A novel C-C single bond formation by use of ketones, alkylmagnesium bromide, and low-valent vanadium in the presence of a catalytic amount of molecular oxygen

Full text of DOI:10.1021/jo9610725

6094
J . Org. Chem. 1996, 61, 6094-6095
Ta ble 1. Red u ctive Cou p lin g Rea ction Med ia ted by a
A Novel C-C Sin gle Bon d F or m a tion by
Use of Keton es, Alk ylm a gn esiu m Br om id e,
a n d Low -Va len t Va n a d iu m in th e P r esen ce
of a Ca ta lytic Am ou n t of Molecu la r Oxygen
VCl2(tm ed a )2-O2 System a
Yasutaka Kataoka,* Hiroaki Akiyama,
Isamu Makihira, and Kazuhide Tani*
Department of Chemistry, Faculty of Engineering Science,
Osaka University, Toyonaka, Osaka 560, J apan
Received J une 7, 1996
New methodologies for C-C bond formation mediated
by transition metal complexes are of considerable interest
in the fields of both organic synthesis and organometallic
chemistry.1 The pinacol coupling reaction is one of the
most useful C-C bond-forming reactions, based on car-
bonyl compounds and mediated by low-valent early
transition metals.2 Although the reductive dehydroxy
coupling of alcohols has also proven to be an efficient
method for forming C-C bonds,3,4 examples of this
reaction beyond those using low-valent titanium3 and
niobium4 are rare. Different from pinacol coupling, this
reaction makes a C-C single bond with accompanying
C-O bond cleavage. In order to remove oxygen from a
C-O single bond without an accompanying dehydration,
the strong oxophilicity of low-valent early transition
metals is utilized. Herein we report a new C-C single
bond-forming reaction by reductive coupling mediated by
a system comprised of MeMgBr, low-valent vanadium,
and a catalytic amount of O2.
resulting reaction mixture was heated under reflux in
the presence of O2 (0.2 equiv) to give a coupling product
1a in 89% isolated yield along with tertiary alcohol 2a
in 11% isolated yield. The coupling product 1a can be
considered to be obtained by homocoupling of an inter-
mediate, alkoxyvanadium species A, with accompanying
C-O bond cleavage, while the alcohol 2a was derived
from the hydrolysis of A or by the Grignard reaction. A
catalytic amount of O2 is essential for the reductive
coupling. Without O2 (under Ar atmosphere) the reduc-
tive coupling did not proceed at all. An excessive amount
of O2 also prevented the coupling reaction.
The representative results of the reductive coupling
starting from several ketones are summarized in Table
1. When propiophenone or acetophenone was employed
as the starting ketone, the coupling product was obtained
in moderate to good yield. Although the easy cleavage
of the C-O bond at the benzylic position was observed,
aliphatic ketones did not afford the corresponding cou-
pling product at all under similar reaction conditions (run
9). When MeMgBr or MeLi was used as an alkylating
reagent, no other product besides the coupling product
and the tertiary alcohol was obtained. When EtMgBr,
C3H5MgBr, or nBuLi was used, the isolated yield of the
coupling product 1 decreased compared to that obtained
with MeMgBr as the alkylating reagent. The coupling
product derived from propiophenone and PhMgBr was
easily transformed into a mixture of 1,1-diphenyl-1-
propene and 1,1-diphenylpropane by homolytic cleavage
of the C-C bond having four phenyl groups of the initial
product (run 6).6 In runs 1 and 8, since the same alkoxy
magnesium bromide was produced from the combination
of propiophenone and MeMgBr or of acetophenone and
EtMgBr, it was expected the same alkoxy vanadium
would be produced as an intermediate in the reaction
We have established that the combination of an alkyl-
ating reagent, VCl2(tmeda)2 [tmeda ) N,N,N′,N′-tetra-
methylethylenediamine],5 and a catalytic amount of O2
does indeed efficiently induce the reductive dimerization
of alcoholates, derived from ketones and an alkylating
reagent, with accompanying C-O bond cleavage, provid-
ing a coupling product with a C-C single bond. For
example, propiophenone was first reacted with methyl-
magnesium bromide (1.0 equiv) in THF and then treated
with VCl2(tmeda)2 (1.0 equiv) at 20 °C for 1 h. The
(1) (a) Advances in Metal-Organic Chemistry; Liebeskind, L. S., Ed.;
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A.; Hegedus, L. S. In Comprehensive Organometallic Chemistry II;
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Oxford, 1995; Vols. 11-12.
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B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, Chapter
2.6. (b) Cintas, P. Activated Metals in Organic Synthesis; CRC Press:
Florida, 1993; pp 130-139.
(3) Review: Lai, Y.-H. Org. Prep. Proced. Int. 1980, 12, 363.
(4) Sato, M.; Oshima, K. Chem. Lett. 1982, 157.
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S.; Smeets, W. J . J .; Spek, A. L. Inorg. Chem. 1990, 29, 1302.
