New efficient nickel-catalyzed cross-coupling reaction between two Csp3 centers

Article abstract of DOI:10.1021/jo982317b

The presence of a remote unsaturation (double bond, carbonyl group, cyano group) in an alkyl halide facilitates its cross-coupling reaction with various diorganozincs in the presence of Ni(acac)₂ (7.5-10 mol % in THF/NMP mixtures). These results were used to develop a new general cross-coupling reaction between functionalized diorganozincs and alkyl iodides using m- or p-trifluoromethylstyrene as a reaction promotor and Ni(acac)2 as a catalyst (7.5-10 mol %; -35 °C, 5-10 h) leading to a broad range of polyfunctional cross-coupling products.

Full text of DOI:10.1021/jo982317b

3544
J . Org. Chem. 1999, 64, 3544-3553
New Efficien t Nick el-Ca ta lyzed Cr oss-Cou p lin g Rea ction betw een
Tw o Csp 3 Cen ter s
Riccardo Giovannini,† Thomas Stu¨demann,† Arokiasamy Devasagayaraj,† Gae¨lle Dussin,† and
Paul Knochel*,†,‡
Fachbereich Chemie der Philipps-Universita¨t Marburg, Hans-Meerwein-Strasse, D-35043 Marburg,
Germany, and Institut fu¨r Organische Chemie der Ludwig-Maximilians-Universita¨t Mu¨nchen,
Butenandtstrasse 5-13, D-81377 Mu¨nchen, Germany
Received November 24, 1998
The presence of a remote unsaturation (double bond, carbonyl group, cyano group) in an alkyl
halide facilitates its cross-coupling reaction with various diorganozincs in the presence of Ni(acac)2
(7.5-10 mol % in THF/NMP mixtures). These results were used to develop a new general cross-
coupling reaction between functionalized diorganozincs and alkyl iodides using m- or p-trifluoro-
methylstyrene as a reaction promotor and Ni(acac)2 as a catalyst (7.5-10 mol %; -35 °C, 5-10 h)
leading to a broad range of polyfunctional cross-coupling products.
Sch em e 1
In tr od u ction
The cross-coupling reaction between an organometallic
reagent R1M and an organic halide R2X is one of the most
important methods for forming a new carbon-carbon
bond.1 Whereas cross-couplings between a Csp3 center
and either a Csp2 or Csp center are well-known,1 transi-
tion-metal-catalyzed cross-coupling reactions between
Csp3 centers are rare2 and mostly only organocuprates3
have been used for such C-C bond formation. This often
requires the use of stoichiometric amounts of copper salts
for the formation of the organocuprate R2CuLi and
consequently often implies the loss of a nontransferred
group R of R2CuLi.3 Alternatively, copper-catalyzed cross-
coupling of alkylmagnesium reagents displays a moder-
ate chemoselectivity as a result of the high reactivity of
the Grignard reagent.3,4 Only recently, a chemoselective
cross-coupling5 reaction involving functionalized diorga-
nozincs6 (FG-R)2Zn in the presence of stoichiometric
amounts of Me2Cu(CN)(MgCl)2 has been developed.5
However, the use of stoichiometric amounts of copper
salts precludes large scale applications. There is the need
for a transition-metal-catalyzed cross-coupling reaction
between two Csp3 centers.7 The proposed catalytic cycle
for such a catalysis (Scheme 1) first involves an oxidative
addition of the transition metal catalyst (ML2; M ) Ni
or Pd) to a carbon-halide (X ) I, Br) bond. Such a
reaction is well-known8 and does not present a major
problem. The resulting organometallic species 1 should
also readily undergo a transmetalation with the zinc
reagent R2 Zn providing the key intermediate 2 (R1(R2)-
2
ML2), which after reductive elimination should afford the
desired cross-coupling product 3. Unfortunately, contrary
to a reductive elimination between two Csp2 centers or a
Csp3 and Csp2 center, the reductive elimination between
two Csp3 centers is slow. A competitive exchange reaction
between the R1 and R2 groups occurs, affording the
symmetrical organometallic species 4 (R1 ML2) and 5 (R2 -
† Philipps-Universita¨t Marburg.
‡ Ludwig-Maximilians-Universita¨t Mu¨nchen.
(1) (a) Diederich, F., Stang, P. J ., Eds. In Metal-catalyzed Cross-
Coupling Reactions; Wiley-VCH: Weinheim, 1998. (b) Nicolaou, K. C.;
Sorensen, E. J . In Classics in Total Synthesis; VCH: Weinheim, 1996;
pp 565-631.
(2) Tamao, K. In Comprehensive Organic Synthesis, Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, pp 435-480.
(3) Lipshutz, B. H.; Sengupta, S. Org. React. 1992, 41, 135-631.
(4) (a) Tanis, S. P. Tetrahedron Lett. 1982, 23, 3115-3118. (b) Tanis,
S. P.; Head, D. B. Tetrahedron Lett. 1984, 25, 4451-4454. (c) Tanis,
S. P.; Herrinton, P. M. J . Org. Chem. 1983, 48, 4572-4580.
(5) For the stoichimetric use of zinc-copper reagents in cross-
coupling between Csp3 centers, see: Tucker, C. E.; Knochel, P. J . Org.
Chem. 1993, 58, 4781-4782.
2
2
ML2), which after reductive elimination furnish the
homocoupling products 6 (R1-R1) and 7 (R2-R2). The key
intermediate 2 can also undergo a further exchange
reaction9 with the zinc reagent R2 Zn, providing the new
2
zinc reagent 8 (R1ZnR2). To avoid most of these side
reactions, a fast reductive elimination of 2 would be
(8) (a) Kramer, A. V.; Labinger, J . A.; Bradley, J . S.; Osborn, J . A.
J . Am. Chem. Soc. 1974, 96, 7145-7147. (b) Kramer, A. V.; Osborn, J .
A. J . Am. Chem. Soc. 1974, 96, 7832-7833. (c) Lau, K. S. Y.; Fries, R.
W.; Stille, J . K. J . Am. Chem. Soc. 1974, 96, 4983-4986. (d) Chanon,
M. Bull. Soc. Chim. Fr. 1982, 2, 197-238. (e) Stadtmu¨ller, H.; Vaupel,
A.; Tucker, C. E.; Stu¨demann, T.; Knochel, P. Chem. Eur. J . 1996, 2,
1204-1220.
(6) For reviews, see: (a) Knochel, P.; Almena Perea, J . J .; J ones, P.
Tetrahedron 1998, 54, 8275-8319. (b) Knochel, P.; Singer R. D. Chem.
Rev. 1993, 93, 2117-2188. (c) Erdik, E. Tetrahedron 1987, 43, 2203-
2206.
(7) Only a few transition-metal-catalyzed reactions between two
Csp3 centers are known: Erdik, E. Tetrahedron 1992, 48, 9577-9648.
10.1021/jo982317b CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/29/1999

Ni-Catalyzed Cross-Coupling of Two Csp3 Centers
J . Org. Chem., Vol. 64, No. 10, 1999 3545
Sch em e 2
Sch em e 3
desirable. This elimination is especially difficult because
of the high electron-donor ability of a Csp3 center, which
provides an electron-rich organometallic intermediate 2
less prone to reductively eliminate the two Csp3 ligands.
Mechanistic studies of Yamamoto10 and Sustmann11
indicate that the complexation of a Ni(II) or Pd(II)
metallic center with an olefin bearing an electron-
withdrawing substituent facilitates the reductive elimi-
nation. Herein, we wish to report a new nickel-catalyzed
cross-coupling reaction between Csp3 centers based on
this principle, allowing the preparation of highly func-
tionalized cross-coupling products.12
obtained in over 85% yield as confirmed by iodolysis
experiments of the crude reaction mixtures (Scheme 2).
The absence of cross-coupling products clearly shows the
importance of the double bond in the alkyl iodide for the
course of the reaction. On the basis of the pioneering
work of Yamamoto10 and Sustmann,11 we have proposed
the following mechanistic scheme (Scheme 3).
The catalytically active species (L2Ni(0)) generated by
the in situ reduction of Ni(acac)2 undergoes an oxidative
addition on the alkyl halide 13 (X ) Br, I), producing a
nickel(II) complex 14, in which the double bond is
complexed to the metal center. After ligand exchange
with diethylzinc, the complex 15 is formed. The coordina-
tion of the double bond by nickel delocalizes the d
electrons of the nickel into the π*-antibonding orbitals
of the double bond, resulting in a faster reductive
elimination reaction leading to the desired cross-coupling
product 16. If a dissociation of the double bond occurs as
a result of steric interactions (or if no double bond is
present), a nickel(II) intermediate of type 17 results. This
intermediate does not readily undergo a reductive elimi-
nation but rather can exchange further its organic
ligands with diethylzinc. This transmetalation reaction
results in the formation of the new zinc reagent 18. It is
formally the result of a halide-zinc exchange (13 f 18).
This mechanistic scheme proves very useful to expand
the scope of the reaction and may also explain why cross-
couplings between Csp2 centers are so efficient.1,2 Thus,
the higher electronegativity (and less donor ability) of
Csp2 centers promotes the reductive elimination, but also
the presence of adjacent double bonds which are able to
remove d electrons from palladium or nickel by transfer
to the p* orbitals (see 19) may be responsable for the fast
cross-coupling reaction.
Resu lts a n d Discu ssion
During the course of the study of radical cyclization
reactions mediated by diethylzinc,9 we have observed that
the unsaturated organic bromides 9a ,b react with dieth-
ylzinc in the presence of catalytic amounts of Ni(acac)2
(7.5 mol %) and LiI (20 mol %) in THF (-35 °C, 4-18 h),
affording the corresponding cross-coupling products 10a,b
in 81-82% yield (Scheme 2).13
This behavior was surprising because in all the previ-
ously performed reactions between alkyl bromides or
iodides with diethylzinc, the halogen-zinc exchange
product (or cyclized organometallic product)9 was ob-
tained. We suspected that the remote double bond could
act as an additional ligand for the nickel intermediates
in the cross-coupling reaction.10,11 The reduction of this
double bond leads to the saturated alkyl bromides 11a ,b;
these were submitted to the same reaction conditions
(Ni(acac)2 (7.5 mol %), LiI (20 mol %), -35 °C, 18 h) and
negligible amounts of cross-coupling products were formed.
Only the bromine-zinc exchange products 12a ,b were
(9) For palladium- or nickel-catalyzed halogen-zinc exchange reac-
tions, see: (a) Stadtmu¨ller, H.; Lentz, R.; Do¨rner, W.; Stu¨demann, T.;
Tucker, C. E.; Knochel, P. J . Am. Chem. Soc. 1993, 115, 7027-7028.
(b) Vettel, S.; Vaupel, A.; Knochel, P. J . Org. Chem. 1996, 61, 7471-
7481.
