Magtrieve (CrO2) and MnO2 mediated oxidation of aldoximes: Studying the reaction course

Article abstract of DOI:10.1016/j.tet.2010.10.029

Magtrieve (CrO₂) and MnO₂ mediated oxidation of aldoximes to nitrile oxides were studied in details. In presence of external radical source, TEMPO, these reagents did not furnish nitrile oxides, instead favoured deoximation to aldehydes. A common trend of deoximation was established from electronically tuned aldoximes, which is: aliphatic>aromatic> aldoximes with strong electron-withdrawing group, though the extent of deoximation was less in case of CrO₂. Above effects were not observed with chloramine-T and diacetoxyiodobenzene, reagents known to produce nitrile oxides via hydroximoyl halide or equivalent ionic intermediates. A putative reaction mechanism is proposed for MO₂ (M=Cr, Mn) mediated oxidation of aldoximes through formation of a nitroso-oxime tautomeric pair. Formation of nitrile oxide is possibly occurred from the oxime tautomer via a σ-type iminoxy radical intermediate. The deoximation process, dominating in presence of external radical environment, is explained following decomposition of the nitroso tautomer.

Full text of DOI:10.1016/j.tet.2010.10.029

Tetrahedron 66 (2010) 9582e9588
Contents lists available at ScienceDirect
Tetrahedron
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MagtrieveÔ (CrO2) and MnO2 mediated oxidation of aldoximes: studying
the reaction course
*
Sandeep Bhosale, Santosh Kurhade, Samir Vyas, Venkata P. Palle, Debnath Bhuniya
Drug Discovery Facility, Advinus Therapeutics, Quantum Towers, Plot-9, Rajiv Gandhi Infotech Park, Phase-I, Hinjewadi, Pune 411057, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 July 2010
Received in revised form 11 October 2010
Accepted 13 October 2010
Available online 20 October 2010
MagtrieveÔ (CrO2) and MnO2 mediated oxidation of aldoximes to nitrile oxides were studied in details.
In presence of external radical source, TEMPO, these reagents did not furnish nitrile oxides, instead
favoured deoximation to aldehydes. A common trend of deoximation was established from electronically
tuned aldoximes, which is: aliphatic>aromatic>aldoximes with strong electron-withdrawing group,
though the extent of deoximation was less in case of CrO2. Above effects were not observed with
chloramine-T and diacetoxyiodobenzene, reagents known to produce nitrile oxides via hydroximoyl
halide or equivalent ionic intermediates. A putative reaction mechanism is proposed for MO2 (M¼Cr, Mn)
mediated oxidation of aldoximes through formation of a nitroso-oxime tautomeric pair. Formation of
DB dedicates this work to Dr. Santosh Maji
on the occasion of his 60th birthday
nitrile oxide is possibly occurred from the oxime tautomer via a s-type iminoxy radical intermediate. The
deoximation process, dominating in presence of external radical environment, is explained following
decomposition of the nitroso tautomer.
Keywords:
MagtrieveÔ (CrO2),
MnO2
Ó 2010 Elsevier Ltd. All rights reserved.
Aldoxime
Nitrile oxide
TEMPO
1. Introduction
here that Pb(OAc)4 has been known5 to produce nitrile oxides only
from (E)-aldoximes via a rigid six-member transition state 3
Nitrile oxides are versatile intermediates in organic synthesis.
The most useful synthetic application of nitrile oxides is perhaps
the synthesis of isoxazoline and isoxazole heterocycles, via 1,3-di-
polar cycloaddition (1,3-DC) reactions.1 Recently we have com-
municated2a an efficient methodology for direct oxidation of
aldoximes to nitrile oxides using MagtrieveÔ (CrO2),3 and sub-
sequent 1,3-DC reactions with dipolarophiles to furnish the desired
five-member heterocycles in one-step. Additionally for this type of
synthesis, the use of CrO2 has been shown to have specific advan-
tages over some other previously known reagents,2b and particu-
(Scheme 1, Eq. 3). Secondly, we noticed that CrO2 led to significantly
less deoximation compared to what was reported by Kiegiel et al.4a
for MnO2 especially in case of aromatic and aliphatic aldoximes. For
MnO2, involvement of iminoxy radical intermediates 4 has been
invoked by the original investigators4a as common intermediates
towards the formation of nitrile oxides 2 as well as the corre-
sponding aldehydes 5 as deoximation product (Scheme 1, Eq. 2).
However, no further mechanistic insights have been reported in the
literature. Therefore, subsequent to our original communication,
a series of experiments were designed and carried out in our lab-
oratory to study the reaction course of MagtrieveÔ and MnO2
mediated oxidation of aldoximes. Herein, we report our observa-
tions, and at the end propose a putative reaction mechanism to
account various facts.
5
larly over direct oxidizing agents, such as MnO2,4 Pb(OAc)4 and
other transition metal complexes.6
While developing the CrO2-methodology, two interesting ob-
servations motivated us to develop further understanding of these
reactions. Firstly, a mixture of (E)- and (Z)-aldoximes 1 was also
oxidized to nitrile oxides 2 in high yields upon treatment with CrO2
(Scheme 1; Eq. 1). Such results hinted us that CrO2 might follow
a mechanism similar to MnO2, which also has been reported4a to
produce nitrile oxide with equivalent yield from both the stereo-
isomers of aldoximes (Scheme 1, Eq. 2). It is important to mention
2. Results and discussion
2.1. Reactions of CrO2 with (E)- and (Z)-aldoximes
In our previous study with CrO2, it was observed that 60:40
regioisomeric mixture of aliphatic aldoximes furnished 1,3-DC
products in 63e75% isolated yields.2a Subsequently for the present
investigation, pure (E)- and (Z)-benzaldoximes, (E)-1a and (Z)-1a
* Corresponding author. Tel.: þ91 20 66539600; fax: þ91 20 66539620; e-mail
address: debnath.b@advinus.com (D. Bhuniya).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.029

S. Bhosale et al. / Tetrahedron 66 (2010) 9582e9588
9583
AcO
OAc
O
Pb(OAc)4 (1 equiv), CH2Cl2,
-78 oC, base, 2h
Pb
O
Ac
2
.
.
H
N
Only for (E)-aldoxime
Eq. 3 (Ref. 5)
-
CrO2 (10 equiv), MeCN,
R
O
N
OH
N
80 oC, 2h
+
3
?
Mix of (Z)- and (E)-aldoximes
also furnished high yield
R
R
2
1
2
[O]
MnO2 (18 equiv), CH2Cl2,
RT, 18h
Eq. 1 (Ref. 2a)
O
N
.
