 8, coordination of ethylene
(or styrene) to form 10, and insertion into the allyl Ni-
bond followed by subsequent â-hydride elimination.
Several crystal structures of complexes related to Ni-allyl
compounds 8 and 9 are known with Cy3P [X ) MeAlCl3],10b
P(menthyl)(Me)(But) [X ) Cl],25a and P(menthyl)2(Me)[X
) Me].25b Addition of the metal hydride to the vinylarene
would lead to the benzyl complex 13, which is shown as
a 16-electron η3-structure. Ligand substitution with
ethylene leads to 14. At higher concentrations of ethylene
and styrene this species could serve as a catalyst resting
state. Strong evidence for such a situation has been
provided by Brookhart and DiRenzo12 in the mechanisti-
cally related [(allyl)Pd(Cy3P)]+[BARF]--mediated dimer-
ization of styrene. Insertion of ethylene followed by
â-hydride elimination from 15 regenerates the metal
hydride catalyst and the product 1. A number of anec-
-
(menthyl)2P(Pri), more dissociating anions such as PF6
-
and SbF6 appear to be the best.3a Another parameter
that could be explored in a new protocol might be the
use of complexes of other metals such as Ru, Pd, and Rh.
It was our expectation that with the correct synergy
between the metal, the phosphine, and the counteranion
we would be able to achieve a more selective reaction by
affecting several individual steps in the catalytic cycle.
For example, selectivity in the first step would arise from
the metal hydride adding to the more reactive olefin (11
f 13). In the other key step, the smaller olefin can be
expected to undergo insertion into the metal-benzyl bond
(13 f 15), especially with a relatively bulky phosphine,
which would increase steric crowding around Ni. Steric
and/or electronic effects would prevent metal hydride-
mediated isomerization (1 f 2) of the relatively hindered
(and unactivated) primary product. After an extensive
scouting program in which we systematically investigated
the effect of varying the ligands, counterions, and metals,
most of these expectations have been borne out. The full
details of this study are disclosed here.
(24) Muller, U.; Keim, W.; Kru¨ger, C.; Betz, P. Angew. Chem., Int.
Ed. 1989, 28, 1011.
(25) (a) Brandes, H.; Goddard, R.; J olly, P. W.; Kru¨ger, C.; Mynott,
R.; Wilke, G. Z. Naturforsch. 1984, 39B, 1139. (b) Barnett, B. L.;
Kru¨ger, C. J . Organomet. Chem. 1974, 77, 407.
Ligan d an d Cou n ter an ion Effects. The initial scout-
ing of ligands and various silver salts was conducted as
8434 J . Org. Chem., Vol. 68, No. 22, 2003

Heterodimerization of Olefins
TABLE 1. Ni-Ca ta lyzed Hyd r ovin yla tion of Styr en e
Liga n d a n d Cou n ter ion Effects
TABLE 2. Scop e of Su bstr a tes in Hyd r ovin yla tion of
Vin yla r en es (Eq 10)
entry
vinylarene
styrene
3-Me-styrene
4-Me-styrene
2-chlorostyrene
4-chlorostyrene
4-methoxystyrene
4-bromostyrene
2-vinylnaphthalene
6-MeO-2-vinyl-
naphthalene (MVN)
4-i-Bu-styrene
% yielda
conditionsb
entry
P
AgX
conditions
conversion (1a :2:16)
1
2
3
4
5
6
7
8
9
Ph3P AgSbF6 -78 °C, 7.5 h
Ph3P AgSbF6 -78 to 25 °C, 14 h 100% (1a + 2 (maj) + 16)
Ph3P AgBF4 -78 to 25 °C,
Ph3P AgBPh4 -78 or -56 °C
Ph3P AgOTf 25 °C, 5 min
Ph3P AgOTf -45 to -37 °C, 2 h 100% (68:1:trace)
Ph3P AgOTf -78 to 25 °C, 14 h 100% (5:1:0)
Ph3P AgOTf -78 °C, 6 h
P h 3P AgOTf -55 °C, 2 h
Cy3P AgOTf -56 °C, 2 h
Cy3P AgOTf -35 °C, 0.5 h
Cy3P AgOTf 0 °C, 45 min
low (1a + 16)
1
2
3
4
5
6
7
8
9
>95 (>99)
(98)
i
i
i
i
i
i
i
i
no reaction
no reaction
100% [mix. 1a + 2 (maj)]
(>99)
30
(>99)
>95 (>99)
>95 (98)
(>99)
trace
100% (100:0:0)
11% (11:0:0), rest st mat.
11% (11:0:0), rest st mat.
54% (50:0:4)
94 (>99) i, 1.4 mol % [Ni]
10
11
12
10
>90 (99) i, 1 mol % [Ni]
>97 (99) ii
a
See eq 9.
11
12
13
3-F-4-C6H5-styrene
3-bromostyrene
3-Ph-C(O)-styrene
88
(99)
(99)
i
i
i
follows: in a nitrogen-filled drybox, stoichiometric amounts
of [(allyl)NiBr]2 and the phosphine (Ni:P ) 1:1) were
mixed in CH2Cl2 at room temperature and the mixture
was added to a suspension of the silver salt in CH2Cl2.
The precipitated salts were removed by filtration through
a pad of Celite and the yellow solution was collected in a
Schlenk flask. The flask was taken outside the drybox,
and after adjusting the reaction mixture to the appropri-
ate temperature, oxygen-free ethylene was introduced.
A solution of the vinylarene in CH2Cl2 was then added
and the mixture was stirred as noted. The reaction was
quenched by adding half-saturated ammonium chloride
solution. The crude product was analyzed by NMR, gas
chromatography, and/or HPLC to ascertain the composi-
tion of the mixture (eq 9).
a
In parentheses are yields based on gas chromatography.
b
Selectivity >98% in all cases. (i) 0.7 mol % [Ni], CH2Cl2/-55 °C/2
h. (ii) (R)-MOP/Ar4B-Na+/CH2Cl2/-56 °C/2 h.
nor oligomerization of styrene is observed. As determined
by gas chromatography and H NMR spectroscopy, the
1
yield and selectivity of 3-phenyl-1-butene exceed 98% in
repeated runs. Isolation usually involved filtration through
a small plug of silica and evaporation of the solvent
(ether/pentane). For the less volatile 3-arylbutenes,
nearly quantitative recovery of the product is possible.
Aliphatic phosphines represented by tricyclohexylphos-
phine are much less reactive under these reaction condi-
tions. At room temperature, nearly quantitative conver-
sion to the product is observed along with some dimeriza-
tion of styrene.
The scope of the new protocol (eq 10) is shown in Table
2. In all cases the chemo- and regioselectivity of the
codimerization with respect to the desired product reaches
nearly 100%. Lewis basic groups such as OMe and
An initial survey of the most commonly available
phosphines and silver salts quickly revealed that tricy-
clohexylphosphine and triphenylphosphine gave the best
results. For initial studies, we chose AgOTf, AgBF4,
AgBPh4, and AgSbF6, which represent a spectrum of
counteranions with varying donor abilities. Typical re-
sults obtained in these studies are shown in Table 1.
As can be seen in Table 1, AgSbF6, AgBF4, and AgBPh4
are poor additives for the reaction done with Ph3P at low
temperatures (entries 1-4). Upon warming to higher
temperatures (∼25 °C), AgSbF6 shows some reactivity.
However, the reaction gives a mixture of products that
include the isomerized butenes and dimers of styrene.
Silver triflate, on the other hand, is a superior additive
for the reaction (entries 5-9). At 25 °C, a mixture of the
desired product 1a and the isomerization product 2 is
obtained, depending on the length of time the reaction
is maintained at higher temperatures (entries 5 and 7).
Between -45 and -37 °C, the proportion of the isomer-
ization is reduced considerably (entry 6). The most
optimum condition for the reaction is to carry out the
dimerization at -55 °C using 0.0035 equiv of [(allyl)-
NiBr]2 and a ratio of P/Ni/AgOTf ) 1:1:1. Under these
conditions, neither the isomerization of the double bond
carbonyl group are tolerated (entries 6, 9, and 13). It
appears that the reactivity of the ortho derivative is less
compared to the corresponding para analogue (entries 4
and 5), this difference arising from the steric effect that
hinders the approach of the [Ni-H]+ to the double bond.
Note that excellent yields of hydrovinylation products
are obtained from a variety of precursors appropriate
for the synthesis of antiinflammatory 2-arylpropionic
acids (entries 9-13). The product of hydrovinylation of
4-bromostyrene (entry 7) is another potentially impor-
tant precursor that may be transformed into a number
of 4-substituted analogues via organometallic cross-
coupling reactions. In most instances, the crude product
is exceptionally clean, as indicated by gas chromatogra-
phy, and no further purification of the product is war-
ranted.