(10) Yamamoto, T.; Yamamoto, A.; Ikeda, S. J . Am. Chem. Soc. 1971,
93, 3350-3359.
(11) (a) Sustmann, R.; Lau, J .; Zipp, M. Tetrahedron Lett. 1986, 27,
5207-5210. (b) Sustmann, R.; Lau, J . Chem. Ber. 1986, 119, 2531-
2541. (c) Sustmann, R.; Lau, J .; Zipp, M. Recl. Trav. Chim. Pays-Bas
1986, 105, 356-359. (d) Sustmann, R.; Hopp, P.; Holl, P. Tetrahedron
Lett. 1989, 30, 689-692. See also: (e) van Asselt, R.; Elsevier, C. J .
Tetrahedron 1994, 50, 323-334. (f) Castle, P. L.; Widdowson, D. A.
Tetrahedron Lett. 1986, 27, 6013-6016. (g) Yuan, K.; Scott, W. J .
Tetrahedron Lett. 1989, 30, 4779-4782. (h) Yuan, K.; Scott, W. J . J .
Org. Chem. 1990, 55, 6188-6194.
(12) For preliminary reports, see (a) Devasagayaraj, A.; Stu¨demann,
T. Angew. Chem. 1995, 107, 2952-2954; Angew. Chem., Int. Ed. Engl.
1995, 34, 2723-2725. (b) Giovannini, R.; Stu¨demann, T.; Dussin, G.;
Knochel, P. Angew. Chem. 1998, 110, 2512-2517; Angew. Chem., Int.
Ed. Engl. 1998, 37, 2387-2390.
(13) (a) Yanagisawa, A.; Nobuyoshi, N.; Yamamoto, H. Tetrahedron
1994, 50, 6017-6028. (b) Landa, S.; Markovec, L. Collect. Czech. Chem.
Commun. 1964, 29, 2309-2322.
Although other dialkylzincs react less readily in THF,
a solvent change to a 2:1 mixture of THF and N-
methylpyrrolidinone (NMP) sufficiently enhances the
reaction rate so that a range of unsaturated iodides
(20a -d )14 undergo this nickel-catalyzed cross-coupling
with good to excellent yields (Table 1). Thus, whereas
20a requires a reaction time of 24 h for the cross-coupling
(14) (a) Dussault, P. H.; Zope, U. R. J . Org. Chem. 1995, 60, 8218-
8222. (b) Bunce, R. A.; Peeples, C. J .; J ones, P. B. J . Org. Chem. 1992,
57, 1727-1733.

3546 J . Org. Chem., Vol. 64, No. 10, 1999
Giovannini et al.
Ta ble 1. P r od u cts 21a -k Obta in ed by th e
Nick el-Ca ta lyzed Cr oss-Cou p lin g of Dia lk ylzin cs w ith
Alk yl Iod id es 20a -d in THF /NMP
Sch em e 4
Sch em e 5
Sch em e 6
have established that the presence of a double bond
facilitates the cross-coupling reaction. To expand the
scope of this reaction, we have now examined if a similar
activation can be obtained with other unsaturated groups.
Therefore, we have submitted the iodonitriles 23a -c17
to the cross-coupling reaction conditions with dipentylzinc
(THF/NMP, Ni(acac)2 (7.5 mol %), -25 °C, 18-48 h), and
we have obtained the cross-coupling products 25a -c in
64-39% yield (Scheme 5).
The efficiency of the cross-coupling decreases with the
chain length between the iodine and cyano group. This
may be due to the better side-on complexation of the
cyanide in the intermediate 24a than in 24b and 24c.
Alternatively, the cyano group may also influence the
rate of the cross-coupling by an inductive effect that
decreases with increasing values of n. Next, we have
examined the case of keto-substituted alkyl iodides and
have obtained fast rates of cross-coupling reactions with
phenyl 2-iodoethyl ketone (26a )18 and phenyl 3-iodopropyl
ketone (26b)19 leading to the desired cross-coupling
products 27a ,b, respectively, in 65% and 71% yield
(Scheme 6).
The crucial importance of the substituent at the
carbonyl group is shown by using an alkyl 3-iodopropyl
ketone instead of the corresponding aryl ketone. Thus,
the reaction of butyl 3-iodopropyl ketone (26c) with
dipentylzinc under our standard conditions provides the
desired cross-coupling product (27c)20 as well as consid-
erable amounts of the iodine-zinc exchange product 28
reaction with dipentylzinc at -35 °C in THF (73%
isolated yield), the reaction of 20a with dipentylzinc in
THF/NMP (2:1) is complete within 3 h, leading to 21a
(80% isolated yield) (see entry 1 of Table 1). Similar
results are observed with functionalized zinc reagents
(see entries 3 and 4). A wide range of diorganozinc
reagents obtained either by the iodine-zinc exchange
reaction15 or by a boron-zinc exchange16 can be used for
this cross-coupling reaction. The presence of a carbethoxy
substituent on the double bond facilitates further the
cross-coupling reaction, and the substrates 20c and 20d
afford the expected products of type 21 in good yields.
Interestingly, palladium(0) complexes are less useful in
this cross-coupling reaction. Thus, whereas the reaction
of 20d with dipentylzinc in the presence of Ni(acac)2 (7
mol %) THF/NMP, -35 °C, 10 h) only produces the cross-
coupling product (21k ), the corresponding reaction of the
tert-amyl ester 20e8e with diethylzinc and PdCl2(CH3CN)2
(1.5 mol %) as catalyst furnishes the cyclization product
22 (THF, 25 °C, 4 h, 74% isolated yield; Scheme 4).8e We
(17) (a) Berk, S. C.; Yeh, M. C. P.; J eong, N.; Knochel, P. Organo-
metallics 1990, 9, 3053-3064. (b) Wolfe, S.; J okinen, M. G. Can. J .
Chem. 1979, 1388-1396. (c) Booth, B. L.; J ibodu, K. O.; Proenc¸a, M.
F. J . R. P. J . Chem. Soc., Perkin Trans 1 1983, 1067-1073.
(18) Trachtenberg, E. N.; Whall, T. J . J . Org. Chem. 1972, 37, 1494-
1499.
(15) Rozema, M. J .; AchyuthaRao, S.; Knochel, P. J . Org. Chem.
1992, 57, 1956-1958.
(16) Langer, F.; Schwink, L.; Devasagayaraj, A.; Chavant, P.-Y.;
Knochel, P. J . Org. Chem. 1996, 61, 8229-8243.
(19) Kimura, N.; Takamuku, S. Bull. Chem. Soc. J pn. 1991, 64,
2433-2437.
(20) Schmitz, E.; Sonnenschein, H.; Gru¨ndemann, C. J . Prakt. Chem.
1980, 322, 261-272.

Ni-Catalyzed Cross-Coupling of Two Csp3 Centers
J . Org. Chem., Vol. 64, No. 10, 1999 3547
Sch em e 7
Sch em e 9
Sch em e 8
°C). We have observed remarkable differences in reactiv-
ity and selectivity (Scheme 9).
(as proven by iodolysis and hydrolysis reactions). This
result demonstrates the importance of the coordination
of the nickel intermediate with an electron-poor unsat-
uration.21 The addition of acetophenone (1 equiv) as an
external ligand has a beneficial effect in this reaction. It
accelerates considerably the rate of the reaction and
completely suppresses the iodine-zinc side product 28
(less than 5% is formed). After workup, the cross-coupling
product (27c) is obtained in 71% isolated yield (Scheme
7).
The presence of trifluoromethyl substituents increases
the reaction rate (compare 29a with 29b and 29c).
However, perfluorinated benzophenone (29d ) was less
efficient than CF3-substituted additives, including the
CF3-substituted benzenes21 (29f and 29g). Interestingly,
1,4-dinitrobenzene (29h ) inhibits the cross-coupling reac-
tion. Although various additives such as 29b,c or 29f,g
led to fast reaction times, in all of these reactions the
competitive formation of the iodine-zinc exchange prod-
uct was observed. By using m-trifluoromethylstyrene
(29e) or p-trifluoromethylstyrene (29i), considerably less
iodine-zinc exchange product was observed and fast
reaction times were obtained. Interestingly, o-trifluoro-
methylstyrene (29j) was far less active, showing that the
complexation to the double bond may be less effective
with 29j as a result of steric hindrance. This indicates
also that a complexation of the ligand to the nickel center
is required and that electron transfer through space is
not operating. It was possible to use substoichiometric
amounts of the cocatalyst 29e (20-50 mol %) with similar
results. With these optimized reaction conditions, it was
now possible to perform a variety of cross-coupling
reactions (Table 2). All of these reactions were completed
within a few hours at -35 °C. The presence of various
functional groups was well tolerated. Some functional
groups such as a thioether or a thioacetal have an
accelerating effect as a result of a complexation of the
nickel intermediates with the sulfur atom.22 The cross-
coupling with ester- or amide-functionalized iodoalkanes
proceeds well with a range of functionalized zinc re-
agents, leading to polyfunctional products of type 27
(Table 2). The presence of a promotor influences also the
chemoselectivity of the new carbon-carbon bond forma-
tion. Thus, the reaction of the iodoketone 26b with
diisopropylzinc (Ni(acac)2, 10 mol %, THF/NMP, -35 °C,
5 h) in the absence of acetophenone furnishes a mixture
of the cross-coupling product 30 and the isomerized
product 31 in the ratio 75:25. This isomerization can be
mostly avoided by adding acetophenone 29a (50 mol %),
thereby leading to the desired product (30)23 in 62% yield
with only 3% of the isomer 31 (Scheme 10).
To evaluate the importance of the electron density of
the arylcarbonyl group, we have treated several substi-
tuted aryl 3-iodopropyl ketones (26b (R ) H),19 26d (R
) OMe), and 26e (R ) CF3)) with R1 Zn (R1 ) Pent, Bu)
2
(Ni(acac)2 (10 mol %), PhCOMe (1 equiv), THF/NMP, -35
°C, 2.5-12 h) (Scheme 8).
The most efficient cross-coupling was obtained with the
CF3-substituted alkyl iodide (26e). The reaction was
complete after 2.5 h, affording the product 27e in 92%
yield. The unsubstituted substrate (26b , R ) H) gave
under these conditions the corresponding product (27b)
in 88% yield, whereas the p-MeO-substituted starting
alkyl iodide (26d ) reacted very slowly (12 h reaction
time), furnishing the cross-coupling product (27d ) in only
71% isolated yield. Similarly, we have observed that
several other cross-coupling reactions can be accelerated
by the addition of an unsaturated molecule as promotor.
