O-alkyl-N-acyl-N-phenylhydroxylamines as photochemical alkoxy radical precursors

Article abstract of DOI:10.1055/s-0031-1290824

A simple and efficient technique for the photolysis of alkoxy radical precursors is developed. Irradiation of O-alkyl-N-acyl-N-phenylhydroxylamines, as representative alkoxy radical precursors, with ultraviolet light (254 nm) results in homolytic N-O bond cleavage to generate singlet alkoxy and acylaminyl caged radical pairs. These radicals, depending on the solvent employed, either escape from the cage to form fragmentation products, or undergo in-cage reactions to produce photorearrangement products. The homolytic cleavage of the N-O bond is analyzed using time-dependent density functional theory calculations. The nature of the N-acyl substituent on the O-alkyl-N-acyl-N- phenylhydroxylamines is shown to influence their ability to generate radicals. Furthermore, identification and trapping of the alkoxy radicals is demonstrated. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290824

PAPER
▌1745
paper
O-Alkyl-N-acyl-N-phenylhydroxylamines as Photochemical Alkoxy Radical
Precursors
Photochemical Alkoxy Radical Precursors
Nilanjana Chowdhury, Anakuthil Anoop,* N. D. Pradeep Singh*
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
Fax +91(3222)282252; E-mail: ndpradeep@chem.iitkgp.ernet.in
Received: 21.12.2011; Accepted after revision: 09.03.2012
Dedicated to Professor Eluvathongal D. Jemmis on the occasion of his 60th birthday
molytic N–O bond cleavage on direct photolysis involv-
Abstract: A simple and efficient technique for the photolysis of
ing the singlet excited state, to form 1,3- and 1,5-acyloxy
alkoxy radical precursors is developed. Irradiation of O-alkyl-N-
photorearrangement products along with fragmentation
compounds (an arenecarboxanilide, a carboxylic acid and
acyl-N-phenylhydroxylamines, as representative alkoxy radical
precursors, with ultraviolet light (≥254 nm) results in homolytic N–
O bond cleavage to generate singlet alkoxy and acylaminyl caged hydrocarbons). The products of photorearrangement were
radical pairs. These radicals, depending on the solvent employed,
either escape from the cage to form fragmentation products, or un-
dergo in-cage reactions to produce photorearrangement products.
tation products was explained via a cage-escape
The homolytic cleavage of the N–O bond is analyzed using time-
dependent density functional theory calculations. The nature of the
found to be derived from in-cage recombination of acyl-
oxy and amido radicals, while formation of the fragmen-
mechanism of the above-mentioned radicals.15,16 Interest-
ingly, the same group showed that when the photolysis of
N,O-diacyl-N-phenylhydroxylamines was carried out in
hydrogen donor solvents, fragmentation products (car-
boxylic acid and carboxanilide) were produced exclusive-
ly, via efficient hydrogen atom abstraction from the
solvent by cage-escaped acyloxy and amido radicals.17
The above facts concerning the efficient photoinduced ho-
molytic N–O bond cleavage chemistry of N,O-diacyl-N-
phenylhydroxylamines, together with our interest in ex-
ploring the applications of those compounds,18 prompted
us to investigate the possibility of utilizing O-alkyl-N-
acyl-N-phenylhydroxylamines as alkoxy radical precur-
sors.
N-acyl substituent on the O-alkyl-N-acyl-N-phenylhydroxylamines
is shown to influence their ability to generate radicals. Furthermore,
identification and trapping of the alkoxy radicals is demonstrated.
Key words: alkoxy radicals, O-alkyl-N-acyl-N-phenylhydroxyl-
amines, homolytic cleavage, acylaminyl radical, alkoxy radical pre-
cursors
Alkoxy radicals have been utilized for the synthesis of a
wide variety of organic products,1 and moreover, they are
pivotal intermediates in several mechanistic1b,e,2 and pho-
tobiological studies.3 Alkoxy radicals primarily undergo
three main reactions, namely β-cleavage,4 1,5-hydrogen
atom transfer5 and cyclization.6 Several precursors for the
generation of alkoxy radicals have been reported which
include alkyl nitrites,7 nitrates,8 hypohalites,9 sulfenyl
ethers10 and alkyl-4-nitrobenzenesulfenates.11 However,
these precursors often require acidic conditions, or reac-
tive reagents to generate the alkoxy radicals, which may
not be compatible with other labile functional groups
present in the molecule. Hence, substrates which generate
alkoxy radicals under photolytic or mild conditions (e.g.,
Bu3SnH–AIBN) have become the subject of interest. Pre-
cursors such as N-alkoxy-pyridine-2-thiones,2b Se-phenyl
benzoselenohydroximates,12 N-alkoxyphthalimides,13 N-
alkoxy-2-pyridones,14 and N-(alkoxy)thiazole-2(3H)-
thiones6c have been used to generate alkoxy radicals effi-
ciently via photoinduced homolytic cleavage of the weak
N–O bond.
Herein, we report O-alkyl-N-acyl-N-phenylhydroxyl-
amines as simple and efficient photochemical alkoxy rad-
ical precursors. The synthesis and characterization of the
alkoxy radical precursors is discussed. We also studied in
detail the photochemistry of O-alkyl-N-acyl-N-phenylhy-
droxylamines on alkoxy radical formation, the solvent ef-
fects on photoproduct distribution, analysis of N–O bond
cleavage using theoretical calculations and the influence
of N-acyl substituents on the ability to generate the alkoxy
radical precursors. Furthermore, identification and trap-
ping of the alkoxy radicals has been discussed.
O-Alkyl-N-benzoyl-N-phenylhydroxylamines
3a–m
were synthesized using the reported procedure19 outlined
in Scheme 1. Treatment of N-benzoyl-N-phenylhydroxyl-
amine (1) with various alcohols 2a–m, in the presence of
diethyl azodicarboxylate (DEAD) and triphenylphos-
phine (Ph3P) in tetrahydrofuran at room temperature for a
period of 18 hours, afforded the corresponding alkoxy
radical precursors 3a–m20 in good to excellent yields (cf.
Table 3). The precursors 3a–m were characterized by 1H,
13C NMR and IR spectroscopy and mass spectrometry.
