1482
J. Am. Chem. Soc. 1997, 119, 1482-1483
Scheme 1
A Facile Synthesis of Chiral γ-Butyrolactones in
Extremely High Enantioselectivity Mediated by
Samarium(II) Iodide
Shin-ichi Fukuzawa,* Kazutaka Seki,
Masahiro Tatsuzawa, and Keisuke Mutoh
Department of Applied Chemistry,
Chuo UniVersity Kasuga, Bunkyo-ku, Tokyo 112, Japan
ReceiVed August 23, 1996
Scheme 2
The lactone functionality is present in a large variety of
natural products and biologically active compounds. For
example, certain functionalized chiral γ-butyrolactones are sex
attractant pheromones for several insect species and some are
utilized as flavoring components. They also constitute a
particularly useful class of synthons and chiral building blocks.
Because the physiological activity of these γ-butyrolactones
often depends on the enantiomeric purity and absolute config-
uration especially for insect sex pheromones, highly selective
asymmetric synthesis of chiral γ-butyrolactones has been of
current interest and is an important subject. Recent useful exam-
ples of the chemical synthesis of chiral γ-butyrolactones are as
follows: transformation of (i) chiral natural products;1 (ii) chiral
allylic alcohols;2 (iii) chiral propagyl alcohols;3 (iv) stoichio-
metric or catalytic chiral induction with chiral organometallic
reagents.4 Although these methods are useful for the synthesis
of chiral γ-butyrolactones, they suffer from certain drawbacks.
In most of these methods, a multistep process (i.e., more than
four steps) is required to reach the desired γ-butyrolactones.
In previous papers, we reported the facile and effective
synthesis of racemic γ-butyrolactones by the reaction of R,â-
unsaturated esters with ketones or aldehydes mediated by
samarium(II) iodide.5 An interesting feature of the reaction is
the stereochemistry. Thus, 3,4-disubstituted-γ-butyrolactones
are produced by the reaction of crotonic acid ester and aldehydes
in favor of the cis isomer (70:30 to 99:1).5,6 Samarium(II) iodide
often produces highly stereoselective reactions as the result of
chelation control of the samarium atom with the oxygen or
nitrogen moiety in organic molecules.7 Highly selective intra-
and intermolecular 1,2- and 1,3-asymmetric inductions are
typical examples of chelation control.8 In our previous γ-bu-
tyrolactone synthesis described above, if chiral R,â-unsaturated
esters could be used in the reaction some steric interactions
between the organic molecule and samarium metal would be
expected to lead to chiral induction. Indeed a chiral γ-buty-
rolactone was obtained in high enantiomeric purity when
N-methylephedrine was used as a chiral auxiliary. We would
like to present here the facile and highly enantioselective
synthesis of γ-butyrolactones by the reaction of acrylates and
crotonates derived from chiral N-methylephedrine with ketones
or aldehydes.
We first surveyed the enantioselectivity in the reaction of
acetophenone with various acrylates derived from chiral sec-
alcohols as a probe reaction. We chose easily accessible and
inexpensive chiral auxiliaries for economic reasons. The
reaction was usually carried out as follows. To the THF solution
of samarium(II) iodide was added a mixture of acetophenone,
the acrylate derivative, and t-BuOH simultaneously at -78 °C
(Scheme 1). The mixture was stirred at that temperature for 1
h, and then the solution was gradually warmed to room
temperature over a period of 5-6 h. The chemical yields and
enantiomeric excesses (ee) of 4-methyl-4-phenyl-γ-butyrolac-
tone prepared from the reaction with acrylate derivatives are as
follows (Scheme 2): L-menthol (1) (39%, 8% ee), (2S,3S)-
diisopropyl tartarate (2) (43%, 28% ee), (2S)-1,1-diphenyl-1,2-
propanediol (3)9 (64%, 54% ee), (R)-1-phenyl-1-propanol10
(purity, 97% ee) (4) (68%, 74% ee), and (1R,2S)-N-methyl-
ephedrine (5)11 (86%, 90% ee). The ee value of the product
was determined by GC using a chiral capillary column (Astec,
Chiraldex GT-A, 30 m).
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