Thus, the addition of an equivalent of ethyl crotonate to
5-iodopentanenitrile (23c) improves the yield of the cross-
coupling product (25c) from 39% to 50%. Similarly, the
reaction of dipentylzinc with 6-iodohexyl pivalate pro-
vides, in the presence of ethyl crotonate (1 equiv) and
our standard reaction conditions, the cross-coupling
product undecyl pivalate (27f) in 59% yield. Less than
30% yield is obtained in the absence of ethyl crotonate.
Preliminary experiments have shown that styrene can
also be used as promotor. On the basis of these results,
we have examined in a more systematic way the nickel-
catalyzed cross-coupling reaction between 1-iodo-4-octa-
none (26c) with dipentylzinc in the presence of 1 equiv
of a cocatalyst or promotor (29), using the standard
reaction conditions (Ni(acac)2, 10 mol %, THF/NMP, -35
(22) For an excellent review on nickel-catalyzed reaction of thioket-
als, see: Luh, T.-Y. Synlett 1996, 201-208.
(23) Wagner, P. J .; Kemppainen A. E. J . Am. Chem. Soc. 1972, 94,
7495-7499.
(21) For the use of C6H5CF3 for accelerating the reductive elimina-
tion of NiEt2(bpy), see: Yamamoto, T.; Abla, M. J . Organomet. Chem.
1997, 535, 209-211.

3548 J . Org. Chem., Vol. 64, No. 10, 1999
Giovannini et al.
Ta ble 2. P r od u cts (27f-z) Obta in ed by Nick el-Ca ta lyzed Cr oss-Cou p lin g Rea ction betw een Dia lk ylzin cs a n d
P olyfu n ction a l Alk yl Iod id es in th e P r esen ce of a P r om otor
a
b
d
Isolated yields of analytically pure products. Performed with 29e (0.5 equiv). c Performed with 29e (0.3 equiv). Performed with
29e (0.2 equiv). e Performed with 29a (0.5 equiv). f Performed with 29e (1.0 equiv). Performed with 29a (1.0 equiv). Performed with
g
h
ethyl crotonate (1.0 equiv).
aliquots. Commercially available starting materials were used
without further purification. Melting points are uncorrected.
Sch em e 10
Sta r tin g Ma ter ia ls. The following starting materials were
prepared according to literature procedures: 5-iodo-3-phenyl-
1-pentene (20a ),14a (E)-ethyl 6-iodo-2-hexenoate (20c),14b
(E)-ethyl 7-iodo-2-heptenoate (20d ),14b (E)-tert-amyl 7-iodo-2-
heptenoate (20e),8e 3-iodopropanenitrile (23a ),17a 4-iodobutane-
nitrile (23b),17b 5-iodopentanenitrile (23c),17c 3-iodo-1-phenyl-
1-propanone (26a),18 4-iodo-1-phenyl-1-butanone (26b),19 6-iodo-
hexyl pivalate (26f),24 4-iodo-1-(2-thienyl)-1-butanone (26h ),25
ethyl 3-iodopropanoate (26j),26 2-(2-iodoethyl)-2-methyl-1,3-
dithiolane (26k ),27 3-iodopropyl phenyl sulfide (26l),28 5-iodo-
pentyl pivalate (26m ),24 benzyl 3-iodopropanoate (26n ),29
4-iodobutyl pivalate,30 3-iodopropyl pivalate,24 5-iodopentyl
acetate,31 3-chloro-1-piperidino-1-propanone,32 4-(4-chloro-
butanoyl)benzonitrile,33 and 1-chloro-4-octanone.34
In summary, we have developed a new nickel-catalyzed
cross-coupling reaction between polyfunctional primary
iodoalkanes and primary diorganozincs using as best
promotor m- or p-trifluoromethylstyrene (29e and 29i).
The cross-coupling reaction appears to have a large scope
and further extensions are currently investigated.
The diorganozinc reagents employed in cross-coupling reac-
tions were prepared according to literature procedures.6
(24) Ostwald, R.; Chavant, P.-Y.; Stadtmu¨ller, H.; Knochel, P. J . Org.
Chem. 1994, 59, 4143-4153.
(25) Acheson, R. M.; Cooper, M. W. J . Chem. Soc., Perkin Trans 1
1980, 1185-1193
Exp er im en ta l Section
(26) Yeh, C. P.; Chaung, C.-N. J . Chem. Soc., Perkin Trans. 1 1996,
17, 2167-2172.
Gen er a l Con sid er a tion s. Unless otherwise indicated, all
reactions were carried out under argon. Solvents (THF,
toluene) were dried and freshly distilled over sodium/benzo-
phenone. N-Methylpyrrolidone (NMP) was freshly distilled
(27) Corey, E. J .; Lin, S. J . Am. Chem. Soc. 1996, 118, 8765-8766.
(28) Rao, S. A.; Cho, T.-S.; Shipor, I.; Knochel, P. Tetrahedron 1992,
48, 2025-2043.
(29) Baldwin, J . E.; Adlington, R. M.; Birch, D. J .; Crawford, J . A.;
Sweeney, J . B. J . Chem. Soc., Chem. Commun. 1986, 17, 1339-1340.
(30) Murakami, M.; Kawano, T.; Ito, H.; Ito, Y. J . Org. Chem. 1993,
58, 1458-1465.
over CaH2
.
Reactions were monitored by gas-liquid phase chromatog-
raphy (GC) or thin-layer chromatography (TLC) of hydrolyzed

Ni-Catalyzed Cross-Coupling of Two Csp3 Centers
J . Org. Chem., Vol. 64, No. 10, 1999 3549
5-Br om o-3-p h en yl-1-p en ten e (9a ). To an ice-cold solution
of PPh3 (2.62 g, 10 mmol) in toluene (15 mL) was added Br2
(1.6 g, 10 mmol), and the reaction mixture was warmed to room
temperature. After 30 h, the solution was cooled at 0 °C, and
pyridine (0.79 g, 10 mmol) followed by 3-phenyl-4-pentenol
(1.62 g, 10 mmol dissolved in toluene) was added. The reaction
mixture was allowed to warm to room temperature and stirred
for 3 h, before being poured into hexanes and filtered. The
organic phase was washed with H2O and brine and dried
(MgSO4). The residue obtained after evaporation of the sol-
vents was purified by flash chromatography (hexanes/t-BuOMe
95:5) affording the desired product as a colorless oil (1.76 g,
78%). IR (neat): 3082, 3063, 1638, 701 cm-1. 1H NMR (CDCl3,
300 MHz): δ 7.39-7.24 (5H, m), 6.04-5.92 (1H, m), 5.20-
5.12 (2H, m), 3.58 (1H, q, J ) 7.5 Hz), 3.44-3.28 (2H, m), 2.37-
2.19 (2H, m). 13C NMR (CDCl3, 50 MHz): δ 143.0, 141.0, 129.1,
128.1, 127.1, 115.6, 48.2, 38.4, 32.2. MS (EI): 225 (M+, 6), 117
(100). Anal. Calcd for C11H13Br: C, 58.69; H, 5.82. Found: C,
58.84; H, 5.97.
4-chloro-1-(4-methoxyphenyl)butanone (7.65 g, 36 mmol). The
residue obtained after evaporation of the solvents was purified
by flash chromatography (hexanes/ether 10:1) affording the
product as a yellow solid (mp 43 °C; 8.2 g, 75%). IR (neat):
1
2957, 1666, 1600, 1262 cm-1. H NMR (CDCl3, 300 MHz): δ
7.85-7.80 (2H, m), 6.84-6.79 (2H, m), 3.74 (3H, s), 3.19 (2H,
t, J ) 6.7 Hz), 2.94 (2H, t, J ) 6.9 Hz), 2.16-2.07 (2H, m). 13
C
NMR (CDCl3, 75 MHz): δ 196.7, 163.3, 130.0, 129.6, 113.5,
55.3, 38.4, 27.7, 6.8. MS (EI): 304 (M+, 0.7), 177 (28), 150 (23),
135 (100). M+ calcd for C11H13IO2: 303.9960. Observed:
303.9961.
4-Iod o-1-(4-tr iflu or om eth ylp h en yl)bu ta n on e (26e). In
a three-necked 250 mL flask equipped with a stirring bar, a
thermometer, and a gas inlet, dry MnCl2 (5 g, 40 mmol)36 and
dry LiCl (3.4 g, 80 mmol) were dissolved in THF (100 mL)
under argon. The reaction mixture was cooled at -60 °C, and
a solution of 4-trifluoromethylphenylmagnesium bromide (1.7M
in THF) (24 mL, 40 mmol) was carefully added by syringe.
The reaction mixture was allowed to warm to 0 °C and after
10 min cooled again at -50 °C. 4-Chlorobutyryl chloride (4.0
mL, 36 mmol) was added followed by CuCl (79 mg, 2 mol %).
The reaction mixture was allowed to reach room temperature
and stirred for 1 h before being poured into an ice-cold aqueous
solution of NH4Cl and extracted with Et2O. The organic phase
was dried (MgSO4), and the residue obtained after evaporation
of the solvents was used in the next step without purification.
The crude product was treated with NaI as described above
and the residue obtained after the workup was purified by
flash chromatography (hexanes/ether 20:1) affording the prod-
uct as a yellow oil (8.5 g, 69%). IR (neat): 3066, 1692, 1326,
5-Br om o-3-bu tyl-1-p en ten e (9b). The procedure described
above for the preparation of 1-bromo-3-phenyl-pent-4-ene (9a )
was used, starting from 3-butyl-4-pentenol (1.42 g, 10 mmol).
The residue obtained after evaporation of the solvents was
purified by flash chromatography (hexanes) affording the
desired product as a colorless oil (1.56 g. 76%). IR (neat): 3078,
2928, 1641, 640 cm-1 1H NMR (CDCl3, 300 MHz): δ 5.46-
.
5.34 (1H, m), 5.01-4.94 (2H, m), 3.41-3.21 (2H, m), 2.10-
1.17 (9H, m), 0.82 (3H, t, J ) 6.8 Hz). 13C NMR (CDCl3, 75
MHz): δ 141.3, 115.7, 42.7, 37.8, 34.5, 32.0, 29.2, 22.7, 14.0.
MS (EI): 205 (M+, 8), 162 (20), 148 (28), 54 (100). Anal. Calcd
for C9H17Br: C, 52.70; H, 8.35. Found: C, 52.91; H, 8.32.
5-Iod o-3-bu tyl-1-p en ten e (20b). 3-Butyl-4-pentenol (1.58
g, 11.2 mmol) and MeI‚2DCC35 (7.39 g, 22.4 mmol) were
dissolved in THF (125 mL), and the mixture was stirred at 35
°C for 8 h. The solvent was removed under reduced pressure,
and the residue was dissolved in hexanes and washed with a
4:1 mixture of MeOH and H2O (60 mL).The aqueous phase
was extracted with hexanes, and the combined organic fraction
was washed with brine and dried (MgSO4). The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes) affording the product as a pale
1169, 1130, 1066 cm-1 1H NMR (CDCl3, 300 MHz): δ 7.97
.