Significant progress has been made to understand the
mechanism of N–O bond cleavage in N,O-diacyl-N-phen-
ylhydroxylamines in connection with photoacyloxy rear-
rangement.15 Sakurai and co-workers15a showed that N,O-
diacyl-N-phenylhydroxylamines underwent efficient ho-
SYNTHESIS 2012, 44, 1745–1754
Advanced online publication: 10.05.2012
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1
1
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DOI: 10.1055/s-0031-1290824; Art ID: SS-2012-N1173-OP
© Georg Thieme Verlag Stuttgart · New York

1746
N. Chowdhury et al.
PAPER
abstraction from the benzyloxy radical by the benzanilidyl
radical to form benzaldehyde (5), and minor processes re-
sulting in dimerization, disproportionation and addition
reactions of benzanilidyl radicals are favored.22 However,
in solvents with an abstractable hydrogen atom (aqueous
methanol and acetonitrile), we noted higher yields of ben-
zyl alcohol (2a) and benzanilide (4). More interestingly,
in anhydrous benzene containing four equivalents of tri-
butyltin hydride (Bu3SnH), we observed the formation of
benzyl alcohol and benzanilide, exclusively, from alkoxy
radical precursor 3a. As a representative example, we
have included the HPLC traces recorded at regular inter-
vals during the photolysis of 3a on irradiation in aqueous
methanol (see Supporting Information, Figure 1s). This
solvent study indicated that the photolysis of 3a proceed-
ed via homolysis of the N–O bond.
Ph3P, DEAD
THF, r.t.
R1OH
O
OH
Ph
+
N
R1
N
O
Ph
O
1
2a–m
3a–m
R1 = benzyl (3a), phenylethyl (3b), phenylpropyl (3c),
3,4-dimethoxy phenylpropyl (3d), cinnamyl (3e),
phenylbutyl (3f), decyl (3g), tetradecyl (3h),
tetrahydrofuran-2-methyl (3i), pent-4-enyl (3j),
2-phenylpent-4-enyl (3k), 5-phenylpent-4-enyl (3l)
4-phenylpent-4-enyl (3m)
Scheme
1
Synthesis of O-alkyl-N-benzoyl-N-phenylhydroxyl-
amines 3a–m
Initially, we investigated the photolysis of O-benzyl-N-
benzoyl-N-phenylhydroxylamine (3a) (0.2 mM) in an ox-
ygen-free acetonitrile solution using a medium pressure
mercury lamp (125 W) with a quartz sleeve. Similar to
Table 1 Distribution of the Photoproducts of O-Benzyl-N-benzoyl-
N,O-diacyl-N-phenylhydroxylamines,15 alkoxy radical N-phenylhydroxylamine (3a) in Various Solvents
precursor 3a underwent photoinduced homolytic N–O
Unreacted 3a (%)a Yield of photoproducts (%)a
Solvent
bond cleavage to generate singlet benzyloxy and benzan-
ilidyl radical cage pairs (Scheme 2). These radicals escape
from the cage to produce the fragmentation products, ben-
zyl alcohol (2a), benzanilide (4) and benzaldehyde (5). In-
terestingly, we also found that an in-cage reaction of the
above-mentioned radical pairs occurred to yield photore-
arrangement products 6a and 6b. Compound 6a was iden-
tified by isolation and comparison with an authentic
sample. Since 1,3-photorearrangement product 6b was
only formed in a small amount, it was not isolated, but in-
stead was identified from the crude NMR spectra of the
photolysate by comparison with that of a known sample.21
4
2a
5
6a
C6H6
25
20
20
18
15
5
25
28
30
32
35
42
26
32
35
38
42
48
8
5
12
10
8
PhCF3
DCE
<2
–
MeCN
aq MeOH
5
–
–
b
–
–
C6H6
a Yield calculated from NMR spectra using anisole as an internal stan-
To study the effect of solvents on the formation of the
photoproducts and their distribution, we carried out the
photolysis of 3a (0.2 mM) in hydrogen atom free solvents
[benzene, trifluorotoluene (PhCF3), dichloroethane
(DCE)], poor hydrogen atom donor solvents (acetonitrile,
aqueous methanol), and an efficient hydrogen atom donor
solvent (anhydrous benzene containing Bu3SnH) over
three hours (Table 1). We observed that alkoxy radical
precursor 3a produced low yields of fragmentation prod-
ucts 2a and 4 in benzene and trifluorotoluene. In these sol-
vents, competing pathways such as α-hydrogen
dard.
b Containing Bu3SnH (4 equiv).
We have also performed time-dependent density func-
tional theory (TDDFT) calculations (see computational
methods for details), on alkoxy radical precursor 3a in or-
der to analyze the N–O bond cleavage mechanism. The
four lowest vertical excitation energies at the TD-
B3LYP/def2-SVP level of theory and their oscillator
strengths are given in Table 2.
O
+
Ph
C
PhCH2OH
+
NHCOPh
H
2a
4
5
1
cage-escape
in-cage
O
Ph
hν
N
•
_
>
•
+
λ
254 nm
O
Ph
N
O
Ph
O
Ph
3a
OCH2Ph
OCH2Ph
+
PhOCHN
NHCOPh
6a
6b
Scheme 2 Photolysis of O-benzyl-N-benzoyl-N-phenylhydroxylamine (3a) in acetonitrile
Synthesis 2012, 44, 1745–1754
© Georg Thieme Verlag Stuttgart · New York

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Photochemical Alkoxy Radical Precursors
1747
Table 2 Low-Lying Excited States, Excitation Energies and Oscilla-
tor Strengths of O-Benzyl-N-benzoyl-N-phenylhydroxylamine (3a)
Obtained from TD-B3LYP/def2-SVP Calculations
State
Excitation energy (eV) Oscillation strength
S1
S2
S3
S4
4.16
4.43
4.71
4.77
0.106114620990912100
0.007424637903512666
0.012829276438581270
0.011781504286684200
The ground state potential energy surface (PES) for N–O
bond cleavage was analyzed by a relaxed surface scan
(Figure 1) with fixed N–O distances, from 1.364–2.263 Å
in 0.1 Å steps. All coordinates, except the N–O bond dis-
tance were allowed to be optimized. The BP86/def2-SVP
method was used for this scan. The energy was found to
increase with increasing N–O bond distance, and the sys-
tem eventually dissociates into two fragments. The bond
dissociation energy (BDE) for the homolytic cleavage
from the ground state minima was 48.21 kcal/mol and the
process was endothermic. The potential energy surface
(TD-BP86/def2-SVP) for the first singlet excited surface
(S1) was analyzed using a similar surface scan to that de-
scribed above. The estimated activation barrier was 11.35
kcal/mol. A similar value (12 kcal/mol) was found for N-
(trifluoromethanesulfonyloxy)-1,8-naphthalimide using
the estimated barrier from the surface scan of the single
point S1 state energies at ground state (S0) geometries.23
In contrast, the N–O bond dissociation in alkyl nitrites
was barrierless.24 The geometry at the highest point was
further optimized using the dimer method which allowed
the transition state to be located. The transition state was
characterized using vibrational frequency analysis. The
activation barrier including zero-point correction was
10.56 kcal/mol. Minima and transition state geometries at
the S1 surfaces were also computed using the B3LYP
functional and def2-SVP basis set; the activation barrier
was found to be 10.64 kcal/mol. All the above computa-
tions were performed using the restricted Kohn–Sham
formalism. When unrestricted formalism was employed, a
lower barrier of 6.1 kcal/mol was obtained. Since unre-
stricted calculations are more reliable for homolysis reac-
tions, the 6.1 kcal/mol value should be considered as a
more accurate barrier for the N–O bond cleavage. The
bond dissociation energy determined from the excited
state minima (S1) was –2.75 kcal/mol and the bond cleav-
age was exothermic. Heterolytic cleavage, leading to dis-
sociation into cationic and anionic fragments, can be ruled
out as it is an endothermic (by 198.11 kcal/mol) process.