O
H
Both (Z)- and (E)-aldoximes
shown to have comparable reactivity
R
H
5
R
4
Eq. 2 (Ref. 4a)
Significant deoximation observed
from aromatic and aliphatic aldoximes
Scheme 1. Comparative literature information of Pb(OAc)4, MnO2, and CrO2 mediated oxidation of aldoximes.
were independently reacted with CrO2 following the reported
procedure2a in presence of various dipolarophiles. As anticipated,
the corresponding 1,3-DC products 7ae11a were obtained in
75e86% isolated yields irrespective of the geometry of starting
aldoximes (Scheme 2). It was also noticed that, the furoxan 6a was
formed as dimerization product in absence of dipolarophile. These
results confirm that both (E)- and (Z)-aldoximes were oxidized to
nitrile oxide with equal ease, as was reported for MnO2, and also
suggest for involvement of a common reactive intermediate during
the course of oxidation.
et al.4a for MnO2, we decided to carry out control experiments
where these reactions would be conducted in presence of stable
external radical. Such experiments are well documented in the
literature to prove the involvement of reactive or high energy
radical intermediates either through scavenging the radial in-
termediates or by quenching excited state towards the formation of
radical intermediates.7 Two model reactions were considered: (i)
intermolecular reaction using aldoxime (E)-1b and ethyl propiolate
and (ii) intramolecular reaction from 12 (Table 1). Following the
2a
methodology as described in literature for CrO2 and MnO2,4a
reported yields were obtained for the 1,3-DC products 7b and 13
starting from the respective aldoximes (E)-1b and 12 (Table 1:
entries 1e3,11e13). When the same set of reactions was carried out
in presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or
Galvinoxyl,7 it was noticed that both the MnO2 and CrO2 mediated
reactions were affected by these external radicals. Galvinoxyl led to
rather untractable reaction mixture (multiple spots on TLC), hence
could not be studied further. The TEMPO mediated reactions was
found to be more composed, from which the corresponding alde-
hydes 5b and 14 were isolated as major products instead of the
cycloaddition products along with the recovery of TEMPO (Table 1:
entries 6e8; 16e18). The effect of TEMPO was consistently ob-
served even if the stoichiometry was varied from 0.2 to
2.0 mol equiv (Table 1, entries: 16, 18 footnote g). Formation of any
stable TEMPO-adduct was not evident from HPLC-Mass analysis of
a crude reaction mixture (see also Experimental section 4.2.2).
In another experiment, (Z)-1b also led to the formation of 4-Cl-
benzaldehyde as major product when treated with MnO2 or CrO2 in
the presence of TEMPO (results not shown here).
A careful monitoring of these reactions by TLC and HPLC further
revealed that the CrO2 mediated reactions in presence of TEMPO
required 15 min for deoximation of aldoximes 1b and 12 (Table 1,
entries 6e7, 16e17). This is particularly interesting as it usually
require 2 h for nitrile oxide formation.
To rule out any possibility of TEMPO interfering with either
formation of nitrile oxide intermediate or with the cycloaddition
reaction, aldoximes (E)-1b and 12 were independently treated with
two different reagents from the literature known for oxidation of
aldoximes to nitrile oxides: (i) chloramine-T8dknown to produce
hydroximoyl chloride, and (ii) diacetoxyiodobenzene (DIB)9da
hypervalent reagent possibly work via an ionic intermediate9b but
not have been investigated in past for the possibility of involvement
of radical intermediate. From the results shown in Table 1 (compare
entry 4 vs 9; and entry 14 vs 19; also see experimental section 4.2.4.
Method A and B), it is evident that TEMPO neither reacted with
Ph
CO2Et
O
N
O
N
8a: 83; 81%
7a: 75; 76%
(10% other regeoisomer)
Ph
Ph
CO2Et
CrO2
Ph
CrO2
OH
N
TMS
Ph
+
Ph
H
O
N
O
H
CrO2
TMS
CrO2
-
+
N
N
Ph
Ph
O
O
Ph
9a: 86; 83%
(E)-1a;
(Z)-1a
6a: 80; 82% 5a: ~10 %
O
(by HPLC)
O
S
O
N
Ph
CrO2
CrO2
O
SO2Ph
11a: 80; 85%
N
O
N
O
N
10a: 86; 80%
Ph
Ph
Scheme 2. CrO2 mediated 1,3-DC reactions from (E) & (Z)-1a.
2.2. Effect of an external radical source
Based on literature knowledge2,4 and the results described
above, it was initially hypothesized that both CrO2 and MnO2 me-
diated oxidation of aldoximes might follow an identical mecha-
nism, which would be completely different than the Pb(OAc)4
mediated reactions.
To confirm whether CrO2 and MnO2 mediated reactions proceed
via a radical intermediate, as particularly was proposed by Kiegiel

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S. Bhosale et al. / Tetrahedron 66 (2010) 9582e9588
Table 1
Effect of TEMPO in CrO2 and MnO2 mediated oxidation of aldoximesa
CO2Et
O
N
OH
N
O
N
OH
N
O
H
H
H
O
H
Reagent
CO2Et
O
O
O
Reagent
+
+
+
Br
Br
Br
Cl
7b
Cl
5b
Cl
1b
12
13
14
Reagent
Condition
Entry
No.
Starting
aldoxime
Major product
(% isolated yield)
Entry
No.
Starting
aldoxime
Major product
(% isolated yield)
CrO2
CrO2
MnO2
Chloramine-T
DIB
MeCN, 80 ꢀC, 2 h
Toluene, 80 ꢀC, 2 h
CH2Cl2, rt, 18 h
1b
2b
3c
4d
5e
6f
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
7b (83)
7b (83)
7b (40); 5b (45)
7b (75)
7b (83)
5b (90)
5b (92)
5b (88)
7b (70)
11b
12b
13c
14d
15e
16f
17f
18f
19f
20f
12
12
12
12
12
12
12
12
12
12
13 (85)
13 (85)
13 (46); 14 (36)
13 (80)
MeOH/CH2Cl2, rt, 2 h
CH2Cl2, rt, 2 h
13 (85)
CrO2þTEMPO
CrO2þTEMPO
MnO2þTEMPO
MeCN, 80 ꢀC, 15 min
13 (12); 14 (70)g
13 (15); 14 (75)
13 (20); 14 (60)g
13 (80)
Toluene, 80 ꢀC, 15 min
CH2Cl2, rt, 18 h
7f
8f
Chloramine-TþTEMPO
DIBþTEMPO
MeOH/DCM, rt, 2 h
CH2Cl2, rt, 2 h
9f
10f
7b (80)
13 (82)
a
Formation of nitrile oxides was correlated to isolated yields of corresponding 1,3-DC products 7b and 13.
Followed Ref 2a.
Followed Ref 4a.
Followed Ref 8b.
Followed Ref 9b.
See Experimental section for typical experiments.