(2H, d, J ) 8.1 Hz), 7.62 (2H, d, J ) 8.1 Hz), 3.25 (2H, t, J )
6.6 Hz), 3.07 (2H, t, J ) 6.9 Hz), 2.21-2.10 (2H, m). 13C NMR
(CDCl3, 75 MHz): δ 197.3, 139.1, 134.2 (q, J ) 32.6 Hz), 128.1,
125.4 (q, J ) 3.6 Hz), 123.3 (q, J ) 271.0 Hz), 39.0, 27.0, 6.1.
19F NMR (CDCl3, 188 MHz): δ -63.2. MS (EI): 323 (1), 254
(2), 215 (29), 173 (100), 145 (27). M+ calcd for C11H10IOF3:
322.9749. Observed: 322.9744.
4-(4-Iod obu ta n oyl)ben zon itr ile (26g). The same proce-
dure as described above for the preparation of 26c has been
used starting from 4-(4-chlorobutanoyl)benzonitrile33 (7.47 g,
36 mmol). The crude product was purified by flash chroma-
tography (hexanes/ether 10:1) affording the product as a yellow
solid (mp 61 °C; 7.75 g, 72%). IR(neat): 3078, 2953, 2226, 1687
yellow oil (1.64 g, 58%). IR (neat): 3076, 2957, 1641, 917 cm-1
.
1H NMR (CDCl3, 300 MHz): δ 5.45-5.36 (1H, m), 5.03-4.97
(2H, m), 3.22-3.14 (1H, m), 3.05-2.96 (1H, m), 2.05-1.16 (9H,
m), 0.83 (3H, t, J ) 6.7 Hz). 13C NMR (CDCl3, 75 MHz): δ
141.3,115.9, 45.0, 38.6, 34.4, 29.3, 22.8, 14.2, 5.4. MS (EI): 252
(M+, 3), 196 (25), 55 (100). Anal. Calcd for C9H17I: C, 42.87;
H, 6.80. Found: C, 43.12; H, 6.90.
1
cm-1. H NMR (CDCl3, 300 MHz): δ 7.99 (2H, d, J ) 8.1 Hz),
7.71 (2H, d, J ) 8.1 Hz), 3.25 (2H, t, J ) 6.5 Hz), 3.08 (2H, t,
J ) 6.8 Hz), 2.23-2.12 (2H, m). 13C NMR (CDCl3, 75 MHz): δ
197.2, 139.6, 132.6, 128.4, 117.8, 116.5, 39.2, 27.1, 6.2. MS
(EI): 299 (M+, 100), 172 (29). Anal. Calcd for C11H10INO: C,
44.17; H, 3.37; N, 4.68. Found: C, 44.05; H, 3.45; N, 4.53.
3-Iod o-1-p ip er id in o-1-p r op a n on e (26i). The same pro-
cedure as described above has been used starting from
3-chloro-1-piperidino-1-propanone32 (6.32 g, 36 mmol). The
crude product was purified by flash chromatography (hexanes/
ether 2:8) affording the product as a pale yellow oil (8.65 g,
90%). IR (neat): 2934, 2853, 1634, 1443 cm-1. 1H NMR (CDCl3,
300 MHz): δ 3.49 (2H, t, J ) 5.5 Hz), 3.34-3.29 (4H, m), 2.88
(2H, t, J ) 7.46 Hz), 1.63-1.43 (6H, m). 13C NMR (CDCl3, 75
MHz): δ 168.7, 46.3, 42.7, 37.4, 26.3, 25.4, 24.3, -1.6. MS
(EI): 267 (M+, 25), 140 (100). Anal. Calcd for C8H14INO: C,
35.97; H, 5.28; N, 5.24. Found: C, 35.86; H, 5.12; N, 5.57.
Ni(a ca c)2-Ca ta lyzed Cr oss-Cou p lin g betw een Dia lk yl-
zin cs a n d Alk yl Iod id es. Typ ica l P r oced u r e A. P r ep a r a -
tion of (E)-Eth yl 12-Acetoxy-2-d ecen oa te (21h ). A 50 mL
two-necked flask equipped with an argon inlet and a rubber
septum was charged with Ni(acac)2 (0.116 g, 7.5 mol %). After
the flask was cooled to -40 °C, THF (2.5 mL), NMP (1.5 mL),
and 20c (1.69 g, 6 mmol) were added successively by syringe.
The reaction mixture was cooled to -78 °C, and a solution of
bis(5-acetoxypentyl)zinc in THF (2 mL) prepared from 5-iodo-
pentyl acetate (6.14 g, 24 mmol) and Et2Zn by an iodine-zinc
1-Iod o-4-octa n on e (26c). 1-Chloro-4-octanone34 (5.85 g, 36
mmol) was treated with NaI (54 g, 360 mmol) in acetone (100
mL), and the mixture was refluxed overnight. The solvent was
evaporated under reduced pressure and Et2O was added (100
mL). The organic layer was washed with an aqueous solution
of Na2S2O3, and the aqueous phase was extracted with Et2O.
The combined organic fractions were dried (Na2SO4).The
residue obtained after evaporation of the solvents was purified
by flash chromatography (hexanes/ether 20:1) affording the
product as a yellow oil (7.14 g, 78%). IR (neat): 2957, 1713,
1
1465 cm-1. H NMR (CDCl3, 300 MHz): δ 3.16 (2H, t, J ) 6.6
Hz), 2.50 (2H, t, J ) 6.9 Hz), 2.35 (2H, t, J ) 7.3 Hz), 2.04-
1.97 (2H, m), 1.54-1.44 (2H, m), 1.30-1.18 (2H, m), 0.84 (3H,
t, J ) 7.2 Hz). 13C NMR (CDCl3, 75 MHz): δ 209.2, 42.6, 42.5,
27.0, 25.8, 22.2, 13.7, 6.5. MS (EI): 254 (M+, 100), 127 (52).
Anal. Calcd for C8H15IO: C, 37.81; H, 5.94. Found: C, 37.80;
H, 6.08.
4-Iod o-1-(4-m eth oxyp h en yl)bu ta n on e (26d ). The same
procedure as described above has been used starting from
(31) Forth, M. A.; Smith, S. Synth. Commun. 1994, 24, 951-959.
(32) Wasserman, H. H.; Dion, R. P.; Fukuyama, J . Tetrahedron
1989, 45, 3203-3216.
(33) Klement, I.; Stadtmu¨ller, H.; Knochel, P.; Cahiez, G. Terahe-
dron. Lett. 1997, 38, 1927-1930.
(34) Cahiez, G.; Laboue, B. Tetrahedron Lett. 1992, 33, 4439-4442.
(35) Scheffold, R.; Saladin, E. Angew. Chem. 1972, 84, 158-160;
Angew. Chem., Int. Ed. Engl. 1972, 11, 229-231.
(36) (a) Cahiez, G.; Alami, M. Tetrahedron Lett. 1989, 30, 3541-
3544 and 7365-7368. (b) Cahiez, G.; Alami, M. Tetrahedron 1989, 45,
4163-4176.

3550 J . Org. Chem., Vol. 64, No. 10, 1999
Giovannini et al.
exchange reaction was slowly added. The reaction mixture was
allowed to warm to -35 °C and was stirred for 15 h at this
temperature. Excess of dialkylzinc was quenched with satu-
rated aqueous NH4Cl solution. After the usual workup, the
resulting crude oil obtained after evaporation of the solvents
was purified by flash chromatography (hexanes/ether 20:1-
5:1) affording the desired product (1.33 g, 78% yield) as a
colorless oil. IR (neat): 2935, 1730, 1660, 1240 cm-1. 1H NMR
(CDCl3, 300 MHz): δ 6.93-6.83 (1H, m), 5.72 (1H, d, J ) 15.6
Hz), 4.10 (2H, q, J ) 7.0 Hz), 3.97 (2H, t, J ) 6.7 Hz), 2.14
(2H, q, J ) 7.3 Hz), 1.96 (3H, s), 1.56-1.18 (17H, m). 13C NMR
(CDCl3, 75 MHz): δ 171.0, 166.6, 149.2, 121.3, 64.5, 60.0, 32.1,
29.3, 29.2, 29.1, 29.0, 28.6, 28.0, 25.9, 20.9, 14.2. MS (EI): 239
(6), 150 (59), 55 (100). Anal. Calcd for C16H28O4: C, 67.57; H,
9.92. Found: C, 67.46; H, 10.12.
Typ ica l P r oced u r e B. P r ep a r a tion of 3-P h en yl-1-h ep -
ten e (10a ).13a LiI (0.13 g, 20 mol %), dried under vacuum (2
h, 100 °C), was dissolved in THF (7 mL) and cooled to -78 °C.
Ni(acac)2 (96 mg, 7.5 mol %) and 1-bromo-3-phenyl-4-pentene
(9a , 1.125 g, 5 mmol) were added followed by Et2Zn (1 mL, 10
mmol).The reaction mixture was allowed to reach room tem-
perature in 4 h, before being quenched with saturated aqueous
NH4Cl solution and extracted with Et2O. The organic phase
was washed with brine and dried (MgSO4). The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes) affording the product as a colorless
oil (0.7 g, 81% yield). The NMR data of the product fits the
literature data.13a
Typ ica l P r oced u r e C. In P r esen ce of a P r om otor .
P r ep a r a tion of Ben zyl Octa n oa te (27r ).37 A 25 mL two-
necked flask equipped with an argon inlet and a rubber septum
was charged with Ni(acac)2 (0.128 g, 10 mol %), THF (3.4 mL),
NMP (1.7 mL), m-trifluoromethylstyrene (0.172 g, 20 mol %),
and 26n (1.45 g, 5 mmol) at room temperature. The reaction
mixture was cooled at -78 °C, and Pent2Zn (2 mL, 10 mmol)
was carefully added. The reaction mixture was allowed to
warm to -35 °C and stirred for 2.5 h, before being poured into
an ice-cold aqueous saturated solution of NH4Cl. After the
usual workup, the resulting crude oil obtained after evapora-
tion of the solvents was purified by flash chromatography
(hexanes/ether 10:1) affording the desired product (0.89 g, 76%
yield) as a colorless oil. The NMR data of the product fits the
literature data.37
3-Bu tyl-1-h ep ten e (10b).13b The reaction was carried out
according to typical procedure B starting from 9b (1.03 g, 5
mmol), Ni(acac)2 (96 mg, 7.5 mol %), and Et2Zn (1 mL, 10
mmol). Reaction time was 18 h at -35 °C. The residue obtained
after evaporation of the solvents was purified by flash chro-
matography (hexanes) affording the product as a colorless oil
(0.63 g, 82% yield). The NMR data of the product fits the
literature data.13b
was 3 h at -35 °C. IR (neat): 3076, 2926, 1640, 1460, 995,
1
960 cm-1. H NMR (CDCl3, 200 MHz): δ 5.48-5.40 (1H, m),
4.89-4.79 (2H, m), 1.88-1.84 (1H, m), 1.26-1.10 (21H, m),
0.82 (3H, t, J ) 6.7 Hz). 13C NMR (CDCl3, 50 MHz): δ 144.3,
114.2, 44.6, 35.6, 35.3, 32.4, 30.3, 30.0, 29.9, 27.7, 23.4, 23.2,
14.6. MS (EI): 196 (M+, 28), 168 (26), 154 (26), 70 (100). Anal.
Calcd for C14H28: C, 85.63; H, 14.37. Found: C, 85.53; H, 14.35.