Figure 1 Potential energy surface for the thermal dissociation (red
solid curve; BP86/def2-SVP) and the reaction profile for the photo-
chemical dissociation (blue dashed line; TD-UB3LYP/def2-SVP) of
N–O bonds. The geometry of the transition state and the HOMO and
LUMO orbitals are also shown.
95%) as shown in Table 3. In each case the photoproducts
were isolated and analyzed by NMR spectroscopy (data
were compared with those of authentic samples). We
found that the free alcohols were the major photoproducts
in addition to benzanilide (4). The quantum yields for the
generation of the alcohols were found to be in the range
0.008–0.015% using valerophenone as an actinometer.25
To demonstrate the requirement of ultraviolet light for the
generation of alkoxy radicals, we carried out control ex-
periments, which involved maintaining a solution of the
alkoxy radical precursor 3a–m in anhydrous benzene
(containing 4 equiv of Bu3SnH) in the dark for a period of
15 days. HPLC analysis showed that under these condi-
tions the alkoxy radical precursors were stable and that no
photoproducts were produced. In addition, we verified the
propensity for alkoxy radical generation from O-alkyl-N-
benzoyl-N-phenylhydroxylamines under standard radical
conditions, by treating 3a with tributyltin hydride (1.2
equiv) and 2,2′-azobis(isobutyronitrile) (AIBN) as the ini-
tiator in benzene at reflux temperature for five hours,
which resulted in formation of benzyl alcohol (2a) in a
good 70% yield.
To demonstrate the applicability of alkoxy radical precur-
sors for the generation of various alcohols, we irradiated
solutions of O-alkyl-N-benzoyl-N-phenylhydroxylamines
3a–m (0.2 mM) in anhydrous benzene (containing 4 equiv
of Bu3SnH) using a medium pressure mercury lamp with
a quartz sleeve for two to five hours. The corresponding
free alcohols 2a–m were obtained in high yields (85–
© Georg Thieme Verlag Stuttgart · New York
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1748
N. Chowdhury et al.
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Table 3 Synthetic Yield, UV/Vis and Photolysis Data of O-Alkyl-N-benzoyl-N-phenylhydroxylamines 3a–m
Yield (%)a
Time (h)d
Photolysis yield (%)e Quantum yield (%)f
Radical precursor
UV/Vis
Alcohol
λ (nm)b
log εc
3a
3b
3c
3d
3e
3f
95
92
85
89
85
80
87
87
90
82
87
92
90
258
259
260
278
261
260
258
258
259
257
260
261
261
4.16
4.16
4.14
4.25
4.20
4.18
4.03
4.02
4.08
4.09
4.17
4.18
4.18
3.0
3.0
3.0
3.5
2.5
3.5
4.5
4.8
3.0
5.0
4.8
5.0
4.5
2a
2b
2c
2d
2e
2f
95
90
88
92
90
89
87
85
85
85
88
90
85
0.015
0.014
0.013
0.012
0.018
0.009
0.008
0.013
0.008
0.009
0.009
0.008
0.008
3g
3h
3i
2g
2h
2i
3j
2j
3k
3l
2k
2l
3m
2m
a Yield of isolated products 3.
b Maximum absorption wavelength (λmax).
c Molar absorption coefficient.
d Time required for photolysis.
e Photolysis yield of 2 based on 1H NMR spectroscopy.
f Quantum yield for the alcohols at room temperature (error limit within ±5%).
We next investigated the effect of various N-acyl substit- der reaction, obtained by linear least-square methodology
uents on the alkoxy radical precursors on their ability to for a straight line (see Supporting Information, Figure 2s).
generate radicals. Thus, O-benzyl-N-acyl-N-phenylhy- Further, we also calculated the first order photolysis rate
droxylamines 8a–d were prepared from substrates 7a–d constant (K) values from the slope [lnC versus irradiation
(Scheme 3).
time (t)] for the formation of benzyl alcohol from the alk-
oxy radical precursors. The quantum yield (Φ) and photol-
ysis rate constant values (Table 4) indicate that the N-acyl
substituents influence the formation of benzyl alcohol.
We found that alkoxy radical precursor 8c, possessing an
electron-donating 3,4-dimethoxybenzoyl substituent,
showed the lowest quantum yield for the formation of
benzyl alcohol among the precursors investigated. The
above effect can be due to destabilization of the newly
generated acylaminyl radical by the strongly electron-
donating acyl substituents.26 Hence, the present study in-
dicates that the N-acyl substituents influence the ability of
the substrates to generate radicals.
Ph3P, DEAD
THF, r.t.
