Dicobaltoctacarbonyl-mediated deoximation

Article abstract of DOI:10.1055/s-1999-3603

Treatment of oxime O-acetates with Co₂(CO)₈ in the presence of a base, followed by H₂O at room temperature efficiently afforded the parent carbonyl compounds in high yields. Direct regeneration of carbonyl functionalities from the corresponding oxime derivatives was realized by successive exposure to acetylation conditions, Co₂(CO)₈ in the presence of base, and H₂O. In addition, N-monosubstituted hydrazone derivatives could generate the parent carbonyl compound under the above conditions.

Full text of DOI:10.1055/s-1999-3603

1872
SHORT PAPER
Dicobaltoctacarbonyl-Mediated Deoximation
Chisato Mukai,* Izumi Nomura, Osamu Kataoka, Miyoji Hanaoka*
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa 920-0934, Japan
Fax +81(76)2344410; E-mail: cmukai@kenroku.kanazawa-u.ac.jp
Received 17 June 1999; revised 14 July 1999
Abstract: Treatment of oxime O-acetates with Co2(CO)8 in the
presence of a base, followed by H2O at room temperature efficiently
afforded the parent carbonyl compounds in high yields. Direct re-
generation of carbonyl functionalities from the corresponding
oxime derivatives was realized by successive exposure to acetyla-
tion conditions, Co2(CO)8 in the presence of base, and H2O. In
addition, N-monosubstituted hydrazone derivatives could generate
the parent carbonyl compound under the above conditions.
Key words: deoximation, dicobaltoctacarbonyl, oxime, hydrazone,
triethylamine
Oxime functionalities are widely used as useful protecting
groups1 and also as important synthetic intermediates in
several reactions. Regeneration of carbonyl compounds
from their oximes under mild conditions, therefore, has
received much attention. As a result, there are now vari-
ous types of convenient and efficient procedures2 avail-
able for deoximation. In our program3 on the development
of stereoselective reactions mediated by dicobaltoctacar-
bonyl [Co2(CO)8], we found that Co2(CO)8 can serve as an
alternative tool for the easy regeneration of carbonyl func-
tionalities from their oxime derivatives. This paper deals
with a newly developed Co2(CO)8-mediated regeneration
of carbonyl functionalities from their oxime as well as hy-
drazone derivatives.
Scheme
ficulty to provide acetophenone (7) and dialkyl carbonyl
compounds 9, 11, respectively, in satisfactory yields (en-
tries 3, 4, 5). In addition, the ester functionality and ketal
group are tolerated under these conditions (entries 6, 7).
It should be emphasized that the parent carbonyl com-
pounds can be more conveniently obtained from the cor-
responding oxime derivatives as follows: Thus 1 was
successively exposed to acetyl chloride, Co2(CO)8, and
H2O (condition B) resulting in exclusive formation of the
parent 2 in 98% yield (entry 8). Similar treatment of ace-
tophenone oxime (16) and 1-phenylbutan-3-one oxime
(17) under condition B directly produced 7 and 11 in 64
and 87% yields, respectively (entries 9, 10) The next
phase of our research was the deoximation of the al-
doxime O-acetate 18. Treatment of 18 under condition A
afforded, after NaBH4 reduction,5 naphthalenemethanol
(19) in 55% yield together with naphthonitrile (20) in 11%
yield as a byproduct (entry 11). Formation of the nitrile
derivative 20 might be tentatively rationalized in terms of
the b-elimination pathway. Both products 19 and 20 were
also obtained under condition B (entry 12), although the
ratio between these two compounds was different from
that observed in entry 11. Similar behavior6 was observed
when 3,4,5-trimethoxybenzaldehyde oxime (22) was ex-
posed to the deoximation reaction (entry 13). Interesting-
ly, Co2(CO)8 was effective for the regeneration of
carbonyl functionalities from N-monosubstituted hydra-
zone derivatives. Thus, 4-phenylcyclohexanone methyl-
hydrazone (25) was successively treated with Co2(CO)8
and H2O at room temperature to afford 2 in 70% yield (en-
try 14). Similar treatment of 4-phenylcyclohexanone phe-
nylhydrazone (26) gave 2 in 85% yield (entry 15). It
Treatment of 4-phenylcyclohexanone oxime (1) with
Co2(CO)8 in Et2O in the presence of Et3N at room temper-
ature for 24 hours gave 4-phenylcyclohexanone (2) in
47% yield together with recovered starting material 1 in
53% yield. Other metal carbonyl species such as Cr(CO)6,
Mo(CO)6, and W(CO)6 were found to be of no use under
similar conditions resulting in the recovery of starting ma-
terial 1. We tentatively envisaged that activation of the hy-
droxy moiety in an oxime functionality as the acyloxy
group2j would result in an improved chemical yield. Thus
the oxime 1 was converted into the corresponding acetate
3 by conventional means; it was subsequently treated with
Co2(CO)8 in the presence of Et3N in Et2O for 15 minutes.