6-P h en yl-7-octen yl P iva la te (21c). The reaction was
carried out according to typical procedure A, starting from 20a
(0.82 g, 3 mmol), Ni(acac)2 (57 mg, 7.5 mol %), and bis(3-
pivaloxypropyl)zinc (6 mmol) in THF (2 mL). Reaction time
was 4 h at -35 °C. The residue obtained after evaporation of
the solvents was purified by flash chromatography (hexanes/
t-BuOMe 95:5) affording the product as a colorless oil (0.78 g,
90% yield). IR (neat): 3063, 3028, 2973, 1728, 1285, 701 cm-1
.
1H NMR (CDCl3, 300 MHz): δ 7.34-7.18 (5H, m), 6.02-5.90
(1H, m), 5.07-5.00 (2H, m), 4.04 (2H, t, J ) 6.6 Hz), 3.24 (q,
1H, J ) 7.5 Hz), 1.77-1.70 (2H, m), 1.63-1.57 (2H, m), 1.41-
1.33 (4H, m), 1.19 (9H, s). 13C NMR (CDCl3, 75 MHz): δ 178.6,
144.5, 142.4, 128.5, 127.6, 126.2, 114.0, 64.4, 49.9, 38.8, 35.4,
28.6, 27.3, 27.2, 26.0. MS (EI): 186 (28), 157 (33), 117 (100),
91 (40), 57 (72). Anal. Calcd for C19H28O2: C, 79.12; H, 9.78.
Found: C, 79.01; H, 9.92.
6-Bu tyl-7-octen yl P iva la te (21d ). The reaction was car-
ried out according to typical procedure A starting from 20b
(0.76 g, 3 mmol), Ni(acac)2 (57 mg, 7.5 mol %), and bis(3-
pivaloxypropyl)zinc (6 mmol) in THF (2 mL). Reaction time
was 3 h at -35 °C. The residue obtained after evaporation of
the solvents was purified by flash chromatography (hexanes/
t-BuOMe 95:5) affording the product as a colorless oil (0.56 g,
70% yield). IR (neat): 3070, 2928, 1731, 1620, 1480, 1285, 1156
cm-1. 1H NMR (CDCl3, 300 MHz): δ 5.50-5.38 (1H, m), 4.90-
4.82 (2H, m), 3.97 (2H, t, J ) 6.6 Hz), 1.90-1.80 (1H, m), 1.59-
1.50 (2H, m), 1.25-1.06 (21H, m), 0.81 (3H, t, J ) 6.7 Hz). 13
C
NMR (CDCl3, 75 MHz): δ 178.5, 143.5, 113.7, 64.3, 43.9, 38.6,
34.8, 34.7, 29.3, 28.5, 27.1, 26.9, 25.8, 22.7, 14.0. MS (EI): 166
(5), 137 (32), 109 (50), 57 (100). Anal. Calcd for C17H32O2: C,
76.06; H, 12.01. Found: C, 76.33; H, 12.30.
(E)-Eth yl 2-Un d ecen oa te (21e).9b The reaction was car-
ried out according to typical procedure A, starting from 20c
(1.34 g, 5 mmol), Ni(acac)2 (96 mg, 7.5 mol %), and Pent2Zn (2
mL, 10 mmol). Reaction time was 3 h at -35 °C. The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes/ether 95:5) affording the product as
a colorless oil (0.88 g, 83% yield). The NMR data of the product
fits the literature data.9b
(E)-Eth yl 2-Non en oa te (21f).38 The reaction was carried
out according to typical procedure A starting from 20d (1.41
g, 5 mmol), Ni(acac)2, (96 mg, 7.5 mol %), and Et2Zn (1 mL, 10
mmol). Reaction time was 3 h at -35 °C. The residue obtained
after evaporation of the solvents was purified by flash chro-
matography (hexanes/ether 15:1) affording the product as a
colorless oil (0.77 g, 84% yield). The NMR data of the product
fits the literature data.38
3-P h en yl-1-d ecen e (21a ). The reaction was carried out
according to typical procedure A starting from 20a (5 mmol,
1.36 g), Ni(acac)2 (96 mg, 7.5 mol %), and Pent2Zn (2 mL, 10
mmol). Reaction time was 3 h at -35 °C. The residue obtained
after evaporation of the solvents was purified by flash chro-
matography (hexanes) affording the product as a colorless oil
(0.86 g, 80% yield). IR (neat): 3082, 3028, 2926, 1636, 699
cm-1. 1H NMR (CDCl3, 300 MHz): δ 7.29-7.14 (5H, m), 5.98-
5.86 (1H, m), 5.02-4.96 (2H, m), 3.20 (1H, q, J ) 7.2 Hz), 1.77-
(E)-Eth yl 9-P iva loxy-2-n on en oa te (21 g). The reaction
was carried out according to typical procedure A, starting from
20c (0.80 g, 3 mmol), Ni(acac)2 (57 mg, 7.5 mol %), and bis-
(3-pivaloxypropyl)zinc (6 mmol) in THF (2.5 mL). Reaction
time was 5 h at -35 °C. The residue obtained after evaporation
of the solvents was purified by flash chromatography (hexanes/
t-BuOMe 90:10) affording the product as a colorless oil (0.67
1.63 (2H, m), 1.22-1.16 (10H, m), 0.84 (3H, t, J ) 6.4 Hz). 13
C
g, 79% yield). IR (neat): 2977, 1727, 1655, 1285, 1159 cm-1
.
NMR (CDCl3, 75 MHz): δ 144.7, 142.5, 128.3, 127.5, 126.2,
113.8, 49.9, 35.4, 31.8, 29.5, 29.2, 27.5, 22.6, 14.1. MS (EI):
216 (M+, 23), 117 (100). Anal. Calcd for C16H24: C, 88.82; H,
11.18. Found: C, 88.95; H, 11.30.
1H NMR (CDCl3, 300 MHz): δ 6.93-6.83 (1H, m), 5.77 (1H,
d, J ) 15.7 Hz), 4.12 (2H, q, J ) 7.1 Hz), 3.97 (2H, t, J ) 6.5
Hz), 2.13 (2H, q, J ) 7.1 Hz), 1.57-1.19 (11H, m), 1.12 (9H,
s). 13C NMR (CDCl3, 75 MHz): δ 178.5, 166.6, 148.9, 121.4,
64.2, 60.0, 38.7, 32.0, 28.7, 28.5, 27.9, 27.1, 25.7, 14.2, MS
(EI): 238 (5), 136 (42), 109 (30), 57 (100). Anal. Calcd for
3-Bu tyl-1-d ecen e (21b). The reaction was carried out
according to typical procedure A, starting from 20b (1.26 g, 5
mmol), Ni(acac)2 (96 mg, 7.5 mol %), and Pent2Zn (2 mL, 10
mmol). The residue obtained after evaporation of the solvents
was purified by flash chromatography (hexanes) affording the
product as a colorless oil (0.71 g, 72% yield). Reaction time
C
16H28O4: C, 67.57; H, 9.92. Found: C, 67.90; H, 9.64.
(E)-Eth yl 13-P iva loxy-2-tr id ecen oa te (21i). The reaction
was carried out according to typical procedure A, starting from
(37) Murahashi, S.-I.; Naota, T.; Ito, K.; Maeda, Y.; Taki, H. J . Org.
Chem. 1987, 52, 4319-4327.
(38) Katzenellenbogen, J . A., Utawanit, T. J . Am. Chem. Soc. 1974,
96, 6153-6158.

Ni-Catalyzed Cross-Coupling of Two Csp3 Centers
J . Org. Chem., Vol. 64, No. 10, 1999 3551
20d (1.69 g, 6 mmol), Ni(acac)2 (115 mg, 7.5 mol %), and bis-
(6-pivaloxyhexyl)zinc (12 mmol) in THF (4 mL). Reaction time
was 15 h at -35 °C. The residue obtained after evaporation of
the solvents was purified by flash chromatography (hexanes/
ether 10:1) affording the product as a colorless oil (1.49 g, 73%
25c as a colorless oil (0.30 g, 39% yield). The NMR data of the
product fits the literature data.42
n -Octa n op h en on e (27a ).43 The reaction was carried out
according to typical procedure C, starting from 26a (0.78 g, 3
mmol), Ni(acac)2 (77 mg, 10 mol %), and Pent2Zn (1.2 mL, 6
mmol). Reaction time was 3 h at -35 °C. The residue obtained
after evaporation of the solvents was purified by flash chro-
matography (hexanes/ether 10:1) affording the product as a
colorless oil (0.43 g, 71% yield). The NMR data of the product
fits the literature data.43
yield). IR (neat): 2935, 1730, 1465, 1160 cm-1 1H NMR
.
(CDCl3, 300 MHz): δ 6.93-6.83 (1H, m), 5.73 (1H, d, 15.7 Hz),
4.09 (2H, q, J ) 7.1 Hz), 3.96 (2H, t, J ) 6.6 Hz), 2.11 (2H, t,
J ) 7.1 Hz), 1.56-1.49 (2H, m), 1.39-1.35 (2H, m), 1.28-1.17
(15H, m), 1.11 (9H, s). 13C NMR (CDCl3, 75 MHz): δ 178.5,
166.6, 149.3, 121.3, 64.4, 60.0, 38.7, 32.1, 29.43, 29.37, 29.32,
29.16, 29.09, 28.6, 28.0, 27.2, 25.9, 14.2. MS (EI): 341 (M+,
100). Anal. Calcd for C20H36O4: C, 70.54; H, 10.65. Found: C,
70.48; H, 10.61.
n -Non a n op h en on e (27b).9b The reaction was carried out
according to typical procedure C, starting from 26b (0.82 g, 3
mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone (0.36 g, 3
mmol), and Pent2Zn (1.2 mL, 6 mmol). Reaction time was 2.5
h at -35 °C. The residue obtained after evaporation of the
solvents was purified by flash chromatography (hexanes/ether
10:1) affording the product as a colorless oil (0.57 g, 88%). The
NMR data of the product fits the literature data.9b
5-Tr id eca n on e (27c).20 The reaction was carried out ac-
cording to typical procedure C, starting from 26c (0.76 g, 3
mmol), Ni(acac)2 (77 mg, 10 mol %), m-trifluoromethylstyrene
(0.103 g, 20 mol %), and Pent2Zn (1.2 mL, 6 mmol). Reaction
time was 1 h at -35 °C. The residue obtained after evaporation
of the solvents was purified by flash chromatography (hexanes/
ether 20:1) affording the product as a colorless oil (0.44 g, 74%).
