Zincate-mediated rearrangement reaction of 2-(1-hydroxyalkyl)-1- alkylcyclopropanol

Article abstract of DOI:10.1039/b901043b

A rearrangement of lithium alkoxide of 2-(1-hydroxyalkyl)-1- alkylcyclopropanol into lithium alkoxide of vic-diol was mediated with an organozincate complex.

Full text of DOI:10.1039/b901043b

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Zincate-mediated rearrangement reaction of
2-(1-hydroxyalkyl)-1-alkylcyclopropanolw
Kenichi Nomura and Seijiro Matsubara*
Received (in Cambridge, UK) 16th January 2009, Accepted 11th February 2009
First published as an Advance Article on the web 3rd March 2009
DOI: 10.1039/b901043b
A rearrangement of lithium alkoxide of 2-(1-hydroxyalkyl)-
1-alkylcyclopropanol into lithium alkoxide of vic-diol was
mediated with an organozincate complex.
In 1960, Julia et al. reported the acid-catalyzed ring
opening rearrangement of 2-hydroxyalkylcyclopropane, which
affords E-homoallylic alcohol via a carbocation species on
the cyclopropyl-substituted carbon.1 When the reaction was
applied to 2-(1-hydroxyalkyl)-1-alkylcyclopropanol 3, the
acid-mediated ring-opening reaction gave the corresponding
a,b-unsaturated ketone 4 as shown in Scheme 1.2
Scheme
1
Acid-mediated isomerization of 2-(1-hydroxyalkyl)-
1-alkylcyclopropanol 3 into the b,a-unsaturated ketone.
We have reported that treatment of a,b-epoxyketones 2 with
bis(iodozincio)methane (1) gave 3 stereoselectively and stereo-
specifically in good yields after aqueous work-up.3,4 The
corresponding zinc alkoxides were formed in situ. When the
reaction mixture was heated to reflux in THF without aqueous
work-up, vic-diol 5a was obtained in 68% yield (Scheme 2).
As shown in Table 1, the rearrangement reaction from
2-hydroxymethyl-1-phenylcyclopropanol (3b) was examined
with various reagents. A simple heating of the zinc or lithium
alkoxide of 3b resulted in the recovery of 3b.5 While addition
of 1 equiv. of zinc(II) chloride to the lithium alkoxide of 3b
gave a complex mixture (entry 3), a use of 1 equiv. of zinc(II)
chloride and 3 equiv. of butyllithium gave the desired product
in good yield (entry 4). The combination was expected to form
a zincate-complex (e.g. Bu(RO)2ZnÀLi+). The pre-formed
Scheme 2 Formation of vic-diol 5a.
Table 1 Rearrangement of 2-hydroxymethyl-1-phenylcyclopropanol
(3b)
Entry
Reagent (equiv.)
Time/h
Yield of 5b (%)a
1
2
3
4
5
6
7
8
Me2Zn (2.0)
BuLi (3.0)
BuLi (2.0)/ZnCl2 (1.0)
BuLi (3.0)/ZnCl2 (1.0)
BuLi (3.0)/ZnCl2 (2.0)
t-Bu3ZnLi (1.0)
3
3
3
3
3
3
6
12
0b
0b
0c
88
53
70
88
65
t
zincate Bu3ZnLi,6 which can be prepared easily from ZnCl2
t
and BuLi, was also effective for this rearrangement (entry 6).
Treatment of the prepared lithium alkoxide of 3b with a
t
catalytic amount of Bu3ZnLi also gave 5b (entries 7 and 8).
t-Bu3ZnLi (0.2)/BuLi (2.0)
t-Bu3ZnLi (0.1)/BuLi (2.0)
In order to study the wider applications of the rearrangement,
we treated various lithium alkoxides of 6, prepared in situ from 3,
with t-Bu3ZnLi as a catalyst (Table 2). The substrates 6b–d gave
the corresponding 1,2-diols 5b–d in good yields (entries 2–4).
Cyclopropyl alkyl carbinol derivatives 6a,e,f were also converted
into the corresponding 1,2-diols 5a,e,f in good yields with a low
diastereoselectivity (entries 1,5,6). In the case of cyclopropyl
dimethyl carbinol derivative 6g, the corresponding diol 5g was
obtained in 57% yield (entry 7). It is notable that ethyl phenyl
ketone was also obtained in this reaction in 30% yield.
a
The yield was detemined by nmr using bromoform as an internal
b
standard. 3b was recovered quantitatively. Complex mixture was
c
obtained.
shown in Fig. 1. The alkoxide 6a, which was formed from 3a
by a deprotonation with BuLi, would form a zincate complex
7 via a ligand-exchange with t-Bu3ZnLi. The high affinity
between Zn and O atoms will benefit this reaction. The
retro-allylation analog would afford acetaldehyde and an allylic
anion that are connected with zinc atom 8. The intermediate 8
reacts rapidly to give the product 9. A hydrolysis of 8 would
form acetaldehyde and 1-phenyl-2-propen-1-ol; the latter will
tautomerize into ethyl phenyl ketone. In entry 1, neither
acetaldehyde nor ethyl phenyl ketone were detected. Only in
the case of entry 7 (Table 2), ethyl phenyl ketone was isolated in
30% yield. The results can be rationalized by considering that
the addition of intermediary allylic anion to acetone is slow
enough to break a pair of the allylic anion and acetone.
We speculated that the reaction proceeded via a zincate
intermediate. The working hypothesis of this rearrangement is
Department of Material Chemistry, Graduate School of Engineering,
