December 1998
SYNLETT
1311
NiCl /CrCl -Mediated Coupling Reaction of Ketones with Alkenyl(or Alkynyl, Aryl) Halides
2
2
Accomplished in the Presence of a Bipyridyl-Type Ligand
Chinpiao Chen*
Department of Medical Technology, Tzu Chi College of Medicine and Humanities, Hualien, 970, Taiwan, Republic of China
Fax 886 3 8574965; chinpiao@cc.tcu.edu.tw
Received 4 September 1998
Abstract: In this work, alkenyl halides (or triflates) and alkynyl (or
aryl) halides are readily coupled with ketones in tetrahydrofuran in the
presence of ligand 1, NiCl and CrCl at room temperature subsequently
2
2
yielding the corresponding allylic alcohols, propargylic alcohols and
benzylic alcohols.
results motivated us to more closely examine the feasibility of the
NiCl /CrCl -mediated coupling reaction between ketones and alkenyl
halides. Ligand 1 was expected to enhance the coupling reaction of
ketones with alkenyl halides at room temperature. First, the ligand 1 was
1
2
2
2
Reacting either alkenyl(or alkynyl, aryl)lithium , or magnesium with
carbonyl compounds facilitates the formation of carbon-carbon bonds.
Unfortunately,
organolithium
and
magnesium
compounds
prepared. Next, it was applied to the NiCl /CrCl -mediated coupling
2
2
indiscriminately add to both aldehyde and ketone groups. In addition,
the alkenyl(or alkynyl, aryl)chromium compounds are readily derived
from alkenyl(or alkynyl, aryl) halides and anhydrous chromium(II)
chloride in N,N-dimethylformamide. Moreover, the organometals add
chemoselectively to aldehydes to produce the corresponding alcohols as
well. However, in the Barbier-like reaction, reacting alkenyl (or alkynyl,
reaction between ketones and alkenyl (or alkynyl, aryl) halides. Under
the current conditions, to our knowledge, the coupling reaction between
ketones and aryl halides has never been reported.
3
4
aryl) halides, and alkenyl triflates with aldehydes facilitates the
preparation of corresponding allylic alcohols, propargylic alcohols and
benzylic alcohols in the presence of nickel(II) chloride and
chromium(II) chloride in N,N-dimethylformamide at room temperature.
Table 1 reveals that the ketone is less reactive and the yield is
insufficient.
Scheme 1
The general procedure is illustrated to synthesize 2-phenyl-3-octen-2-ol
(Scheme 1). A mixture of ligand 1 (1.00 g, 4.0 mmol) and NiCl /CrCl
2
2
(167 mg/333 mg) in tetrahydrofuran (50 mL) was stirred for 1 h at room
temperature. To this mixture was added a solution of acetophenone (120
mg, 1.0 mmol) and 1-iodo-1-hexene (848 mg, 4.0 mmol) in
tetrahydrofuran (10 mL) which was stirred for 11 h at room temperature.
Next, the reaction was quenched by adding water (40 mL) and by
extracting with diethyl ether. The extracts were then dried over
anhydrous magnesium sulfate and concentrated. Finally, the crude
product was purified by column chromatography (ethyl acetate-hexane,
1:50) leading to 2-phenyl-3-octen-2-ol (201 mg, 99% yield).
Table 2 summarizes the applicability of the NiCl /CrCl -mediated
2
2
coupling reaction of ketones and alkenyl(or alkynyl, aryl) halides,
alkenyl triflate by the addition of auxiliary ligand 1. Compared with
Table 1, the yields of the reaction between alkenyl halides and ketones
were significantly improved and the temperature was decreased from
o
50 C to room temperature. According to our results, reacting alkynyl
halides with ketones improves the yields from less than 5% to 27-75%.
In addition, the alkenyl triflates did not react with ketones even when
the reaction mixture was heated to 60 C. In the presence of ligand 1, the
Kishi et. al indicated that the chiral dipyridyls can be used to induce
stereoselectivity in the asymmetric process of the Ni(II)/Cr(II)-mediated
coupling reaction of aldehydes and alkenyl iodides . The coupling
o
5
reactions proceeds at room temperature producing a yield of 32-72%. In
reaction proceeds smoothly in the presence of ligand 1 (10,10-dimethyl-
o
addition, the reaction of aldehydes and bromobenzene is heated to 90 C
2,7
6
5-pyridin-2-yl-6-aza-tricyclo[7.1.1.0 ]undeca-2(7),3,5-triene) with a
substituent at the 6-position. In addition, the homocoupling of alkenyl
halides is effectively suppressed in the presence of these dipyridyls.
producing a yield of 13-31% with some aldolic product. In the presence
of ligand 1, the reactions of ketones and phenyl halides proceeds very
well, producing a yield of 70-94%. Our results further demonstrates that
iodobenzene adds more effectively to ketones than bromobenzene does.
Moreover, a 1:2 mixture of NiCl and CrCl significantly enhances the
2
2
rate of coupling. Under these conditions, even ketones couple with
alkenyl iodides at an appreciable rate.
In the syntheses of natural and non-natural products, the mild reaction
conditions are always preferred in key bond-forming steps. In this study,
the coupling reaction between ketones and alkenyl halides provides a
Results obtained from the Barbier-like reaction indicate the limited
applicability of the coupling reaction between ketones and alkenyl
halides due to the less reactive and insufficient yield. In addition, Kishi
et al. demonstrated that the ligand 1 can enhance the coupling reaction,
even when ketones couple with iodoolefins at an appreciable rate. These
sufficient yield in the presence of ligand 1 and NiCl /CrCl at room
2
2
temperature. Moreover, under these conditions, the coupling reaction
between ketones and aryl halides furnishes a satisfying yield.