The NMR data of the product fits the literature data.20
1-(4-Meth oxyp h en yl)octa n on e (27d ).44 The reaction was
carried out according to typical procedure C, starting from 26d
(0.91 g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone
(0.36 g, 3 mmol), and Bu2Zn (1 mL, 6 mmol). Reaction time
was 12 h at -35 °C. The residue obtained after evaporation of
the solvents was purified by flash chromatography (hexanes/
ether 10:1) affording the product as a white solid (mp 44 °C;
0.50 g, 72%). The NMR data of the product fits the literature
data.44
(E)-E t h yl 6-(3-Oxocycloh exyl)-2-h exen oa t e (21j). The
reaction was carried out according to typical procedure A,
starting from 20c (0.8 g, 3 mmol), Ni(acac)2 (57 mg, 7.5 mol
%), and bis(3-trimethylsilyloxy cyclohex-2-en-1-yl)zinc (7 mmol)
in THF (2.5 mL). Reaction time was 12 h at -35 °C. The
residue obtained after evaporation of the solvents was purified
by flash chromatography (hexanes/t-BuOMe 75:25) affording
the product as a colorless oil (0.46 g, 65% yield). IR (neat):
1
2926, 1723, 1656, 1145 cm-1. H NMR (CDCl3, 200 MHz): δ
7.00-6.87 (1H, m), 5.88 (1H, d, J ) 15.7 Hz), 4.18 (2H, q, J )
7.1 Hz), 2.38-1.26 (18H, m). 13C NMR (CDCl3, 75 MHz): δ
213.0, 166.7, 148.9, 121.6, 60.2, 50.6, 42.1, 34.0, 32.4, 29.1, 28.1,
25.8, 25.0, 14.3. MS(EI): 238 (M+, 20), 141 (25), 98 (100). M+
calcd for C14H22O3: 238.1644. Observed: 238.1643.
(E)-Eth yl 2-Dod ecen oa te (21k ).39 The reaction was car-
ried out according to typical procedure A, starting from 20d
(1.69 g, 6 mmol), Ni(acac)2 (115 mg, 7.5 mol %), and Pent2Zn
(2.4 mL, 12 mmol). Reaction time was 10 h at -40 °C.The
residue obtained after evaporation of the solvents was purified
by flash chromatography (hexanes/ether 20:1) affording the
product as a yellow oil (1.10 g, 81% yield). The NMR data of
the product fits the literature data.39
ter t-Am yl Cyclop en tyl Aceta te (22).8eA three-necked
flask equipped with a magnetic stirring bar, a thermometer,
and a gas inlet was charged with PdCl2(MeCN)2 (17 mg, 1.5
mol %) in THF (5 mL) and cooled at -78 °C. The iodide 20e
(1.38 g, 4.3 mmol) and Et2Zn (0.86 mL, 8.6 mmol, 2 equiv) were
added. The reaction mixture was slowly (over 4 h) warmed to
room temperature and quenched with water. The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes/ether 20:1) affording the product as
a colorless oil (0.62 g, 74% yield). The NMR data of the product
fits the literature data.8e
Octa n en itr ile (25a ).40 The reaction was carried out ac-
cording to typical procedure A, starting from 23a (0.45 g, 2.5
mmol), Ni(acac)2 (64 mg, 10 mol %), and Pent2Zn (1 mL, 5
mmol). Reaction time was 48 h at -25 °C. The residue obtained
after evaporation of the solvents was purified by flash chro-
matography (hexanes/ether 20:1-10:1) affording the product
25a as a yellow oil (0.20 g, 64%). The NMR data of the product
fits the literature data.40
Non a n en itr ile (25b).41 The reaction was carried out ac-
cording to typical procedure A, starting from 23b (0.97 g, 5
mmol), Ni(acac)2 (0.128 g, 10 mol %), and Pent2Zn (2 mL, 10
mmol). Reaction time was 48 h at -25 °C. The residue obtained
after evaporation of the solvents was purified by flash chro-
matography (hexanes/ether 20:1-10:1) affording the product
25b as a colorless oil (0.36 g, 52% yield). The NMR data of
the product fits the literature data.41
1-(4-Tr iflu or om eth ylp h en yl)n on a n on e (27e). The reac-
tion was carried out according to typical procedure C, starting
from 26e (1 g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), and Pent2-
Zn (1.2 mL, 6 mmol). Reaction time was 1 h at -35 °C. The
residue obtained after evaporation of the solvents was purified
by flash chromatography (hexanes/ether 20:1) affording the
product as a solid (mp 36 °C; (0.78 g, 91% yield). IR (neat):
2955, 2926, 1695, 1330, 1170 cm-1 1H NMR (CDCl3, 300
.
MHz): δ 7.94 (2H, d, J ) 8.1 Hz), 7.59 (2H, d, J ) 8.1 Hz),
2.88 (2H, t, J ) 7.3 Hz), 1.66-1.62 (2H, m), 1.24-1.17 (10H,
m), 0.79-0.74 (3H, m). 13C NMR (CDCl3, 75 MHz): δ 199.2,
139.6, 134.0 (q, J ) 32.3 Hz), 128.2, 125.4 (q, J ) 3.6 Hz),
123.5 (q, J ) 270.9 Hz), 38.7, 31.7, 29.3, 29.1, 24.0, 22.5, 13.8.
19F NMR (CDCl3, 188 MHz): δ -63.4. MS (EI): 286 (M+, 4),
201 (12), 188 (100), 173 (62), 145 (22). M+ calcd for C16H21
OF3: 286.1542. Observed: 286.1544.
-
Un d ecyl P iva la te (27f). The reaction was carried out
according to typical procedure C, starting from 26f (0.94 g, 3
mmol), Ni(acac)2 (77 mg, 10 mol %), ethyl crotonate (68 mg,
20 mol %), and Pent2Zn (1.2 mL, 6 mmol). Reaction time was
15 h at -35 °C. The residue obtained after evaporation of the
solvents was purified by flash chromatography (hexanes/ether
15:1) affording the product as a colorless oil (0.45 g, 59%). IR
(neat): 2926, 2855, 1732, 1157 cm-1 1H NMR (CDCl3, 300
.
MHz): δ 3.97 (2H, t, J ) 6.6 Hz), 1.56-1.49 (2H, m), 1.38-
1.18 (16H, m), 1.12 (9H, s), 0.82-0.78 (3H, m). 13C NMR
(CDCl3, 75 MHz): δ 178.5, 64.4, 38.7, 31.9, 29.6, 29.5, 29.4,
29.3, 29.2, 28.6, 27.2, 25.9, 22.6, 14.0. MS (EI): 256 (M+, 0.1),
154 (23), 103 (77), 57 (100). M+ calcd for C16H32O2: 256.2396.
Observed: 256.2402.
4-Non a n oylben zon itr ile (27g). The reaction was carried
out according to typical procedure C, starting from 26g (0.90
g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone (0.36
Deca n en itr ile (25c).42 The reaction was carried out ac-
cording to typical procedure A starting from 23c (1.04 g, 5
mmol), Ni(acac)2 (0.128 g, 10 mol %), and Pent2Zn (2 mL, 10
mmol). Reaction time was 48 h at -25 °C. The residue obtained
after evaporation of the solvents was purified by flash chro-
matography (hexanes/ether 20:1-10:1) affording the product
(42) Yoshida, J .; Itoh, M.; Matsunaga, S.; Isoe, S. J . Org. Chem.
1992, 57, 4877-4882.
(39) Piva, O. Tetrahedron 1994, 50, 13687-13696.
(40) Sharo, T.; Matsumura, Y.; Inoue, K. J . Am. Chem. Soc. 1984,
106, 6075-6076.
(41) (a) Correia, J . Synthesis 1994, 1127-1128. (b) Bergbreiter, D.
E.; Blanton, J . R. J . Org. Chem. 1985, 50, 5828-5833.
(43) (a) Tanner, D. D.; Chen, J . J . J . Org. Chem. 1989, 54, 3842-
3846. (b) Russel, G. A.; Kulkarni, S. V. J . Org. Chem. 1993, 58, 2678-
2685.
(44) Muzart, J .; N’Ait Ajjou, A. Synthesis 1993, 785-787.

3552 J . Org. Chem., Vol. 64, No. 10, 1999
Giovannini et al.
g, 3 mmol), and Pent2Zn (1.2 mL, 6 mmol). Reaction time was
5 h at -35 °C. The residue obtained after evaporation of the
solvents was purified by flash chromatography (hexanes/ether
10:1) affording the products as a white solid (mp 36 °C; 0.59
g, 81%). IR (neat): 2955, 2921, 2872, 2232, 1691, 1467, 837
(2H, q, J ) 7.0 Hz), 3.98 (2H, t, J ) 6.5 Hz), 2.23 (2H, t, J )
7.4 Hz), 1.64-1.53 (4H, m), 1.37-1.27 (2H, m), 1.17 (3H, t, J
) 7.0 Hz), 1.11 (9H, s). 13C NMR (CDCl3, 75 MHz): 178.2,
173.2, 63.9, 60.0, 38.5, 34.0, 28.2, 27.0, 26.8, 25.4, 24.4, 14.1.
MS (EI): 142 (31), 115 (36), 101 (23), 57 (100). Anal. Calcd for
1
cm-1. H NMR (CDCl3, 300 MHz): δ 7.79 (2H, d, J ) 9.0 Hz),
C
13H24O4: C, 63.90; H, 9.90. Found: C, 63.65; H, 10.05.
