Zinc-induced deoximation of α,α′-dioxo-type oximes and oxime ethers leading to α,β-diketo esters

Article abstract of DOI:10.1246/bcsj.77.1407

The deoximation of a variety of α,α′-dioxo-type oximes and oxime ethers was achieved under mild conditions using zinc/AcOH, which gave good yields of α,β-diketo esters.

Full text of DOI:10.1246/bcsj.77.1407

Short Articles
Bull. Chem. Soc. Jpn., 77, 1407–1408 (2004) 1407
Using methyl 2-(benzyloxyimino)-3-oxobutanoate (1a) as a
model compound, we attempted its deoximation under a variety
of reaction conditions. Attempted oxidative deoximation using
ozone, KIO4, Oxone (2KHSO5/KHSO4/K2SO4), Cu(NO3)2,
and Mn(OAc)37 were all unsuccessful. An attempted reductive
cleavage of 1a with Raney Ni at room temperature8 resulted in
the recovery of 1a. On the other hand, a treatment of 1a with
3 mol% of fresh 10% Pd on C under an atmosphere of hydro-
gen in EtOH/AcOH/H2O (15:2:10) at room temperature un-
derwent simple debenzylation to give an oxime in 93% yield.
Interestingly, a stoichiometric use of Pd/C gave a moderate
yield of 2a.
Zinc-Induced Deoximation of
ꢀ,ꢀ0-Dioxo-Type Oximes and Oxime
Ethers Leading to ꢀ,ꢁ-Diketo Esters
ꢀ
Ilhyong Ryu, Hiroki Kuriyama,1
Hironari Miyazato,1 Satoshi Minakata,1
Mitsuo Komatsu,1 Joo-Yong Yoon,2
ꢀ;2
and Sunggak Kim
Consequently, we were pleased to find that a quite inexpen-
sive and familiar reduction system solved the problem. Reduc-
tive deoximation induced by zinc in acetic acid proved to be
useful to convert 1 to 2. Thus, when ethyl 2-(benzyloxyimi-
no)-3-oxohexanoate (1b) was treated with an excess amount
of zinc powder in acetic acid, the desired product, ethyl 2,3-di-
oxohexanoate (2b), was prepared in 72% yield after purifica-
tion by HPLC (Table 1, run 3). Each isolated product showed
Department of Chemistry, Faculty of Arts and Sciences,
Osaka Prefecture University, Sakai, Osaka 599-8531
1Department of Applied Chemistry, Graduate School of
Engineering, Osaka University, Suita, Osaka 565-0871
2Center for Molecular Design and Synthesis,
Department of Chemistry, Korea Advanced Institute of
Science and Technology, Taejon 305-701, Korea
1
clear H and 13C NMR spectra, which can support the vic-tri-
carbonyl structure, whereas the IR spectra, which showed weak
absorption at 3412 cmꢁ1, as in the case of 2b, do not necessa-
rily exclude the possibility of water-inclusion in each case.2 Ir-
respective of the shapes of zinc being a powder or a dust, this
deoximation gave identical results (runs 1 and 2). Some other
results are summarized in Table 1. Besides benzyl oxime
ethers, methyl and 2-propynyl oxime ethers underwent smooth
deoximation reaction (runs 4 and 5). Oximes can also be deoxi-
mated to give corresponding vic-tricarbonyl compounds, al-
though the yields were rather modest compared with the corre-
sponding oxime ethers (runs 7–11). The procedure can be ap-
plied to the amide-type oxime ether 1k, which provided the cor-
responding ꢀ,ꢀ0-diketo amide 2g (run 12).
In summary, we have shown that vic-tricarbonyl compounds
can be prepared conveniently from ꢀ,ꢀ0-dioxo-type oximes or
