Zirconium-mediated conversion of homoallylic ethers into cyclopropane derivatives

Article abstract of DOI:10.1016/S0040-4039(03)01125-0

Homoallylic ethers react with Cp₂ZrCl₂/2 n-BuLi reagent to afford cyclopropane derivatives. Cyclopropylcarbinyl-homoallyl rearrangements involving zirconium species are observed depending on the substrate structure.

Full text of DOI:10.1016/S0040-4039(03)01125-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4827–4829
Zirconium-mediated conversion of homoallylic ethers into
cyclopropane derivatives
Vincent Gandon, Christophe Laroche and Jan Szymoniak*
Re´actions Se´lectives et Applications (UMR 6519), CNRS and Universite´ de Reims, 51687 Reims Cedex 2, France
Received 9 April 2003; revised 3 May 2003; accepted 3 May 2003
Abstract—Homoallylic ethers react with Cp2ZrCl2/2 n-BuLi reagent to afford cyclopropane derivatives. Cyclopropylcarbinyl–
homoallyl rearrangements involving zirconium species are observed depending on the substrate structure. © 2003 Elsevier Science
Ltd. All rights reserved.
Allylic ethers react with (1-butene)zirconocene to afford
allylzirconium derivatives.1 This reaction proceeds
through ligand exchange, formation of a zirconacyclo-
propane and the following b-elimination of the alkoxy
group (Scheme 1, Eq. (1)). We speculated that,
analogously, homoallylic ethers might be converted into
cyclopropylcarbinylzirconium complexes through the g-
elimination of the alkoxy-group (Eq. (2)).2 The corre-
sponding cyclopropanes could then be generated from
these species under protonolysis conditions.3 Here we
report on the feasibility of performing such
transformations.
1 (1 mmol) were dissolved in THF (5 mmol), n-BuLi (2
mmol) was added at −78°C, and the mixture was
allowed to warm to 20°C. The reactions were moni-
1
tored by H NMR and ended after a 3–5 h period with
a hydrolytic work-up. Starting from 1c (R=MOM) and
1d (R=SiMe3) complex mixture of products were
observed. In contrast, significant amounts of the cyclo-
Various
cyclopropylcarbinyl-
or
(cyclopropyl-
methyl)metal complexes have been described, based on
transition metals such as Fe, Co, Pd, Ni, Rh, Mn, Pt
and Ti.4 Some of them were demonstrated to equili-
brate through the cyclopropylcarbinyl–homoallyl rear-
rangement (Scheme 1, Eq. (3)) and to react with ring
opening, thus operating as homoallyl equivalents. Fur-
thermore, the hypothetical cyclopropylcarbinyl–
homoallyl rearrangement involving zirconium was
estimated to be slightly exothermic (DHꢀ−6 kcal/
mol).5 We began our study bearing these features in
mind.
Scheme 1.
In the first experiments, unsaturated ethers 1a–d
(Scheme 2) were used in ligand exchange with (1-
butene)ZrCp2, preformed in situ from Cp2ZrCl2 and
n-BuLi.6 Typically, Cp2ZrCl2 (1 mmol) and compound
Keywords: cyclopropanes; homoallylic ethers; rearrangement; zirco-
nium.
* Corresponding
author.
Fax:
+33-326-913-166;
e-mail:
jan.szymoniak@univ-reims.fr
Scheme 2.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01125-0