Similar result obtained even if when different stoichiometries of TEMPO, such as 0.2, 1.0 and 2.0 mol equiv were used.
b
c
d
e
f
g
nitrile oxides nor interfered with the conversion of hydroximoyl
chlorides to nitrile oxides and subsequent cycloaddition reactions
using chloramine-T. Use of DIB provided us similar result like of
chloramine-T (Table 1; compare entry 5 vs 10; and entry 15 vs 20)
which is in line with the originally proposed mechanism of DIB
mediated oxidation of aldoximes.9b,c
Possibility of deactivation or poisoning of CrO2 or MnO2 in
presence of TEMPO was also ruled out as both the oxidizing agents
indeed oxidized benzyl alcohol to benzaldehyde, as known in the
literature,3b,c even when the reactions were carried out in presence
of the radical source (results not shown here).
radical intermediate. Such early intermediate has two paths to
progress: a radical pathway for nitrile oxide formation and a non-
radical path towards deoximation.
In absence of direct evidence of TEMPO-adduct of any radical
intermediate, precise mechanism of these reactions and structure
of the radical intermediate remains unclear. While further mech-
anistic investigation is beyond our scope, we propose here a puta-
tive mechanism for these reactions as depicted in Scheme 3.
Interaction of aldoxime on MO2 surface (heterogeneous!) may lead
to formation of a complex structure I, which in turn can rearrange
to structure II as suggested in the literature10a for MnO2 mediated
deoximation of oximes into carbonyl compounds. The structure II,
which is predicted here to be the non-radical common in-
termediate, as described in Fig. 1, can lead to either deoximation or
formation of nitrile oxide. The nitroso intermediate II can stay in
equilibrium with its oxime tautomeric structure III. A hydrogen
radical capture from oxime-OH by M(II) in an intramolecular
fashion11 may lead to formation of a high energy radical in-
2.3. Probable reaction mechanism
The above results (Table 1) strongly suggest that both CrO2 and
MnO2 mediated oxidation of aldoximes to nitrile oxides involve
a radical pathway7b,h and might have originated from the common
intermediate conceptualized in previous Section 2.1. In presence of
an external radical environment, such a high energy radical path-
way could be interfered and hence did not yield nitrile oxide. That
raises a question of how to explain the formation of aldehyde as
deoximation product when the radical path is blocked? None the
less, a simplistic diagram is initially put forward in Fig.1 to integrate
the observed experimental results. Upon treatment with MO2
(M¼Mn or Cr), both (E)- and (Z)-aldoximes form a common non-
termediate IV. Such radical intermediate IV is a kind of
s-type
iminoxy radical, well documented in the literature.12 The in-
termediate IV would subsequently undergo homolytic cleavage to
furnish nitrile oxide and M(OH)2 (Scheme 3, path A). In presence of
TEMPO, it is possible that an exited-state structure, towards for-
mation of the high energy iminoxy radical IV from the oxime tau-
tomeric structure III, is quenched. There are literature reports
suggesting such a role of TEMPO.7iek Under such condition, the
radical generation is slowed down. Therefore, decomposition of the
nitroso intermediate II becomes a major process resulting into
aldehyde as deoximation product (Scheme 3, path B).
(Z)-aldoxime
(E)-aldoxime
Non-radical
common Intermediate
It is fundamental to conceive that an electron-withdrawing
group eR attached to a-C of structure II could certainly make the a-
CeH more labile and therefore shift the equilibrium towards the
right (in favour of oxime structure III). Thus the present mechanism
can also explain why MnO2 led to exclusive formation of 1,3-DC
product from electron deficient aldoxime (e.g., R¼eCO2Me)
whereas, aldehydes were the sole products from aliphatic aldox-
imes (e.g., R¼eC11H23), as reported by Kiegiel et al.4a
Non-radical path
Radical path
nitrile oxide
aldehyde
(deoximation)
Fig. 1. Diagram to fit facts with MO2 (M¼Mn, Cr).

S. Bhosale et al. / Tetrahedron 66 (2010) 9582e9588
9585
(R-group has electronic effect
on product distribution possibly
controlling this tautomeric
equilibrium)
(Addition of TEMPO inhibits formation of
nitrile oxide but promotes deoximation)
N
O
.
H
O
.
O
(II)
O
O
O
H
.
H
.
(IV) OH
M
O
N
O
.
N
.
M OH
H
M
N
O
N
N
M(III)
M
O
O
OH
OH
O
R
R
R
H
R
R
H
Homolytic cleavage
I
Iminoxy radical IV
Nitroso Tautomer II
Oxime Tautomer III
alfa-H
-
+
O
N
OH
H
(II)
R
H
(II)
M(II)
+
O
O
N M
+
M
HO
O
OH
OH
R
(Path B)
(Path A)
Scheme 3. A putative reaction mechanism for MO2 (M¼Cr, Mn) mediated oxidation versus deoximation of aldoximes.
Further support to the proposed mechanism was obtained from
a comparative reaction profile between CrO2 and MnO2 towards
1,3-DC reaction versus deoximation of electronically tuned aldox-
imes (results in Table 2). The observed trend of deoximation of
aldoximes having various ‘R-group’ are: aliphatic (Phe(CH2)2e;
1d)>aromatic (Phe; 1a)>strong EWG (eCO2Et; 1c) for both the
CrO2 and MnO2 mediated reactions (Table 2, entries 1e6) with the
difference that CrO2 led to significantly lesser deoximation com-
pared to MnO2. In a controlled study, such differential effect of the
‘R-group’ was not observed from chloramin-T mediated reactions
(Table 2, entries 7e9).
contrary, MnO2 mediated deoximation has been proposed to pro-
ceed via non-radical pathway.10a Together with the literature re-
ports and our experimental results with TEMPO, we believe that
both the MnO2 and CrO2 mediated deoximation processes do not
involve radical intermediate. However, in presence of TEMPO,
deoximation via the proposed nitroso tautomer II may not be an
exclusive path. As shown in Scheme 4, TEMPO could form adduct
through metal centre of both the tautomeric forms II and III and
might facilitate the deoximation process via intermediates like V
and VI in a competitive manner against formation of the iminoxy
radical intermediate IV. Such a mechanism also accounts why
TEMPO mediate deoximation is a faster process (requiring 15 min
compared to 2 h for nitrile oxide formation; see Table 1) as well as,
why less than 1 equiv of TEMPO was equally effective to promote
deoximation.
Table 2
Electronic effect on deoximation versus nitrile oxide formationa
O
(II)
OH
O
OH
N
O
O
H
(II)
O
O
N M
+
O
N
Reagent
O
O
H
N
+
M OH
H
N
R
O
+
M
R
R
O
OH
R
R
R
O
H
15
5
H
1
Nitroso Tautomer II
Oxime Tautomer III
Entry No.