7.50 (2H, d, J ) 9.0 Hz), 2.73 (2H, t, J ) 9.0 Hz), 1.52-1.42
(2H, m), 1.10-1.00 (10H, m), 0.6 (3H, t, J ) 6.66 Hz). 13C NMR
(CDCl3, 75 MHz): δ 198.6, 139.8, 132.2, 128.2, 117.7, 115.9,
38.6, 31.3, 29.1, 29.0, 28.9, 23.8, 22.4, 13.8. MS (EI): 243 (M+,
3), 145 (100), 130 (52), 102 (30). M+ calcd for C16H21NO:
243.1631. Observed: 243.1624.
Eth yl 7-Oxo-u n d eca n oa te (27m ). The reaction was car-
ried out according to typical procedure C starting from 26c
(0.76 g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone
(0.18 g, 50 mol %), and bis(2-carbethoxyethyl)zinc (6 mmol)
in THF (2.5 mL). Reaction time was 8 h at -35 °C. The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes/ether 10:1) affording the product as
a colorless oil (0.40 g, 58%). IR (neat): 2957, 2935, 1736, 1715,
1180, 1033 cm-1. 1H NMR (CDCl3, 300 MHz): δ 4.04 (2H, q, J
) 7.1 Hz), 2.36-2.29 (4H, m), 2.22 (2H, t, J ) 6.0 Hz), 1.58-
1.44 (6H, m), 1.27-1.15 (7H, m), 0.8 (3H, t, J ) 6.0 Hz). 13C
NMR (CDCl3, 75 MHz): δ 210.8, 173.3, 59.9, 42.2, 42.1, 33.8,
28.4, 25.7, 24.4, 23.1, 22.1, 13.9, 13.5. MS (EI): 186 (11), 129
(59), 125 (54), 101 (31), 85 (97), 69 (49), 97 (100), 29 (75). Anal.
Calcd for C13H24O3: C, 68.38; H, 10.59. Found: C, 68.24; H,
10.65.
Octyl P h en yl Su lfid e (27n ).45 The reaction was carried
out according to typical procedure C, starting from 26l (1.39
g, 5 mmol), Ni(acac)2 (0.128 g, 10 mol %), m-trifluoromethyl-
styrene (0.43 g, 50 mol %), and Pent2Zn (2 mL, 10 mmol).
Reaction time was 2 h at -35 °C. The residue obtained after
evaporation of the solvents was purified by flash chromatog-
raphy (hexanes/ether 35:1) affording the product as a colorless
oil (0.79 g, 71% yield). The NMR data of the product fits the
literature data.45
Decyl P iva la te (27o). The reaction was carried out ac-
cording to typical procedure C, starting from 26m (1.49 g, 5
mmol), Ni(acac)2 (0.128 g, 10 mol %), m-trifluoromethylstyrene
(0.172 g, 20 mol %), and Pent2Zn (2 mL, 10 mmol). Reaction
time was 1 h at -35 °C. The residue obtained after evaporation
of the solvents was purified by flash chromatography (hexanes/
ether 10:1) affording the product as a colorless oil (0.95 g, 78%
yield). IR (neat): 2957, 2928, 2856, 1732, 1157 cm-1. 1H NMR
(CDCl3, 300 MHz): δ 3.97 (2H, t, J ) 6.6 Hz), 1.59-1.49 (2H,
m), 1.33-1.19 (14H, m), 1.12 (9H, s), 0.8 (3H, t, J ) 6.7 Hz).
13C NMR (CDCl3, 75 MHz): δ 178.2, 64.1, 38.4, 31.6, 29.2, 29.0,
28.9, 28.4, 26.9, 25.9, 25.7, 22.4, 13.8. MS (EI): 140 (8), 103
(43), 57 (100). Anal. Calcd for C15H30 O2: C, 74.32, H, 12.47.
Found: C, 74.35; H, 12.64.
6-Ben zoylh exyl P iva la te (27p ). The reaction was carried
out according to typical procedure C, starting from 26b (0.82
g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone (0.18
g, 50 mol %), and bis(3-pivaloxypropyl)zinc (6 mmol) in THF
(2.5 mL). Reaction time was 10 h at -35 °C. The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes/ether 10:1) affording the product as
a yellow oil (0.66 g, 76%). IR (neat): 2935, 2867, 1727, 1688,
1286, 1157 cm-1. 1H NMR (CDCl3, 300 MHz): δ 7.87-7.84 (2H,
m), 7.48-7.33 (3H, m), 3.96 (2H, t, J ) 6.6 Hz), 2.87 (2H, t, J
) 7.2 Hz), 1.74-1.53 (4H, m), 1.36-1.30 (4H, m), 1.10 (9H, s).
13C NMR (CDCl3, 75 MHz): δ 200.0, 178.3, 136.9, 132.7, 128.4,
127.9, 64.1, 38.5, 38.2, 28.7, 28.3, 27.0, 25.5, 24.0. MS (EI):
290 (M+, 1), 120 (100), 105 (95). M+ calcd for C18H26O3:
290.1882. Found: 290.1890.
2-Non a n oylth iop h en e (27h ). The reaction was carried out
according to typical procedure C, starting from 26h (0.84 g, 3
mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone (0.18 g, 50
mol %), and Pent2Zn (1.2 mL, 6 mmol). Reaction time was 8 h
at -35 °C. The residue obtained after evaporation of the
solvents was purified by flash chromatography (hexanes/ether
10:1) affording the product as a yellow oil (0.45 g, 67%). IR
1
(neat): 2955, 2926, 2854, 1664, 1417 cm-1. H NMR (CDCl3,
300 MHz): δ 7.78 (1H, dd, J ) 1.1 Hz, J ) 3.8 Hz), 7.68 (1H,
dd, J ) 1.1 Hz, J ) 5 Hz), 7.20-7.17 (1H, m), 2.96 (2H, t, J )
6.0 Hz), 1.89-1.76 (2H, m), 1.44-1.35 (10H, m), 0.96 (3H, t, J
) 6.75 Hz). 13C NMR (CDCl3, 75 MHz): δ 193.1, 144.3, 133.0,
131.4, 127.8, 39.2, 31.6, 29.2, 29.1, 28.9, 24.6, 22.5, 13.9. MS
(EI): 224 (M+, 4), 126 (100), 111 (95). M+ calcd for C13H20SO:
224.1237. Observed: 224.1235.
7-Oxo-7-p ip er id in oh ep tyl P iva la te (27i). The reaction
was carried out according to typical procedure C, starting from
26i (1.33 g, 5 mmol), Ni(acac)2 (0.128 g, 10 mol %), m-
trifluoromethylstyrene (0.43 g, 50 mol %), and bis(4-pivaloxy-
butyl)zinc (10 mmol) in THF (3 mL). Reaction time was 6 h at
-30 °C. The residue obtained after evaporation of the solvents
was purified by flash chromatography (hexanes/ether 2:8)
affording the product as a yellow oil (0.95 g, 64% yield). IR
(neat): 2935, 2857, 1727, 1645, 1435, 1157 cm-1 1H NMR
.
(CDCl3, 300 MHz): δ 3.97 (2H, t, J ) 6.5 Hz), 3.47 (2H, t, J )
5.35 Hz), 3.32 (2H, t, J ) 5.35 Hz), 2.24 (2H, t, J ) 7.6 Hz),
1.58-1.42 (10H, m), 1.36-1.28 (4H, m), 1.12 (9H, s). 13C NMR
(CDCl3, 75 MHz): δ 178.5, 171.2, 64.2, 46.6, 42.6, 38.7, 33.2,
29.0, 28.4, 27.1, 26.5, 25.7, 25.5, 25.2, 24.5. MS (EI): 113 (15),
95 (100). Anal. Calcd for C17H31NO3: C, 68.65; N, 4.71; H,
10.50. Found: C, 68.53; N, 4.90; H, 10.70.
Eth yl Octa n oa te (27j). The reaction was carried out
according typical procedure C, starting from 26j (1.14 g, 5
mmol), Ni(acac)2 (0.128 g, 10 mol %), m-trifluoromethylstyrene
(0.172 g, 20 mol %), and Pent2Zn (2 mL, 10 mmol). Reaction
time was 4 h at -35 °C. The residue obtained after evaporation
of the solvents was purified by flash chromatography (hexanes/
ether 15:1) affording the product as a colorless oil (0.62 g, 72%).
The NMR data of the product fits the literature data (Aldrich
catalog).
2-Hep tyl-2-m eth yl-1,3-d ith iola n e (27k ). The reaction was
carried out according to typical procedure C, starting from 26k
(1.37 g, 5 mmol), Ni(acac)2 (0.128 g, 10 mol %), m-trifluoro-
methylstyrene (0.172 g, 20 mol %), and Pent2Zn (2 mL, 10
mmol). Reaction time was 1 h at -35 °C. The residue obtained
after evaporation of the solvents was purified by flash chro-
matography (hexanes/ether 30:1) affording the product as a
colorless oil (0.85 g, 78%). IR (neat): 2955, 2925, 1457, 1375,
1
1276 cm-1. H NMR (CDCl3, 300 MHz): δ 3.39-3.25 (4H, m),
7-Oxou n d ecyl P iva la te (27q). The reaction was carried
out according to typical procedure C starting from 26c (0.76
g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone (0.18
g, 50 mol %), and bis(3-pivaloxypropyl)zinc (6 mmol) in THF
(2.5 mL). Reaction time was 8 h at -35 °C. The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes/ether 10:1) affording the product as
a yellow oil (0.55 g, 68%). IR (neat): 2935, 2872, 1728, 1286
1.95-1.89 (2H, m), 1.75 (3H, s), 1.52-1.43 (2H, m), 1.30-1.28
(8H, m), 0.88 (3H, t, J ) 6.7 Hz). 13C NMR (CDCl3, 75 MHz):
δ 67.0, 45.9, 39.7, 32.3, 31.8, 29.8, 29.2, 27.4, 22.6, 14.1. MS
(EI): 218 (M+, 18), 119 (100). Anal. Calcd for C11H22S2: C,
60.49; H, 10.15. Found: C, 60.41; H, 10.37.
Eth yl 6-P iva loxyh exa n oa te (27l). The reaction was car-
ried out according to typical procedure C, starting from 26l
(0.68 g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone
(0.36 g, 1 equiv) and bis(3-pivaloxypropyl)zinc (6 mmol) in THF
(2.5 mL). Reaction time was 4 h at -35 °C. The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes/ether 10:1) affording the product as
a colorless oil (0.44 g, 60%). IR(neat): 2960, 2827, 1732, 1481,
1
cm-1. H NMR (CDCl3, 300 MHz): δ 3.96 (2H, t, J ) 6.6 Hz),
2.35-2.29 (4H, m), 1.59-1.42 (6H, m), 1.33-1.16 (6H, m), 1.11
(9H, s), 0.82 (3H, t, J ) 7.2 Hz). 13C NMR (CDCl3, 75 MHz):
(45) Screttas, C. G.; Screttas, M. M. J . Org. Chem. 1987, 52, 4319-
4327.
1286, 1159, 1035 cm-1
.
1H NMR (CDCl3, 300 MHz): δ 4.04

Ni-Catalyzed Cross-Coupling of Two Csp3 Centers
J . Org. Chem., Vol. 64, No. 10, 1999 3553
211.0, 178.4, 64.2, 42.5, 42.4, 38.7, 28.8, 28.5, 27.2, 26.0, 25.8,
23.6, 22.3, 13.8. MS (EI): 270 (M+, 100), 228 (30). Anal. Calcd
for C16H30O3: C, 71.06; H, 11.18. Found: 70.69; H, 11.36.