Under conditions where styrene gives a quantitative
yield of the product, its derivatives substituted in the
vinyl fragment show negligible reactivity (Table 3).
Compared to R-methylstyrene, â-methylstyrene gave
higher conversions (entries 1-3). At higher temperatures,
J . Org. Chem, Vol. 68, No. 22, 2003 8435

RajanBabu et al.
TABLE 3. Hyd r ovin yla tion of Sid e-Ch a in -Su bstitu ted Styr en es
a
b
Typical conditions: (i) 0.35 mol % [(allyl)2NiBr]2, Ph3P, AgOTf, CH2Cl2/-55 °C/2 h. Rest cis- and trans-3-phenylpentenes (15%:4%).
c Rest cis- and trans-3-phenylpentenes (35%:10%) and unidentified products (20%). 2.0 mol % catalyst. e Mixture of olefins.
d
TABLE 4. Heter od im er iza tion of P r op en e a n d
up to 34% yield of the primary product is formed from
E-â-methylstyrene in a reaction that proceeds with
excellent conversion (entry 2 and eq 11). The isomers
Vin yla r en es (Eq 13)
no.
R
temp, °C
time, min
% yielda
17:18
1
2
3
4
5
i-Bu
OMe
Cl
-15
-15
0
0
-10
-55 to -40
10
10
-5
15
60
15
10
30
30
15
25
60
96
86
94
95
93
98b
94
92
88
3:1
4:1
4:1
4:1
4:1
5:1
4:1
2:1
10:1
Br
OAc
OAc
PhC(O)c
6
7
8
c
NTs2
MVNc,d
a
b
Isolated yield. 1.4 mol % Ni used. c 3 mol % Ni used.
d
2-Methoxy-6-vinylnaphthelene.
were fully characterized by NMR experiments including
NOE studies. Trisubstituted styrene derivatives react
sluggishly. Z-Stilbene gives a mixture of olefinic products
in low yields. Not unexpectedly, the recovered stilbene
is a mixture of Z- and E-isomers, providing further
support for a [(L)Ni-H]+ intermediate in these reactions.
Other related substrates that fail to undergo the hydrovi-
nylation reaction under a variety of conditions include
3,5-bis(trifluromethyl)styrene, 2-vinylpyridine, and N-
vinylcarbazole (eq 12). While the electron-deficient nature
propene reacts with styrene and substituted styrenes
under conditions slightly modified from what was previ-
ously described for ethylene, giving excellent yields of the
expected products (eq 13, Table 4). The reaction with
propene proceeds at a higher temperature (-15 to 10 °C
vs -56 °C for ethylene), especially in the case of the more
electron-deficient styrene derivatives. As expected, a
mixture of regioisomeric products (with propene-C1 ad-
dition to the benzylic position, 17, as the major one) is
obtained. Details of this reaction have since been pub-
lished.26
Reaction of styrene alone with [(allyl)2NiBr]2 and Ph3P
at room temperature in the presence of AgOTf leads to
the formation of 14% styrene dimer along with extensive
of the styrene may preclude Ni-coordination, the lack of
reactivity of vinylpyridine may have its origin in the
formation of stable intermediates assisted by the pyridine
nitrogen. Vinylcarbazole gives a polymer that is insoluble
in most organic solvents. No further characterization of
this material was undertaken.
Heter od im er iza tion of Styr en e w ith Oth er Ole-
fin s. Unlike heterodimerization reactions of ethylene, no
synthetically useful heterodimerization reaction using
propene was known before our work. We find that
(26) J in, J .; RajanBabu, T. V. Tetrahedron 2000, 56, 2145.
8436 J . Org. Chem., Vol. 68, No. 22, 2003

Heterodimerization of Olefins
polymerization (eq 14). Attempts to effect heterodimer-
ization of styrene and cylohexene or ethyl vinyl ether also
lead to polymer formation. Varying amounts of styrene
dimer can be detected in gas chromatography (eq 15)
F IGURE 2. Chelating ligands used for the Ni-catalyzed
hydrovinylation reactions.
SCHEME 2. Wh y a Ch ela tin g Liga n d Ma y Not
Wor k in Hyd r ovin yla tion of a Vin yla r en e
under these conditions. Codimerization of styrene and
ethyl acrylate does not proceed under the standard
hydrovinylation conditions (eq 16) using Ph3P and AgOTf,
R ea ct ion s Usin g Ch ela t ed P h osp h in es. If the
proposed mechanism (Scheme 1) has any validity, there
is only one ligand per metal in the catalytically active
species. A number of studies have indicated that the Ni-
catalyzed hydrovinylation reaction might be inhibited by
chelating phosphines, even when the reactions are car-
ried out under widely different conditions.3b,15a Nonethe-
less, we investigated the viability of different classes of
chelating phosphines under the newly discovered protocol
(eq 10). A list of ligands and some typical reaction
conditions tested are listed in Figure 2. Careful examina-
tion of the crude reaction products by gas chromatogra-
phy and NMR spectroscopy revealed that no C-C cou-
pling products (oligomers, hetero- or homodimers) were
formed under these reaction conditions, even when the
reaction is run at higher temperatures.
In retrospect, the conspicuous lack of activity of che-
lated phosphines in the hydrovinylation is not surprising.
As shown in Scheme 2, the generation of the active
catalyst is possible only if the OTf in the initially formed
complex 19 is efficiently displaced by one of the olefins
(ethylene or styrene), and this event is followed by an
insertion (e.g., to form 22) and a â-hydride elimination.
A strongly chelating bis-phosphine would either prevent
whereas with norbornene a complex mixture of hydro-
carbons is obtained (eq 17). Treatment of a typical
terminal olefin, 1-tert-butyldimethylsiloxy-5-hexene, with
ethylene under hydrovinylation conditions leads to clean
isomerization of the double bond to give a mixture of Z-
and E-1-tert-butyldimethylsiloxy 4-hexenes (eq 18). No
trace of dimerization products could be detected under
these conditions.
J . Org. Chem, Vol. 68, No. 22, 2003 8437

RajanBabu et al.
SCHEME 3. Effect of Cou n ter a n ion Y on Ca ta lyst
Gen er a tion
the formation of 20 or effectively reduce its concentration
such that the insertion pathway is no longer available.
Use of Hem ila bile Liga n d s. An attractive solution
to such a problem would be to use a chelating ligand with
one strongly coordinating group and one weakly coordi-
nating group.27 The strength of the bond between this
latter group and the metal would be a critical element
in the successful execution of this idea. A number of
“hemilabile” groups, including carboxylate (anionic), ester
carbonyl, triarylphosphonoyl, and sufur (from a thiophene)
moiety, have been investigated in a variety of reactions,
including oligomerization of ethylene,28a-d codimerization
ethylene and styrene,28e and ethylene/CO oligomeriza-
tion.28f Since our eventual goal was to develop an asym-
metric version of the hydrovinylation reaction, we decided
to explore the use of a hemilabile ligand in the context
of a chiral ligand. In the absence of any clear lead, an
ether-oxygen was chosen as the hemilabile group in the
first ligands we investigated. This choice was not entirely
arbitrary, since phosphino-ether systems have been
extensively investigated,27 starting with the initial o-
diphenylphosphinoanisole, which was the first hemilabile
ligand to be so named.27a
In the event, (R)-2-diphenylphosphino-2′-methoxy-1,1′-
binaphthyl (MOP),29 in which the methoxy moiety would
play the role of the hemilabile ligand, was chosen for the
initial study. The BINAP structural motif was considered
especially attractive, since it allowed considerable flex-
ibility in ligand tuning, including variations of the 2′-
substituents, which would allow further explorations of
the hemilabile ligand concept.
Hydrovinylation of styrene and 2-methoxy-6-vinyl-
naphthalene (MVN) was carried out using the MOP
ligand under the standard protocol described earlier (eq
10) using AgOTf, and the results are shown in eq 19. A
tions reported earlier (Table 2). Even though the exact
origin of the diminished activity of a Ni-catalyst with a
hemilabile ligand under these conditions remains un-
known, further development of the reaction would rely
upon the following rationale (Scheme 3).
The initially formed complex 23 could be in equilibrium
with a chelated complex 24. The generation of the
catalyst is possible only if the hemilabile ligand is
successfully displaced by an olefin to form 25. The
relative concentrations of 23-25 thus become an impor-
tant factor in the catalyst turnover. Low concentrations
of the catalytically competent species 25 and/or side
reactions, which remove the catalyst (for example, by
methylation of the triflate to give catalytically inactive30
27), may account for the poor reactivity under these
reaction conditions. Support for this conjecture comes
from the fact that upon replacement of the triflate by a
totally dissociated, nonnucleophilic counteranion, BARF
(B[(3,5-(CF3)2C6H3)]4-),31 the activity of the catalyst sys-
tem is completely restored. The primary products from
4-isobutylstyrene and MVN are formed in more than 95%
yields with enantioselectivities of 40% and 62% (eq 20),
respectively.
highly selective reaction ensues, yielding the expected
product, albeit in disappointingly low conversion (12%
and 24% yield) and enantioselectivity (33% and 58% ee).