O
R
Ph
OH
N
+ PhCH2OH
N
O
O
R
7a–d
8a–d
R = Me (8a), 4-O2NC6H4 (8b), 3,4-(MeO)2C6H3 (8c), 4-ClC6H4 (8d)
Scheme 3 Synthesis of O-benzyl-N-acyl-N-phenylhydroxylamines
8a–d
To compare the efficiency of different N-acyl derivatives
of O-benzyl-N-phenylhydroxylamines for the generation
of benzyloxy radicals, we irradiated compounds 3a and
8a–d in anhydrous benzene (containing 4 equiv of
Bu3SnH) for three hours using a light source of ≥254 nm,
and monitored the formation of benzyl alcohol by HPLC
at regular time intervals. From the HPLC data, the natural
logarithm of the concentration of benzyl alcohol formed
(lnC) versus irradiation time (t) was plotted for each alk-
oxy radical precursor. We observed linear correlations for
the formation of benzyl alcohol which suggested a first or-
We were also interested in demonstrating these O-alkyl-
N-acyl-N-phenylhydroxylamines as synthetic precursors
for the stereoselective synthesis of tetrahydrofurans, as
has been previously reported in the literature.6 Photolysis
of compounds 3j–l in the presence of four equivalents of
tributyltin hydride in trifluorotoluene for three hours re-
sulted in formation of substituted tetrahydrofurans 10j–l
(Scheme 4). Among the precursors, photolysis of 3l pro-
duced 2-benzyltetrahydrofuran (10l, 75%, Table 5, entry
2),27 along with benzanilide (4, 85%), aldehyde 9l (5%)
Synthesis 2012, 44, 1745–1754
© Georg Thieme Verlag Stuttgart · New York

PAPER
Photochemical Alkoxy Radical Precursors
1749
Table 5 Synthesis of Tetrahydrofurans 10j–l
Table 4 Synthetic Yield, UV/Vis and Photolysis Data of O-Benzyl-
N-acyl-N-phenylhydroxylamines 3a and 8a–d
R1
R2
Solventa
C6H6
Entry Substrate
Product Yield (cis/trans)
log εc
Radical Yield λmax
precursor
K
Photolysis Quantum
yield (%)e yield (%)f
(%)a
(min–1)d
(nm)b
65b
1
2
3
4
5
6c
3l
H
Ph
Ph
H
10l
75 [72]b
30b
3l
H
PhCF3 10l
PhCF3 10j
2.00 × 10–2
1.90 × 10–2
1.37 × 10–2
0.33 × 10–2
1.40 × 10–2
3a
8a
8b
8c
8d
92
90
90
88
85
258
247
278
290
264
4.16
4.06
4.02
4.14
4.49
95
92
90
88
90
0.015
0.015
0.014
0.006
0.013
3j
3k
3k
3l
H
59 (80/20)b
64 (80/20)b
–
Ph
Ph
H
H
C6H6
PhCF3 10k
C6H6 10l
10k
H
Ph
a In each case, the solvent contained Bu3SnH (4 equiv).
b Yield calculated by NMR spectroscopy of the crude reaction mix-
ture using anisole as an internal standard. Yield of isolated product is
provided in square brackets.
a Yield of isolated product.
b Maximum absorption wavelength.
c Molar absorption coefficient.
d Rate constant.
c No product was obtained in the absence of light.
e Photolysis yield of benzyl alcohol based on 1H NMR spectroscopy
of the crude reaction mixture using anisole as an internal standard.
f Quantum yield for the formation of benzyl alcohol at room temper-
ature (error limit within ±5%).
(BrCCl3) as a bromine atom donor and alkoxy radical pre-
cursor 3f as the O-radical source. Photolysis of compound
3f and bromotrichloromethane in trifluorotoluene using a
medium pressure mercury lamp (125 W) produced a 37%
yield of 4-bromo-4-phenylbutanol (11);6b,c,28 the yield was
calculated by 1H NMR spectroscopy of the crude reaction
mixture using anisole as an internal standard. The forma-
tion of compound 11 can be explained via 1,5-hydrogen
transfer from carbon to the oxygen-centered radical fol-
lowed by bromine atom abstraction by the newly generat-
ed carbon-centered radical (Scheme 5). Further,
compound 11 cyclized into 2-phenyltetrahydrofuran
(12)29 on purification by silica gel column chromatogra-
phy.
and alkenol 2l (4%). The formation of 2-benzyltetrahy-
drofuran can be explained via 5-exo ring-closure of the
alkoxy radical intermediate. In contrast, photolysis of
compound 3l in benzene in the presence of tributyltin hy-
dride produced 2-benzyltetrahydrofuran in 65% yield
(Table 5, entry 1). Irradiation of 3k in trifluorotoluene
(containing 4 equiv of Bu3SnH) resulted in formation of
the substituted tetrahydrofuran 10k in 64% yield (Table 5,
entry 5), whereas compound 3j, under similar conditions,
produced a 30% yield of unsubstituted tetrahydrofuran
(Table 5, entry 3).
The possibility of heteroatom-trapping under photolytic
conditions was explored using bromotrichloromethane
O
Ph
R2
O
+
+
N
Ph
R1
H
R1
4
9j–l
hν
O
R2
N
PhCF3, Bu3SnH
H
R1
R1
O
Ph
3j–l
R2
H
HO
+
R2
O
10j–l
2j–l
Scheme 4 Synthesis of tetrahydrofurans 10j–l from O-alkyl-N-acyl-N-phenylhydroxylamines 3j–l
•
•
OH
OH
O
1,5-H abstraction
hν
O
N
Ph
PhCF3, BrCCl3
O
Ph
3f
Br
column purification
Ph
O
12
11
Scheme 5 Trapping of a carbon-centered radical using bromotrichloromethane (BrCCl3)
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1745–1754

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N. Chowdhury et al.
PAPER
O-Benzyl-N-benzoyl-N-phenylhydroxylamine (3a)
The crude residue was purified by column chromatography
(EtOAc–hexane, 9:41) to give the title compound.
In summary, we have reported O-alkyl-N-acyl-N-phenyl-
hydroxylamines as efficient alkoxy radical precursors
based on photoinduced N–O bond cleavage chemistry.
Formation of the photoproducts and their distribution in
different solvents along with time-dependent density
functional theory calculations indicated that photolysis of
the alkoxy radical precursors proceeded through homoly-
sis of the N–O bond from the singlet excited state.
Yield: 1.00 g (95%); white solid; mp 85–87 °C.
IR (KBr): 1648 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 4.87 (s, 2 H), 7.17 (d, J = 4.0 Hz,
2 H), 7.24–7.47 (m, 9 H), 7.56 (d, J = 8.0 Hz, 2 H), 7.65 (d, J = 6.6
Hz, 2 H).
Interestingly, the ability of O-alkyl-N-acyl-N-phenyl- 13C NMR (50 MHz, CDCl3): δ = 73.9, 124.2 (2 C), 126.9, 127.9 (2
C), 128.5 (2 C), 128.6 (2 C), 128.9, 129.0 (2 C), 129.7 (2 C), 130.6,
hydroxylamines to generate alkoxy radicals was shown to
be altered by different N-acyl substituents. Further, we
demonstrated the identification and trapping of the newly
generated alkoxy radicals via intramolecular addition to
134.1, 134.9, 139.7, 168.6.
HRMS (ES+): m/z [M + Na]+ calcd for C20H17NO2Na: 326.1157;
found: 326.1129.
double bonds and homolytic substitution.
O-Phenylethyl-N-benzoyl-N-phenylhydroxylamine (3b)
The crude residue was purified by column chromatography
(EtOAc–hexane, 1:5) to give the title compound.
Reactions were monitored using precoated silica gel 60 F254 TLC
Yield: 1.08 g (92%); brown solid; mp 90–92 °C.