The resulting reaction mixture was then exposed to H2O
in MeOH4 at room temperature for 30 minutes (condition
A) to give 2 in 98% yield.
For the evaluation of this procedure, several other oxime
O-acetates were submitted to the deoximation conditions
previously described. The results are summarized in the
Table. There are several points that deserve comment.
Benzophenone oxime O-acetate (4) gave the parent ben-
zophenone (5) in 93% yield (entry 2). Deoximation of the
oxime O-acetates 6, 8, and 10 proceeded without any dif-
Synthesis 1999, No. 11, 1872–1874 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Dicobaltoctacarbonyl-Mediated Deoximation
1873
Table Regeneration of Carbonyl Functionality
Entry Substrate
Conditiona Product
Yield
(%)
1
2
3
4
5
6
4-phenylcyclohexanone oxime O-acetate (3)
benzophenone oxime O-acetate (4)
acetophenone oxime O-acetate (6)
1,3-diphenylpropanone oxime O-acetate (8)
1-phenylbutan-3-one oxime O-acetate (10)
4-ethoxycarbonylcyclohexanone oxime
O-acetate (12)
A
A
A
A
A
A
4-phenylcyclohexanone (2)
benzophenone (5)
acetophenone (7)
1,3-diphenylpropanone (9)
1-phenylbutan-3-one (11)
4-ethoxycarbonylcyclohexanone (13)
98
93
87
93
81
84
7
4-(ethylenedioxy)cyclohexanone oxime
O-acetate (14)
A
4-ethylenedioxycyclohexanone (15)
74
8
9
10
11
4-phenylcyclohexanone oxime (1)
acetophenone oxime (16)
1-phenylbutan-3-one oxime (17)
1-naphthaldehyde oxime O-acetate (18)
B
B
B
A
4-phenylcyclohexanone (2)
acetophenone (7)
1-phenylbutan-3-one (11)
1-naphthalenemethanol (19) and
1-naphthonitrile (20)
1-naphthalenemethanol (19) and
1-naphthonitrile (20)
3,4,5-trimethoxybenzaldehyde (23) and
3,4,5-trimethoxybenzonitrile (24)
4-phenylcyclohexanone (2)
4-phenylcyclohexanone (2)
98
64
87
55
11
19
33
21
30
70
85
12
13
1-naphthaldehyde oxime (21)
B
B
3,4,5-trimethoxybenzaldehyde oxime (22)
14
15
4-phenylcyclohexanone methylhydrazone (25)
4-phenylcyclohexanone phenylhydrazone (26)
A
A
a Condition A: (i) Co2(CO)8, Et3N, (ii) H2O, MeOH; condition B: (i)AcCl, Et3N, (ii) Co2(CO)8, Et3N, (iii) H2O, MeOH. In the cases of aldoximes
18 and 21, the products were isolated after NaBH4 treatment.
should be mentioned that N,N,-disubstituted hydrazones,
such as the dimethylhydrazone of 2 are inactive toward
the above conditions resulting in the complete recovery of
the starting materials. In addition, the regeneration of car-
bonyl functionality from N-tosylhydrazones could not be
realized.
4-Ethoxycarbonylcyclohexanone Oxime O-Acetate (12)
To a solution of 4-ethoxycarbonylcyclohexanone (850 mg, 5.0
mmol) in THF (30 mL) was successively added a soln of
NH2OH∑HCl (700 mg, 10 mmol) in H2O (5.0 mL) and a soln of
Na2CO3 (360 mg, 3.4 mmol) in H2O (5.0 mL) at r.t. After stirring
for 5 h, the mixture was poured into H2O and extracted with EtOAc.
The extract was washed with water and brine, dried, and concentrat-
ed to dryness. The resulting crude oxime was dissolved in dry Et2O
(20 mL), to which Ac2O (1.3 mL, 14 mmol) and Et3N (1.9 mL, 14
mmol) were added. The mixture was allowed to stand at r.t. for 7 h;
it was poured into H2O and extracted with EtOAc. The extract was
washed with water and brine, dried, and concentrated to dryness.