The conversions were of special concern, since nearly
quantitative reactions were routinely observed in reac-
Effect of Va r iou s Hem ila bile Gr ou p s. To probe the
effect of the hemilabile atom, we prepared a number of
2′-derivatives of BINAP (Figure 3) and examined the
hydrovinylation of MVN. The results are summarized in
Table 5. Increasing the steric bulk of the 2′-O-alkyl
substituent has little effect on the enantioselectivity of
the MVN reaction, but the yield of the product is reduced.
(27) For reviews on hemilabile ligands, see: (a) J effrey, J . C.;
Rauchfuss, T. B. Inorg. Chem. 1979, 18, 2658. (b) Bader, A.; Lindner,
E. Coord. Chem. Rev. 1991, 108, 27. (c) Slone, C. S.; Weinberger, D.
A.; Mirkin, C. A. The Transition Metal Coordination Chemistry of
Hemilabile Ligands. In Progress in Inorganic Chemistry; Karlin, K.
D., Ed.; J ohn Wiley: New York, 1999; Vol. 48, pp 233-350.
(28) (a) Keim, W. Angew. Chem., Int. Ed. Engl. 1990, 29, 235. (b)
Bonnet, M. C.; Dahan, F.; Ecke, A.; Keim, W.; Schulz, R. P.; Tkatch-
enko, I. Chem. Commun. 1994, 615. (c) Meking, S.; Keim, W. Orga-
nometallics 1996, 15, 2650. (d) Komon, Z. J . A.; Bu, X.; Bazan, G. C.
J . Am. Chem. Soc. 2000, 122, 1830. (e) Britovsek, G. J . P.; Cavell, K.
J .; Keim, W. J . Mol. Catal. A, Chemical 1996, 110, 77. (f) Keim, W.;
Maas, H.; Mecking, S. Z. Naturforsch. 1995, 50B, 430.
(30) For structurally related, unreactive, neutral Pd-complexes see,
ref 28e.
(31) (a) Nishida, H.; Takada, N.; Yoshimura, M.; Sonoda, T.;
Kobayashi, H. Bull. Chem. Soc. J pn. 1984, 57, 2600. (b) Brookhart,
M.; Grant, B.; Volpe, A. Organometallics, 1992, 11, 3920. For the use
of Ar4B- in related reactions, see: DiRenzo, G. M.; White, P. S.;
Brookhart, M. J . Am. Chem. Soc. 1996, 118, 6225.
(29) Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J . Org. Chem.
1993, 58, 1945.
8438 J . Org. Chem., Vol. 68, No. 22, 2003

Heterodimerization of Olefins
one should expect different reactivities from ligands with
varying donor properties.27,28 Allyl(Ni) complexes of 2′-
acetoxy (35) and diphenylphosphosphoryl (36) analogues
failed to produce any hydrovinylation products under the
standard reaction conditions (entries 9 and 10). Phos-
phinoxide is known to be a strongly coordinating group28c
and it is not surprising if the catalyst generation is
prevented due to the inability of an olefin to displace this
group. As for the acetoxy derivative 35, the carbonyl
oxygen is known to be a strongly coordinating atom as
compared to an ether-oxygen in a variety of metal
complexes.32 Finally, the electronic effect of ligands on
the hydrovinylation selectivity was examined by com-
parison of ee’s obtained using ligands 37 and 38 with that
from 29 (entries 2, 11, and 12). In sharp contrast to the
Ni(0)-catalyzed hydrocyanation, Rh(I)-catalyzed hydro-
genation, or the Pd(0)-catalyzed allylation,33 ligand elec-
tronic properties appear to have little effect on hydrovi-
nylation; in each case, the chemical yield and ee were
almost identical. Note that a significant difference be-
tween these reactions and the hydrovinylation is that
there is no change in the oxidation state of the metal in
the catalytic cycle of the hydrovinylation reaction. Nickel-
(II) with its ligands plays the role of a complex Lewis
acid!
F IGURE 3. BINAP ligands for hydrovinylation.
TABLE 5. Effects of BINAP 2′-Su bstitu en ts on th e
Hyd r ovin yla tion of 2-Meth oxy-6-vin yln a p h th a len e
(MVN)a
(2 group,
entry
ligand
Figure 4)
% yield % eeb
0
remarks
Hydrovinylation of styrene using the ligands 29 and
37 gave >80% yield 25-27% ee at -55 °C (eq 21). The
1
2
3
4
(R)-BINAP Ph2P
29
30
31
OCH3
i-Pr
OCH2Ph
>98
69
62
69
97
73 -55 °C;
AgNTf2 87%
5
6
7
8
9
10
11
12
31
32 (aRR)
33 (aRS)
34
35
36
37
38
OCH2Ph
93
>98
79
12
0
0
94
93
80 at -70 °C
OC(H)(Ph)(CH3)
OC(H)(Ph)(CH3)
CH2CH3
OC(O)CH3
P(O)Ph2
71
65
<3 styrene 13%
OMe
OMe
63
63
a
b
See eq 20 for a typical procedure. Ee determined by HPLC.
Thus O-i-Pr derivative 30 under identical conditions gave
69% yield and 70% ee. For MVN, a benzyloxy analogue
of MOP (31) gave 80% ee when the reaction was carried
reactions are exceptionally clean as judged by gas chro-
matographic and NMR analysis of the product, and the
observed low yield of the product is most likely a result
of its high volatility.
As expected from the proposed mechanism, the reac-
tion shows pronounced solvent effects (Table 6). Under
conditions described in eq 20 (-55 °C, 0.7 mol % [(allyl)-
NiBr]2, NaBARF, 2 h), the following yields and enanti-
oselectivities were observed for the solvents indicated:
CH2Cl2 (97, 73); ether (87, 77); toluene (88, 74); THF (0,
out at -70 °C. Evidence of the involvement of hemilabile
oxygen may also be inferred from the different activities
of catalysts prepared from BINAP derivatives with (R)-
and (S)-phenethyl ether side chains (32 and 33). While
the former gave an excellent yield (96%) (71% ee) of the
product, the latter gave only 79% yield (65% ee). In an
attempt to probe the effect of the hemilabile ligand, we
prepared the 2′-ethyl analogue 34 and tested this ligand
under both sets of conditions, viz., using AgOTf and
NaBARF as additives. For the hydrovinylation of MVN
using BARF counteranion, 12% yield and 3% ee of the
product were obtained, whereas AgOTf gave less than
2% conversion. If the hemilabile ligation is important,
(32) Braunstein, P.; Chauvin, Y.; Na¨hring, J .; DeCian, A.; Fischer,
J .; Tiripicchio, A.; Ugozzoli, F. Organometallics 1996, 15, 5551.
(33) Examination of electronic effects has become a common practice
in asymmetric catalysis. For some of the early examples of electronic
tuning of asymmetric catalysts, see: (a) Inoguchi, K.; Sakuraba, S.;
Achiwa, K. Synlett 1992, 169. (b) J acobsen, E. N.; Zhang, W.; Guler,
M. L. J . Am. Chem. Soc. 1991, 113, 6703. (c) RajanBabu, T. V.;
Casalnuovo, A. L. J . Am. Chem. Soc. 1992, 114, 6265. (d) RajanBabu,
T. V.; Ayers, T. A.; Casalnuovo, A. L. J . Am. Chem. Soc. 1994, 116,
4101. (e) Schnyder, A.; Hintermann, L.; Togni, A. Angew. Chem., Int.
Ed. 1995, 34, 931. Other examples from our work: Casalnuovo, A. L.;
RajanBabu, T. V.; Ayers, T. A.; Warren, T. H. J . Am. Chem. Soc. 1994,
116, 9869.; RajanBabu, T. V.; Casalnuovo, A. L. J . Am. Chem. Soc.
1996, 118, 6325.; RajanBabu, T. V.; Ayers, T. A.; Halliday, G. A.; You,
K. K.; Calabrese, J . C. J . Org. Chem. 1997, 62, 6012.; Clyne, D. S.;
Mermet-Bouvier, Y. C.; Nomura, N.; RajanBabu, T. V. J . Org. Chem.
1999, 64, 7601.; Yan, Y.; RajanBabu, T. V. Org. Lett. 2000, 2, 4137.
J . Org. Chem, Vol. 68, No. 22, 2003 8439

RajanBabu et al.
