Copper(I)-catalyzed cross-coupling reaction of acylzirconocene complexes with allylic and/or propargylic halides

Article abstract of DOI:10.1016/S0040-4039(99)02015-8

Efficient cross-coupling reaction of acylzirconocene chloride with allylic and/or propargylic halides was attained by utilizing a catalytic amount of a Cu(I) salt to give allylic and/or allenic ketones, respectively, in good yields. The mild Cu(I)-catalyzed reaction of acylzirconocene chloride offered an alternative protocol for the generation of an 'unmasked' acyl anion.

Full text of DOI:10.1016/S0040-4039(99)02015-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 109–112
Copper(I)-catalyzed cross-coupling reaction of acylzirconocene
complexes with allylic and/or propargylic halides
Yuji Hanzawa,∗ Kensuke Narita and Takeo Taguchi ∗
School of Pharmacy, Tokyo University of Pharmacy and Life Science 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 22 September 1999; revised 18 October 1999; accepted 22 October 1999
Abstract
Efficient cross-coupling reaction of acylzirconocene chloride with allylic and/or propargylic halides was attained
by utilizing a catalytic amount of a Cu(I) salt to give allylic and/or allenic ketones, respectively, in good yields.
The mild Cu(I)-catalyzed reaction of acylzirconocene chloride offered an alternative protocol for the generation of
an ‘unmasked’ acyl anion. © 1999 Elsevier Science Ltd. All rights reserved.
Keywords: zirconium; zirconium compounds; coupling reactions; copper catalyst.
The cross-coupling reaction of an acylmetal species with organic halides has attracted attention for
the synthesis of the unsymmetrical ketone derivatives. However, the instability and/or toxicity of the
starting acylmetal species sometimes restricts its practical use for the synthesis.1 Our recent studies2
on the reactivity of the stable acylzirconocene chloride complex 1,3 which is easily accessible through
hydrozirconation of alkene or alkyne with Cp2Zr(H)Cl (Schwartz reagent)4 and subsequent insertion of
carbon monoxide, have indicated a promising use of 1 as an ‘unmasked’ acyl anion donor (Scheme 1).
In these studies, the Pd-catalyzed cross-coupling reaction with organic halides showed the usability of 1
for the preparation of unsymmetrical ketones.2c
However, in the Pd-catalyzed coupling reactions of 1 with allylic halides and/or acetate, the puri-
fication of the coupling product, β,γ-unsaturated ketone, was sometimes hampered by the formation
of a side product, α,β-unsaturated ketone, which is derived from the isomerization of the β,γ-double
bond. For practical purposes, exclusive formation of the β,γ-unsaturated ketones is desirable. In this
communication, we describe Cu(I)-catalyzed cross-coupling reactions of 1 with allylic and propargylic
halides under mild reaction conditions. Reactions of the acylzirconocene chlorides 1 [R; Ph(CH2)4 (1a)
or R; (E)-Ph(CH2)2CH=CH (1b)] with allyl halides in the presence of a catalytic amount (10 mol%) of
Cu(I) in DMF or THF were completed within 1 h at 0°C to give acyl–allyl coupled products 2 in good
yields, and no isomerized side product 3 was obtained (Eq. (1)). The results are listed in Table 1. Most of
the examined Cu(I) salts except CuBr·SMe2 (entry 6) can be used as an efficient catalyst. Allyl tosylate
is also an excellent reactant in the present reaction (entry 4) while allyl acetate is not. Not only 1a but also
∗
Corresponding authors. Tel: +81 426 76 3274; fax: +81 426 76 3257; e-mail: hanzaway@ps.toyaku.ac.jp (Y. Hanzawa)
0040-4039/00/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02015-8
tetl 15943

110
Scheme 1. Reactions of acylzirconocene chloride 1 as an ‘unmasked’ acyl anion
α,β-unsaturated acylzirconocene 1b gave 2 in a good yield (entry 9). Thus, the mild reaction conditions
of Cu(I)-catalyzed coupling reactions of 1 compared to the previously reported Pd-catalyzed reactions2c
exert a desirable influence on the formation of 2.
(1)
Table 1
Cu(I)-catalyzed coupling reaction of 1 with allyl compounds
Substituted allylic bromides also reacted with 1 under identical conditions to give a mixture of
regioisomers (4 and 5) (Eq. (2) and Table 2). In the reaction of prenyl bromide, it required a longer
reaction time (10 h) for the completion of the reaction (entries 1 and 2). Reactions of propargyl bromide
and/or tosylate derivatives 6 with 1 afforded allenyl ketone derivatives 7 as the sole product, and propargyl
ketone 9 was not detected in the reaction mixture (Eq. (3)).