IR (KBr): 1645 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 2.86 (t, J = 6.8 Hz, 2 H), 4.12 (t,
J = 6.8 Hz, 2 H), 7.09–7.13 (m, 2 H, ArH), 7.18–7.46 (m, 11 H),
7.65 (d, J = 8.0 Hz, 2 H).
sheets (Merck). Chromatographic purification was performed using
60–120 mesh silica gel (Merck). Petroleum ether (PE) refers to the
fraction boiling in the 40–60 °C range. Melting points were ob-
tained using a REICO apparatus and are uncorrected. FT-IR spectra
1
were obtained using a Perkin Elmer RXI spectrometer. H NMR
(200 MHz) spectra were recorded on a Bruker-AC 200 MHz spec-
trometer. Chemical shifts are reported in ppm relative to tetrameth-
ylsilane with the solvent resonance as the internal standard (CDCl3:
7.26 ppm). Data are reported as follows: chemical shift, multiplicity
(s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), cou-
pling constant (Hz), integration. 13C NMR (50 MHz) spectra (pro-
ton decoupled) were recorded on a Bruker-AC 200 MHz
spectrometer. Chemical shifts are reported in ppm relative to tetra-
methylsilane with the solvent resonance as the internal standard
(CDCl3: 77.0 ppm). UV/Vis absorption spectra were recorded on a
Shimadzu UV-2450 UV/Vis spectrophotometer. High-resolution
mass spectra were obtained using an LCT Micromass spectrometer.
HPLC was performed using a Shimadzu Prominence (LC 20 AT)
liquid chromatography instrument on a C18 column (4.5 mm × 250
mm) with a UV/Vis detector. Photolysis of all compounds was car-
ried out using a 125 W medium pressure mercury lamp supplied by
SAIC (India).
13C NMR (50 MHz, CDCl3): δ = 34.5, 74.8, 123.9 (2 C), 126.6,
126.8, 128.0 (3 C), 128.5 (4 C), 128.9 (3 C), 130.7, 134.7, 137.5,
139.7, 168.3.
HRMS (ES+): m/z [M + H]+ calcd for C21H20NO2: 318.1494; found:
318.1425.
O-Phenylpropyl-N-benzoyl-N-phenylhydroxylamine (3c)
The crude residue was purified by column chromatography
(EtOAc–hexane, 1:5) to give the title compound.
Yield: 1.08 g (85%); brown liquid.
IR (neat): 1645 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 1.77–1.90 (m, 2 H), 2.54 (t, J = 7.4
Hz, 2 H), 3.88 (t, J = 6.2 Hz, 2 H), 7.02 (d, J = 7.4 Hz, 2 H), 7.16–
7.27 (m, 4 H), 7.30–7.50 (m, 7 H), 7.63 (d, J = 6.4 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 29.6, 31.9, 73.6, 124.3 (2 C), 126.0,
127.0, 128.0 (2 C), 128.4 (4 C), 128.6 (2 C), 129.0 (2 C), 130.6,
134.8, 139.8, 141.2, 168.2.
Computational Methods
Density functional theory (DFT) calculations were performed using
the BP8630 and B3LYP31 functionals with empirical dispersion cor-
rection (DFT-D)32 in conjunction with the def2-SVP33 basis set.
Resolution of the identity (RI) approximation was used to speed-up
the BP86 calculations. TURBOMOLE V6.234 was used for all cal-
culations. For excited state calculations, time-dependent density
functional theory (TDDFT) was employed. We included the four
lowest roots for each calculation. Dl-find,35 implemented in
ChemShell36 was used for optimizations. The dimer method37 was
employed in order to compute transition states at the excited state
potential energy surface (PES). Vibrational analysis for excited
states was performed using finite-difference Hessian evaluation im-
plemented in ChemShell, and for ground state structures, analytic
gradients from TURBOMOLE V6.2 were used.
HRMS (ES+): m/z [M + H]+ calcd for C22H22NO2: 332.1650; found:
332.1603.
O-(3,4-Dimethoxyphenylpropyl)-N-benzoyl-N-phenylhydroxyl-
amine (3d)
The crude residue was purified by column chromatography
(EtOAc–hexane, 1:4) to give the title compound.
Yield: 1.20 g (89%); yellow liquid.
IR (neat): 1647 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 1.79–1.86 (m, 2 H), 2.50 (t, J = 8.0
Hz, 2 H), 3.83 (s, 6 H), 3.90 (t, J = 6.2 Hz, 2 H), 6.54–6.60 (m, 2 H),
6.73 (d, J = 8.0 Hz, 1 H), 7.24–7.39 (m, 6 H), 7.47 (d, J = 8.8 Hz, 2
H), 7.62 (d, J = 8.0 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 29.8, 31.6, 55.8, 55.9, 73.6, 111.3,
111.7, 120.2, 124.3 (2 C), 127.0, 127.9 (2 C), 128.5 (2 C), 128.9 (2
C), 130.5, 133.9, 134.8, 139.8, 147.3, 148.9, 168.2.
O-Alkyl-N-benzoyl-N-phenylhydroxylamines 3a–m; General
Procedure
To a soln of N-benzoyl-N-phenylhydroxylamine (1) (789 mg, 3.70
mmol), alcohol 2 (3.08 mmol) and Ph3P (1.2 g, 4.6 mmol) in THF
(10 mL) was added DEAD (0.73 mL, 4.6 mmol) in THF (10 mL) at
r.t. under an N2 atm. After stirring for 18 h at r.t., the mixture was
diluted with H2O (5 mL) and extracted with EtOAc (50 mL). The
combined organic layer was dried over anhyd MgSO4, filtered, con-
centrated and purified.
HRMS (ES+): m/z [M + H]+ calcd for C24H26NO4: 392.1862; found:
392.1894.
O-Cinnamyl-N-benzoyl-N-phenylhydroxylamine (3e)
The crude residue was purified by column chromatography
(EtOAc–hexane, 1:4) to give the title compound.
Yield: 1.05 g (89%); brown liquid.
Synthesis 2012, 44, 1745–1754
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Photochemical Alkoxy Radical Precursors
1751
IR (neat): 1648 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 1.30–1.34 (m, 1 H), 1.41–1.53 (m,
1 H), 1.70–1.89 (m, 2 H), 3.63–3.69 (m, 2 H), 3.73–3.88 (m, 2 H),
3.92–4.08 (m, 1 H), 7.16–7.27 (m, 1 H), 7.29–7.42 (m, 5 H), 7.46
(d, J = 9.6 Hz, 2 H), 7.52–7.59 (m, 2 H).
13C NMR (50 MHz, CDCl3): δ = 25.5, 28.0, 63.8, 75.8, 76.5, 123.9
(2 C), 126.8, 127.9 (2 C), 128.5 (2 C), 128.9 (2 C), 130.6, 134.7,
139.6, 168.3.
