Stereospecific and stereoselective preparation of 2-(1-hydroxyalkyl)-1- alkylcyclopropanols from α,β-epoxy ketones and bis(iodozincio)methane

Article abstract of DOI:10.1002/anie.200501644

(Chemical Equation Presented) A coordinated attack: The reaction of α,β-epoxy ketones with bis(iodozincio)methane produces 2-(1-hydroxyalkyl)-1-alkylcyclopropanols diastereoselectively (see scheme). The reaction proceeds by the coordination and diastereos

Full text of DOI:10.1002/anie.200501644

Communications
Diastereoselectivity
DOI: 10.1002/anie.200501644
Stereospecific and Stereoselective Preparation of
2-(1-Hydroxyalkyl)-1-alkylcyclopropanols from
a,b-Epoxy Ketones and
Bis(iodozincio)methane**
Kenichi Nomura, Koichiro Oshima, and
Seijiro Matsubara*
The most common method used to prepare cyclopropane
compounds involves the reaction of electrophilic Simmons–
Smith-type reagents with alkenes.[1] In contrast to this
electrophilic [2+1] reaction,a gem-organodimetal compound
also has the possibility of participating in a nucleophilic
[2+1] reaction because it has two nucleophilic sites on one
carbon atom.[2,3] In fact,we have already reported the
reaction of bis(iodozincio)methane (1) with 1,2-diketone to
give cis-1,2-cyclopropanediol with high diastereoselectivity.[4]
In this transformation, 1 acts as a bidentate Lewis acid and
fixes the conformation of the 1,2-diketone in the s-cis form.[4c]
Thus,a substrate which has two Lewis basic sites may interact
at two sites with 1,and may show some characteristic
stereochemical performance during subsequent useful molec-
ular transformations.[5] Following this observation,we treated
1 with a,b-epoxy ketone and found that the reaction resulted
in the stereospecific formation of 2-(1-hydroxyalkyl)-1-alkyl-
cyclopropanol.[6]
Treatment of 2-benzoyl-1,1-dimethyloxirane (2a) with 1
gives (1R*,2R*)-2-(1-methyl-1-hydroxyethyl)-1-phenylcyclo-
propanol (3a) as the sole product (Scheme 1). The stereo-
chemistry of the product was determined by single-crystal X-
ray analysis (Figure 1).[7] Other examples of reactions con-
ducted that led to formation of a cyclopropane ring are
Scheme 1. Reaction of bis(iodozincio)methane (1) with a,b-epoxy
ketone 2a.
[*] K. Nomura, Prof. Dr. K. Oshima, Prof. Dr. S. Matsubara
Department of Material Chemistry
Graduate School of Engineering
Kyoto University
Kyoutodaigaku-Katsura, Nishikyo, Kyoto 615-8501 (Japan)
Fax: (+81)75-383-2438
E-mail: matsubar@orgrxn.mbox.media.kyoto-u.ac.jp
[**] This work was supported financially by the Japanese Ministry of
Education, Science, Sports, and Culture. The financial support
provided by Chugai Pharmaceutical Co., Ltd. and the Takahashi
Industrial and Economical Research Foundation are also
acknowledged.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Scheme 2. Preparation of 2-(1-hydroxyalkyl)-1-alkylcyclopropanol 3.
Figure 1. Structure of 3a as determined by X-ray analysis.
summarized in Scheme 2. In all cases,the reaction yielded a
single diastereomer selectively.
An optically active epoxy ketone[8] 2g was treated with 1
to give (1S,2S)-2-(S-1-hydroxyethyl)-1-phenylcyclopropanol
(3g) without loss of enantiomeric purity. The reaction
involving the enantiomer of 2g (namely, 2h) gave the
corresponding enantiomer 3h (Scheme 3).
The diastereoselective formation of cyclopropanol 3 can
be explained as follows. The reaction starts with the diaster-
eoselective attack of 1 at the carbonyl group as a consequence
of the stereogenic center at the a-carbon atom (Scheme 4).[4,9]
This step is followed by stereospecific attack on the epoxide.
The explanation shown in Scheme 4 requires diastereose-
lective attack to the b face of 4,which needs to be
rationalized,since previous reports concerning the diaster-
eoselective metal-mediated nucleophilic
Scheme 3. Preparation of optically active 2-(1-hydroxyalkyl)-1-alkylcyclo-
propanol from optically active a,b-epoxy ketones and bis(iodozincio)-