SCHEME 4. A Sin gle-Com p on en t Ca ta lysts for
TABLE 6. Solven t Effects on th e Ni-ca ta lyzed
Hyd r ovin yla tion of MVN u sin g 31 a s a Liga n d
Hyd r ovin yla tion of Styr en e
entry
solvent
selectivity
% yield
% eeb
1
2
3
4
CH2Cl2
ether
toluene
THF
>99
>99
>99
>98
87
88
0
73
77
74
0
a
b
See eq 20 for a typical procedure (-55 °C). Ee determined
by HPLC.
TABLE 7. Hyd r ovin yla tion Usin g Di(2-n a p h th yl)-
MOP -OBn (39)
Ru th en iu m -Ca ta lyzed Rea ction s. In a modern ver-
sion of the Ru-catalyzed hydrovinylation,5a,6 Yi et al. has
recently reported that (Cy3P)2Ru(CO)(H)(Cl) in the pres-
ence of HBF4‚Et2O effects hydrovinylation of vinylarenes
and dienes.22 We have examined this reaction under
activation of this Ru-catalyst using AgOTf instead of
HBF4‚OEt2 and find that nearly quantitative conversion
of styrene maybe achieved. However, competitive forma-
tion of the isomerization products, (Z)- and (E)-2-phenyl-
3-butenes, and the formation of head-to-tail styrene
dimer could not be avoided under a variety of conditions
(eq 23). Further optimization of this system might yield
a catalyst that works at or near room temperature.
temp (°C)/
entry
vinylarene
styrene
styrene
styrene
additive
time (h) % yieldb % ee (S)c
1
2
3
4
NaBARF
AgSbF6
AgNTf2
-35/2
-25/3
-25/2.5
-20/3
73
76
57
99
32
28
27
40
4-i-Bu-styrene NaBARF
a
b
See eq 20 for typical procedure. The rest was starting
material. c Ee determined by HPLC.
0). Tetrahydrofuran is a strongly coordinating solvent
and it is no surprise that under these conditions no
hydrovinylation is observed.
A limited effort was made to modify the diaryl sub-
stituents of BINAP to examine the effect of this structural
variation on the selectivity in the hydrovinylation reac-
tions. The results are shown in Table 7. Increasing the
size of the aryl units from phenyl to 2-naphthyl affects
the overall rate of the reaction. The overall yield and
enantioselectivity remains the same when the reaction
is carried out at -20 °C. The experiments using styrene
also showed for the first time that other dissociated silver
salts (AgSbF6 and AgNTf2) could effectively replace
NaBARF in these reactions.
Oth er P r otocols for Nick el-Ca ta lyzed Hyd r ovi-
n yla tion Rea ction s. During the course of these inves-
tigations, we have uncovered a number of other viable
procedures for this exacting reaction. Thus, a catalyst
prepared from allyl 2-diphenylphosphinobenzoate 40 and
Ni(COD)2 or the corresponding potassium salt of the acid
(41) and allyl nickel bromide (Scheme 4) shows very good
activity and excellent selectivity in the hydrovinylation
reactions of styrene when activated with (C6F5)3B28d (eq
22). Structurally related catalysts have been used for
P a lla d iu m -Ca ta lyzed Rea ction s. As noted earlier,
several studies in the literature indicate that the forma-
tion of isomerization products seriously limits the Pd-
catalyzed hydrovinylation reactions, especially when the
reactions are carried to completion. We find that the use
of [(allyl)PdCl]2 in the place of [(allyl)NiCl]2 in our
protocol leads to similar results. For a given ligand and
counterion, the catalyst is noticeably less active vis-a`-
vis the corresponding Ni-analogue. As represented in the
eq 24, at low conversions, the primary product, 3-phenyl-
oligomerization of ethylene.28a-d These novel methods
(Scheme 4) for the preparation of the neutral carboxylate
complexes (e.g., 43) from the allyl ester or the acid might
find other applications.
1-butene, is formed with excellent isomeric purity. Asym-
metric hydrovinylation reactions have been much less
8440 J . Org. Chem., Vol. 68, No. 22, 2003

Heterodimerization of Olefins
TABLE 8. P d -Ca ta lyzed Hyd r ovin yla tion of Styr en ea
st
temp (°C)/ mat. 3-Ph-bute (Z+E)-2-Ph-
entry ligand additive
time (h)
(%)
(%)
2-butenes(%)
1
2
3
4
5
6
44
44
44
45
29
46
AgOTfb
AgOTfb
-55/3
-5/3
100
61
41
0
100
30
0
27
39
65
<5
57
0
11
18
32
AgOTfb
25/3
NaBARFb
NaBARFc
-20/3
-55/2
NaBARFc 0-10/2
13
a
b
See eq 21/25 for typical procedures. [(allyl)PdBr]2 used.
c [(allyl)PdI]2 used.
successful (eq 25). Attempts to circumvent this problem
with alternate ligands (31, 44-46, Table 8) and counter-
ions have not yet been successful. Recall that all of these
ligands give excellent yield and selectivities (>95%) for
the 3-arylbutenes in the Ni-catalyzed reactions at low
temperature.34,35
F IGURE 4. A model TS for the addition of a chelated metal
hydride to the vinylarene in [(R)-MOP)] M(H)(vinylarene).
working model to be applicable for other asymmetric
catalysts with different ligands.23,34
A Mod el Tr a n sition Sta te for th e Asym m etr ic
In d u ction in th e Hyd r ovin yla tion Ca ta lyzed by (R)-
MOP -Ni(a llyl)-BARF . Even though the details of the
mechanism of asymmetric hydrovinylation including the
nature of the rate- and enantioselectivity-determining
steps remain unknown, a useful, working model for the
transition state maybe constructed based on reasonable
assumptions derived from experimental observations.
Addition of a chelated metal hydride through one of the
four possible square planar Ni(II) complexes (47-50) is
shown in Figure 4. In this preferred transition state, the
olefin is coordinated trans to the phosphine (sterically
less encumbered compared to the corresponding cis-
olefin/PAr2 structures) and the metal-hydride addition
takes place from the re-face of the olefin (e.g., through
the transition state 51), eventually leading to the ob-
served major product. In this orientation, the interaction
between the hydrogen ortho to the OR group and the
aromatic moiety of the vinylarene is minimized as the
distance between the Ni-atom and the benzylic carbon
is reduced during the bond-formation. Such interaction
would retard addition to the si-face. In partial support
of this argument, the observed ee for a bulky vinylarene
(2-methoxy-3-vinylnaphthalene) is significantly higher
than that for simple styrene derivatives (80% vs <30%)
under identical conditions. We have since found this
Syn th esis of Liga n d s. Synthesis of ligands with
specific electronic and steric requirements is an essential,
often tedious, part of any asymmetric catalysis program
that relies on ligand tuning to bring about optimum
results, and the present case is no exception. Syntheses
of a number of ligands used during this study have been
described in the literature, while several others are new.
Ligands 29-31, 34 (Figure 3) were prepared via proce-
dures described by Hayashi29 using 2,2′-trifluromethyl-
sulfonyloxy-1,1-binaphthyl (52)38 as a starting material
(Scheme 5). The ligands 32 and 33 were prepared by
Mitsunobu reaction of 2-diphenylphosphinoyl-2′-hydroxy-
1,1′-binaphthyl (54) with either (S)- or (R)-2-phenyletha-
nol (Scheme 5), respectively. Acetylation of 57 with acetic
anhydride in the presence of Et3N and DMAP gave 35
(Scheme 6).
While the synthesis of the bis-3,5-dimethylphenyl
derivative 37 posed no problem (Scheme 7), the corre-
sponding bis(3,5-bis(trifluoromethyl)phenyl) derivative 38
could not be synthesized by the standard protocol (Scheme
8). The diarylphosphonous acid failed to react with the
bis-triflate 52 under catalysis by Pd(OAc)2/dppb/EtN(i-
Pr)2. The problem was overcome by Pd-catalyzed coupling
of 52 with diethyl phosphite, followed by conversion of
the resulting phosphonate 61 to a dichloride, which was
(34) Kumareswaran, R.; Nandi, M.; Park, H.; J in, J .; RajanBabu,
T. V. (unpublished results).
(35) For ligands 44, 45 and 46, see ref 23 and 36. For the use of a
phosphinite ligand see also, Bayersdo¨rfer, R.; Ganter, B.; Englert, U.;
Keim, W.; Vogt, D. J . Organomet. Chem. 1998, 552, 187.
(36) Park, H.; RajanBabu, T. V. J . Am. Chem. Soc. 2002, 124, 734.
(37) Hayashi, T.; Konishi, M.; Fukushima, M.; Kanehira, K.; Hioki,
T.; Kumada, M. J . Org. Chem. 1983, 48, 2195.
