Synthesis of o-(diphenylphosphinoyloxy)anilines by the rhodium-catalyzed reaction of nitroarenes and diphenylphosphine oxide

Article abstract of DOI:10.1016/j.tetlet.2010.04.029

A rhodium complex Rh₂(OAc)₄ catalyzed the reaction of nitrobenzenes and diphenylphosphine oxide HP({double bond, long}O)Ph₂ giving o-(diphenylphosphinoyloxy)anilines predominantly, which were accompanied by small amounts of the p-isomers. Nitorobenzenes possessing a bulky o-substituent, particularly o-(t-butyl)nitrobenzenes, underwent the reaction in high yields. The reaction is considered to involve the reductive formation of O-phosphinoyl-N-arylhydroxyamines from nitrobenzenes, and o-phosphinoyloxylation by the rearrangement.

Full text of DOI:10.1016/j.tetlet.2010.04.029

Tetrahedron Letters 51 (2010) 3116–3118
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Tetrahedron Letters
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Synthesis of o-(diphenylphosphinoyloxy)anilines by the rhodium-catalyzed
reaction of nitroarenes and diphenylphosphine oxide
Mieko Arisawa a, Manabu Kuwajima a, Masahiko Yamaguchi a,b,
*
a Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
b WPI Research Center, Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A rhodium complex Rh2(OAc)4 catalyzed the reaction of nitrobenzenes and diphenylphosphine oxide
HP(@O)Ph2 giving o-(diphenylphosphinoyloxy)anilines predominantly, which were accompanied by
small amounts of the p-isomers. Nitorobenzenes possessing a bulky o-substituent, particularly o-(t-
butyl)nitrobenzenes, underwent the reaction in high yields. The reaction is considered to involve the
reductive formation of O-phosphinoyl-N-arylhydroxyamines from nitrobenzenes, and o-phosphinoyloxy-
lation by the rearrangement.
Received 6 February 2010
Revised 5 April 2010
Accepted 9 April 2010
Available online 13 April 2010
Ó 2010 Elsevier Ltd. All rights reserved.
The Bamberger reaction is the rearrangement of N-arylhydroxy-
amines under strong acid conditions giving p-aminophenols, and is
considered to proceed via nitrenium cations.1 This method intro-
duces an oxygen functional group directly to the aromatic nuclei.
Modified methods using carboxylate2 and sulfonate3 derivatives of
hydroxyamines were reported, which often gave the o-substituted
products. Nitrobenzenes, which are readily available compared to
N-arylhydroxyamines, could be converted to p-aminophenols under
acidic conditions in the presence of reducing agents.4 Electrochem-
ical method or metal-catalyzed hydrogenation was generally em-
ployed for the reduction,4,5 and the use of phosphinic acid in the
presence of palladium catalyst was reported.6 The reaction using
nitrobenzenes is considered to proceed via in situ formed
N-arylhydroxyamines.
When o-(t-butyl)nitrobenzene and diphenylphosphine oxide
HPOPh2 (3 equiv) were reacted in the presence of Rh2(OAc)4
(5 mol %) at 80 °C in toluene for 7 h, 2-(diphenylphosphinoyl-
oxy)-6-(t-butyl)aniline was obtained in 56% yield along with the
4-isomer in 23% yield (Scheme 2). No reaction occurred in the ab-
sence of the rhodium complex. Rh2L4 complexes with L = acetate,
trifluoroacetate, and pivalate exhibited similar catalytic activities,
while those with L = benzoate and o-methylbenzoate gave very
small amounts of the product. Among other rhodium complexes
examined, Rh(acac)(CH2@CH2)2 showed a similar activity with
Rh2(OAc)4, whereas the yields lowered to 10–20% using phosphine
complexes, RhH(PPh3)4, RhCl(PPh3)3, and [Rh(cod)(PPh3)2]PF6.
Previously, we reported rhodium-catalyzed phosphinoylation
and phosphination reaction of 1-alkynes with tetraphenyldiphos-
phine in the presence of 2,4-dimethylnitrobenzene.7,8 The diphos-
phine was converted to tetraphenyldiphosphine monooxide or
N-phosphinyl-N-phosphinoylaniline without catalyst. The former
was the phosphinoylation reagent of 1-alkynes and the latter
phosphination reagent. During the examination on the rhodium-
catalyzed reaction of nitrobenzenes and organophosphorus com-
pounds, reductive phosphinoyloxylation reaction of nitrobenzene
was developed, which gave o-(phosphinoyloxy)anilines predomi-
nantly (Scheme 1). This method introduces a diphenylphosphinoyl-
oxy group at the o-position of nitrobenzenes without using strong
acid. Such aromatic phosphinoyloxylation was not known before,
and O-phosphinoyl-N-arylhydroxyamines were reported not to give
the phosphorous compounds.9
NO2
O
NH2
Rh2(OAc)4
t-Bu
Ph2PO
t-Bu
+
HPOPh2
X
X
Scheme 1.
NO2
Rh2(OAc)4 (5 mol%)
toluene, 80 °C, 7 h
t-Bu
+
HPOPh2
3 eq
O
Ph2PO
NH2
NH2
t-Bu
t-Bu
+
OPPh2
23%
56%
O
* Corresponding author. Tel.: +81 22 795 6812; fax: +81 22 795 6811.
E-mail address: yama@mail.pharm.tohoku.ac.jp (M. Yamaguchi).
Scheme 2.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.029

