New efficient nickel- and palladium-catalyzed cross-coupling reactions mediated by tetrabutylammonium iodide

Article abstract of DOI:10.1021/ol9907872

(formula presented) The addition of Bu₄NI has been found to accelerate the palladium(0)-catalyzed cross-coupling between benzylic zinc bromides and aryl or alkenyl triflates. Remarkably, it further allows a new nickel(0)-catalyzed cross-coupling between functionalized benzylic zinc reagents and primary alkyl iodides leading to polyfunctional products in good yields under mild reaction conditions (0-20 °C, 4-16 h).

Full text of DOI:10.1021/ol9907872

ORGANIC
LETTERS
1
999
Vol. 1, No. 9
323-1326
New Efficient Nickel- and
Palladium-Catalyzed Cross-Coupling
Reactions Mediated by
1
Tetrabutylammonium Iodide
†
†
‡
,†
Michael Piber, Anne Eeg Jensen, Mario Rottl a1 nder, and Paul Knochel*
Institut f u¨ r Organische Chemie, Ludwig-Maximilians-UniVersit a¨ t M u¨ nchen,
Butenandtstrasse 5-13, Haus F, 81377 M u¨ nchen, Germany, and H. Lundbeck A/S,
OttiliaVej 9, DK-2500 Valby, Denmark
paul.knochel@cup.uni-muenchen.de
Received July 6, 1999
ABSTRACT
4
The addition of Bu NI has been found to accelerate the palladium(0)-catalyzed cross-coupling between benzylic zinc bromides and aryl or
alkenyl triflates. Remarkably, it further allows a new nickel(0)-catalyzed cross-coupling between functionalized benzylic zinc reagents and
primary alkyl iodides leading to polyfunctional products in good yields under mild reaction conditions (0−20 °C, 4−16 h).
Transition metal-catalyzed cross-coupling reactions beetween
C sp centers have been extensively studied and several
of dialkylzincs or arylzinc derivatives in the presence of m-
or p-trifluoromethylstyrene or 4-fluorostyrene (1) as promotor
proceeds under mild conditions and in satisfactory yields.
Attempts to perform cross-coupling reactions between ben-
zylic zinc bromides and alkyl iodides in the presence of the
nickel catalytical system failed completely, whereas sluggish
reactions were observed between benzylic zinc derivatives
and various aryl triflates in the presence of palladium(0).
What attracted our attention was the use of ammonium salts
2
1
2
3
efficient Pd-, Ni-, or Fe-catalyzed reactions are now
available. Recently, we have investigated cross-coupling
3
4
3
between two C sp centers as well as between C sp and C
sp centers and found that Ni(acac) -catalyzed cross-coupling
2
2
5
†
Ludwig-Maximilians-Universit a¨ t M u¨ nchen.
H. Lundbeck A/S.
‡
(1) Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang, P.
J., Eds.; Wiley-VCH: Weinheim, 1998.
2) (a) Kumada, M. Pure Appl. Chem. 1980, 52, 669. (b) Luh, T.-Y.
6
for accelerating Sonogashira cross-couplings, and we have
(
Acc. Chem. Res. 1991, 24, 257. (c) Sengupta, S.; Leite, M.; Raslan, D. S.;
Quesnelle, C.; Snieckus, V. J. Org. Chem. 1992, 57, 4066. (d) Indolese, A.
F. Tetrahedron Lett. 1997, 38, 3513. (e) Shirakawa, E.; Yamasaki, K.;
Hiyama, T. Synthesis 1998, 1544. (f) Lipshutz, B. H.; Kim, S.-K.; Mollard,
P.; Blomgren, P. A.; Stevens, K. L. Tetrahedron 1998, 54, 6999. (g) Sofia,
A.; Karlstr o¨ m, E.; Itami, K.; B a¨ ckvall, J.-E. J. Org. Chem. 1999, 64, 1745.
found that these additives allow, for the first time, the Ni-
(5) Giovanni, R.; Knochel, P. J. Am. Chem. Soc. 1998, 120, 11186.
(6) (a) Wright, S. W.; Hageman, D. L.; McClure, L. D. J. Org. Chem.
1994, 59, 6095. (b) Nguefack, J.-F.; Bollit, V.; Sinou, D. Tetrahedron Lett.
1996, 33, 5527. (c) Powell, N. A.; Rychnovsky, S. D. Tetrahedron Lett.
1996, 37, 7901. (d) Albanese, D.; Landini, D.; Penso, M.; Petricci, S. Synlett,
1999, 199. (e) Nakamura, K.; Okubo, H.; Yamaguchi, M. Synlett 1999,
549. (f) Herrmann, W. A.; Brossmer, C.; Reisinger, C.-P.; Riedermeier, T.
H.; O¨ fele, K.; Beller, M. Chem. Eur. 1997, 3, 1357.
(
3) (a) Cahiez, G.; Marquais, S. Pure Appl. Chem. 1996, 68, 53. (b)
Cahiez, G. Synthesis 1998, 1199.
4) (a) Giovanni, R.; St u¨ demann, T.; Dussin, G., Knochel, P. Angew.
(
Chem., Int. Ed. Engl. 1998, 37, 2387. (b) Giovanni, R.; Knochel, P. J. Org.
Chem. 1999, 64, 3544.
1
0.1021/ol9907872 CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/02/1999