The residue was chromatographed with EtOAc/hexane (1:2) to give
12 as a colorless oil; yield: 1.1 g (97%).
IR (CHCl3): n = 1645, 1725, 1751 cm-1.
1H NMR: d = 1.27 (t, 3H, J = 6.9 Hz, CH3), 1.95–1.71 (m, 2H,
CH2), 2.16 (s, 3H, OAc), 2.36–2.00 (m, 4H, CH2), 2.70–2.54 (m,
2H, CH2), 3.06 (m, 1H, C4-H),4.16 (q, 2H, J = 6.9 Hz, OCH2).
13C NMR: d = 14.14, 19.61, 24.98, 27.35, 28.43, 30.23, 41.28,
60.61, 166.59, 168.73, 174.03.
In conclusion, we have developed a convenient procedure
for the regeneration of carbonyl functionality from the
corresponding oxime derivatives by simple treatment
with Co2(CO)8. Although the deoximation reactions using
the iron carbonyl species such as Fe(CO)5 or Fe2(CO)9 un-
der anhydrous conditions2j have already been shown to be
effective, the former reagent is known to be highly toxic
and the latter requires a temperature of 60 °C. In compar-
ison with those conditions, the newly developed method
with Co2(CO)8 proceeds under mild conditions (anhy-
drous conditions and higher temperatures are not neces-
sary). In addition, this method has been shown to be
applicable for the N-monosubstituted hydrazone deriva-
tives.
MS (FAB): m/z (%) = 228 (M+ + 1, 52), 168 (100), 122 (63), 94
(60), 73 (24), 29 (25).
Anal calcd for C11H17NO4: C, 58.14; H, 7.54; N, 6.16. Found: C,
58.04; H, 7.57; N, 6.27.
The following measurements were made: IR spectra were measured
with a Shimadzu FTIR-8700 spectrometer for a solution in CHCl3,
MS with a JEOL JMS-SX 102 A mass spectrometer, 1H NMR and
13C NMR with a JEOL EX-270 spectrometer for a solution in
CDCl3 with TMS as an internal standard. Silica gel (silica gel 60,
230–400 mesh, Merck) was used for chromatography. Organic ex-
tracts were dried over anhyd Na2SO4. The known starting materials
employed for regeneration of carbonyl functionality were obtained
by conventional means except for compounds 12, 14, 25, and 26.
4-(Ethylenedioxy)cyclohexanone Oxime O-Acetate (14)
According to the procedure described for the preparation of 12, 14
was obtained as a colorless oil from 4-(ethylenedioxy)cyclohex-
anone (780 mg, 5.0 mmol); yield: 875 mg (82%)
IR (CHCl3): n = 1646, 1758 cm-1.
1H NMR: d = 1.93–1.77 (m, 4H, CH2), 2.17 (s, 3H, OAc), 2.58 (t,
2H, J = 6.6 Hz, CH2), 2.72 (t, 2H, J = 6.6 Hz, CH2), 4.00 (s, 4H,
OCH2CH2O).
Synthesis 1999, No. 11, 1872–1874 ISSN 0039-7881 © Thieme Stuttgart · New York

1874
C. Mukai et al.
SHORT PAPER
13C NMR: d = 19.59, 23.58, 28.99, 33.25, 34.11, 64.57, 107.40,
at the same temperature for 1 h. Co2(CO)8 (6.0 mmol) and Et3N (5.0
mmol) were added to the mixture at r.t. The mixture was then treat-
ed as described for condition A. In the cases of 18 and 21, the result-
ing mixture of carbonyl compound and nitrile derivative was
dissolved in MeOH (50 mL), to which NaBH4 (15 mmol) was add-
ed. The mixture was stirred for 2 h at 0 °C, and MeOH was evapo-
rated off. The residue was diluted with H2O and extracted with
EtOAc. The extract was washed with water and brine, dried, and
concentrated to dryness. Chromatography of the residue with
EtOAc/hexane afforded the corresponding alcohol and nitrile com-
pounds.
166.31, 168.73.
MS (EI): m/z (%) = 213 (M+, 5), 154 (100), 126 (47), 99 (99), 82
(35).
Anal. calcd for C10H15NO4: C, 56.33; H, 7.09; N, 6.57. Found: C,
56.21; H, 7.25; N, 6.53.