(38) Kurz, L.; Lee, G.; Morgans, D., J r.; Waldyke, M. J .; Ward, T.
Tetrahedron Lett. 1990, 31, 6321.
J . Org. Chem, Vol. 68, No. 22, 2003 8441

RajanBabu et al.
SCHEME 5. Syn th esis of Liga n d s 32 a n d 33
SCHEME 6. Syn th esis of Liga n d 35
SCHEME 7. Syn th esis of Liga n d 37
subsequently treated with an excess of the Grignard
reagent. The phosphine oxide 63 was reduced under the
standard conditions using HSiCl3/Et3N to get a modest
overall yield of the ligand 38. Incidentally, the dieth-
ylphosphonate 61 failed to react with the Grignard
reagent at 0 °C in ether.
26).39 A mixture of mono- and diphosphineoxides are
The BINAP-monophosphine oxide 36 is prepared by
selective oxidation of (S)-BINAP with oxaziridine (eq
8442 J . Org. Chem., Vol. 68, No. 22, 2003

Heterodimerization of Olefins
SCHEME 8. Syn th esis of Liga n d 38
SCHEME 9. Syn th esis of Liga n d 39
Recognition of a synergistic relationship between a chiral
hemilabile ligand (MOP) and a highly dissociated coun-
teranion (BARF or SbF6) in an enantioselective version
of the Ni-catalyzed reaction raises the prospects of
developing a practical route for the synthesis of 3-aryl-
butenes. Several pharmaceutically relevant compounds,
including widely used 2-arylpropionic acids, can be
synthesized from these key intermediates.
Exp er im en ta l Section
For general methods and details of experimental procedures
for items listed in the tables see the Supporting Information.
Only preparatively useful typical procedures, and synthesis
and characterization of key compounds are described below.
Ni-Ca ta lyzed Hyd r ovin yla tion Usin g 1,3-Bis(Dip h en -
ylp h osp h in o)p r op a n e (d p p p ) Liga n d (w ith Ad d ed Silver
Sa lt). Typ ica l Ru n for Rea ction s Usin g Ch ela ted P h os-
p h in es (F igu r e 2 A-D) a n d Th ose Sh ow n in En tr ies 1-8,
Ta ble 1. This is a typical procedure for all hydrovinylation
reactions with added silver salts when a chelated ligand was
used. To [(allyl)NiBr]2 (3.4 mg, 9.5 µmol; 1.0 mol % Ni) in CH2-
Cl2 (0.5 mL) was added dppp (7.8 mg, 19 µmol) in CH2Cl2 (1.5
mL) at 25 °C. The mixture was cooled at -30 °C and it was
transferred into AgOTf (5.2 mg, 20 µmol) in CH2Cl2 (2 mL),
which was also precooled at -30 °C. The mixture was stirred
for 2 h at 25 °C. The resulting suspension was filtered through
a plug of Celite in a disposable pipet. The precipitate was
rinsed with CH2Cl2 (1 mL). The filtrate was collected in a
Schlenk flask, and it was taken out of the drybox. The mixture
was cooled at -78 °C, and N2-evacuation and ethlene-purge
were repeated several times, carefully avoiding oxygen. Under
an ethylene atmosphere (∼1 atm), styrene (0.230 mL, 2.01
mmol) was added drop by drop at -78 °C. The reaction mixture
was slowly warmed to 25 °C in 12 h, and it was stirred for an
additional 12 h at 25 °C. GC analysis indicated no reaction.
formed even at low temperatures, from which the mono-
oxide is isolated by column chromatography.
The ligand 39 was prepared along the lines outlined
in Scheme 7,29 starting with the coupling of bis(2-
naphthyl)P(O)H with the bis-triflate 52 to form 64,
followed by the same reactions used in the preparation
of 37 (Scheme 9).
Su m m a r y a n d Con clu sion s
New protocols for nearly quantitative and highly
selective codimerization of ethylene and various func-
tionalized vinylarenes are described. Excellent functional
group tolerance and high turnover numbers in the Ni-
catalyzed reaction have been demonstrated. Reactions
using Pd and Ru catalysts appear to be much less
efficient and less selective and may require further
development before a viable system can be identified.
P r ep a r a tive Ru n s Usin g Tr ip h en ylp h osp h in e a n d
AgOTf (P r oced u r e i, Ta ble 2). The following is a typical
procedure for the Ni-catalyzed hydrovinylation reactions. To
a red solution of 0.0035 equiv of [Ni(allyl)Br]2 in dichlo-
(39) Davis, F. A.; Ray, J . K.; Kasperowicz, S.; Preslawski, R. M.;
Durst, H. D. J . Org. Chem. 1992, 57, 2594.
J . Org. Chem, Vol. 68, No. 22, 2003 8443

RajanBabu et al.
romethane (1.5 mL) was added a solution of 0.0070 equiv of
triphenylphosphine in dichloromethane (1.5 mL) in a nitrogen-
filled drybox. Then, the resulting yellow solution was added
to a suspension of 0.0080 equiv of silver triflate in dichlo-
romethane (2 mL). After 1.5 h of stirring at room temperature,
the brown suspension was filtered through a short pad of Celite
into a Schlenk flask, removed from the drybox, and cooled to
-55 °C. Oxygen-free ethylene (∼1 atm) was then introduced
into the yellow catalyst solution, and 1.0 equiv of a hydrovi-
nylation substrate was added dropwise through a rubber
septum with a syringe. The resulting reaction mixture was
stirred for 2 h at -55 °C under an ethylene atmosphere (∼1
atm) and was then quenched with half-saturated aqueous
ammonium chloride solution (5 mL). The product was ex-
tracted with diethyl ether or dichloromethane (50 mL). The
organic phase was dried over magnesium sulfate and analyzed
by GC to determine the conversion of the substrate. The
solution was concentrated under reduced pressure to isolate
the corresponding hydrovinylation product. The isomeric
purity was determined by NMR and further confirmed by gas
chromatographic analysis, where the limits of detection were
established as >0.2%.
146.1096, found 146.1106. Alkene 18: 1H NMR (250 MHz,
CDCl3) δ 1.39 (d, J ) 7.1 Hz, 3 H), 1.61 (s, 3 H), 3.35-3.49 (m,
1 H), 4.86 (s, 1 H), 4.87 (s, 1 H), 7.16-7.37 (m, 5 H); EI MS
m/z (relative intensity) 146 (M+, 7), 105 (100); HRMS calcd
for C11H14 146.1096, found 146.1106. Ratio of 17 to 18, 4.2:
1.0. Ratio of (E)- to (Z)-phenyl-2-pentene by GC, 8:1; by NMR,
7.3:1.
Attem pted Cr oss-Dim er ization of Eth ylen e with 6-ter t-
Bu tyld im eth ylsiloxy-1-h exen e, a Typ ica l Ter m in a l Ole-
fin (Eq 18). To a solution of [(allyl)NiBr]2 (5.2 mg, 14.4 µmol)
in 1 mL of CH2Cl2 under nitrogen at room temperature was
added a solution of triphenylphosphine (7.6 mg, 28.8 µmol) in
1 mL of CH2Cl2. The resulting brown solution was added to a
mixture of AgOTf (10.3 mg, 40.0 µmol) in 1 mL of CH2Cl2. After
stirring for 1.5 h at room temperature, the mixture was filtered
through a small plug of Celite, and the precipitate was rinsed
with 2 mL of CH2Cl2. The filtrate was collected in a Schlenk
flask, and was taken out of the drybox. The catalyst solution
was cooled to -55 °C. Under one atmosphere of ethylene, 0.428
g (2.00 mmol) of 6-tert-butyldimethylsiloxy-1-hexene was added
dropwise to the catalyst solution. After stirring at -55 °C for
4 h, the mixture was quenched with saturated aqueous NH4-
Cl solution and extracted three times with 10 mL portions of
CH2Cl2. The combined organic layers were dried over MgSO4
and concentrated in vacuo. The crude product was analyzed
by GC, which indicated that two olefins were produced in a
ratio of 3.5:1.0 (E:Z) with no starting material left. The crude
product was purified by flash chromatograghy on silica gel,
eluting with hexanes/ethyl acetate (98:2), to give the product
as a clear oil (406 mg, 95%): 1H NMR (250 MHz, CDCl3) δ
0.05 (s, 6 H), 0.90 (s, 9 H), 1.54-1.67 (m, 5 H), 1.97-2.10 (m,
2 H), 3.57-3.65 (m, 2 H), 5.40-5.46 (m, 2 H).
Sin gle-Com p on en t Ca t a lyst s for H yd r ovin yla t ion
(Sch em e 4). Allyl 2-Dip h en ylp h osp h in oben zoa te (40). To
a mixture of 2-diphenylphosphinobenzoic acid (205 mg, 0.67
mmol), K2CO3 (185 mg, 1.33 mmol), and Bu4NCl (8.4 mg, 0.003
mmol) was added THF (3 mL). After stirring at room temper-
ature for 5 h, a solution of allyl bromide in THF (1.0 mL) was
added, and the resulting mixture was stirred for 4 days in
glovebox. The reaction was quenched by degassed, saturated
NH4Cl aqueous solution and extracted with ether three times.