1
Re
Reagent
Product (% isolated
yield)
TEMPO
TEMPO
TEMPO
b
1
2
3
4
5
6
7
8
9
1a
1c
1d
1a
1c
1d
1a
1c
1d
Phe
eCO2Et
e(CH2)2ePh
Phe
eCO2Et
e(CH2)2ePh
Phe
eCO2Et
CrO2
15a (84); 5a (10)
15c (95); dc
15d (75); 5d (20)
15a (42); 5a (40)
15c (84); dc
d
O
N
MnO2
OH
O
O
M
N
N
O
M
N
15d (18); 5d (80)
OH
Chloramin-Te
15a (85); dc
O
R
OH
H
R
15c (95); dc
V
VI
e(CH2)2ePh
15d (75); dc
a
Formation of nitrile oxides was correlated to isolated yields of corresponding
Scheme 4. TEMPO mediated deoximation, another possibility.
1,3-DC products 15.
b
Procedure from Ref. 2a.
No aldehyde observed in TLC and HPLC-MS analysis of the crude reaction
c
In another consideration, CrO2 or MnO2 could also oxidize
TEMPO, at least in catalytic quantity, to the corresponding oxoam-
monium species (Tþ), a species known in the literature.13 As shown
in Eq. 4 and 5, in Scheme 5, adducts like VII and VIII have been
proposed in the literature to explain Tþ mediated oxidation of al-
cohols to carbonyl compounds. However, in light of what is recorded
in the literature, a hypothetical oxidative deoximation reaction (Eq.
6) is unlikely from an equivalent adduct structure IX derived from
aldoxime and Tþ. A nitroso intermediate XI may be conceived either
from IX or from an assembly X following Eq. 7 and 8 respectively.
mixture.
d
Procedure from Ref. 4a.
Procedure from Ref. 8b.
e
We would also like to put forward the alternative mechanistic
possibilities in addition to what has been hypothesized in Scheme
3. In literature, deoximation of oximes to carbonyl compounds have
also been reported to proceed via iminoxy radical, however, under
photosensitized electron-transfer reaction conditions.10b On the

9586
S. Bhosale et al. / Tetrahedron 66 (2010) 9582e9588
Again the structure XI is very unlikely to produce aldehyde and re-
generate the reduced product of oxoammonium species.
distribution between nitrile oxide versus aldehyde arguably by
influencing on pKa of -CeH in structure II. Thus the aldoximes
a
bearing electron-withdrawing groups preferentially yield nitrile
oxide. A shift in product formation (from nitrile oxide to aldehyde)
in presence of TEMPO is probably due to excited-state quenching
phenomena towards generation of the radical intermediate IV in
presence of the external radical environment. Another possible
mechanism of TEMPO mediated deoximation has also been pro-
posed in Scheme 4, which accounts the fact that TEMPO was
equally effective when used in less than 1 equiv. Further support to
the proposed mechanism was gathered from the facts that neither
TEMPO nor the ‘R-group’ of aldoximes affects the product distri-
bution in chloramine-T mediated reactions (Tables 1 and 2), which
are known to proceed via hydroximoyl chloride intermediate and
not via direct oxidation of aldoximes. We hope that all these new
informations will further drive for a more precise mechanistic
study, which is beyond our scope of investigation.
VII
VIII
X
IX
+
+
+
N
.
N
H
N
N
.
O
N
O
N
O
O
O
O
O
O
-
-
R1
R2
H
H
H
H
R
R
R2
R1
Eq. 7
Eq. 8
Eq. 6
H
?
Eq. 5
Eq. 4
O
N
O
R
N
OH
O
O
N
R
XI
H
+
O
4. Experimental section
?
4.1. Synthesis of 6a, 7a, 8a, 9a, 10a, 11a
R2
R1
Following the procedure described in our previous communi-
cation, the above compounds were synthesized.2a Both (E) and (Z)-
benzaldoximes provided us identical results. Analytical data of 6a,14
7a,15 8a,16 9a17 and 11a8b were matched with the literature values.
H
+
(Ref. 13a)
N
OH
R
Scheme 5. Feasibility of TEMPO-derived oxoammonium species to promote
deoximation.
4.1.1. 3,4-Diphenylfuroxan (6a). Rf value: 0.8 (10% ethyl acetate in
hexanes). Mp: 115e117 ꢀC (observed), 114e115 ꢀC (lit.14b). 1H NMR
2.4. Fate of CrO2, reactivation and recycling
(400 MHz; CDCl3):
d
7.52e7.63 (aromatics, 6H); 8.17e8.25 (aro-
124.58, 127.25, 127.83
matics, 4H). 13C NMR (100 MHz; CDCl3):
d
CrO2 has several unique advantages over many other reagents
towards industrial or large scale use. For the reactions discussed in
this work, simple decantation of solvent or magnetic retrieval of
CrO2 allowed us complete recovery of the reagent. It has been
known in the literature that upon oxidation of substrates, the sur-
face of CrO2 gets reduced, which can be reactivated by heating in
air.3b To demonstrate potential for the present CrO2 methodology
towards industrial application, synthesis of 7b, 8a and 13 were
chosen as examples. Following a typical experimental procedure
given for 8a, we were able to carry out three consecutive reactions
upon a recovery, followed by reactivation using simple laboratory
condition, and recycling of CrO2 for each of these examples without
losing any significant yield thereof. It was also observed that
without the reactivation of CrO2 the next recycled reaction did not
progress, which suggests that the reagent was reduced while
aldoximes were oxidized to nitrile oxides.
(2C), 128.47(2C), 129.18(2C), 129.42(2C), 131.51, 133.06, 169.26,
176.01. HPLC-MS (m/z): 239.1 [Mþ1], 222.9 [(Mꢁ16)þ1] base peak.
HPLC purity: 98%; tR: 15.21 min.
4.1.2. 3-Phenylisoxazole-5-carboxylic acid, ethyl ester (7a). Rf value:
0.8 (20% ethyl acetate in hexanes). Mp: 45e46 ꢀC (observed), 47 ꢀC
(lit.15b). 1H NMR (400 MHz; CD3OD):
d
1.42 (t, J¼7.1 Hz, 3H); 4.44 (q,
J¼7.1 Hz, 2H); 7.48e7.51 (aromatics, 3H), 7.54 (s, 1H), 7.88e7.91
(aromatics, 2H). 13C NMR (100 MHz; CDCl3):
14.48, 62.63, 107.65,
d
127.19 (2C), 128.37, 129.41 (2C), 130.86, 157.13, 161.30, 163.28. HPLC-
MS (m/z): 218.0 [Mþ1]. HPLC purity: 99.1%; tR: 26.69 min.
