Surprising secondary photochemical reactions observed on conventional photolysis of diazotetrahydrofuranones

Article abstract of DOI:10.1016/j.tetlet.2010.03.050

The formation of C-H insertion products of the terminal N-atom of a diazo group into the α-S{cyrillic}N{cyrillic}-bond of tetrahydrofuran during direct photolysis of regioisomeric 2,2-dimethyl-5,5-diphenyl and 5,5-dimethyl-2,2-diphenyl-substituted 3-diazotetrahydrofuran-4-ones in THF is dictated by photochemical cycloelimination of the originally formed (1,1-dimethyl-2-oxa-3,3-diphenyl-propano)ketene and oxetanecarboxylic acid derivatives to yield benzophenone. The latter, under subsequent UV irradiation of the reaction mixture, initiates sensitized photolysis of the starting diazoketones resulting in the appearance of the insertion products with the solvent.

Full text of DOI:10.1016/j.tetlet.2010.03.050

Tetrahedron Letters 51 (2010) 2713–2716
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Tetrahedron Letters
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Surprising secondary photochemical reactions observed on conventional
photolysis of diazotetrahydrofuranones
a
b
a
Valerij A. Nikolaev a, , Olesja S. Galkina , Jochim Sieler , Ludmila L. Rodina
*
a Saint-Petersburg State University, University Prosp. 26, St.-Petersburg 198504, Russia
b Universität Leipzig, Institut für Anorganische Chemie, Johannisallee 29, D-04103 Leipzig, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The formation of C–H insertion products of the terminal N-atom of a diazo group into the a-CH-bond of
Received 30 January 2010
Revised 1 March 2010
Accepted 12 March 2010
Available online 17 March 2010
tetrahydrofuran during direct photolysis of regioisomeric 2,2-dimethyl-5,5-diphenyl and 5,5-dimethyl-
2,2-diphenyl-substituted 3-diazotetrahydrofuran-4-ones in THF is dictated by photochemical cycloeli-
mination of the originally formed (1,1-dimethyl-2-oxa-3,3-diphenyl-propano)ketene and oxetanecarb-
oxylic acid derivatives to yield benzophenone. The latter, under subsequent UV irradiation of the
reaction mixture, initiates sensitized photolysis of the starting diazoketones resulting in the appearance
of the insertion products with the solvent.
Keywords:
Diazo compounds
Ketenes
Ó 2010 Elsevier Ltd. All rights reserved.
Carbenes
Photochemistry
Wolff rearrangement
Insertion and cycloelimination reactions
Direct photolysis of cyclic and heterocyclic diazoketones nor-
mally proceeds with elimination of nitrogen and subsequent Wolff
rearrangement (WR), a process which is widely used in organic
synthesis.1–3 It was recently demonstrated however that irradia-
tion of 2,2,5,5-tetraphenyl-substituted diazofuranone A in tetrahy-
drofuran (THF), along with the ordinary WR product B gave rise to
the adduct C of the initial diazoketone with THF in yields of up to
dures,7 and their photochemical reactions in THF in the presence
of different nucleophiles (H2O, MeOH, Me2NH) to trap the interme-
diate ketene were studied.8
However, the photochemical reactions of diazoketones 1a,b
showed that both regioisomers exhibited almost identical reactivity
and produced, upon photolysis, four basic reaction products 2–5
with similar structures, and essentially in the same ratio (Scheme 2).
Thus, no dependence of the efficiency of the C–H insertion pro-
cess on the position of the phenyl substituents relative to the diazo
group was revealed. At the same time, a well-defined effect of the
nature of the nucleophile on the yields of the C–H insertion prod-
ucts 3 was observed (MeOH > H2O ꢀ Me2NH).9
50%.4 The formation of unexpected
mally considered as a C–H insertion of the terminal N-atom of
the diazo group into the -CH bond of tetrahydrofuran (Scheme 1).
a-oxohydrazone C can be for-
a
To the best of our knowledge, the reactions of this type have not
been previously described in the chemistry and photochemistry of
diazo compounds,2,3,5 prompting this study of the origin, along
with the scope and limitations of this photochemical process.
As the above-mentioned reaction was observed only with
2,2,5,5-tetraphenyl-substituted diazoketone A, and did not occur
upon photolysis of the corresponding tetraalkyl-substituted diazo
The main objective of the current research was to elucidate the
origin of the C–H insertion products 3 in the above-mentioned
photochemical reactions as well as the reason behind the unex-
pected influence of the nucleophile on the yields.
analogues,6 it appeared that the
a,a-diphenyl substituents adja-
cent to the diazo group in diazofuranone A were pivotal to the out-
come of this photochemical process.
Ph Ph
O
Ph Ph
O
Ph
O
Ph
To check this experimentally, regioisomeric 2,2-dimethyl-5,5-
diphenyl- and 5,5-dimethyl-2,2-diphenyl-substituted diazoke-
tones 1a and 1b were prepared using previously described proce-
O
O
N
O
H
N
hv, THF
+
NuH
Nu
N2
Ph
Ph
Ph Ph
Ph
Ph
O
B
A
C
* Corresponding author at present address: 8 Linija 35, Apt. 5, St.-Petersburg
199004, Russia. Tel.: +7 812 323 10 68; fax: +7 812 428 69 39.
E-mail address: vnikola@VN6646.spb.edu (V.A. Nikolaev).
Scheme 1. Ordinary
photolysis of diazoketone A.
B
and unusual C–H insertion product
C
formed during
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.050