The dried organic layer was evaporated and chromatographed
to get the desired product (170 mg, 74%): 1H NMR (250 MHz,
CDCl3) 4.91 (d, 2 H), 5.35 (d, 1 H), 5.45 (d, 1 H), 5.98-6.15
(m, 1 H), 7.32-7.45 (m, 12 H), 8.04 (d, 2 H); 13C NMR (100
MHz, CDCl3) 65.8, 118.5, 128.9, 128.9, 129.4, 129.5, 129.6,
130.3, 132.4, 133.3, 133.5, 134.1, 134.3, 136.3, 136.5, 144.3,
144.5, 166.2; 31P NMR (162 MHz, CDCl3) -3.71 (s).
The absolute configuration of (S)-3-phenyl-1-butene was
determined by GC analysis using a 50 m Lipodex C capillary
column [conditions: 1.5 mL helium/min, 35 °C (50 min), 0.1
°C/min (60 min), 41 °C (30 min); retention times: R-isomer
95.8 min, S-isomer 97.2 min]. The configurations were con-
firmed by measurement of optical rotation measurements.37
Hyd r ovin yla tion of 3-Br om ostyr en e. 2-(3-Br om op h en -
yl)-1-bu ten e. To a solution of allylnickel bromide (2.2 mg,
0.0061 mmol) in CH2Cl2 (1.0 mL) was added a solution of
triphenylphosphine (3.2 mg, 0.0122 mmol) in CH2Cl2 (2.0 mL).
The resulting orange solution was added to a suspension of
silver triflate (3.8 mg, 0.015 mmol) in CH2Cl2 (1.0 mL) and
the resulting mixture was stirred at room temperature for 1.5
h. The mixture was filtered through Celite to get a clear yellow
solution that was subsequently cooled to -52 °C. Ethylene was
introduced to the reaction followed by addition of 3-bromosty-
rene (148 mg, 0.86 mmol) in 1 mL CH2Cl2. The reaction was
stirred at -52 °C for 3 h and was quenched by adding
saturated NH4Cl aqueous solution (5 mL). The mixture was
extracted twice with ether. Gas chromatographic analysis
showed >99% conversion and >99% selectivity for the 3-aryl-
butene. The dried organic layer was evaporated to afford the
crude product (170 mg, 99%, 99% pure by GC, >95% pure by
NMR): 1H NMR (400 MHz, CDCl3) 1.35 (d, J ) 7.0, 3 H), 3.45
(q, J ) 6.8, 1 H), 5.03-5.13 (m, 2 H), 5.93-6.08 (m, 1 H), 7.10-
7.21 (m, 2 H), 7.31-7.42 (m, 2 H); 13C NMR (100 MHz, CDCl3)
20.8, 43.1, 114.0, 112.7, 126.2, 129.4, 130.2, 130.6, 142.6, 148.2.
Hydr ovin ylation (Eq 22,Meth od A) Usin g Allyl 2-Diph en -
ylp h osp h in oben zoic Acid (40) a s a Liga n d P r ecu r sor
(Sch em e 4). To a solution of Ni(COD)2 (5.4 mg, 0.020 mmol)
in toluene (1.0 mL) at -30 °C was added a solution of the allyl
ester 40 (7.1 mg, 0.020 mmol) in toluene (1.5 mL). The
resulting mixture was stirred for 1 h at room temperature and
was concentrated to dryness over 2 h to get a yellow residue.
To the residue was added toluene (2.0 mL) and tris(pentafluo-
rophenyl)borane (10.2 mg, 0.020 mmol) solution in toluene (1.0
mL). The resulting mixture was stirred for 15 min as it became
a homogeneous solution. The solvent was evaporated in vacuo,
and the residue was dissolved in CH2Cl2 (3.0 mL). The
resulting solution was filtered through a pad of Celite and
washed with CH2Cl2 (2.0 mL). The filtrate was cooled to -32
°C and was placed under ethylene atmosphere in a Schlenk
flask. Into this flask was added styrene (0.15 mL, 1.3 mmol)
dropwise. The reaction mixture was stirred for 1 h and then
quenched by adding aqueous NaHCO3 solution. The product
was extracted with ether. Gas chromatographic analysis
showed >99% conversion with 88% of the desired product.
Heter od im er iza tion of Styr en e a n d P r op en e. To a
solution of [(allyl)NiBr]2 (10.8 mg, 30.1 µmol) in 1 mL of CH2-
Cl2 under nitrogen at room temperature was added a solution
of triphenylphosphine (15.8 mg, 60.2 µmol) in 4 mL of CH2-
Cl2. The resulting brown solution was added to a mixture of
AgOTf (21.6 mg, 84.1 µmol) in 5 mL of CH2Cl2. After stirring
for 1.5 h at room temperature, the mixture was filtered
through a small plug of Celite, and the precipitate was rinsed
with 5 mL of CH2Cl2. The filtrate was collected in a Schlenk
flask and was taken out of the drybox. The catalyst solution
was cooled to -20 °C. Under one atmosphere of propene, 0.23
mL (2.00 mmol) of styrene was added dropwise to the catalyst
solution. After stirring at -20 °C for 35 min, the mixture was
quenched with saturated aqueous NH4Cl solution and ex-
tracted three times with 10 mL portions of CH2Cl2. The
combined organic layers were dried over MgSO4 and concen-
trated in vacuo. The crude product was purified by flash
chromatograghy on silica gel, eluting with hexanes to give an
inseparable mixture of alkenes 17 and 18 as a clear oil (275
mg, 94%). Alkene 17: 1H NMR (250 MHz, CDCl3) δ 1.35 (d, J
) 7.0 Hz, 3 H), 1.66-1.71 (m, 3 H), 3.35-3.49 (m, 1 H), 5.41-
5.70 (m, 2 H), 7.16-7.37 (m, 5 H); EI MS m/z (relative
intensity) 146 (M+, 7), 105 (100); HRMS calcd for C11H14
Hyd r ovin yla tion (Eq 22, Meth od B) Usin g th e P ota s-
siu m Sa lt of 2-Dip h en ylp h osp h in oben zoic Acid (41) a s
a Liga n d P r ecu r sor (Sch em e 4). To a solution of 2-diphen-
ylphosphinobenzoic acid (4.6 mg, 0.015 mmol) in CH2Cl2 (1.0
8444 J . Org. Chem., Vol. 68, No. 22, 2003

Heterodimerization of Olefins
mL) was added a suspension of KH (0.8 mg, 0.020 mmol) in
CH2Cl2 (1.0 mL). The resulting mixture was stirred for 10 min
at room temperature before it was filtered through Celite. To
the filtrate was added a solution of allylnickel bromide (2.7
mg, 0.0075 mmol) in CH2Cl2 (1.5 mL). The resulting solution
was stirred at room temperature for 1.5 h and was then filtered
through Celite. To the filtrate was added a solution of tris-
(pentafluorophenyl)borane (8.4 mg, 0.016 mmol) in CH2Cl2 (1.5
mL). The resulting solution was stirred for 5 min before it was
taken out of the drybox and cooled to -30 °C. The flask was
connected to a ballon containing ethylene, and to the catalyst
solution was added styrene (0.13 mL, 1.1 mmol) in a dropwise
fashion. The reaction was stirred for 110 min before it was
quenched by adding aqueous NaHCO3. The product was
extracted with ether. Gas chromatographic analysis showed
99% conversion with 97% selectivity. The dried organic layer
was carefully evaporated to get the crude product (143 mg,
97% yield).
was transferred into AgOTf (4.3 mg, 17 µmol) in CH2Cl2 (2
mL) at 25 °C. The mixture was stirred for 1.5 h at 25 °C. The
resulting mixture was filtered on Celite purged with glasswool
in a pipet, and the precipitate was rinsed with CH2Cl2 (1 mL).
The filtrate was collected in a Schlenk flask, and the flask was
taken out of the drybox. The catalyst solution was cooled to
-50 °C and the flask was connected to the ethylene line (∼1
atm). 6-Methoxy-2-vinylnaphthalene (0.368 g, 2.00 mmol) in
CH2Cl2 (4 mL) was added to this mixture drop by drop. Soon
the reaction mixture turned red. After 3 h at -50 °C, the
reaction was quenched with aqueous NH4Cl. The crude product
was purified by flash column chromatography to afford a
mixture (351 mg) of the desired product (24% yield) and MVN
(68% yield). The enantiomeric excess of the product (58%) was
determined by HPLC using Chiracel OJ column, where base-
line separation of the two isomers was observed (see Support-
ing Information for a chromatogram).