4.1.3. 3,5-Diphenylisoxazole (8a). Rf value: 0.8 (20% ethyl acetate in
hexanes). Mp: 141e143 ꢀC (observed), 140e142 ꢀC (lit.16d). 1H NMR
(400 MHz; CDCl3):
d
6.84 (s, 1H); 7.44e7.52 (aromatics, 6H);
97.79,
7.84e7.89 (aromatics, 4H). 13C NMR (100 MHz; CDCl3):
d
126.14 (2C), 127.12 (2C), 127.78, 129.22 (2C), 129.30 (2C), 129.46,
130.30, 130.51, 163.28, 170.72. HPLC-MS (m/z): 221.9 [Mþ1]. HPLC
purity: 98.6%; tR: 30.24 min.
3. Conclusions
Based on several experimental results (Scheme 2; Table 1, 2)
a putative mechanism is derived for CrO2 and MnO2 mediated di-
rect oxidation of aldoximes to nitrile oxides. To illustrate the
mechanism, initial interaction of either (E)- or (Z)-aldoximes with
MO2 (M¼Cr, Mn) lead to formation of a nitroso-oxime tautomeric
pair II and III as non-radical common intermediates (Scheme 3).
The formation of nitrile oxide is proposed to occur from the oxime
4.1.4. 3-Phenyl-5-trimethylsilanylisoxazole (9a). Rf value: 0.5 (20%
ethyl acetate in hexanes). 1H NMR (400 MHz; CDCl3):
d
0.39 (s, 9H);
6.74 (s, 1H); 7.41e7.48 (aromatics, 3H); 7.82 (dd, J¼7.8 Hz, 1.9 Hz,
2H). 13C NMR (100 MHz; CDCl3):
d
ꢁ1.60 (3C), 110.99, 127.33 (2C),
129.15 (2C), 129.55, 129.96, 161.08, 179.08. HPLC-MS (m/z): 218.3
[Mþ1]. HPLC purity: 98.3%; tR: 29.44 min.
tautomer III via a s-type iminoxy radical intermediate IV (path A).
The involvement of radical intermediate is evident only for the
nitrile oxide formation and not for deoximation process based on
the experimental results with TEMPO. The observed deoximation
(minor for CrO2 and occasionally major for MnO2) is explained
through decomposition of nitroso tautomer II as previously de-
scribed by Yoshihara (path B). Electronics of the ‘R-group’ in
aldoximes is shown to play a key role in dictating product
4.1.5. 5-Benzenesulfonyl-3-phenyl-4,5-dihydroisoxazole (11a). Rf value:
0.3 (20% ethyl acetate in hexanes). MP: 135e137 ꢀC (observed),
137e138 ꢀC (lit.8b). 1H NMR (400 MHz; DMSO-d6):
d 3.95 (dd,
J¼18.8 Hz, 4.6 Hz, 1H); 4.03 (dd, J¼18.8, 10.3 Hz, 1H); 6.13 (dd, J¼10.3,
4.6 Hz, 1H); 7.41e7.51 (aromatics, 3H), 7.62e7.67 (aromatics, 4H), 7.76
(dt, J¼7.5 Hz, 1.4 Hz, 1H), 7.93 (dd, J¼7.2 Hz, 1.5 Hz, 2H). 13C NMR
(100 MHz; DMSO-d6):
d 36.59, 92.87, 127.04 (2C), 127.17, 128.83 (2C),

S. Bhosale et al. / Tetrahedron 66 (2010) 9582e9588
9587
129.28 (2C), 129.40 (2C), 130.95, 134.62, 135.18, 157.24. HPLC-MS (m/z):
288.2 [Mþ1] base peak, 305.2 [Mþ18]. HPLC purity: 98.2%; tR:
21.99 min.
dichloromethane (5.0 mL), was added MnO2 (168 mg, 1.93 mmol,
3 equiv) and the reaction mixture was stirred at rt. After every 3 h,
additional 3 equiv of MnO2 was added and the reaction was mon-
itored by checking TLC till 18 equiv of MnO2 was used up in a total
18 h, when the starting material was fully consumed. The reaction
mixture was filtered through Celite bed. MnO2 was washed with
dichloromethane (20 mLꢂ2). The combined filtrate was condensed
to obtain the crude product. 4-Chlorobenzaldehyde 5b (79.4 mg,
88%) was isolated as major product after column chromatography
(silica gel; ethyl acetate/hexanes). A trace amount of the cycload-
dition product 7b was observed in TLC, which was found to be less
than 5 mg after isolation.
4.1.6. (3-Phenyl-4,5-dihydroisoxazol-5-yl)pyrrolidin-1-yl-meth-
anone (10a). Analytical data were in agreement with its 4-Cl ana-
logue reported2a previously. Rf value: 0.5 (40% acetone in hexanes).
MP: 115e116 ꢀC (observed). IR (neat): 1649 (amide) cmꢁ1. 1H NMR
(400 MHz; DMSO-d6):
d 1.77e1.82 (m, 2H); 1.86e1.96 (m, 2H);
3.30e3.34 (m, 2H); 3.51e3.62 (m, 3H); 3.74 (dd, J¼17.1, 7.3 Hz, 1H);
5.40 (dd, J¼11.3 Hz, 7.3 Hz, 1H); 7.43e7.47 (aromatics, 3H); 7.69 (dd,
J¼7.6 Hz, 2.2 Hz 2H). 13C NMR (100 MHz; CD3OD):
d 24.96, 26.98,
38.35, 47.53, 47.77, 79.73, 127.93 (2C), 129.87 (2C), 130.25, 131.48,
158.29, 169.05. HPLC-MS: m/z 245.3 [Mþ1] base peak, 489.4
[M2þ1]; purity: 99.8%; tR: 17.48 min.
4.2.4. For chloramine-T (Table 1, entry 9). Reaction was done fol-
lowing two different methods as described in the literature.8
TEMPO was added at different stages of the reaction.
4.2. Typical procedure for conducting experiments in
presence of TEMPO
Method A:8b chloramine-T trihydrate (99.7 mg, 0.35 mmol,
1.1 equiv) was added to a solution of 4-chlorobenzaldoxime (50 mg,
0.32 mmol,1.0 equiv) in MeOH (1.5 mL) and was allowed to stir at rt
for 10 min. The reaction mixture was concentrated (rotavapor,
operated at rt) to remove MeOH, dissolved in diethylether (10 mL),
and was washed with 1(N) aq NaOH (10 mL). The organic layer was
concentrated (rotavapor, operated at rt) to get 4-chlorobenzoni-
trile-N-oxide (confirmed by the appearance of strong signal at
4.2.1. For CrO2 (Table 1, entry 6). Reaction was done following the
CrO2-methodology as described in our previous communication2a
however in presence of TEMPO. MagtrieveÔ (Aldrich cat. No.