1H NMR (200 MHz, CDCl3): δ = 4.53 (d, J = 7.0 Hz, 2 H), 6.07–
6.18 (m, 1 H), 6.52 (d, J = 16.0 Hz, 1 H), 7.21–7.46 (m, 11 H), 7.55
(d, J = 8.2 Hz, 2 H), 7.66 (d, J = 7.6 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 75.0, 122.3, 124.5 (2 C), 126.8 (2
C), 127.0, 128.0 (2 C), 128.4, 128.6 (2 C), 128.7 (2 C), 129.0 (2 C),
130.7, 134.9, 136.0, 136.4, 139.9, 168.4.
HRMS (ES+): m/z [M + H]+ calcd for C18H20NO3: 298.1443; found:
298.1454.
HRMS (ES+): m/z [M + H]+ calcd for C22H20NO2: 330.1494; found:
330.1478.
O-(Pent-4-enyl)-N-benzoyl-N-phenylhydroxylamine (3j)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:22) to give the title compound.
O-Phenylbutyl-N-benzoyl-N-phenylhydroxylamine (3f)
The crude residue was purified by column chromatography
(EtOAc–hexane, 9:41) to give the title compound.
Yield: 0.95 g (82%); brown liquid.
IR (neat): 1640 (C=O) cm–1.
Yield: 1.02 g (80%); yellow liquid.
IR (neat): 1642 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 1.48–1.67 (m, 2 H), 1.92–2.02 (m,
2 H), 3.86 (t, J = 6.4 Hz, 2 H), 4.84–4.92 (m, 2 H), 5.56–5.76 (m, 1
H), 7.13–7.25 (m, 1 H), 7.33–7.42 (m, 5 H), 7.49 (d, J = 7.6 Hz, 2
H), 7.63 (d, J = 6.2 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 36.6, 44.3, 77.6, 116.7, 123.8,
126.7, 127.8 (2 C), 127.9 (2 C), 128.4 (2 C), 128.8 (2 C), 130.5,
135.6, 140.9, 168.2.
1H NMR (400 MHz, CDCl3): δ = 1.43–1.46 (m, 4 H), 2.47–2.60 (m,
2 H), 3.88 (s, 2 H), 7.09 (d, J = 7.6 Hz, 2 H), 7.18 (t, J = 7.2 Hz, 1
H), 7.24–7.29 (m, 3 H), 7.33–7.42 (m, 5 H), 7.50 (d, J = 7.6 Hz, 2
H), 7.63 (d, J = 7.2 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 27.4 (2 C), 35.4, 74.1, 123.9 (2 C),
125.8, 126.8, 127.9 (2 C), 128.3 (2 C), 128.4 (2 C), 128.5 (2 C),
129.0 (2 C), 130.5, 134.9, 139.8, 141.9, 168.4.
HRMS (ES+): m/z [M + H]+ calcd for C18H20NO2: 282.1494;
found:282.1428.
HRMS (ES+): m/z [M + H]+ calcd for C23H24NO2: 346.1807; found:
346.1797.
O-(2-Phenylpent-4-enyl)-N-benzoyl-N-phenylhydroxylamine
(3k)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:17) to give the title compound.
O-Decyl-N-benzoyl-N-phenylhydroxylamine (3g)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:17) to give the title compound.
Yield: 1.10 g (87%); brown liquid.
IR (neat): 1640 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 0.89 (t, J = 5.4 Hz, 3 H), 1.16–1.24
(m, 14 H), 1.38–1.48 (m, 2 H), 3.83 (t, J = 6.4 Hz, 2 H), 7.17–7.29
(m, 1 H), 7.34–7.39 (m, 5 H), 7.53 (d, J = 8.0 Hz, 2 H), 7.65 (d, J =
8.0 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 14.3, 22.9, 25.9, 28.0, 29.4, 29.5,
29.6 (2 C), 32.1, 74.6, 123.8 (2 C), 126.8, 128.0 (2 C), 128.6 (2 C),
129.0 (2 C), 130.6, 135.1, 139.9, 168.5.
Yield: 0.92 g (87%); brown liquid.
IR (neat): 1642 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 2.18–2.43 (m, 2 H), 2.79–2.93 (m,
1 H), 4.03–4.08 (m, 2 H), 4.88 (d, J = 13.8 Hz, 2 H), 5.44–5.60 (m,
1 H), 7.05–7.77 (m, 15 H).
13C NMR (50 MHz, CDCl3): δ = 36.7, 44.3, 76.6, 116.7, 123.8,
126.7, 127.8 (2 C), 127.9 (3 C), 128.5 (4 C), 128.8 (3 C), 130.5,
134.7, 135.6, 139.4, 141.0, 168.2.
HRMS (ES+): m/z [M + H]+ calcd for C24H24NO2: 358.1807; found:
358.1834.
HRMS (ES+): m/z [M + H]+ calcd for C23H32NO2: 354.2433; found:
354.2481.
O-(5-Phenylpent-4-enyl)-N-benzoyl-N-phenylhydroxylamine
(3l)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:17) to give the title compound.
O-Tetradecyl-N-benzoyl-N-phenylhydroxylamine (3h)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:17) to give the title compound.
Yield: 1.22 g (87%); brown liquid.
IR (neat): 1640 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.0 Hz, 3 H), 1.14–1.26
(m, 20 H), 1.30–1.38 (m, 2 H), 1.39–1.47 (m, 2 H), 3.81 (t, J = 6.4
Hz, 2 H), 7.19 (t, J = 7.2 Hz, 1 H), 7.33–7.39 (m, 5 H), 7.52 (d, J =
7.6 Hz, 2 H), 7.63 (d, J = 6.8 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 14.1, 22.7, 25.7, 27.9, 29.2, 29.4,
29.5, 29.6 (5 C), 31.9, 74.4, 123.6 (2 C), 126.6, 127.8 (2 C), 128.4
(2 C), 128.8 (2 C), 130.5, 134.9, 139.7, 168.3.
HRMS (ES+): m/z [M + H]+ calcd for C27H40NO2: 410.3059; found:
410.3025.
Yield: 1.21 g (92%); brown liquid.
IR (neat): 1641 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 1.68–1.81 (m, 2 H), 2.15–2.25 (m,
2 H), 3.97 (t, J = 6.2 Hz, 2 H), 6.01–6.16 (m, 1 H), 6.30 (d, J = 16.0
Hz, 1 H), 7.12–7.50 (m, 11 H), 7.58 (d, J = 7.8 Hz, 2 H), 7.72 (d, J =
7.8 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 27.7, 29.2, 73.6, 124.1 (2 C), 126.0
(2 C), 126.9, 127.1, 128.0 (2 C), 128.6 (4 C), 129.0 (2 C), 129.3,
130.7, 130.8, 134.9, 137.6, 139.8, 168.4.
HRMS (ES+): m/z [M + H]+ calcd for C24H24NO2: 358.1807; found:
358.1836.
O-[(Tetrahydrofuran-2-yl)methyl]-N-benzoyl-N-phenyl-
hydroxylamine (3i)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:22) to give the title compound.