4-Phenylcyclohexanone N-Methylhydrazone (25)
A solution of 2 (870 mg, 5.0 mmol), N-methylhydrazine (0.40 mL,
7.5 mmol), and Na2SO4 (5.0 g) in dry CH2Cl2 (30 mL) was heated
under reflux for 3 h. After cooling, the mixture was concentrated to
leave the residual oil, which was passed through a short pad of
Celite with EtOAc to give 25 as a colorless oil; yield: 970 mg
(96%).
References
(1) Green, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York; 1991, p 214.
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(b) Corey, E. J.; Richman, J. E. J. Am. Chem. Soc. 1970, 92,
5276.
IR (CHCl3): n = 1632, 3309 cm-1.
1H NMR: d = 1.83–1.55 (m, 2H, CH2), 1.91 (dt, 1H, J = 13.9, 5.0
Hz, CH2), 2.13–1.99 (m, 2H, CH2), 2.32 (dt, 1H, J = 13.9, 5.0 Hz,
CH2), 2.54 (m, 1H, C4-H), 2.90–2.71 (m, 2H, CH2), 2.93 (s, 3H,
NMe), 7.35–7.16 (m, 5H, Ar-H).
13C NMR: d = 24.93, 32.92, 33.93, 34.14, 35.15, 38.22, 41.33,
43.70, 126.24, 126.70, 128.43, 145.95, 151.91.
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MS (EI): m/z (%) = 202 (M+, 10), 174 (100), 145 (17), 130 (14), 117
(64), 104 (88), 91 (89), 70 (37).
HRMS: m/z calcd for C13H18N2:202.1470, found 202.1473.
4-Phenylcyclohexanone N-Phenylhydrazone (26)
A solution of 2 (1.7 g, 9.8 mmol) and phenylhydrazine (1.1 mL, 11
mmol) in dry CH2Cl2 (50 mL) was stirred in the presence of molec-
ular sieves 4Å (150 mg) at r.t. for 12 h. The mixture was concentrat-
ed to leave the residual solids, which were recrystallized, from
EtOAc/hexane to afford 26 as yellow crystals; yield: 1.2 g (47%).
IR (CHCl3): n = 3365 cm-1.
1H NMR: d = 2.27–1.87 (m, 8H, CH2), 2.73 (m, 1H, C4-H), 7.37–
7.18 (m, 5H, Ar-H), 7.54–7.46 (m, 3H, Ar-H), 7.80–7.71 (m, 2H,
Ar-H), 9.51 (s, 1H, NH).
13C NMR: d = 29.02, 30.28, 33.95, 41.35, 43.34, 103.68, 122.52,
126.20, 126.65, 128.32, 128.41, 128.59, 129.13, 131.32, 146.47,
150.94.
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(71), 78 (43).
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(4) The desired 2 could be isolated without exposing to H2O.
However, the yield of 2 was rather low compared to entry 1 in
the Table.
(5) Treatment of 18 with Co2(CO)8 gave an inseparable mixture
of 1-naphthaldehyde and 1-naphthonitrile (20).
(6) In the case of 22, 3,4,5-trimethoxybenzaldehyde (23) and
3,4,5-trimethoxybenzonitrile (24) could be isolated by column
chromatography.
General Procedure for the Regeneration of Carbonyl Function-
ality
Condition A
To a solution of oxime O-acetate or hydrazone derivatives (5.0
mmol) in Et2O (50 mL) were successively added Co2(CO)8 (5.0
mmol) and Et3N (5.0 mmol) at r.t. The mixture was stirred for 15
min at r.t., and the solvent was evaporated off. The residue was dis-
solved in a combined solvent (50 mL) of H2O and MeOH in a ratio
of 1:2. The mixture was stirred for 30 min at r.t., diluted with H2O,
and extracted with EtOAc. The extract was washed with water and
brine, dried, and concentrated to dryness. Chromatography of the
residue with EtOAc/hexane afforded the corresponding carbonyl
compounds.
Condition B
Article Identifier:
To a solution of oxime (5.0 mmol) in Et2O (50 mL) was added AcCl
(6.0 mmol) and Et3N (5.0 mmol) at 0 °C, and the mixture was stirred
1437-210X,E;1999,0,11,1872,1874,ftx,en;F03899SS.pdf
Synthesis 1999, No. 11, 1872–1874 ISSN 0039-7881 © Thieme Stuttgart · New York