480037; CAS no. 12018-01-8; 538 mg, 6.45 mmol, 10 equiv) was
added in one portion to a solution of 4-chlorobenzaldoxime 1b
(100 mg, 0.64 mmol, 1.0 equiv), ethyl propiolate (190 mg,
1.93 mmol, 3.0 equiv) and TEMPO (100 mg, 0.64 mmol, 1.0 equiv) in
acetonitrile (3.2 mL), and the reaction mixture was stirred under
heating at 80 ꢀC. Progress of the reaction was monitored by TLC. In
contrast to the previous occasion,2a the starting aldoxime 1b was
fully consumed in 15 min of heating in presence of TEMPO. The
reaction mixture was filtered through Celite bed. MagtreiveÔ was
washed with ethyl acetate (20 mLꢂ2). The combined filtrate was
condensed to obtain the crude. 4-Chlorobenzaldehyde 5b (81.4 mg,
90%) was isolated as major product after column chromatography
(silica gel; ethyl acetate/hexanes) along with essential recovery of
TEMPO. Only trace amount of cyloaddition product 7b could be
seen on TLC, which was found to be less than 5 mg after isolation.
d
100.93 ppm in 13C NMR), which was then dissolved in dichloro-
methane (1.5 mL). To this, TEMPO (50.3 mg, 0.32 mmol, 1.0 equiv)
and ethyl propiolate (98.4 mg, 0.96 mmol, 3.0 equiv) were added
and the reaction mixture was stirred at rt for 2 h (guided by TLC).
After a column chromatography (silica gel; ethyl acetate/hexanes)
of the crude reaction mixture, the cycloaddition product 7b was
isolated as major product (56.6 mg, 70%) with no indication for the
formation of aldehyde 5b (by TLC and HPLC of the reaction mix-
ture). This experiment ruled out two possible scenario: (i) possi-
bility of TEMPO interfering with the 1,3-DC reaction, (ii) possibility
of TEMPO reacting with nitrile oxide.
Method B:8a the above reaction was also carried out having
added TEMPO from the beginning. Thus, to a solution of 4-chloro-
benzaldoxime 1b (50 mg, 0.32 mmol, 1.0 equiv), ethyl propiolate
(98.4 mg, 0.96 mmol, 3.0 equiv) and TEMPO (50.3 mg, 0.32 mmol,
1.0 equiv) in MeOH (1.5 mL), was added chloramine-T trihydrate
(99.7 mg, 0.35 mmol, 1.1 equiv) at rt. This reaction mixture was
stirred at rt for 10 min (to allow formation of the nitrile oxide), and
then diluted with dichloromethane (1.5 mL) before the stirring was
continued for 2 h (needed for cycloaddition reaction). Outcome was
essentially the same as observed in Method A. This result further
ruled out the possibility of TEMPO interfering with the formation
nitrile oxide in a reaction, that is, known to proceed without in-
volving radical intermediate.
4.2.2. For CrO2 (Table 1, entry 16). To a solution of 2-Allyloxy-5-
bromo-benzaldehyde oxime 12 (300 mg, 1.17 mmol, 1.0 equiv) and
TEMPO (182.8 mg, 1.17 mmol, 1.0 equiv), in 6.0 mL acetonitrile,
MagtrieveÔ (984.4 mg, 11.72 mmol, 10 equiv) was added in one
portion, and the reaction mixture was stirred under heating at
80 ꢀC. Progress of reaction was monitored by TLC, which indicated
consumption of the starting material after 15 min. An aliquot was
analyzed by HPLC, which revealed a product distribution of the
corresponding aldehyde 14 and TEMPO as major components (75
and 100%, respectively) along with a minor amount of the cyclo-
addition product 13 (16%), and trace amounts of starting aldoxime
12 (3%) and the corresponding nitrile oxide (6%) in the reaction
mixture. There was no other HPLC signal noticed, which could
provide an indication of possible TEMPO-adduct. The reaction
mixture was filtered through Celite bed and MagtreiveÔ was
washed with ethyl acetate (20 mLꢂ2). The combined filtrate was
condensed to get the crude product, which was then purified by
silica gel column chromatography (ethyl acetate/hexanes) to isolate
pure 14 (198.1 mg, 70%),13 (36.2 mg,12%), the corresponding nitrile
4.2.5. For DIB (Table 1, entry 20). To a solution of 2-Allyloxy-5-
bromo-benzaldehyde oxime 12 (100 mg, 0.39 mmol, 1.0 equiv) and
TEMPO (60.9 mg, 0.39 mmol, 1.0 equiv), in 8.0 mL CH2Cl2, was
added DIB (138.4 mg, 0.43 mmol, 1.1 equiv) at 0 ꢀC in one portion.
The reaction mixture was stirred at rt for 2 h at which point TLC
indicated consumption of the starting material. The reaction mix-
ture was diluted with 20 mL CH2Cl2 and then washed with water
(20 mL), dried over anhydrous sodium sulfate, and concentrated to
obtain the crude product, which was then purified by silica gel
column chromatography (ethyl acetate/hexanes) to isolate pure 13
(82.0 mg, 82%). This result further suggests that TEMPO has no
effect on DIB mediated oxidation of aldoximes to nitrile oxides.
Therefore it is inferred here that the DIB mediated reactions work
solely via ionic intermediates as was suggested by Das et al.9b
Analytical data of 7b, 13 and 14 were matched with our pre-
viously reported values from authentic samples.2a
oxide (8 mg, 3%; characteristic signals IR: 2230 cmꢁ1 13C NMR:
.
d
104.4 ppm, mass: m/z 255.1 (79Br) and 256.9 (81Br) as [Mþ1])
along with recovery of TEMPO (150 mg, 82%).
4.2.3. For MnO2 (Table 1, entry 8). Reaction was done following
MnO2-methodology as described in the literature4a however in
presence of TEMPO. To
a solution of 4-chlorobenzaldoxime
(100 mg, 0.64 mmol, 1.0 equiv), ethyl propiolate (190 mg,
1.93 mmol, 3.0 equiv) and TEMPO (100 mg, 0.64 mmol, 1.0 equiv) in

9588
S. Bhosale et al. / Tetrahedron 66 (2010) 9582e9588
A. 1,3-Dipolar Cycloaddition Chemistry; John Wiley: New York, NY, 1984; Vols.
4.3. Synthesis of 15a, 15c and 15d (Table 2)
1, 2; (d) Torssell, K. B. G. Nitrile Oxides, Nitrones and Nitronates in Organic
Synthesis; VCH: New York, NY, 1988; (e) Gothelf, K. V.; Jùrgensen, K. A. Chem.
Rev. 1998, 98, 863e909; (f) Kanemasa, S.; Tsuge, O. Heterocycles 1990, 30,
719e736; (g) Stanley, L. M.; Sibi, M. P. Chem. Rev. 2008, 108, 2887e2902; (h)
Belen’kii, L. I. In Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis:
Novel Strategies in Synthesis, 2nd ed.; Feuer, H., Ed.; John Wiley: New Jersey,
2008; pp. 1e128.