M. Arisawa et al. / Tetrahedron Letters 51 (2010) 3116–3118
3117
NO2
When o-nitrotoluene was subjected to the reaction, 2- and 4-
(phosphinoyloxy)aniline were obtained in 17% and 19% yields,
respectively (Scheme 3). The reaction of 4-(t-butyl)nitrobenzene
gave 4-(t-butyl)-2-(phosphinoyloxy)aniline in 29% yield, which
was accompanied by a considerable amount of azoxybenzene
(39%) (Scheme 4). Thus, the presence of a bulky o-substituent in-
creased the yield, which was ascribed to the suppression of the
nitrogen coupling reaction during the reduction of nitro group. For-
mation of azoxy compounds was observed in the conventional
Bamberger reaction.1
Several 2-(t-butyl)nitrobenzenes with different 4-substituents,
alkyl, phenyl, phenoxy, halogen, and trifluoromethyl groups were
reacted, and the corresponding o-(phosphinoyloxy)anilines were
obtained in good yields (Scheme 5). The electronic effect of the
p-substituent was small. The reaction of 2,5-di(t-butyl)nitroben-
zene gave the o-phospinoyloxylated product in 54% yield along
with the p-product in 18% yield (Scheme 6). A small amount of a
product derived from the ipso-substitution at the 2-(t-butyl) group
was also formed in 13% yield.
Rh2(OAc)4 (2 mol%)
Me
+
HPOPh2
3 eq
toluene, 80 °C, 24 h
O
NH2
NH2
Me
Ph2PO
Me
+
OPPh2
19%
17%
O
Scheme 3.
NO2
Rh2(OAc)4 (5 mol%)
toluene, 80 °C, 7 h
HPOPh2
3 eq
+
t-Bu
O
Ph2PO
NH2
O
A model mechanism is as follows: the formation of O-phosphi-
noyl-N-arylhydroxyamines; the rearrangement to the products
(Scheme 7). Since no reaction occurred in the absence of the rho-
dium complex, the catalyst should be involved in the reduction
of the nitro group to form the O-phosphinoylated intermediate.
The second step, the rearrangement of phosphinoyloxy group to
the aromatic nuclei is presumed also to be the rhodium-catalyzed
process. The lack of electronic effect on the nitrobenzene may not
be consistent with the generation of nitrenium cation.
Typical experimental procedures: In a two-necked flask equipped
with a reflux condenser were placed Rh2(OAc)4 (5.0 mol %, 5.5 mg),
2-(t-butyl)nitrobenzene (0.25 mmol, 44.8 mg), and diphenylphos-
phine oxide (0.75 mmol, 151.6 mg) under an argon atmosphere.
Degassed dry toluene (2 mL) was added, and the solution was
heated at 80 °C for 7 h. Then, satd NaHCO3 was added, and the
mixture was extracted with ethyl acetate. The organic layer was
washed with brine, dried over Na2SO4, and concentrated under
reduced pressure. The residue was purified by flash column
chromatography on silica gel giving 6-(t-butyl)-2-(diphenylphos-
phinoyloxy)aniline (51.4 mg, 56%) and 2-(t-butyl)-4-(diphenyl-
phosphinoyloxy)aniline (20.6 mg, 23%). Diphenylphosphinic acid
(74.3 mg) was also obtained.
t-Bu
N
N
t-Bu
t-Bu
29%
39%
Scheme 4.
O
Ph2PO
NH2
NO2
Rh2(OAc)4 (5 mol%)
toluene, 80 °C, 7 h
t-Bu
t-Bu
+ HPOPh2
4
3 eq
X
X
X = Me 52%
X = t-Bu 71%
X = Ph 77%
X = OPh 54%
X = Br 42%
X = CF3 58%
Scheme 5.
NO2
Rh2(OAc)4 (5 mol%)
t-Bu
+
HPOPh2
3 eq
Acknowledgments
toluene, 80 °C, 9 h
t-Bu
This work was supported by Grant-in-Aid for Scientific Re-
search (No. 21229001), GCOE program, and WPI Initiative from
JSPS. M.A. expresses her thanks to the Grant-in-Aid for Scientific
Research on Priority Areas, ‘Advanced Molecular Transformation
of Carbon Resources’ from MEXT (Nos. 18037005 and 19020008)
and Naito Foundation.
NH2
t-Bu
O
Ph2PO
NH2
O
NH2
13%
t-Bu
OPPh2
+
+
t-Bu
t-Bu
t-Bu
OPPh2
54%
O
18%
Scheme 6.
O
Ph2PO
O
Ph2PO
NO2
NH
NH2
O
Rh cat
O
Rh cat
O
+
HPPh2
+
HOPPh2
+
HOPPh2
X
X
X
Scheme 7.

3118
M. Arisawa et al. / Tetrahedron Letters 51 (2010) 3116–3118
T. M.; Curtin, T. J. J. Am. Chem. Soc. 1984, 106, 5623; Gassman, P. G.; Granrud, J. E.
Supplementary data
J. Am. Chem. Soc. 1984, 106, 1498; Novak, M.; Roy, A. K. J. Org. Chem. 1985, 50,
571.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.04.029.
4. Gattermann, L. Chem. Ber. 1893, 26, 1844; Harman, R. E.; Cason, J. J. Org. Chem.
1952, 17, 1047; Harman, R. E. Org. Synth. 1963, Coll. Vol. 4, 148.
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6. Zoran, A.; Khodzhaev, O.; Sasson, Y. J. Chem. Soc., Chem. Commun. 1994, 2239.
7. Arisawa, M.; Onoda, M.; Hori, C.; Yamaguchi, M. Tetrahedron Lett. 2006, 47, 5211.
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