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes/ether 15:1) affording the product as
colorless oil (1.06 g, 67% yield). Reaction time was 7 h at -35
°C. IR (neat): 2956, 2930, 1728, 1284, 1157 cm-1.1H NMR
(CDCl3, 300 MHz): δ 4.05 (2H, t, J ) 6.59 Hz), 3.39-3.26 (4H,
m), 1.95-1.89 (2H, m), 1.75 (3H, s), 1.65-1.57 (2H, m), 1.55-
1.48 (2H, s), 1.40-1.30 (6H, m), 1.13 (9H, s). 13C NMR (CDCl3,
75 MHz): δ 178.6, 66.9, 64.4, 45.8, 39.8, 38.8, 32.4, 29.6, 29.1,
28.6, 27.3, 27.2, 25.9. MS (EI): 318 (M+, 1), 119 (100), 57 (20),
41 (10), 28 (20). Anal. Calcd for C16H30O2S2: C, 60.32; H, 9.49.
Found: C, 60.41; H, 9.26.
1-P ip er id in o-1-octa n on e (27s).46 The reaction was carried
out according to typical procedure C, starting from 26i (1.33
g, 5 mmol), Ni(acac)2 (0.128 g, 10 mol %), acetophenone (0.6 g,
5 mmol), and Pent2Zn (2 mL, 10 mmol). Reaction time was 4
h at -30 °C. The residue obtained after evaporation of the
solvents was purified by flash chromatography (hexanes/ether
2:8) affording the product as a pale yellow oil (0.74 g, 70%).
The NMR data of the product fits the literature data.46
5-[(1S,2S,5S)-6,6-Dim et h ylb icyclo[3.1.1]h ep t -2-yl]-1-
p h en yl-1-p en ta n on e (27y). The reaction was carried out
according to procedure C, starting from 26b (0.82 g, 3 mmol),
Ni(acac)2 (77 mg, 10 mol %), acetophenone (0.180 g, 50 mol
%), and bis(myrtanyl)zinc (6 mmol) in THF (2.5 mL). Reaction
time was 8 h at -35 °C. The residue obtained after evaporation
of the solvents was purified by flash chromatography (hexanes/
ether 15:1) affording the product as a colorless oil (0.56 g, 66%).
7-Oxo-7-(2-th ien yl)h ep tyl P iva la te (27t). The reaction
was carried out according to typical procedure C, starting from
26h (0.84 g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), acetophe-
none (0.18 g, 50 mol %), and bis(3-pivaloxypropyl)zinc (6 mmol)
in THF (2.5 mL). Reaction time was 18 h at -35 °C. The
residue obtained after evaporation of the solvents was purified
by flash chromatography (hexanes/ether 10:1) affording the
product as a yellow oil (0.62 g, 70%). IR (neat): 3060, 2955,
IR (neat): 2932, 1687, 1598, 1467, 1219, 748, 734 cm-1 1H
.
1
2862, 1669, 1602, 1255, 1179. H NMR (CDCl3, 300 MHz): δ
NMR (CDCl3, 300 MHz): δ 7.86-7.82 (2H, m), 7.41-7.30 (3H,
m); 2.83 (2H, t, J ) 7.38 Hz), 2.22-2.18 (1H, m), 1.85-1.71
(6H, m), 1.65-1.58 (2H, m), 1.35-1.22 (5H, m), 1.07 (3H, s),
0.88 (3H, s), 0.76-0.67 (1H, m). 13C NMR (CDCl3, 75 MHz): δ
200.1, 137.0, 132.6, 128.3, 127.9, 46.3, 41.5, 41.3, 38.6, 38.4,
37.4, 33.7, 28.1, 27.7, 26.4, 24.5, 23.2, 22.4. MS (EI): 284 (M+,
1), 164 (26), 120 (34), 105 (100). Anal. Calcd for C20H28O: C,
84.45; H, 9.92. Found: C, 84.35; H, 10.07.
7.62 (1H, dd, J ) 3.0 Hz, J ) 1.1 Hz), 7.53 (1H, dd, J ) 5.0
Hz, 1.1 Hz), 7.03-7.00 (1H, m), 3.94 (2H, t, J ) 6.5 Hz), 2.80
(2H, t, J ) 7.3 Hz), 1.70-1.60 (2H, m), 1.58-1.49 (2H, m),
1.36-1.25 (4H, m), 1.08 (9H, s).13C NMR (CDCl3, 75 MHz): δ
192.9, 178.2, 144.3, 133.2, 131.6, 127.9, 64.0, 38.7, 38.5, 28.7,
28.3, 27.0, 25.6, 24.5. MS (EI): 296 (M+, 1), 126 (100), 111
(86), 57 (41). M+ calcd for C16H24SO3: 296.1443. Found:
296.1446.
6-[(1S,2S,5S)]-6,6-Dim eth ylbicyclo[3.1.1]h ep t-2-ylh ex-
yl P iva la te (27z). The reaction was carried out according to
typical procedure C, starting from 26m (0.89 g, 3 mmol), Ni-
(acac)2 (77 mg, 10 mol %), m-trifluoromethylstyrene (0.516 g,
3 mmol), and bis(myrtanyl)zinc (6 mmol) in THF (2.5 mL).
Reaction time was 8 h at -35 °C. The residue obtained after
evaporation of the solvents was purified by flash chromatog-
raphy (hexanes/ether 15:1) affording the product as a colorless
5-(2-Meth yl-1,3-d ith iola n -2-yl)p en tyl P iva la te (27u ).
The reaction was carried out according to typical procedure
C, starting from 26k (1.37 g 5 mmol), Ni(acac)2 (0.128 g, 10
mol %), m-trifluoromethylstyrene (0.43 g, 50 mol %), and bis-
(3-pivaloxypropyl)zinc (10 mmol) in THF (3 mL). Reaction time
was 6 h at -35 °C. The residue obtained after evaporation of
the solvents was purified by flash chromatography (hexanes/
ether 15:1) affording the product as colorless oil (1.01 g, 70%).
IR (neat): 2957, 2931, 1728, 1284, 1157 cm-1.1H NMR (CDCl3,
75 MHz): δ 4.05 (2H, t, J ) 6.51 Hz), 3.39-3.25 (4H, m), 1.96-
1.90 (2H, m), 1.75 (3H, s), 1.70-1.50 (4H, m), 1.44-1.36 (2H,
m), 1.13 (9H, s). 13C NMR (CDCl3, 75 MHz): δ 178.5, 66.7,
64.2, 45.7, 39.8, 38.7, 32.3, 28.5, 27.2, 27.0, 26.1. MS (EI): 119
(100). Anal. Calcd for C14H26S2O2: C, 57.88; H, 9.02. Found:
C, 57.80; H, 9.04.
oil (0.68 g, 74%). IR (neat): 2923, 2858, 1732, 1480, 1159 cm-1
.
1H NMR (CDCl3, 300 MHz): δ 3.97 (2H, t, J ) 6.6 Hz), 2.27-
2.21 (1H, m), 1.88-1.74 (6H, m), 1.56-1.51 (2H, m), 1.37-
1.18 (m, 9H), 1.11 (9H, s), 1.09 (3H, s), 0.91 (3H, s), 0.8-0.76
(1H, m). 13C NMR (CDCl3, 75 MHz): δ 178.2, 64.2, 46.3, 41.45,
41.4, 39.1, 38.52, 38.50, 33.6, 29.4, 29.2, 28.4, 28.1, 27.8, 27.0,
26.4, 25.8. MS (EI): 308 (M+, 0.5), 163 (34), 123 (64), 95 (41),
82 (100). Anal. Calcd for C20H36O2: C, 77.86; H, 11.76. Found:
C, 77.60; H, 11.61.
6-Oxo-6-p ip er id in oh exyl P iva la te (27v). The reaction
was carried out according to typical procedure C, starting from
26i (1.33 g, 5 mmol), Ni(acac)2 (0.128 g, 10 mol %), m-
trifluoromethylstyrene (0.86 g, 1 equiv), and bis(3-pivaloxy-
propyl)zinc (10 mmol) in THF (3 mL). Reaction time was 6 h
at -30 °C. The residue obtained after evaporation of the
solvents was purified by flash chromatography (hexanes/ether
2:8) affording the product as a pale yellow oil (0.96 g, 68%).
5-Meth yl-1-p h en ylh exa n on e (30).23 The reaction was
carried out according to typical procedure C, starting from 26b
(0.82 g, 3 mmol), Ni(acac)2 (77 mg, 10 mol %), acetophenone
(0.36 g, 3 mmol), and i-Pr2Zn (1.5 mL of a 4 M solution in THF,
6 mmol). Reaction time was 5 h at -35 °C. The residue
obtained after evaporation of the solvents was purified by flash
chromatography (hexanes/ether 20:1) affording the product as
a colorless oil (0.37 g, 65%). The ratio 30:31 was 95:5. The
NMR data of the product fits the literature data.23
1
IR (neat): 2937, 2858, 1726, 1635 cm-1. H NMR (CDCl3, 300
MHz): δ 3.98 (2H, t, J ) 6.56 Hz), 3.47 (2H, t, J ) 5.27), 3.32
(2H, t, J ) 5.27 Hz), 2.26 (2H, t, J ) 7.6 Hz), 1.63-1.30 (12H,
m), 1.12 (9H, s). 13C NMR (CDCl3, 75 MHz): δ 178.3, 170.9,
64.0, 46.5, 42.5, 38.5, 33.0, 28.4, 27.0, 26.4, 25.7, 25.4, 24.9,
24.4. MS (EI): 283 (M+, 8), 182 (21), 140 (23), 127 (100). M+
calcd for C16H29NO3: 283.2147. Observed: 283.2144.
7-(2-Meth yl-1,3-d ith iola n -2-yl)h ep tyl P iva la te (27w ).
The reaction was carried out according to typical procedure
C, starting from 26k (1.37 g, 5 mmol), Ni(acac)2 (0.128 g, 10
mol %), m-trifluoromethylstyrene (0.258 g, 30 mol %), and bis-
(5-pivaloxypentyl)zinc (10 mmol) in THF (3 mL).The residue
Ack n ow led gm en t. We thank the DFG (SFB 260
and Leibniz program) for financial support and
Chemetall GmbH (Frankfurt), Degussa AG (Hanau),
Bayer AG (Leverkusen), and BASF AG (Ludwigshafen)
for the generous gift of chemicals.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral data for unknown compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(46) Grieco, P. A.; Clark, D. S.; Withers, G. P. J . Org. Chem. 1979,
44, 2945-2947.
J O982317B