As described inTable 2, reported procedures were followed for the
respective methodologies using CrO2, MnO2 and chloramine-T. Ana-
lytical data of 15a18 and 15c19 were matched with the literature values.
2. (a) Bhosale, S.; Kurhade, S.; Prasad, U. V.; Palle, V. P.; Bhuniya, D. Tetrahedron Lett.
2009, 50, 3948e3951; (b) Cross-references cited in 2a for previous methodologies.
3. For literature and synthetic applications of MagtrieveÔ (CrO2) see: (a) Liu, Y.-H.
Synlett 2008, 1103e1104 and references cited herein.; (b) Lee, R. A.; Donald, D. S.
Tetrahedron Lett. 1997, 38, 3857e3860; (c) Liao, Y.; Shabany, H.; Spilling, C. D.
4.3.1. 3-Phenyl-5-acetoxy-4,5-dihydroisoxazole (15a). Rf value: 0.5
(30% ethyl acetate in hexanes). Mp: 99e100 ꢀC (observed),
98e100 ꢀC (lit.18a). IR (neat): 1755 (ester) cmꢁ1. 1H NMR (400 MHz;
CDCl3):
d
2.08 (s, 3H); 3.37 (dd, J¼17.9 Hz, 1.2 Hz, 1H); 3.62 (dd,
ꢀ
Tetrahedron Lett. 1998, 39, 8389e8392; (d) Contour-Galcera, M.-O.; Piotout, L.;
J¼17.9 Hz, 6.8 Hz, 1H); 6.84 (dd, J¼6.9 Hz, 1.2 Hz, 1H); 7.42e7.48
Moinet, C.; Morgan, B.; Gordon, T.; Roubert, P.; Thurieau, C. Bioorg. Med. Chem.
Lett. 2001, 11, 741e745; (e) Wan, H.; Peng, Y. Monatsh. Chem. 2008, 139, 909e912.
4. For oxidation of aldoximes using MnO2, see: (a) Kiegiel, J.; Poplawska, M.;
(aromatics, 3H); 7.70e7.73 (aromatics, 2H). 13C NMR (100 MHz;
CDCl3):
d 21.24, 41.61, 96.19, 127.31 (2C), 128.57, 129.13 (2C), 131.07,
ꢀꢀ
Jozwik, J.; Kosior, M.; Jurczak, J. Tetrahedron Lett. 1999, 40, 5605e5608;
157.28, 169.93. HPLC-MS (m/z): 206.1 [Mþ1], 223.1 [Mþ18], 228.2
(b) Kudyba, I.; Jozwik, J.; Romanski, J.; Raczko, J.; Jurczak, J. Tetrahedron:
Asymmetry 2005, 16, 2257e2262.
5. For oxidation of aldoximes using Pb(OAc)4, see: Just, G.; Dahl, K. Tetrahedron
1968, 24, 5251e5269.
6. For oxidation of aldoximes using potassium ferricyanide and ceric ammonium
nitrate, see: (a) Gagneux, A. R.; Meier, R. Helv. Chim. Acta 1970, 53,
1883e1892; (b) Giurg, M.; Mlochowski, M. Pol. J. Chem. 1997, 71, 1093e1101;
(c) Arai, N.; Iwakoshi, M.; Tanabe, K.; Narasaka, K. Bull. Chem. Soc. Jpn. 1999,
72, 2277e2285.
7. Use of external radical source e.g., TEMPO and Galvinoxyl, selected in this study,
are well documented in the literature. Please see: (a) Barriga, S. Synlett 2001,
563; (b) Yanagisawa, S.; Ueda, K.; Taniguchi, T.; Itami, K. Org. Lett. 2008, 10,
4673e4676; (c) Li, F.; Tartakoff, S. S.; Castle, S. L. J. Org. Chem. 2009, 74,
9082e9093; (d) Deprez, N. R.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131,
11234e11241; (e) Villamena, F. A. J. Phys. Chem. 2010, 114, 1153e1160; (f) Ka-
shiwabara, T.; Fuse, K.; Muramatsu, T.; Tanaka, M. J. Org. Chem. 2009, 74,
9433e9439; (g) Zhu, Z.-B.; Shi, M. Org. Lett. 2009, 11, 5278e5281; (h) Liu, W.;
Cao, H.; Zhang, H.; Chung, K.H.; He, C.; Wang, H.; Kwong, F.Y.; Lei, A. J. Am. Chem.
Soc., in press. doi:10.1021/ja103050x (i) Suzuki, T.; Obi, K. Chem. Phys. Lett. 1995,
246, 130e134; (j) Chattopadhay, S. K.; Das, P. K.; Hug, G. L. J. Am. Chem. Soc. 1983,
105, 6205e6210; (k) Mitsui, M.; Kobori, Y.; Kawai, A.; Obi, K. J. Phys. Chem. A
2004, 108, 524e531.
8. For 1,3-DC reactions using chloramine-T, see: (a) Hassner, A.; Rai, K. M. L.
Synthesis 1989, 57e59; (b) Rai, K. M. L.; Hassner, A. Synth. Commun. 1997, 27,
467e472 and ref. cited herein.
9. (a) Radhakrishna, A. S.; Sivaprakash, K.; Singh, B. B. Synth. Commun. 1991, 21,
1625e1629; (b) Das, B.; Holla, H.; Mahender, G.; Banerjee, J.; Ravinder Reddy,
M. Tetrahedron Lett. 2004, 45, 7347e7350; (c) Prakash, O.; Pannu, K. Arkivoc
2007, xiii, 28e33; (d) Mendelsohn, B. A.; Lee, S.; Kim, S.; Teyssier, F.; Aulakh, V.
S.; Ciufolini, M. A. Org. Lett. 2009, 11, 1539e1542.
[Mþ23], 433.1 [M2þ23]. HPLC purity: 99.79%, tR: 19.22 min.
4.3.2. 5-Acetoxy-4,5-dihydroisoxazole-3-carboxylic acid, ethyl ester
(15c). Rf value: 0.5 (30% ethyl acetate in hexanes).1H NMR (400 MHz;
CDCl3):
d
1.39 (t, J¼7.1 Hz, 3H); 2.09 (s, 3H); 3.24 (dd, J¼18.8 Hz,1.7 Hz,
1H); 3.45 (dd, J¼19.1 Hz, 7.3 Hz, 1H); 4.39 (q, J¼7.1 Hz, 2H); 6.83 (dd,
J¼7.3 Hz,1.7 Hz,1H).13C NMR (100 MHz; CDCl3):
d 14.29, 21.03, 40.13,
62.74, 96.77, 152.224, 159.95, 169.38. HPLC-MS (m/z): 202.2 [Mþ1],
425.1 [M2þ23]. HPLC purity: 97.2%; tR: 7.62 min.