Asym m etr ic Hyd r ovin yla tion of Styr en e Usin g MOP -
OMe Liga n d a n d BARF a s a Cou n ter a n ion (Eq 21). To
[(allyl)NiBr]2 (2.5 mg, 7.0 µmol; 0.7 mol % Ni) in CH2Cl2 (0.5
mL) was added (R)-MOP-OMe (7.1 mg, 15 µmol) in CH2Cl2
(1.5 mL) at 25 °C. The brown solution was transferred into
NaBAr4 (20.0 mg, 23 µmol) in CH2Cl2 (2 mL) at 25 °C. The
mixture was stirred for 1.5 h at 25 °C. The resulting mixture
was filtered through Celite in a glass pipet, and the precipitate
was rinsed with CH2Cl2 (1 mL). The filtrate was collected in a
Schlenk flask and taken out of the drybox. The catalyst
solution was cooled at -53 °C. N2 in the Schlenk flask was
evacuated and ethylene was purged at -53 °C, and under an
ethylene atmosphere (∼1 atm), styrene (0.230 mL, 2.01 mmol)
was added to this mixture drop by drop. After 2 h, the reaction
was quenched with aqueous NH4Cl. The crude product was
analyzed by GC and 1H NMR. The crude mixture contained
the desired product (80%) and styrene (19%) by 1NMR. The
enantiomeric excess of the product was 25% ee by HPLC
analysis.
Asym m etr ic Hyd r ovin yla tion of Styr en e Usin g 29 a n d
AgOTf (Eq 19). In a drybox, to [(allyl)NiBr]2 (2.6 mg, 0.0072
mmol) in CH2Cl2 (0.5 mL) was added (R)-MOP-OMe (29, 7.3
mg, 0.016 mmol) in CH2Cl2 (1.5 mL) at 25 °C. The brown
solution was transferred into AgOTf (5.3 mg, 0.021 mmol) in
2 mL of CH2Cl2 at 25 °C. The mixture was stirred for 1.5 h at
25 °C. The resulting suspension was filtered through Celite
in a disposable pipet, and the precipitate was rinsed with CH2-
Cl2 (1 mL). The filtrate was collected in a Schlenk flask, and
it was taken out of the drybox. The catalyst solution was cooled
to -54 °C and the nitrogen in the Schlenk flask was evacuated
and replaced by ethylene. Under an ethylene atmosphere was
added styrene (0.230 mL, 2.01 mmol). After 2 h, the reaction
was quenched with aqueous NH4Cl solution. The crude product
was analyzed by GC and 1H NMR. The crude mixture
1
contained the desired product (12%) and styrene (72%) by H
NMR. The enantiomeric excess of the product was 33% ee. The
ee was determined by HPLC analysis using a CHIRALCEL
OB column (Daicel) (hexane/i-PrOH ) 95:5, 0.5 mL/min), after
the mixture was converted to the corresponding acetate of the
alcohols obtained by a hydroboration/oxidation sequence as
described; see below.
Asym m etr ic Hyd r ovin yla tion of 6-Meth oxy-2-vin yl-
n a p h th a len e (MVN) Usin g 31 a n d [3,5-(CF 3)2C6H3]4B]-
Cou n ter a n ion : Syn th esis of 3-(6-Meth oxy-2-n a p h th yl)-
1-bu ten e (Eq 20 a n d Ta ble 5). To a solution of [(allyl)NiBr]2
(2.6 mg, 0.0072 mmol) in CH2Cl2 (0.5 mL) under nitrogen at
room temperature was added a solution of (R)-MOP-OBn (31,
7.8 mg, 0.014 mmol) in CH2Cl2 (1.5 mL). The resulting brown
solution was added to a solution of NaBARF (15.3 mg, 0.017
mmol) in CH2Cl2 (2 mL). After stirring for 1.5 h at room
temperature, the mixture was filtered through a small plug
of Celite, and the precipitate was rinsed with CH2Cl2 (1 mL).
The filtrate was collected in a Schlenk flask and was taken
out of the drybox. The catalyst solution was cooled to -55 °C.
Under one atmosphere of ethylene, a solution of 2-methoxy-
6-vinylnaphthalene (0.184 g, 1.00 mmol) in CH2Cl2 (1 mL) was
added dropwise to the catalyst solution. After stirring at -55
°C for 2 h, the mixture was quenched with saturated aqueous
NH4Cl solution and extracted three times with 10 mL portions
of CH2Cl2. The combined organic layers were dried over MgSO4
and concentrated in vacuo. The crude product was analyzed
by GC, which indicated that the alkene product was produced
in >99% yield and selectivity with no starting material left.
The crude product was purified by flash chromatograghy on
silica gel, and eluting with hexanes/ethyl acetate (19:1) gave
a clear oil (206 mg, 97%): 1H NMR (250 MHz, CDCl3) 7.10-
7.75 (m, 6 H), 6.09 (ddd, J ) 6.0, 10.0, 17.0 Hz, 1 H), 5.09 (dt,
J ) 1, 17.0 Hz, 1 H), 5.07 (dt, J ) 1.0, 10.0 Hz, 1 H), 3.92 (s,
3 H), 3.61 (m, 1 H), 1.45 (d, J ) 7.0 Hz, 3 H). The enantiomeric
excess (ee) of product alkene was determined as 73% (S) by
HPLC on Chiracel OJ column (hexane/i-PrOH ) 95:5, 0.5 mL/
min).
(R)- a n d (S)-3-P h en yl-1-bu ta n ol a n d 3-P h en yl-1-bu tyl
Aceta te (for HP LC An a lysis). To 9-BBN (0.5M, 3 mL, 1.5
mmol) in THF (2 mL) was added the 3-phenyl-1-butene (133
mg, 1.01 mmol) at 0 °C. The mixture was stirred for 15 min
at 0 °C and 16 h at 25 °C. After the mixture was cooled at 0
°C, 2 N NaOH (3 mL, 6 mmol) and 30% H2O2 (1 mL) were
added to this mixture. Stirring was continued for 16 h at 25
°C. The mixture was diluted with aqueous NH4Cl, and the
organic compounds were extracted with ether. The organic
layer was dried over MgSO4, and the crude material was
purified by flash column chromatography to afford 2-phe-
nylbutan-4-ol (124 mg, 82% yield); TLC Rf ) 0.33 (hexane/
1
EtOAc ) 3:1); H NMR (250 MHz) δ 7.15-7.35 (m, 5H), 3.57
(m, 2H), 2.89 (sextet, J ) 7.1 Hz, 1H), 1.86 (q, J ) 6.9, 2H),
1.28 (d, J ) 6.9 Hz, 3H).
To the alcohol (13 mg, 0.087 mmol) dissolved in 2 mL of
CH2Cl2 were added Ac2O (4 drops by pipet), Et3N (50 µL), and
DMAP (catalytic amount) at 25 °C. The mixture was stirred
for 2 h. Then aqueous NH4Cl was added to this mixture. The
organic compounds were extracted with ether. The crude
compound was purified by column chromatography to afford
the acetylated product: TLC Rf ) 0.69 (hexane/EtOAc ) 3:1);
1H NMR (250 MHz) 7.05-7.25 (m, 5 H), 3.91 (dt, J ) 11.1, 6.7
Hz, 1 H), 3.85 (dt, J ) 11.2, 7.2 Hz, 2 H), 2.74 (sextet, J ) 7.1
Hz, 1 H), 1.90 (s, 3 H), 1.82 (q, J ) 7.0 Hz, 1 H), 1.19 (d, J )
7.0 Hz, 3 H). This product was analyzed by HPLC on a
Chriracel OB column using 95:5 hexane/i-PrOH as solvent
(0.0.5 mL/min).
The same reaction carried out at -70 °C for 7 h gave an
Hyd r ovin yla tion of MVN w ith MOP (OMe) in th e P r es-
en ce of AgOTf (Eq 19). To [(allyl)NiBr]2 (2.6 mg, 7.2 µmol;
0.7 mol % Ni) in CH2Cl2 (0.5 mL) was added (R)-MOP (7.3
mg, 16 µmol) in CH2Cl2 (1.5 mL) at 25 °C. The brown solution
yield of 93% and ee of 80%.
Hydrovinylation of MVN using ligands 30 and 32- 38 as
well as those shown in Figure 2 (E-H) were carried out at
J . Org. Chem, Vol. 68, No. 22, 2003 8445

RajanBabu et al.
-55 °C using the above-described procedure and the results
are shown in Table 5.
The same experiments with 36 at temperatures in the range
of -55 to 25 °C did not yield any products.