methane (1).
attack to an a,b-epoxy ketone occurred from
the a face of 4.[10]
For example,treatment of
2b with
NaBH4/LaCl3 resulted in the exclusive forma-
tion of erythro-epoxy alcohol.[11] The diaster-
eoselective reaction was explained by chela- Scheme 4. Stereochemical requirements for the reaction.
tion effects to form intermediate 6,as shown
in Scheme 5. Other metal salts,such as CaCl 2,
MnCl2,and ZnCl 2 as well as LaCl3 showed the
same effect. Sato et al reported the prepara-
tion of 2-(1-hydroxyalkyl)-1-alkylcyclopropa-
nol from an a,b-epoxy ketone and trimethyl-
stannylmethyllithium.[6] Their results did not
reveal any diasteromeric selectivity for trisub-
stituted oxirane substrates such as 3c. The
Scheme 5. Diastereoselective reduction of epoxy ketone with NaBH4·LaCl3.
major isomers were also postulated to be
produced by a-face attack of 4 in the case of
disubstituted oxirane substrates (namely,
3a,b,d–f).[6] In the present cyclopropanation
reaction,the addition of 1 cannot be explained
by a simple chelation intermediate such as
6,[6,10,11] because the first nucleophilic attack
also occurred by b-face attack on 4. From our
ab initio calculations,we propose that coordi-
nation of 1 to 2,3-dioxobutane occurs in a
face-to-face arrangement,as shown in
Figure 2. Initial complex formed in the reaction of 2,3-dioxobutane with 1 based on
Figure 2 (9: side view; 10: bottom view).[4c] B3LYP/II//B3LYP/I calculations. See ref. [4c].
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Such coordination has two characteristic features: first,the
dihedral angle of the diketone part (aO(1)-C(1)-C(2)-
O(2) = 47.78); and second,the mechanism through which
the zinc reagent coordinates to the diketone. A line drawn
between the two oxygen atoms of the diketone,and another
between the two zinc atoms in the initial complex,cross at
almost right angles. In the same way,the nucleophilic attack
of 1 on epoxy ketone 2h can be explained via intermediate 11
(Scheme 6). Attack from the other face via intermediate 13
will be constrained by steric hindrance between 1 and the
epoxide ring. Thus,face-to-face coordination will promote
attack on the opposite face relative to traditional Cram-
chelation intermediates such as 6.
A cyclic substrate such as 14 or 16 (Scheme 7) will
experience some difficulty in differentiating between the
intermediate corresponding to 11 and 13 because of steric
Figure 3. Structure of diester (3,5-dinitrobenzoylester) of 17a obtained
by X-ray analysis.
ture is crucial when demonstrating its
function as an effective bidentate
Lewis acid in a stereoselective reac-
tion.
Received: May 13,2005
Published online: August 9,2005
Scheme 6. Proposal for the stereoselective reaction of 2h with 1.
Keywords: diastereoselectivity · epoxy
.
ketones · small ring systems · zinc
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A derivative of 2-(1-hydroxyalkyl)-1-alkylcyclopropanol
is an important intermediate structure of some natural
products.[13] In our present method,we report a new
diastereofacial selective attack of epoxy ketone by utilizing
the Lewis acidity of the dizinc reagent 1. Bis(iodozincio)-
methane (1),prepared from diiodomethane and zinc powder,
exists as monomeric form without aggregation or a contribu-
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6.1690(7), b = 16.0965(17), c = 22.395(2) Š, b = 90.08, V=
2223.8(4) Š3, Z = 9, 1calcd = 1.148 MgmÀ3, l(MoKa) = 0.71073 Š,
5862
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T= 296 K,2 qmax = 54.18, R = 0.0371 for 4852 reflections (I >
2s(I)).
[8] An optically active epoxy alcohol was oxidized by (COCl)2/
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90.536(3)8, V= 2335.9(6) Š3, Z = 4, 1calcd = 1.508 MgmÀ3
, l-
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5098 reflections (I > 2s(I)).
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