4.3.3. 3-(2-Phenylethyl)-5-acetoxy-4,5-dihydroisoxazole
value: 0.6 (20% ethyl acetate in hexanes). IR (neat): 1755 (ester)
cmꢁ1. 1H NMR (400 MHz; CDCl3):
(15d). Rf
d
2.06 (s, 3H); 2.76 (t, J¼8.3 Hz,
2H), 2.81 (d, J¼18.0 Hz, 1H); 2.96 (t, J¼8.1 Hz, 2H), 3.15 (dd,
J¼18.0 Hz, 6.8 Hz, 1H); 6.63 (d, J¼6.6 Hz, 1H); 7.20e7.26 (aromatics,
3H); 7.28e7.34 (aromatics, 2H). 13C NMR (100 MHz; CDCl3):
d 21.23,
29.19, 32.78, 43.85, 95.57, 126.71, 128.50 (2C), 128.83 (2C), 140.33,
159.10, 169.92. HPLC-MS: m/z 234.2 [Mþ1], 256.1 [Mþ23]; purity:
98.5%; tR: 10.73 min.
4.4. Recycling MagtrieveÔ (CrO2) in synthesis of 8a
To a solution of benzaldoxime (1.0 g, 8.26 mmol, 1.0 equiv) and
phenyl acetylene (2.71 mL, 24.79 mmol, 3.0 equiv) in 41 mL ace-
tonitrile, taken in a single neck round bottom flask, was added
MagtrieveÔ (6.93 g, 82.6 mmol, 10 equiv) and the reaction mixture
was heated at 80 ꢀC for 2 h while stirring. The solvent was decanted
and MagtreiveÔ was washed with acetonitrile (50 mLꢂ2). The
combined acetonitrile pool was condensed to get a crude product.
Whereas, the recovered MagtrieveÔ (6.90 g) was sequentially
treated with acetonitrile (50 mL) and distilled water (20 mLꢂ2)
each at 60 ꢀC for 0.5 h to remove traces of organic materials. Finally
the flask containing MagtrieveÔ was heated on a sand bath at
320e340 ꢀC for 4 h (air exposed).3b Reactivated MagtrieveÔ, thus
obtained, was reused for the synthesis of another crop of 8a.
The whole process was repeated two more times to get three
crops of crude compounds, which were then combined and puri-
fied by silica gel column chromatography (EtOAc/hexane) to obtain
8a in pure form (4.16 g, combined yield 76%).
10. (a) For MnO2 assisted deoximation of oximes into carbonyl compounds and
a proposed mechanism, see: Shinada, T.; Yoshihara, K. Tetrahedron Lett. 1995,
36, 6701e6704; (b) For photosensitized deoximation of oximes and mechanism
involving iminoxy radical, see: (i) Lijser, H. J. P.; Fardoun, F. H.; Sawyer, J. R.;
Quant, M. Org. Lett. 2002, 4, 2325e2328 and references cited herein; (ii) Lijser,
H. J. P.; Hsu, S.; Marquez, B. V.; Park, A.; Sanguantrakun, N.; Sawyer, J. R. J. Org.
Chem. 2006, 71, 7785e7792.
11. In absence of any direct evidence for intramolecular hydrogen radical transfer
from oxime-OH to Cr, we looked at any literature evidence for similar process.
For examples of hydrogen transfer to Cr]O and Cr moieties to form CreOeH
and CreH bonds, please see: (a) Parsell, T. H.; Yang, M.-Y.; Borovik, A. S. J. Am.
Chem. Soc. 2009, 131, 2762e2763; (b) Bakac, A.; Guzei, I. A. Inorg. Chem. 2000,
39, 736e740; (c) Agapie, T.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2007,
129, 14281e14295.
12. For
s-type iminoxy radicals, see: (a) Chapman, O. L.; Heckert, D. C. Chem.
Commun. 1966, 242e243; (b) Norman, R. O. C.; Gilbert, B. C. J. Phys. Chem. 1967,
71, 14e19; (c) Ref. 5 and 10b. (d) Lindsay, D.; Horswill, E. C.; Davidson, D. W.;
Ingold, K. U. Can. J. Chem. 1974, 52, 3554e3556.
13. For use of TEMPO-derived oxoammonium species in oxidation of alcohols to
carbonyl compounds, and mechanistic studies of these reactions, please see: (a)
de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Synthesis 1996, 1153e1174; (b)
Bolm, C.; Fey, T. Chem. Commun. 1999, 1795e1796; (c) Ansari, I. A.; Gree, R. Org.
Lett. 2002, 4, 1507e1509; (d) Comminges, C.; Barhdadi, R.; Doherty, A. P.;
O’Toole, S.; Troupel, M. J. Phys. Chem. A 2008, 112, 7848e7855.
Acknowledgements
14. For 6a: (a) Kaufman, J. V. R.; Picard, J. P. Chem. Rev. 1959, 59, 429e461; (b) Wiley,
R. H.; Wakefield, B. J. J. Org. Chem. 1960, 25, 546e551; (c) Yu, Z.-X.; Caramella, P.;
Houk, K. N. J. Am. Chem. Soc. 2003, 125, 15420e15425.
15. For 7a: (a) Franz, J. E.; Pearl, H. K. J. Org. Chem. 1976, 41, 1296e1297; (b) Harada,
K.; Kaji, E.; Zen, S. Chem. Pharm. Bull. 1980, 28, 3296e3303.
Authors are grateful to Drs. Rashmi Barbhaiya and Kasim
Mookhtiar for their support and encouragement. SB is thankful to
Andhra University for registering in Ph.D. program, and Professors
Y.L.M. Murthy and U.V. Prasad for their guidance. Authors also
acknowledge the reviewers for their important suggestions.
16. For 8a: (a) Beam, C. F.; Dyer, M. C. D.; Schwarz, R. A.; Hauser, C. R. J. Org. Chem.
ꢀ
1970, 35, 1806e1810; (b) L’abbe, G.; Mathys, G. J. Org. Chem. 1974, 39,
1221e1225; (c) Ref. 13b. (d) Tang, S.; He, J.; Sun, Y.; He, L.; She, X. Org. Lett. 2009,
11, 3982e3985.
17. For 9a: Padwa, A.; MacDonald, J. G. J. Org. Chem. 1983, 48, 3189e3195.
18. For 15a: (a) Rahman, A.; Clapp, L. B. J. Org. Chem. 1976, 41, 122e125; (b) Ref. 4a.
19. For 15c: Conti, D.; Rodriquez, M.; Sega, A.; Taddei, M. Tetrahedron Lett. 2003, 44,
5327e5330.
References and notes
1. For nitrile oxide and 1,3-DC reactions, see: (a) Grundmann, C. Synthesis 1970,
344e359; (b) Kozikowski, A. P. Acc. Chem. Res. 1984, 17, 410e416; (c) Padwa,