Kyoto University, Kyoutodaigaku-Katsura, Nishikyo, Kyoto,
615-8501, Japan. E-mail: matsubar@orgrxn.mbox.media.kyoto-u.ac.jp;
Fax: (+81)75-3832461
w Electronic supplementary information (ESI) available: Experi-
mental. See DOI: 10.1039/b901043b
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Table 2 Rearrangement of lithium alkoxide of 2-(1-hydroxyalkyl)-
1-alkylcyclopropanol (3) with t-Bu3ZnLi
Scheme 3 Stereospecificity of the rearrangement of 3b.
Entry R1
R2
R3
R4
T/h Yield (%)a Product
1
2
3
4
5
6
7
Ph
Ph
Ph
Pentyl
Ph
H
H
CH3
H
H
H
H
H
H
H
H
24
24
24
24
24
24
1
78 (3/2)b
88
89
5a
5b
5c
5d
5e
5f
CH3
H
CH3 CH3
H
H
H
89
98 (2/1)c
86 (3/1)d
57e
CH3
Ph
Ph
CH3 CH3
5g
a
b
Isolated yields. The diastereomer ratio was shown in parenthesis.
c
The major product’s stereochemistry was (2S*, 3S*). The major
d
product’s stereochemistry was (2S*, 3S*). The major product’s
e
stereochemistry was (2S*, 3R*). Ethyl phenyl ketone was isolated
in 30% yield.
Scheme 4 Ring-expansion and -contraction via cyclopropanediol.
not common. A study including the mechanistic details is now
under way.
Notes and references
1 (a) M. Julia, S. Julia and R. Guegan, Bull. Soc. Chim. Fr., 1960,
1072; (b) K. Sakaguchi, M. Fujita and Y. Ohfune, Tetrahedron
Lett., 1998, 39, 4313; (c) M. Honda, Y. Yamamoto, H. Tsuchida,
M. Segi and T. Nakajima, Tetrahedron Lett., 2005, 46, 6465;
(d) S. R. Wilson, A. E. Davey and M. E. Guazzaroni, J. Org.
Chem., 1992, 57, 2007; (e) C. Singh, S. Pandey, G. Saxena,
N. Srivastava and M. Sharma, J. Org. Chem., 2006, 71, 9057.
2 K. Nomura and S. Matsubara, Synlett, 2008, 1412.
Fig. 1 Possible route for rearrangement.
3 (a) K. Nomura, K. Oshima and S. Matsubara, Angew. Chem., Int.
Ed., 2005, 44, 5860; (b) K. Nomura and S. Matsubara, Chem. Lett.,
2007, 36, 164.
4 S. Matsubara, H. Yoshino, Y. Yamamoto, K. Oshima,
H. Matsuoaka, K. Ishikawa and E. Matsubara, J. Organomet.
Chem., 2005, 690, 5546.
5 Treatment of a,b-unsaturated ketone with aldehyde in the presence
of chromium(II) affords 2-(1-hydroxyalky)-1-alkylcyclopropanol.
Meanwhile the same reaction with the addition of TMSCl affords
cross pinacol coupling product. See, (a) K. Takai, R. Morita and
C. Toratsu, Angew. Chem., Int. Ed., 2001, 40, 1116; (b) K. Takai,
R. Morita, H. Matsushita and C. Toratsu, Chirality, 2003,
15, 17.
6 (a) T. Harada, T. Katsuhira, D. Hara, Y. Kotani, K. Maejima,
R. Kaji and A. Oku, J. Org. Chem., 1993, 58, 4897;
(b) M. Uchiyama, T. Furuyama, M. Kobayashi, Y. Matsumoto
and K. Tanaka, J. Am. Chem. Soc., 2006, 128, 8404.
Starting from an optically pure (1R,2R)-3b, we examined
the stereospecificity of the transformation (Scheme 3).7,8 The
obtained diol has an S-configuration with loss of optical
purity. The low stereospecificity may be unavoidable, as the
optical purity is based on the enantiofacial selectivity in the
intermediary corresponding to 8.
Although the low stereospecificity shown in Scheme 3 is
disappointing, the skeletal rearragement can be applied to
ring-contraction starting from a bicyclo[n.1.0] compound such
as 10 as shown in Scheme 4. Our previous method concerning
acid-catalyzed rearrangement can be adapted to ring-expansion
from 10 (Scheme 4).2 Epoxidation of cyclopentadec-2-enone
with basic hydrogenperoxide, followed by treatment with
bis(iodozincio)methane (1), gave cyclopropanediol 10 in 80%
yield. While treatment with TFA afforded E-cyclohexadec-3-
enone (12) quantitatively, that with BuLi and t-Bu3ZnLi gave
1-vinylcyclotetradecane-1,2-diol (11) in 94% yield.9
7 Compared with the result of specific rotation of the literature, it
was found that the obtained 5b has (S)-configuration. See:
M. E. Vargas-Diaz, L. Chacon-Garcia, P. Velazquez, J. Tamariz,
P. Joseph-Nathan and L. G. Zepeda, Tetrahedron: Asymmetry,
2003, 14, 3225.
8 The enantiomeric purity of 5b was determined by 1H NMR after
converting into the corresponding Mosher ester using (R)-(+)-
a-methoxy-a-(trifluoromethyl)phenylacetyl chloride. The enantio-
meric excess of the product was determined by 1H NMR focused
on methoxy group (the chemical shift at 3.40 ppm corresponds to
(S)-isomer and that at 3.44 ppm, (R)-isomer).
Thus we can show a novel rearrangement of the lithium
alkoxide of cyclopropanediol, which is mediated with an
organozincate catalyst. While the organozincate complex
was shown as an efficient stoichiometric reagent for halogen–
metal exchange,6 its use for organic synthesis as a catalyst is
9 The major product of 11 was (1R*,2S*) isomer.
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This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 2212–2213 | 2213