O-(4-Phenylpent-4-enyl)-N-benzoyl-N-phenylhydroxylamine
(3m)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:17) to give the title compound.
Yield: 0.99 g (90%); brown liquid.
IR (neat): 1638 (C=O) cm–1.
Yield: 1.24 g (92%); brown liquid.
IR (neat): 1641 (C=O) cm–1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1745–1754

1752
N. Chowdhury et al.
PAPER
1H NMR (200 MHz, CDCl3): δ = 1.64–1.71 (m, 2 H), 2.47 (t, J = 7.2
Hz, 2 H), 3.93 (t, J = 6.2 Hz, 2 H), 4.97 (s, 1 H), 5.29 (s, 1 H), 7.20–
7.41 (m, 11 H), 7.61 (d, J = 8.0 Hz, 2 H), 7.72 (d, J = 7.8 Hz, 2 H).
O-Benzyl-N-acetyl-N-phenylhydroxylamine (8a)
The crude residue was purified by column chromatography
(EtOAc–hexane, 1:5) to give the title compound.
13C NMR (50 MHz, CDCl3): δ = 26.4, 31.4, 73.8, 112.7, 123.8 (2
C), 126.1 (2 C), 126.8, 127.6, 128.0 (2 C), 128.4 (2 C), 128.5 (2 C),
129.0 (2 C), 130.6, 135.1, 139.9, 140.8, 147.3, 168.4.
HRMS (ES+): m/z [M + H]+ calcd for C24H24NO2: 358.1807; found:
358.1824.
Yield: 0.73 g (92%); yellow liquid.
IR (neat): 1660 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.19 (s, 3 H), 4.82 (s, 2 H), 7.26
(t, J = 7.2 Hz, 1 H), 7.34–7.44 (m, 7 H), 7.55 (d, J = 7.2 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 21.9, 76.2, 128.4 (3 C), 128.7 (3
C), 128.9, 129.5 (3 C), 134.2, 138.6, 170.2.
N-[4-(Benzyloxy)phenyl]benzamide (6a)
An oxygen-free soln of 3a (100 mg, 0.33 mmol) in MeCN (30 mL)
was irradiated with a 125 W medium pressure Hg lamp filtered by
a quartz glass for 3 h. The extent of reaction was monitored by TLC
at regular intervals. After complete consumption of the starting ma-
terial as indicated by TLC, the solvent was removed under vacuum
and the photoproducts were isolated by column chromatography
(see below). The structures of the isolated photoproducts, benzani-
lide (4) (55 mg, 85%), benzyl alcohol (2a) (27 mg, 75%) and 6a (3
mg, 4%) were confirmed by NMR spectroscopy and by comparison
with authentic samples. The other photoproducts, benzaldehyde (5)
and 1,3-alkoxy photorearrangement product 6b were characterized
by NMR spectroscopy of the crude reaction mixture using anisole
as an internal standard. The title compound 6a was obtained follow-
ing purification of the crude residue by column chromatography
(EtOAc–hexane, 7:13).
HRMS (ES+): m/z [M + H]+ calcd for C15H16NO2: 242.1181; found:
242.1103.
O-Benzyl-N-(4-nitrobenzoyl)-N-phenylhydroxylamine (8b)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:7) to give the title compound.
Yield: 0.63 g (90%); white solid; mp 112–115 °C.
IR (KBr): 1653 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 4.78 (s, 2 H), 7.04 (d, J = 7.0 Hz,
2 H), 7.23–7.37 (m, 4 H), 7.45 (t, J = 8.0 Hz, 2 H), 7.57 (d, J = 7.4
Hz, 2 H), 7.67 (d, J = 8.2 Hz, 2 H), 8.17 (d, J = 8.0 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 76.5, 123.0 (2 C), 124.1, 127.6,
128.6 (2 C), 129.2 (2 C), 129.3 (2 C), 129.5 (2 C), 129.7 (2 C),
133.5, 138.5, 140.8, 148.6, 166.4.
Yield: 3 mg (4%); white solid.
1H NMR (400 MHz, CDCl3): δ = 5.07 (s, 2 H), 6.99 (d, J = 8.8 Hz,
2 H), 7.33–7.55 (m, 10 H), 7.69 (br s, 1 H), 7.86 (d, J = 7.6 Hz, 2 H).
HRMS (ES+): m/z [M + H]+ calcd for C20H17N2O4: 349.1188;
found: 349.1116.
13C NMR (100 MHz, CDCl3): δ = 70.2, 115.3 (2 C), 121.9, 125.1,
126.9 (2 C), 127.4 (2 C), 127.9, 128.5 (2 C), 128.6, 128.7 (2 C),
131.1, 131.7, 136.8, 155.8, 165.7.
O-Benzyl-N-(3,4-dimethoxybenzoyl)-N-phenylhydroxylamine
(8c)
The crude residue was purified by column chromatography
(EtOAc–hexane, 3:7) to give the title compound.
Photolysis of O-Benzyl-N-benzoyl-N-phenylhydroxylamine
(3a); Solvent Effect
Yield: 0.57 g (88%); yellow liquid.
IR (neat): 1648 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 3.75 (s, 3 H), 3.87 (s, 3 H), 4.87
(s, 2 H), 6.77 (d, J = 8.4 Hz, 1 H), 7.17–7.46 (m, 12 H).
13C NMR (50 MHz, CDCl3): δ = 55.8, 55.9, 76.5, 110.1, 112.3,
122.9, 124.5 (2 C), 126.6, 126.9, 128.4 (2 C), 128.8, 129.0 (2 C),
129.6 (2 C), 134.4, 140.4, 148.2, 151.2, 167.7.
Photolysis of 3a (100 mg, 0.33 mmol) was carried out in 25 mL
each of anhyd benzene, PhCF3, MeCN, aq MeOH and Bu3SnH (4
equiv) in benzene for 3 h. The solvent was removed under vacuum
and the yields of the photoproducts in the crude reaction mixture de-
termined by NMR spectroscopy using anisole as an internal stan-
dard.
Photogeneration of Alcohols from O-Alkyl-N-benzoyl-N-phen-
ylhydroxylamines 3 and Quantum Yield Measurements
A soln of compound 3a–m (100 mg, 0.33 mmol) in anhyd benzene
(30 mL) containing Bu3SnH (0.8 mmol) was irradiated with a 125
W medium pressure Hg lamp filtered by a quartz glass. The extent
of reaction was monitored at regular intervals by HPLC (hexane–
iPrOH, 9:1), at a flow rate of 1 ml/min (UV detection at 254 nm).
After completion of the reaction, the solvent was removed under
vacuum and the major photoproducts, benzanilide (4) and alcohols
2a–m were isolated by column chromatography (PE–EtOAc, 7:1)
and then analyzed by NMR spectroscopy.