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V. A. Nikolaev et al. / Tetrahedron Letters 51 (2010) 2713–2716
R
O
R
R
O
R
R
R
R
O
R
R
R
O
O
O
O
N
O
O
hv
H
N
+
O
+
+
THF/NuH
Nu
N2
R1 R1
R1
R1 R1
R1 R1
O
R1
R1
R1
1a: R, R1 = Me, Ph
1b: R, R1 = Ph, Me
2a,b,c
3
4
5
Nu = OH (a), OMe (b), NMe2 (c)
Scheme 2. Major reaction products 2–5 upon photolysis of diazoketones 1a,b.
Careful study of the conventional photolysis10 of isomeric dia-
zoketones 1a,b has shown that
O
O
O
O
Ph
hv, THF
(a) the primary reaction products were photochemically rather
unstable, and during the course of the succeeding UV irradi-
ation, they underwent further transformations. Thus, by the
time of complete conversion of diazoketones 1a,b (40–
60 min), the reaction mixture usually contained at least 10
reaction products 2–11 (as indicated by 1H NMR and IR spec-
troscopy and GC–MS analysis11) (Schemes 2 and 3);
(b) one of the principal products of these secondary photochem-
ical reactions regardless of the structure of the initial diazok-
etones 1a,b was benzophenone (7);12 the content of Ph2C@O
in the reaction mixture usually amounted to 2–5%, and
sometimes even more, but then it decreased as irradiation
was continued.
Ph
4a
11; 54%
Scheme 5. Intramolecular photochemical cyclization of 4,5-diphenyldihydrofura-
none (4a).
(accompanied by the formation of 3,3-dimethylacrylic acid or its
dimethylamide 8c) (Scheme 4), while irradiation of unsaturated
4,5-diphenyldihydrofuranone (4a) produced exclusively phenan-
threne derivative 11 (Scheme 5).
Finally, sensitized photolysis of diazoketone 1a in the presence
of 1.5 mol equiv of benzophenone gave rise to the formation of the
C–H insertion product 3a (Fig. 1) along with a small amount of
monoketone 5a (Scheme 6).
Thus, irradiation with short wavelength UV light (k >210 nm) of
ketene 6, acid 2a and amide 2c leads to photochemical cleavage of
the oxetane heterocycle, and one of the key products of this pro-
cess is benzophenone. The observed photochemical transformation
can be considered as a reverse Paterno–Büchi reaction.17 A few
examples of similar photochemical cycloelimination processes
with aryl-substituted oxetanes have been previously described in
the literature.18
The mechanism of the above-mentioned photochemical reac-
tion in the case of oxetane derivatives 2 and 6 remains unknown.
It is conceivable that in the case of ketene 6 the reaction proceeds
either by direct photochemical cycloelimination with the forma-
tion of benzophenone and isopropylideneketene D (pathway a),
or through the initial decarbonylation of ketene 6 followed by
cycloelimination of benzophenone from the intermediate oxetane-
carbene E with simultaneous generation of isopropylidenecarbene
F (Scheme 7, pathways b, c).
We suggest that the appearance of benzophenone (7) during
photolysis of diazoketones 1a,b was due to the secondary photo-
chemical processes of the initially formed reaction products.
To check this assumption experimentally, photochemical reac-
tions of a few of the products were studied under the same reac-
tion conditions, namely: photolysis of ketene 6, generated by
conventional UV irradiation (k >210 nm) of diazofuranone 1a in
neat THF (without addition of NuH); photolysis of the dimethyla-
mide of oxetanecarboxylic acid 2c; irradiation of the product of
1,2-migration of the phenyl group—unsaturated ketone 4a, as well
as the sensitized photolysis of diazoketone 1a in the presence of
benzophenone.
It was found that ketene 6, initially generated via Wolff rear-
rangement, on further irradiation of the reaction mixture rapidly
disappears,13 and according to 1H NMR data and GC–MS analysis,
benzophenone and other reaction products are formed14
(Scheme 4).
The production of benzophenone (7) was also observed during
photolysis of oxetanecarboxylic acid 2a and dimethylamide 2c
CONu
O
O
N
O
H
N
8
C
O
O
O
O
Ph
Ph
H
O
Ph
Ph
Ph
Ph
Ph
Ph
6
9
7
10a
11
Scheme 3. Secondary reaction products 7–11 formed upon photolysis of diazoketones 1a,b.
Ph
Ph
Ph
hv,
neat THF
hv,
O
O
O
THF, Me2NH
hv'
Ph
hv'
O
7
6
1a
+
- N2
- N2
+
NMe2
CONMe2
IR (THF):
other reaction
products
IR (THF):
2127, 790 cm-1
Ph Ph
2091, 759 cm-1
2c
8c; 29%
Scheme 4. Photochemical cycloelimination of oxetane derivatives 6 and 2c to produce Ph2C@O.

