α-oxygen-atom induced methylenation of ketones by CH2(ZnI)2

Article abstract of DOI:10.1055/s-2001-12336

Ketones bearing a hetero-atom at α-position were methylenated selectively by CH₂(ZnI)₂ to give allylic alcohols; a nucleophilic attack of the zinc species was accelerated with a coordination of a hetero-atom at α-position.

Full text of DOI:10.1055/s-2001-12336

LETTER
513
-
Oxygen-atom Induced Methylenation of Ketones by CH (ZnI)2
2
Katsumi Ukai, Daisuke Arioka, Hideaki Yoshino, Hideo Fushimi, Koichiro Oshima, Kiitiro Utimoto, Seijiro
Matsubara*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo, Kyoto 606-8501, Japan
Fax 75-753-4863; E-mail: matsubar@mc.kyoto-u.ac.jp
Received 26 January 2001
tion facilitated the reaction of CH (ZnI) (1), while an ac-
2
2
Abstract: Ketones bearing a hetero-atom at -position were meth-
etoxy group did not (entry 4). A reaction of a ketone
carrying an oxygen atom at the -position with 1 resulted
in the recovery of the starting material (entry 11). In the
case of enone, a hetero-atom at the -position also in-
duced methylenation(entry 12), thus preventing 1,4-addi-
tion (entry 13).8
ylenated selectively by CH (ZnI) to give allylic alcohols; a nucleo-
2
2
philic attack of the zinc species was accelerated with a coordination
of a hetero-atom at -position.
Key words: dimetal, methylenation, regioselective, zinc
,9
Olefination of a carbonyl group has been an important
method for organic syntheses. For this transformation, the Table 1 Methylenation of Ketones by CH (ZnI) (1)
a
2
2
Wittig reagent has been extensively utilized since it was
1
devised. This useful reaction, however, does not work in
some cases owing to the lack of nucleophilicity and the
relatively high basicity of the reagent. In these cases, it has
been replaced with a more reactive oraganometallic re-
agent, such as the Tebbe reagent, a titanium alkylidene
2
complex, or gem-dimetal compounds. Although these
olefination methods have shown the high performance in
stereo- and chemoselective olefination reaction, a regiose-
lective olefination has not been well studied except a few
examples. For example, Kauffmann et al. had reported a
methylenation of benzoin methyl ether in the presence of
3
phenyl propyl ketone with a moderate selectivity. We
wish to describe the highly regioselective methylenation
of ketones with or without carrying an oxygen substituent
-position using bis(iodozincio)-methane2
a
at the
(
CH (ZnI) , 1). Fried et al. had also shown an -hydroxy
2 2
group assisted methylenation of ketone by CH I Zn(Cu)
2
2
in ether based on an intramolecular nucleophilic attack of
the reagent which reacted with hydroxy group at first.4
Our method was applied not only to -hydroxy substituted
ketone but also to -alkoxy, -acetoxy, and -amino substi-
tuted ketones to see the scope and limitations.
a1(1.0 or 2.0 mmol as indicated in Table, 0.5 M solution in THF), 2
1.0 mmol), and THF 3 mL were mixed and stirred at 25 °C for 0.5 h.
Isolated yields. The reaction mixture was stirred for 6 h. Cyclohe-
xyl 2-methylpropyl ketone which was produced via 1,4-addition was
isolated in 32% yield.
(
b
c
d
We had reported a gem-dizinc reagent as an effective
alkylidenation reagent of ketones under mediation of tita-
nium(II) chloride; a simple ketone did not react with the
2
a
gem-dizinc reagent without titanium salt. For example,
treatment of acetophenone with two molar equivalents of
bis(iodozincio)-methane (1) in THF at 25 °C for 6 h re-
sulted in a complete recovery of the starting material. On
the contrary, treatment of -hydroxy acetophenone with
two molar equivalents of 1 in THF at 25 °C for 0.5 h yield-
ed 2-phenyl-2-propen-1-ol in 71% yield. In the reaction of
-
hetero-atom substituted carbonyl compounds with an
organometallic reagent, the nucleophilic attack to the car-
bonyl group was often accelerated with coordination of
5
the -hetero-atom. In Table 1, the results of the methyl-
enation of -oxygen-atom substituted ketones with 1 are
6
,7
summarized. Hydroxy and benzyloxy groups at -posi-
Synlett 2001 No. 4, 513–514 ISSN 0936-5214 © Thieme Stuttgart · New York

5
14
K. Ukai et al.
LETTER
As shown in Table 2, a substrate containing two types of Thus, the methylenation of -hydroxy/alkoxy/amino ke-
ketone group was treated with CH (ZnI) (1) to examine tone with bis(iodozincio)methane proceeded selectively
2
2
the regioselective reaction. The -oxygen-induced meth- even in the presence of ketone carrying no hetero-atom at
ylenation by 1 gave ketoalkene 5 selectively (entry 1). The -position. This method will offer a useful tool for a com-
2
a
titanium(II) chloride-mediated methylenation proceeded plex molecular transformation.
with the reverse selectivity (entry 2). The alkoxy group at
the -position might cause steric hindrance which inter-
rupts the nucleophilic attack of the titanium mediated re-
Acknowledgement
agent to the carbonyl group. The Wittig reagent did not This work was supported by a Grant-in-Aid from the Ministry of
Education, Science, Sports, and Culture.
show selectivity.
Table 2 Regioselective Methylenation of Diketone 4a
References and Notes
(
(
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(
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(
3) Kauffmann, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 1258;
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a
1
b
The ratio of the products was obtained by H NMR analysis. Reco-
vered starting material.
(4) Harrison I. T.; Rawson, R. J.; Turnbull, P.; Fried, J. H. J. Org.
Chem. 1971, 36, 3515.
(
(
(
5) Chen, X.; Hortelano, E. R.; Eliel, E. L.; Frye, S. V. J. Am.
Chem. Soc. 1992, 114, 1778; Utimoto, K.; Nakamura, A.;
Matsubara, S. J. Am. Chem. Soc. 1990, 112, 8189.
6) A reaction of 1,2-diketone with bis(iodozincio)methane (1)
gave cyclopropane-1,2-diol; Ukai, K.; Oshima, K.;
A nitrogen atom at -position of ketone also accelerated
the reaction. As shown in Scheme 1, the transformation
gave an allylic amines in good yields.
Matsubara, S. J. Am. Chem. Soc. 2000, 122, 12047.
7) Study for diastereoselectivity in the reaction of -hydroxy
ketone with ethylidenetriphenylphosphorane; Koreeda, M.;
Patel, P. D.; Brown, L. J. Org. Chem. 1985, 50, 5910; Garner,
P.; Ramakanth, S. J. Org. Chem. 1987, 52, 2629.
(
(
8) Matsubara, S.; Arioka, D.; Utimoto, K. Synlett 1999, 1253.
9) Bis(iodozincio)methane (1) in THF was prepared following
2
a
the reported procedure. To a solution of hetero-atom
substituted ketone (1.0 mmol) in THF (3.0 mL) was added 1
(
0.5 M THF solution, 2.0 mmol) dropwise at 25 °C. The
mixture was stirred for 0.5 h at 25 °C. The mixture was poured
into 1 M HCl (15 mL) and extracted with ether. The product
was isolated with a short silica gel column chromatography.
Scheme 1
Article Identifier:
437-2096,E;2001,0,04,0513,0514,ftx,en;Y01201ST.pdf
1
Synlett 2001, No. 4, 513–514 ISSN 0936-5214 © Thieme Stuttgart · New York