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S0022-3263(96)01072-9 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 18, 1996 6095
Ta ble 2. Sever a l Va n a d iu m Sp ecies Med ia ted Red u ctive
Cou p lin g Rea ction sa
can oxidize vanadium(II) species A to a higher-valent
vanadium species B which may act also as a catalyst for
the deoxycoupling.
Next, we examined the effect of several higher-valent
vanadium species on the coupling reaction (Table 2).
When a vanadium(III) complex, VCl3(thf)3, was employed
instead of the VCl2(tmeda)2-O2 system, the coupling
reaction also occurred to some extent, but the isolated
yield was much lower (run 1 of Table 2 vs run 1 of Table
1). Addition of O2 into the VCl3(thf)3 system did not affect
the result seriously (run 2). In a system employing a
vanadium(IV) complex, the VCl4 or VCl4-O2 system, the
â-elimination of the oxometal species from the alkoxy
complexes occurred instead of the coupling reaction (run
3, 4). It was found that the vanadium(III) or vana-
dium(IV) species had a similar effect to that of O2 or allyl
bromide. A combination system of VCl2(tmeda)2 and a
catalytic amount of VCl3(thf)3 or VCl4 afforded the
coupling product 1a in good isolated yield just as the
VCl2(tmeda)2-O2 system did (run 5, 6). In a VCl2-
(tmeda)2-O2 system, a catalytic amount of the vana-
dium(III) or vanadium(IV) species10 should be produced
and their collaboration11 with a low-valent vanadium(II)
complex having higher reduction power and oxo-
philicity12-14 would induce the C-O cleavage to promote
the coupling reaction. The unsuccessful coupling reaction
in pure O2 atmosphere indicated that the vanadium(II)
species is requisite for the present deoxygenative cou-
pling. It has been reported that reaction of VCl3(thf)3
with RMgBr gave the vanadium(II) and vanadium(IV)
species by disproportionation.15 Thus, in the VCl3(thf)3
system (run 1) some vanadium(II) species would be also
produced by disproportionation of the vanadium(III)
species, and the coupling product 1a was obtained in 58%
isolated yield.
yield/%b
run
vanadium species
VCl3(thf)3
VCl3(thf)3 + 0.2 O2
VCl4
VCl4 + 0.2 O2
VCl2(tmeda)2 + 0.2 VCl3(thf)3
VCl2(tmeda)2 + 0.2 VCl4
1a c
2a
1
2
3
4
5
6
58
56
0
22
22
26d
58d
6
0
91
88
2
a
Propiophenone (1.0 equiv), MeMgBr (1.0 equiv), and vanadium
species (1.0 equiv) were employed. Isolated yield. c meso:dl ) 1:1.
b
d
A mixture of 2-phenyl-1-butene and 2-phenyl-2-butene was
obtained in 20% (run 3) and 23% (run 4) isolated yield.
mixture; however, the yield of the coupling product in
run 8 was very poor compared to that in run 1. The
reason for the difference in yield is not clear at the
moment.
The cleavage of the C-O bond at the allylic position
also proceeded similarly (run 11). Although a low-valent
titanium3 or niobium4 is capable of carrying out the
reductive coupling of allyl or benzyl alcohol, neither is
effective in our system for the cleavage of the C-O bond
of alcoholates. When low-valent titanium or niobium was
employed instead of a low-valent vanadium in our
system, a tertiary alcohol and/or its dehydrogenated
product was mainly obtained.
7,8
In order to clarify the effect of the added O2 other
initiators for this deoxygenative coupling reaction were
also examined. In the course of our study on the
deoxygenative allylation of ketones mediated by a com-
bination of vanadium(II) and allyl bromide we found a
similar coupling product to 1a was obtained as a byprod-
uct.9 Thus, at first, a catalytic amount of allyl bromide
(0.1 equiv) instead of O2 in eq 1 was added after the
formation of alkoxyvanadium A. The same coupling
product 1a was obtained in 91% isolated yield along with
a small amount of the allylation product 3 and the alcohol
2a (eq 2). As the amount of allyl bromide increased, the
yield of the coupling product 1a decreased gradually
while the amount of 3 increased. With 4 equiv of allyl
bromide, 1a was obtained in 50% isolated yield along
with 3 in 46% isolated yield.
Different from conventional reductive coupling reac-
tions such as the McMurry coupling, the present method
forms a C-C single (instead of a double) bond and yields
a product which contains components derived from the
ketone and a Grignard reagent in a one-pot reaction. The
collaboration of both a low-valent vanadium(II) species
and a higher-valent vanadium species produced from
vanadium(II) and a catalytic amount of O2 should induce
the removal of oxygen from the C-O bond.
Ack n ow led gm en t. This work was supported by the
Ciba-Geigy Foundation (J apan) for the Promotion of
Science and by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Science, Sports, and
Culture, J apan.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for all compounds (4 pages).
J O9610725
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We have reported that an alkoxy vanadium species,
Ph(Me)(Et)COVLn′(allyl) B, is postulated as a reaction
intermediate for the allylation.9 That is, allyl bromide
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