111
(2)
Table 2
Cu(I)-catalyzed coupling reaction of 1a with substituted allylic halides
(3)
It is interesting to note that the utilization of an increased amount (3 equiv.) of 1a versus 6 gave a
significant amount of 1,4-dicarbonyl compound 8 together with 7 (entry 2, Table 3). The observation that
the independent reaction of 7 (R0=H) with 1a under identical conditions afforded 8 in 59% yield indicates
Table 3
Cu(I)-catalyzed coupling reaction of 1 with propargylic compounds

112
the Cu(I)-catalyzed Michael addition of 1a to 7.5 The formation of 7 as the sole product was attained by
utilizing an excess amount (2 equiv.) of propargyl bromide versus 1 (entries 3–7). The attempted reactions
of 1 with alkyl, vinyl, homoallyl and aryl halides failed to yield the coupling products. 6
Although the exact role of the Cu(I)-catalyst in the present reaction is, as yet, unclear, it has
been reported that the transmetalation of an acyl group from zirconium to aluminum occurs to yield
acylaluminum.7 It has also been reported that the transmetalation of an alkyl or vinyl group from
zirconium to copper has been applied to carbon–carbon bond formations.8 Thus, in the present reactions,
the transmetalation of the acyl group from zirconium to copper giving an ‘acyl–Cu’ species as a transient
species might have been involved (Eq. (4)).9
(4)
In summary, this paper describes an efficient coupling reaction of acylzirconocene chlorides with allyl
and/or propargyl halides in the presence of a Cu(I) salt. The methodology opened further possibility of
acylzirconocene chloride as an ‘unmasked’ acyl anion. Further studies towards an actual reactive species
of this process are under current investigation in our laboratory.
General experimental procedure: 1 (1.5 mmol) in DMF or THF (10 mL) was prepared through: (i)
a reaction of 4-phenyl-1-butene (1.5 mmol) and Cp2Zr(H)Cl (1.5 mmol) in CH2Cl2 (5 mL) at ambient
temperature for 0.5 h followed by the insertion of CO (stirring at ambient temperature for 2 h using a
CO balloon); (ii) concentration of the solvent to dryness in vacuo and addition of THF or DMF. To the
solution of 1 was added a solution of allylic or propargylic halide (1 mmol) in THF or DMF (2 mL) at
0°C. After addition of Cu(I) (10 mol%) at 0°C, the mixture was stirred for 1–10 h at the same temperature.
The reaction mixture was filtered through a short dry silica gel pad and the filtrate was concentrated to
dryness to give a crude oil. Purification by silica gel column chromatography (hexane:ethyl acetate) gave
a pure product.
References
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6494. (b) Wipf, P.; Xu, W.; Smitrovich, J. H; Lehmann, R.; Venanzi, L. M. Tetrahedron 1994, 50, 1935. (c) Wipf, P.; Takahashi,
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6. Cu(I)-catalyzed reactions of acetyl halides with 1a gave enol acetate as a mixture of E,Z-isomeric forms. This suggests the
generation of a metal enolate species via oxymetal carbene and subsequent 1,2-migration of the hydrogen atom. Similar
reaction has been observed in the generation of acyl zinc from acyl chloride and Zn in ethyl acetate. Chemla, F.; Normant, J.
F. Tetrahedron 1997, 53, 17265.
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107, 4551. (b) Seyferth, D.; Hui, R. C. Tetrahedron Lett. 1986, 27, 1473. (c) Lipshutz, B. H.; Elworthy, T. R Tetrahedron Lett.
1990, 31, 477.