catalyzed cross-coupling between various aryl and alkenyl
7
8
triflates and benzylic zinc reagents was substantially
accelerated.
Table 1. Optimization of the Reaction Conditions for the
Cross-Coupling between Benzylzinc Bromide and the Aryl
Triflate (3a)
In preliminary experiments, we have investigated the
palladium-catalyzed cross-coupling between benzyl zinc
bromide (2a) and 4-chlorophenyl triflate (3a) in the presence
of palladium bis(dibenzylideneacetone) (Pd(dba)
2
,7 mol %)
and diphenylphosphinoferrocene (dppf, 7 mol %) in THF at
9
6
0 °C (Scheme 1). In the absence of additive almost no
Scheme 1
reaction occurs after a reaction time of 1 h. In the presence
of tetrabutylammonium fluoride or perchlorate as well as
CsI little of the cross-coupling product 4a was observed.
Better results are obtained with LiI and both Bu
NBr give 23-24% yield of 4a after only 1 h of reaction
time. The amount of Bu NI added is also of importance for
the reaction rate. Thus, a conversion of 2.4% is obtained
with 0.1 equiv of Bu NI. With 1.0 equiv, 38% of 4a is
4 4
NI and Bu -
4
4
catalyzed cross-coupling between polyfunctional benzylic
zinc reagents and functionalized alkyl iodides. Also, the Pd-
formed after a reaction time of 1.5 h, whereas with 3.0 equiv,
a conversion of 90% is obtained (Scheme 1 and Table 1).
Table 2. Pd(0)-Catalyzed Cross-Coupling between Benzylic or Alkyl Zinc Halides and Alkenyl or Aryl Triflates in the Presence of
Bu NI
4
1324
Org. Lett., Vol. 1, No. 9, 1999