oxime ethers as precursors by using a zinc–AcOH system. The
mild reaction conditions, a simple reaction procedure, and
the use of conventional reagents are attractive features of this
deoximation method.
Received January 8, 2004; E-mail: ryu@ms.cias.osakafu-u.ac.jp
The deoximation of a variety of ꢀ,ꢀ0-dioxo-type oximes
and oxime ethers was achieved under mild conditions using
zinc/AcOH, which gave good yields of ꢀ,ꢁ-diketo esters.
vic-Tricarbonyl compounds represent a useful synthon for
the preparation of biologically active natural and unnatural
compounds.1,2 It is also known that some important natural
compounds, such as rapamycin and FK-506, contain the vic-tri-
carbonyl substructure. Recently, we have reported that an inter-
molecular radical cascade reaction, which employs multiple
radical one-carbon (C1) units,3 such as CO and sulfonyl oxime
ethers,4,5 can be successfully achieved. With this strategy in
hand, ꢀ,ꢀ0-dioxo-type oxime ethers 1 can be prepared conven-
iently, which represent potential precursors for vic-tricarbonyl
compounds. The deoximation of 1 having an adjacent acyl
functionality was found to be particularly difficult, with HCl–
HCHOaq, which can affect the deoximation of the usual oxime
ethers.4 A literature survey showed that there was one group
that achieved the deoximation of a bis-acylated oxime using
200 mol% TiCl3/acetone.6 However, the reported yield of
19% of the corresponding vic-tricarbonyl compound, as well
as the procedure requiring pH control, is obviously in need of
a significant improvement. In this paper, we describe a useful
method for the deoximation of 1, leading to ꢀ,ꢁ-diketo esters
2, which employs a system simply comprised of zinc powder
and AcOH (Eq. 1). We found that the procedure is applicable
to both oximes and oxime ethers, and that the preparation of
an ꢀ,ꢁ-diketo amide by this procedure is also possible.
Experimental
1H NMR spectra were recorded with a JEOL FT-NMR JNM-EX
270 (270 MHz) spectrometer and a JNM-EX 400 (400 MHz) spec-
trometer. 13C NMR spectra were recorded with a JEOL JNM-EX
270 (68 MHz) spectrometer. Infrared spectra were recorded with
a JASCO FT/IR-410 spectrometer. The products were purified
by flash chromatography on silica gel (Fuji Silysia BW-300) or
by recycling preparative HPLC (JAI, LC-908). Both zinc powder
and zinc dust were purchased from Nakarai Tesque and Aldrich,
respectively. For all instances, except for 2a, EIMS spectra showed
unidentified prominent peaks corresponding to 2M-36.
Preparation of Ethyl 2,3-Dioxohexanoate (2b). To a solution
of ethyl 2-(benzyloxyimino)-3-oxohexanoate (1b) (183.5 mg,
0.66 mmol) in AcOH (0.5 mL), zinc powder (385 mg, 5.89 mmol)
was added in one portion. After stirring at room temperature for
1 h, the reaction mixture was diluted with Et2O and filtered
through NaHCO3 to remove AcOH and the remaining zinc. The fil-
trate was evaporated to dryness to give a crude product. Purifica-
tion by HPLC (CHCl3) provided the desired product 2b
ð1Þ
Published on the web July 9, 2004; DOI 10.1246/bcsj.77.1407