4828
V. Gandon et al. / Tetrahedron Letters 44 (2003) 4827–4829
propane 2 were formed from 1a (R=Me) and 1b
(R=Bn). In the first case (1a), the cyclopropane 2 was
even the major product (65% NMR yield). It was
accompanied by smaller quantities of 1-phenyl-1-butene
and 1-phenyl-2-octene. In the second case (1b), a mix-
ture of 2 and the same as well as two other deoxygena-
tion and coupling products were formed. Similar results
were obtained when using benzene as solvent in place
of THF.
(entries 3 and 4). Furthermore, spirocyclopropane 14
was formed in good yield starting from 13 (entry 5).
The trans configuration was assigned to the major
diastereomers of compounds 4, 7 and 10 based on their
1H NMR spectra and in accordance with the literature
data.7,8 The degree of diastereoselectivity does not
depend significantly neither on the solvent used (THF,
Et2O, PhH) nor on the nature of the -OR group
(R=Me, Bn, MOM) (entry 1).
To further investigate the cyclopropanation reaction we
next used homoallylic ethers with a tertiary a-C atom
as substrate. These reactions, performed as previously,
led to trisubstituted cyclopropanes which proved to be
major or even unique products as shown in Table 1.
Starting from ethers 3 and 6 with Ph and respectively
Me or n-Bu groups on a-C atom, mixtures of cyclo-
propanes (major) and alkenes were formed (entries 1
and 2). In contrast, cyclopropanes were solely obtained
from ethers 9 or 11 with Ph and i-Pr or Ph groups
The ratios of cyclopropanes versus the open chain-
products in entries 1 and 2 (respectively 4:5 and 7:8) are
not sharply influenced by the solvent nor the OR
group. We have noticed, however, that these ratios
were markedly increased in favour of the cyclopropane
by deacreasing of the temperature for hydrolysis. For
example, when starting from 3a and hydrolysing the
reaction mixture at 50, 20, −10 and −40°C, the ratios of
4:5 were 6.8, 7.8, 10.4 and 14.0, respectively (GC mon-
itoring). The 4:5 ratio seems almost constant during the
a
Table 1. Reaction of homoallylic ethers with 2 n-BuLi/Cp2ZrCl2

V. Gandon et al. / Tetrahedron Letters 44 (2003) 4827–4829
4829
References
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2. Only a few examples of the g-elimination involving zir-
conocenes have been reported, see: (a) Davis, J. M.;
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3. We recently reported a new approach to cyclopropanes
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Scheme 3.
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reaction, which was demonstrated to come to completion
within 3 h. Finally, deuterolysis of the reaction mixture
with D2O/D2SO4 (1 M) afforded the deuterated com-
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6. For reviews of ‘Cp2Zr’ chemistry, see: (a) Negishi, E.;
Takahashi. T. Bull. Chem. Soc. Jpn. 1998, 71, 755; (b)
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7. Selected data for 1,2-dimethyl-1-phenylcyclopropane (4).
Major isomer (trans): 1H NMR (CDCl3, 250 MHz) l:
0.21–0.30 (m, 1 H), 0.93–1.06 (m, 2 H), 1.13 (d, J=5.8,
3 H), 1.30 (s, 3 H), 7.15–7.30 (m, 5 H); 13C NMR
The concomitant formation of cyclopropanes and alkenes
in entries 1 and 2 is consistent with a cyclopropylcarbinyl–
homoallyl rearrangement as shown in Scheme 3. Partic-
ularly, the deuteration experiments and the temperature
effect further support an equilibrium between the cyclo-
propyl- and homoallyl zirconium species. In this context,
the lack of rearrangement for the homoallylic ethers 9,
11 and 13 is noteworthy. It might be attributed to the
Thorpe–Ingold effect, i.e. angle compression at the
substituted carbon.9 Thus, the equilibrium totally in
favour to the cyclopropyl zirconium species with 9, 11
and 13, would be attributed to a steric repulsion of the
attached groups stronger than with 3 and 6.
(CDCl3, 62.5 MHz) l: 14.1, 19.8, 20.5, 22.1, 23.4, 125.2,
+
’
126.6, 128.1, 148.9; MS (EI) m/z (%) 146 (22, M ), 131
(100), 91 (42), 77 (24). Minor isomer (cis): 1H NMR
(CDCl3, 250 MHz) l: 0.51–0.59 (m, 1 H), 0.66 (d, J=
5.8, 3 H), 0.71–0.90 (m, 2 H), 1.26 (s, 3 H), 7.15–7.30
(m, 5 H); NOE +5%: irrad. Me-1, obs. H-2; 13C NMR
(CDCl3, 62.5 MHz) l: 16.0, 19.2, 19.6, 26.1, 28.6, 128.0,
In summary, we have shown that cyclopropanes can be
obtained from homoallylic ethers via zirconium-mediated
g-elimination reaction. In several cases, cyclopropyl-
carbinyl–homoallyl rearrangement has been noticed
to occur. We are currently exploring these new transfor-
mations and particularly focus on their synthetic poten-
tial.
+
’
128.1, 129.5; MS (EI) m/z (%): 146 (24, M ), 131 (100).
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