Table 3. Ni(0)-Catalyzed Cross-Coupling between Benzylic Zinc Bromides and Primary Alkyl Iodides in the Presence of 1c and
Bu NI
4
Thus, in the presence of 3 equiv of Bu
4
NI, efficient cross-
NI led to reaction times between 20 and 30 h. Further trials
with Bu NBr showed that the initial reaction rate slows down
faster than in the case of Bu NI, leading to slighty longer
reaction times. As indicated above, benzylic zinc reagents
were found to be unreactive in nickel-catalyzed cross-
coupling with primary alkyl iodides of type 5. We found
coupling reactions could be realized with a range of aryl
and alkenyl triflates (Table 2). Remarkably the reaction can
be extended to functionalized alkylzinc iodides1 without
the extensive formation of homocoupling side products. In
4
4
,10
1
1
all cases, the reaction was complete within 6 h at 60 °C.
Comparative experiments performed in the absence of Bu
4
-
4
that in the presence of Bu NI (3 equiv) and 1 as promotor
(
(
7) Ritter, K. Synthesis 1993, 735.
8) Berk, S. C.; Yeh, M. C. P.; Jeong, N.; Knochel, P. Organometallics
(i) Preparation of Benzylic Zinc Bromide (2e). A 25-mL flask charged
with cut zinc foil (1.5 g, 22.5 mmol) and a stirring bar was flame-dried
and flushed with argon. THF (1 mL) and 1,2-dibromoethane (400 mg, 2.3
mmol) were added, and the zinc was activated by heating to reflux, then
allowing to cool. This procedure was repeated until foam no longer occurred
as a result of heating. The mixture was cooled to 0 °C before adding
3-cyanobenzyl bromide (1.8 g, 7.5 mmol) in THF (5 mL) dropwise (0.1
drop/s). The mixture was keept at 0 °C until the reaction had completed as
checked by GC (∼2 h). The solution was concentrated in vacuo to 2.5 M
before use. (ii) Preparation of 5-[3-Cyanophenyl]pentyl Phenyl Ketone
(6f). A dried 10-mL two-neck flask was charged with Ni(acac)2 (77 mg,
0.3 mmol). Dry THF (2 mL), NMP (1 mL), 4-iodobutyl phenyl ketone 5a
(820 mg, 3 mmol), 4-fluorostyrene (1) (74 mg, 0.6 mmol), and Bu4NI (3.3
g, 9 mmol) were successively added at room temperature. The mixture was
cooled to -35 °C before slowly adding a solution of 3-cyanobenzyl zinc
bromide (2.5 M, 7.5 mmol). The reaction mixture was then allowed to warm
to 0 °C and after 1 h to 10 °C. The reaction was complete after 16 h as
checked by GC. The reaction mixture was worked up as usual and extracted
with diethyl ether (4 × 70 mL). The combined organic phases were dried
(MgSO4) before evaporating the solvents in vacuo. Flash chromatography
on silica gel (pentane/diethyl ether 20:1) furnished the cross-coupling product
6f as pale yellow crystals (582 mg, 74%).
1
990, 9, 3053.
9) Klement, I.; Rottl a¨ nder, M.; Tucker, C. E.; Majid, T. N.; Knochel,
P.; Venegas, P.; Cahiez, G. Tetrahedron 1996, 52, 7201.
10) (a) Negishi, E.; Valente, L. F.; Kobayashi, M. J. Am. Chem. Soc.
980, 102, 3298. Kobayashi, M.; Negishi, E. J. Org. Chem. 1980, 45, 5223.
b) Negishi, E. Acc. Chem. Res. 1982, 15, 340. (c) Tamaru, Y.; Ochiai, H.;
Nakamura, T.; Yoshida, Z. Tetrahedron Lett. 1986, 27, 955.
11) By using nonaflates (ArONf) even faster reactions were observed;
(
(
1
(
(
this observation is consistent with earlier results: Rottl a¨ nder, M.; Knochel,
P. J. Org. Chem. 1998, 63, 203.
(
12) Typical Procedure. (a) Palladium-Catalyzed Cross-Coupling.
Preparation of 4-(4-Ethyloxycarbonylphenyl)butyl Pivalate (4g). The
aryl triflate 3d (299 mg, 1.00 mmol), Pd(dba)2 (40 mg, 0.07 mmol), dppf
38 mg, 0.07 mg), and Bu4NI (1.11 g, 3.00 mmol) were dissolved in THF/
NMP (1.5 mL, 1:1). To this mixture was added organozinc halide 2c (1.45
mL, 1.60 mmol, 1.1 M in THF). The reaction mixture was stirred at 60 °C
for 4 h. The mixture was cooled to room temperature and quenched as
usual. The crude product was purified by flash chromatography (silica gel,
pentane/ethyl acetate 95:5) to give 282 mg (0.92 mmol, 92%) of the desired
product as a clear, colorless oil. (b) Nickel Catalyzed Cross-Coupling.
(
Org. Lett., Vol. 1, No. 9, 1999
1325

(
0.2 equiv) efficient cross-coupling reactions were now
(ketone, ester, nitrile, thioether) both in the benzylic zinc
reagent and in the alkyl iodide. In summary, the addition of
Bu NI significantly accelerates the Pd(0)-catalyzed cross-
4
3
3
obtained leading to the desired C sp -C sp cross-coupling
products of type 6 in good yields (Scheme 2 and Table 3).
coupling between benzylic zinc bromides and alkenyl or aryl
triflates. It allows a new and efficient Ni(0)-catalyzed cross-
coupling between alkyl iodides and benzylic zinc reagents.
Scheme 2
4
Further application of the dramatic effect of Bu NI in cross-
coupling reactions as well as some mechanistic aspects of
this acceleration are currently investigated in our laborato-
1
2
ries.
Acknowledgment. We thank the Leibniz program and
the BMBF (03D00562), BASF AG for financial support
A.E.J. thanks L’Or e´ al (Paris, France) for a fellowship.
Supporting Information Available: Experimental pro-
cedures and full characterization for compounds 4a-i and
6
a-f. This information is available free of charge via the
Internet at http://pubs.asc.org.
The reaction is complete within a few hours at 0-20 °C
and importantly tolerates a range of functional groups
OL9907872
1326
Org. Lett., Vol. 1, No. 9, 1999