1408 Bull. Chem. Soc. Jpn., 77, No. 7 (2004)
Ó 2004 The Chemical Society of Japan
Table 1. Zn-Induced Deoximation of 1 Leading to vic-Tri-
carbonyl Compounds 2a)
164.95, 172.84; IR (neat) 3412, 2982, 2939, 1735, 1448, 1414,
1375, 1304, 1254, 1130, 1024 cmꢁ1
.
Metꢂhyl 2,3-Dioxopentanoate (2d): Light yellow crystals: mp
78–80 C: 1H NMR (270 MHz, CDCl3) ꢂ 1.33 (t, 3H, J ¼ 7:59
Hz), 3.11 (q, 2H, J ¼ 7:59 Hz), 4.02 (s, 3H); 13C NMR (68
MHz, CDCl3) ꢂ 13.71, 28.23, 53.17, 143.80, 155.06, 165.46; IR
(KBr) 3425, 2980, 2954, 1723, 1444, 1330, 1244, 1166,
Run Oximes or oxime ethers Tricarbonyl compounds Yield b)
%
OBz
O
1
85
80
N
OMe
OMe
2c)
O
O
1a
1b
1c
1d
2a
2b
2a
2a
O
O
1120 cmꢁ1
.
Methyl 4-Methoxy-2,3-dioxobutanoate (2e): Yellow crys-
OBz
O
N
OEt
3
4
5
72
86
78
OEt
O
O
ꢂ
tals: mp 73–75 C: 1H NMR (270 MHz, CDCl3) ꢂ 3.45 (s, 3H),
O
N
O
OMe
4.02 (s, 3H), 4.90 (s, 2H); 13C NMR (68 MHz, CDCl3) ꢂ 52.81,
59.09, 72.45, 143.85, 151.30, 164.64; IR (KBr) 3412, 2987,
O
OMe
OMe
O
O
O
O
O
O
O
2932, 1717, 1444, 1367, 1271, 1253, 1165, 1139, 1108 cmꢁ1
.
O
O
N
OMe
Metꢂhyl 2,3-Dioxoheptanoate (2f): Light yellow crystals: mp
41–43 C: 1H NMR (270 MHz, CDCl3) ꢂ 0.94 (t, 3H, J ¼
7:26 Hz), 1.42 (sex, 2H, J ¼ 7:26 Hz), 1.70 (tt, 2H, J ¼ 7:92,
7.26 Hz), 3.07 (t-like, 2H, J ¼ 7:92 Hz), 4.02 (s, 3H); 13C NMR
(68 MHz, CDCl3) ꢂ 13.90, 22.71, 31.76, 34.55, 53.12, 143.92,
154.07, 165.50; IR (KBr) 2953, 2873, 1731, 1686, 1597, 1450,
OMe
O
OBz
O
O
N
EtO
OEt
6
7
8
9
75
72
55
EtO
OEt
O2c
O
O
O
O
1e
OH
O
1289, 1262, 1249, 1192 cmꢁ1
.
N
OMe
OMe
O
O
N,N-Diethyl 2ꢂ,3-Dioxobutanamide (2g): Yellow crystals: de-
O
O
1f
2a
composed at 70 C to form a white solid which did not melt at
OH
O
ꢂ
300 C: 1H NMR (270 MHz, CDCl3) ꢂ 1.11 (t, 3H, J ¼ 7:09
N
OMe
OMe
O
O
Hz), 1.30 (t, 3H, J ¼ 7:09 Hz), 2.52 (s, 3H), 3.14 (q, 2H, J ¼
7:09 Hz), 3.60 (q, 2H, J ¼ 7:09 Hz); 13C NMR (68 MHz, CDCl3)
ꢂ 12.50, 13.72, 19.96, 39.52, 42.84, 146.81, 147.91, 166.81; IR
O
O
2d
1g
OH
O
N
OMe
49
57
OMe
O
(KBr) 3425, 1561, 1460, 1415, 1356, 1050, 1033, 696 cmꢁ1
.
O
O
O
O
O
2e
1h
1i
OH
O
N
OMe
We acknowledge a Grant-in-Aid for Scientific Research on
Priority Areas (A) ‘‘Exploitation of Multi-Element Cyclic
Molecules’’ from the Ministry of Education, Culture, Sports,
Science and Technology, for financial support. S.K. thanks
the Korea Science and Engineering Foundation (KOSEF) for
financial support.
10
OMe
O
O
O
O
2f
OH
O
N
EtO
OEt
EtO
OEt
11
12
40
54
O
O
N
O
O
O
O
2c
1j
OBz
NEt
O
N
2
O
O
O
O
2g
References
1k
1
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gel (hexane/AcOEt = 19/1–4/1) or preparative HPLC (CHCl3).
c) Zinc dust (<10 micron) was used.
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1
(81.7 mg, 72% yield) as yellow crystals: mp 55–57 C: H NMR
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CDCl3) ꢂ 14.01, 14.12, 22.85, 36.56, 62.16, 144.40, 153.26,
165.23; IR (KBr) 2963, 1724, 1466, 1414, 1382, 1304, 1262,
4
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.
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135 C: 1H NMR (400 MHz, CDCl3) ꢂ 2.81 (s, 3H), 4.00 (s, 3H);
5
For reviews on radical carbonylations, see: a) I. Ryu, N.
ꢂ
Sonoda, and D. P. Curran, Chem. Rev., 96, 177 (1996). b) I. Ryu
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13C NMR (68 MHz, CDCl3) ꢂ 22.33, 53.16, 143.58, 151.20,
165.25; IR (KBr) 1721, 1453, 1418, 1381, 1263, 1190, 1129
cmꢁ1; EIHRMS m=z calcd for C5H6O4 130.0266, found 130.0235.
Diethyl 2,3-Dioxopimelate (2c): Yellow oil: 1H NMR (270
MHz, CDCl3) ꢂ 1.25 (t, 3H, J ¼ 7:26 Hz), 1.44 (t, 3H, J ¼
7:26 Hz), 2.10 (quint, 2H, J ¼ 7:59 Hz), 2.42 (t, 2H, J ¼
7:59 Hz), 3.11 (t-like, 2H, J ¼ 7:59 Hz), 4.13 (q, 2H, J ¼
7:26 Hz), 4.48 (q, 2H, J ¼ 7:26 Hz); 13C NMR (68 MHz, CDCl3)
ꢂ 14.20, 14.27, 24.25, 33.74, 33.80, 60.28, 62.35, 144.32, 152.79,
8
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9
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