Asym m etr ic Hyd r ovin yla tion of Styr en e Usin g 34 a n d
37. Asymmetric hydrovinylation of styrene was examined
using ligands 37 (89% yield and 27% ee) and 34 (17% yield
and 0% ee) under the same conditions.
Solven t Effects on Ni-Ca ta lyzed Asym m etr ic Hyd r ovi-
n yla tion (Ta ble 6). The same procedure as described in the
previous experiment was used in examining the solvent effects
shown in Table 6.
P r ep a r a tion of Liga n d 36. To a solution of 99 mg (0.159
mmol) of (R)-BINAP in 5 mL of CH2Cl2 at room temperature
under nitrogen was added 42 mg (0.161 mmol) of N-(phenyl-
sulfonyl)-3-phenyloxaziridine.39 The mixture was stirred at
room temperature for 20 h and the concentrated residue was
purified by flash chromatograghy on silica gel, eluting with
hexanes/ethyl acetate (3:1), to produce 36 as a white solid (21
mg, 21%): 1H NMR (250 MHz, CDCl3) 6.62-7.96 (m, aro-
matic); 31P NMR (101 MHz, CDCl3) -15.8, 27.6.
P r ep a r a tion of P h en ol 62. To a solution of 292 mg (0.543
mmol) of 6138 in 2 mL of SOCl2 under nitrogen was added 0.1
mL of DMF. The mixture was refluxed at 90 °C for 16 h. After
cooling to room temperature, the mixture was concentrated
in vacuo. The residue was used for the next step without
further purification.
P r oced u r e for th e Use of [(Allyl)P d (X)]2 (Ta ble 8). The
following is a typical procedure for the Pd(II)-catalyzed asym-
metric hydrovinylation reactions. A solution of 0.030 equiv of
the phosphorus ligand (L) in dichloromethane (1.5 mL) was
added to a solution of 0.015 equiv of [Pd(allyl)Cl]2 or [Pd-
(allyl)I]2 in dichloromethane (1.5 mL). The resulting yellow
solution was added to a suspension of 0.031 equiv of NaBARF
in dichloromethane (2 mL), stirred for 1.5 h at room temper-
ature, filtered through a short pad of Celite into a Schlenk
flask, and then taken out of the drybox. Oxygen-free ethylene
(∼1 atm) was introduced into the yellow catalyst solution at 0
to -10 °C, and 1.0 equiv of styrene was added dropwise via a
syringe. The resulting reaction mixture was stirred for 2 h at
0 to -10 °C under an ethylene atmosphere (∼1 atm), quenched
with half-saturated aqueous ammonium chloride (5 mL), and
extracted with diethyl ether (50 mL). The results are shown
in Table 8.
Syn th esis of Liga n d s. P r ep a r a tion of P h en ol 57. To a
mixture of 220 mg (0.468 mmol) of 5438 and 2.6 mL (18.7 mmol)
of Et3N in 10 mL of toluene at 0 °C under nitrogen was added
0.47 mL (4.68 mmol) of HSiCl3. After stirring at 0 °C for 10
min, the mixture was heated and refluxed at 120 °C for 23 h.
After cooling to room temperature, the mixture was diluted
with ether, quenched with 20 drops of saturated aqueous
NaHCO3 solution, and dried over MgSO4. The resulting
mixture was filtered through a small plug of Celite and the
filtrate was concentrated in vacuo to produce 57 as a white
solid (179 mg, 84%): 1H NMR (250 MHz, CDCl3) 6.70-7.98
(m, 22 H); 31P NMR (101 MHz, CDCl3) -14.4.
P r ep a r a tion of 32. To a solution of 120 mg (0.689 mmol)
of DEAD, 84 mg (0.689 mmol) of (S)-1-phenylethanol, and 181
mg (0.689 mmol) of PPh3 in 5 mL of THF at 0 °C under
nitrogen was added a solution of 108 mg (0.230 mmol) of
phenol 54 in 2 mL of THF. The mixture was allowed to warm
to room temperature and stirred for 20 h. The mixture was
concentrated and the residue was purified by flash chro-
matograghy on silica gel, eluting with hexanes/ethyl acetate
(1:1), to produce 55 as a white solid (93 mg, 71%): 1H NMR
(250 MHz, CDCl3) 1.40 (d, J ) 6.4 Hz, 3 H), 5.28 (q, J ) 6.4
Hz, 1 H), 6.81-8.10 (m, 27 H); 31P NMR (101 MHz, CDCl3)
27.8.
To a mixture of 80 mg (0.139 mmol) of 55 and 0.8 mL (5.57
mmol) of Et3N in 5 mL of toluene at 0 °C under nitrogen was
added 0.14 mL (1.39 mmol) of HSiCl3. After stirring at 0 °C
for 10 min, the mixture was heated and refluxed at 120 °C for
23 h. After cooling to room temperature, the mixture was
diluted with ether, quenched with 5 drops of saturated aqueous
NaHCO3 solution, and dried over MgSO4. The resulting
mixture was filtered through a small plug of Celite, the filtrate
was concentrated, and residue was purified by flash chroma-
tography on silica gel, eluting with hexanes/ethyl acetate (98:
2), to produce 32 as a white solid (63 mg, 81%): 1H NMR (250
MHz, CDCl3) 1.16 (d, J ) 6.4 Hz, 3 H), 5.34 (q, J ) 6.4 Hz, 1
H), 6.76-7.98 (m, 27 H); 31P NMR (101 MHz, CDCl3) -14.2;
HRMS (EI) calcd for C40H31OP 558.2113, found 558.2118.
Ligand 33 was prepared by a similar procedure starting
with (R)-1-phenylethanol and 54.
To a solution of the above residue in 2 mL of ether under
nitrogen was added 5 mL (3.75 mmol) of a 0.75 M solution of
3,5-bis(trifluoromethyl)phenylmagnesium bromide in ether.
The mixture was stirred at room temperature for 5 h and
refluxed at 45 °C for 12 h. After cooling to room temperature,
the mixture was quenched with 2 N aqueous HCl solution (10
mL). The aqueous layer was extracted three times with 10 mL
portions of ether. The combined organic layers were dried over
MgSO4 and concentrated in vacuo. The residue was purified
by flash chromatograghy on silica gel, eluting with hexanes/
ethyl acetate (3:1), to give phenol 62 as a white solid (100 mg,
1
25% from 61). H NMR (250 MHz, CDCl3) δ 6.85-8.38 (m, 18
H); 31P NMR (101 MHz, CDCl3) δ 23.5.
P r ep a r a tion of Eth er 63. To a solution of 100 mg (0.135
mmol) of 62 in 5 mL of acetone under nitrogen was added 94
mg (0.674 mmol) of K2CO3 and 0.086 mL (1.348 mmol) of MeI.
The mixture was heated to reflux for 24 h. After cooling to
room temperature, the mixture was filtered through a small
plug of Celite and washed with 10 mL of CH2Cl2. The filtrate
was concentrated in vacuo. The residue was purified by flash
chromatograghy on silica gel, eluting with hexanes/ethyl
acetate (6:1), to produce 63 as a white solid (87.6 mg, 86%):
1H NMR (250 MHz, CDCl3) δ 3.75 (s, 3 H), 6.76-8.14 (m, 18
H); 31P NMR (101 MHz, CDCl3) δ 22.9.
P r ep a r a tion of MOP Liga n d 38. To a mixture of 47 mg
(0.0622 mmol) of 63 and 0.35 mL (2.49 mmol) of Et3N in 3 mL
of toluene at 0 °C under nitrogen was added 0.063 mL (0.622
mmol) of HSiCl3. After stirring at 0 °C for 10 min, the mixture
was heated and refluxed at 120 °C for 17 h. After cooling to
room temperature, the mixture was diluted with ether,
quenched with 5 drops of saturated aqueous NaHCO3 solution,
and dried over MgSO4. The resulting mixture was filtered
through a small plug of Celite and the filtrate was concen-
trated in vacuo. The residue was purified by flash chro-
matograghy on silica gel, eluting with hexanes/ethyl acetate
(9:1), to produce 38 (43.3 mg, 94%): 1H NMR (250 MHz, CDCl3)
δ 3.63 (s, 3 H), 6.75-8.08 (m, 18 H); 31P NMR (101 MHz,
CDCl3) δ -11.5; FABMS m/z (relative intensity) 741 (M++H,
52).
Ack n ow led gm en t. Financial assistance by the US
National Science Foundation (CHE-0079948, CHE-
0308378) and the Petroleum Research Fund adminis-
tered by the ACS is also gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Full experimental
details of entries listed in various tables and equations,
synthesis and characterization of ligands not listed in the
Experimental Section. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O035171B
8446 J . Org. Chem., Vol. 68, No. 22, 2003