Solubilized zirconocene dihydride as a promotor of alkene coupling reactions

Article abstract of DOI:10.1016/S0040-4039(00)01468-4

The THF-soluble bis(methoxyethyl)zirconocene dihydride 3 displayed novel reactivity patterns and was used to reductively couple alkenes, dienes, and enynes. A plausible mechanism involves the formation of a 14-electron zirconium(II) and zirconacyclopentane species. (C) 2000 Published by Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01468-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8237–8241
Solubilized zirconocene dihydride as a promotor of alkene
coupling reactions
Peter Wipf* and Xiaodong Wang
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
Received 6 July 2000; revised 24 August 2000; accepted 25 August 2000
Abstract
The THF-soluble bis(methoxyethyl)zirconocene dihydride 3 displayed novel reactivity patterns and was
used to reductively couple alkenes, dienes, and enynes. A plausible mechanism involves the formation of
a 14-electron zirconium(II) and zirconacyclopentane species. © 2000 Published by Elsevier Science Ltd.
Keywords: zirconocene dihydride; zirconium(II); reductive cyclization; intra- and intermolecular coupling.
The reductive coupling of two unsaturated substrates can be mediated by low-valent metals
1
from the two extremes of the transition series (Ni, Ti, Zr). The intermediate metallacycle can
2
be transformed into a variety of useful products. The reductive coupling of alkenes mediated by
a zirconocene(II) equivalent provides fairly stable zirconacycles, which react with protons,
3
4
5
6
7
8
halogens, isocyanides, oxygen, carbon monoxide, ketones and other electrophiles to afford
9
mono- and bicyclic organic compounds with high regio- and stereoselectivities. Ligands and
ligand substituents strongly effect the reactivity of zirconocene complexes. The modification of
the cyclopentadiene ring of polymeric and insoluble zirconocene dihydride changes its solubility
and promotes new reaction pathways. While Cp ZrH is essentially unreactive toward alkenes
2
2
5
and alkynes, the reaction of (h -C Me )ZrH with propyne to form monocyclic zirconacy-
5
0
5
2
1
clopentenes was reported in 1985. In this paper, we report the reaction of alkenes with
zirconocenes containing alkyl ether attachments to the Cp ring that increase solubility and
reactivity of the early transition metal complex and promote a reaction manifold reminiscent of
zirconocene(II) chemistry.
*
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01468-4

8238
Scheme 1. Preparation of bis(methoxyethyl)zirconocene dihydride 3
11
After reaction of the known zirconocene dichloride 1 with aniline and water, the resulting
oxo-bridged compound 2 was reduced with 1 equiv. of LiAlH to give the zirconocene
4
1
2
1
dihydride complex 3 (Scheme 1). As expected, the H NMR of 3 showed two resonances for
the hydride protons at 4.07 and −2.86 ppm. Treatment of terminal alkenes, dienes, and
enynes with 3 in THF led to the formation of acyclic and cyclic coupling products in
moderate to high yields after quenching with Br , D O or H O (Table 1). For 1-octene,
2
2
2
different solvents such as toluene, 1,2-dichloroethane, 1,4-dioxane, N-methylmorpholine, and
1
0% oxetane/THF were tested, but THF was found to be superior. In the conversion of
1
,7-octadiene, additives such as PPh , AsPh , and P(OPh) also failed to improve cyclization
3
3
3
yields. Only products derived from coupling at the internal alkene positions could be
observed for substrates 4, 6, and 8 (entries 1–3). cis-Cyclohexane 11 was formed exclusively
in the coupling of a,v-diene 10 after quenching with Br (entry 4). Homoallylic diamine 12
2
provide the tetrasubstituted cyclohexyl diamine 13 as a single stereoisomer (entry 5), in
13
contrast to a recent literature protocol for the formation of this compound. Interestingly,
trans-alkene 16 showed a higher diastereoselectivity in the coupling reaction than the corre-
sponding cis-alkene 18 (6:1 vs 1.7:1), but the yield was considerably higher for the cis-sub-
strate (entries 7 and 8). The reason for the differential stereoselectivity is not yet clear, but it
is possible that the slower reacting 16 experiences more severe steric interactions in the
transition state of the process. In general, intramolecular coupling reactions, which were
carried out under moderate dilution conditions, required longer reaction times, and in the
case of enynes, slight heating was necessary to effect reasonable turnover. Yields are based on
reactants, and since one full equivalent of alkene is used for zirconocene generation (vide
14
infra), they are based on a maximum conversion of 50%. Significant amounts of reduced
compounds were indeed isolated from all reaction mixtures.
A possible mechanism for these novel coupling reactions is shown in Scheme 2. Based in
1
6
part on analogies to Bercaw’s studies, we propose that the THF-soluble zirconocene dihy-
17
dride 3 adds to alkene to produce the alkyl hydride complex 20 via hydrozirconation.
Subsequently, this complex reacts with another alkene to give the transient complex 21.
Reductive elimination of RCH CH from 21 produces zirconacyclopropane 23, which ring
2
3
expands to zirconacyclopentane 24 in the presence of another olefin. Metallacycle 23 could
also be formed via zirconocene 22 by reductive elimination of RCH CH from 20, followed
2
3
by insertion into an alkene. Zirconacyclopentane 24 is quenched with suitable electrophiles to
give the final isolated products. Both pathways are possible according to our experimental
results.

8239
Table 1
15
Coupling of unsaturated substrates with dihydride 3
n
Treatment of Cp ZrCl with two equivalents of BuLi generates a ‘Cp Zr’ equivalent that is
2
2
2
9
particularly useful for cyclization of enynes and a,v-dienes. However, substrates containing
terminal alkynes cannot be used in this protocol, presumably due to the ready oxidative addition
18
of the electron-rich metallocene into the acidic acetylenic carbonꢀhydrogen bond. Barluenga et
al. used a b-hydrogen activation process, followed by insertion of unactivated unsaturated
19
molecules for the intramolecular coupling of terminal alkynes. In the latter method, two
t
equivalents of BuLi were used to remove the acidic acetylene hydrogen before the coupling
reaction. However, in our protocal, terminal a,v-enynes can be used directly to give cyclic
products. Disubstituted alkenes lead to a moderate level of diasteroselectivity even with remote

8240
Scheme 2. Proposed mechanism for the activation of 3 and reductive coupling reactions
1
,6-stereoinduction, whereas excellent stereocontrol can be achieved with homoallylic substitu-
tion. Intermolecular reductive alkene–alkene couplings proceed in an analogous fashion. In
conclusion, the introduction of ether side chains on the Cp ligands of zirconocene dihydride 3
20
led to a THF-soluble early transition metal complex that displayed a novel reactivity pattern.
Monoenes, dienes, and enynes with terminal alkynes and internal alkenes can be reductively
coupled with 3 in moderate to good yields. A plausible mechanism involves the formation of a
1
4-electron zirconium(II) species and zirconacyclopentane 24 that is trapped by electrophiles to
give functionalized derivatives.
Acknowledgements
This work was supported by the National Science Foundation (CHE-9453461).
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2
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6
6
6
13
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6
6
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1
13
1
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1
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2
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2
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2
3
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4
2
−
1 1
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2
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