HRMS (ES+): m/z calcd for C22H22NO4: 364.1549; found:
364.1532.
O-Benzyl-N-(4-chlorobenzoyl)-N-phenylhydroxylamine (8d)
The crude residue was purified by column chromatography
(EtOAc–hexane, 1:4) to give the title compound.
Yield: 0.62 g (90%); yellow liquid.
IR (neat): 1652 (C=O) cm–1.
1H NMR (200 MHz, CDCl3): δ = 4.81 (s, 2 H), 7.11–7.16 (m, 2 H),
7.24–7.44 (m, 8 H), 7.53 (t, J = 6.0 Hz, 4 H).
13C NMR (50 MHz, CDCl3): δ = 76.5, 124.2 (2 C), 127.2, 128.2 (2
C), 128.6 (2 C), 129.0, 129.1 (2 C), 129.7 (2 C), 130.3 (2 C), 133.1,
133.9, 136.7, 139.4, 167.4.
1
The quantum yields of the alcohols were analyzed by H NMR
spectroscopy employing valerophenone as an actinometer. The per-
centage of alcohol generated was determined by calculating the
gradual increase in the peak area of the alcohol using anisole as an
internal standard.
HRMS (ES+): m/z [M + H]+ calcd for C20H17ClNO2: 338.0948;
found: 338.0988.
O-Benzyl-N-acyl-N-phenylhydroxylamines 8a–d; General Pro-
cedure
Photolysis of Compounds 3a and 8a–d
A soln of compound 3a or 8a–d (100 mg, 0.33 mmol) in anhyd ben-
zene (30 mL) containing Bu3SnH (4 equiv) was irradiated using a
125 W medium pressure Hg lamp filtered by a quartz glass. The ex-
tent of reaction was monitored at regular intervals by HPLC (hex-
ane–i-PrOH, 9:1), at a flow rate of 1 ml/min (UV detection at 254
nm) . The HPLC data was used to plot the logarithm of concentra-
tion of benzyl alcohol generated (lnC) versus the irradiation time (t)
for each alkoxy radical precursor.
To a soln of N-acyl-N-phenylhydroxylamine 7 (3.30 mmol), benzyl
alcohol (2a) (0.3 g, 3.08 mmol) and Ph3P (1.2 g, 4.6 mmol) in THF
(10 mL) was added DEAD (4.6 mmol) in THF (10 mL) at room
temperature under an N2 atm. After stirring for 18 h at r.t., the mix-
ture was diluted with H2O (5 mL) and extracted with EtOAc (50
mL). The combined organic layer was dried over anhyd MgSO4, fil-
tered, concentrated and purified.
Synthesis 2012, 44, 1745–1754
© Georg Thieme Verlag Stuttgart · New York

PAPER
Photochemical Alkoxy Radical Precursors
1753
2-Benzyltetrahydrofuran (10l);27 Typical Procedure
In a quartz glass test-tube, O-(5-phenyl-4-pentenyl)-N-benzoyl-N-
phenylhydroxylamine (3l) (100 mg, 0.28 mmol) was dissolved in
PhCF3 (50 mL). Bu3SnH (0.25 mL, 1.1 mmol) was added and the
mixture degassed under an N2 atm for 20 min. The soln was irradi-
ated using a 125 W medium pressure Hg lamp filtered by a quartz
glass for 3 h. After completion of the reaction, the solvent was evap-
orated under reduced pressure and the residue purified by column
chromatography (PE–Et2O, 2:1) to afford 2-benzyltetrahydrofuran
(10l).
2019. (e) Sperry, J.; Liu, Y. C.; Brimble, M. A. Org. Biomol.
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A. C.; Francisco, J. S. J. Am. Chem. Soc. 2011, 133, 18208.
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Yield: 30 mg (72%); colorless liquid.
1H NMR (200 MHz, CDCl3): δ = 1.55–1.60 (m, 1 H), 1.83–1.97 (m,
3 H), 2.69–2.79 (m, 1 H), 2.88–2.98 (m, 1 H), 3.68–3.79 (m, 1 H),
3.84–3.91 (m, 1 H), 3.98–4.10 (m, 1 H), 7.16–7.36 (m, 5 H).
13C NMR (50 MHz, CDCl3): δ = 25.7, 31.1, 42.0, 67.9, 80.1, 126.2,
128.3 (2 C), 129.3 (2 C), 139.0.
The same procedure described above was employed for the photol-
ysis of compounds 3j and 3k and the resulting cyclized tetrahydro-
furans were characterized by NMR spectroscopy of the crude
photoproducts.
2-Phenyltetrahydrofuran (12);29 Carbon-Centered Radical
Trapping
In a quartz glass test tube, O-(4-phenylbutyl)-N-benzoyl-N-phenyl-
hydroxylamine (3f) (75 mg, 0.21 mmol) was dissolved in PhCF3 (15
mL). BrCCl3 (0.06 mL, 0.63 mmol) was added and the mixture de-
gassed under an N2 atm for 20 min. The soln was irradiated using a
125 W medium pressure Hg lamp filtered by a quartz glass for 6 h.
After completion of the reaction, the solvent was evaporated under
reduced pressure and the residue purified by column chromatogra-
phy to furnish 4-phenyl-4-bromobutanol (11) (characterized from
the crude 1H NMR spectrum) and 2-phenyltetrahydrofuran (12).
Yield: 4 mg (25%); colorless liquid.
1H NMR (200 MHz, CDCl3): δ = 1.83–2.00 (m, 1 H), 2.03–2.18 (m,
2 H), 2.31–2.34 (m, 1 H), 3.85–3.92 (m, 2 H), 4.82 (t, J = 6.6 Hz, 1
H), 7.40–7.60 (m, 5 H).
Generation of Alkoxy Radicals from Compound 3a under Stan-
dard Radical Conditions
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A soln of compound 3a (100 mg, 0.33 mmol) in anhyd benzene (15
mL) containing Bu3SnH (0.11 mL, 1.2 equiv) and AIBN (0.03
equiv) was heated at 80 °C for 5 h. The solvent was evaporated and
the crude residue purified by column chromatography (EtOAc–hex-
ane, 3:17) to afford benzyl alcohol (2a) (24 mg, 70%) and benzani-
lide (4) (51 mg, 80%).
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Acknowledgment
We thank DST (SERC Fast Track Scheme) for financial support
and DST-FIST for 400 MHz NMR facilities. N.C. is grateful to the
University Grand Commission (UGC), New Delhi for her research
fellowship. We thank Professor S. Nanda for assistance with HPLC
analysis.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.onmorinIfatgnonmSorti
i
npfurotIangSiuptor
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