V. A. Nikolaev et al. / Tetrahedron Letters 51 (2010) 2713–2716
2715
derivative 2c (Scheme 4), whereas the tandem decarbonylation–
cycloelimination process (paths b, c) is corroborated by the identi-
fication of 2,2-dimethyl-4,4-diphenyloxetane (9) in the reaction
mixture (evidently formed via carbene E; Scheme 7) and by anal-
ogy to the similar well-known decarbonylation reactions in the
chemistry and photochemistry of ketenes.19 One cannot rule out
the formation of benzophenone or the occurrence of the alternative
reactions involving 1,2-alkyl(aryl) shifts20 in the assumed oxetan-
ecarbene E and subsequent cycloelimination of the relevant oxet-
enes G and H (pathways b, d, e or b, f, g) (Scheme 7).
But, independent of the pathways of benzophenone formation,
the foregoing experimental data provides evidence in favour of
secondary benzophenone-sensitized photolysis of diazofuranones
1a,b which gives rise to the formation of the C–H insertion prod-
ucts 3 and, at least in part, monoketones 5.
The unexpected effect of the nucleophile on the yield of inser-
tion products 3a,b may be associated with the rate of nucleophilic
interaction with ketene 6, which is one of the principal sources of
benzophenone in the reaction mixture. Photolysis of diazoketone
1a with an equimolar amount of the nucleophilic reagents (MeOH,
H2O, Me2NH = 1:1:1) demonstrated that the concurrent reaction of
three nucleophiles with ketene 6 furnished predominantly the
dimethylamide of oxetanecarboxylic acid 2c (the ratio of the Wolff
rearrangement products 2b/2a/2c under these reaction conditions
was ꢁ1:13:170) (Scheme 8).
Figure 1. ORTEP plot15 of the crystal structure of the C–H insertion product 3a.16
This experiment furnishes a plausible explanation concerning
the reasons for the profound effect of the nature of the nucleophile
on the yields of the insertion products 3. Since dimethylamine re-
acts with ketene 6 many times faster than methanol or water, it
rapidly consumes the ketene thus preventing subsequent photo-
chemical transformation of the ketene into benzophenone, and
thereby strongly minimizing subsequent formation of the C–H
insertion products 3.
O
N
O
hv, THF
+ Ph2C=O
O
H
N
O
O
O
+
N2
Ph Ph
Ph
Ph Ph
O
Ph
1a
3a; 56%
5a; 7%
Scheme 6. Benzophenone-sensitized photolysis of diazoketone 1a.
In summary, the formation of C–H insertion products 3 during
the direct conventional photolysis of regioisomeric diazofuranones
The direct cycloelimination (path a) is supported by the forma-
tion of dimethyl acrylamide (8c) during photolysis of oxetane
1a,b is not caused by the effect of the
a,a-diphenyl substituents
Me
Me
Ph
Ph
O
9
.
+ 2H
Me
O
Me
Me
Me
O
Ph2C=O
+
Ph2C=O
+
a)
b)
hv;
hv;
c)
:
C
O
Me
Me
Me
- C=O
O
C
C
C:
Ph Ph
Ph Ph
Me
D
6
E
F
d)
f)
~ Me
~ Ph
Me
Me
Me
O
Me2C=O
+
Ph2C=O
+
e)
g)
O
Me
Ph
Me
Me
Ph
Ph
Ph Ph
Ph
G
H
Scheme 7. The assumed pathways of Ph2C@O formation upon photolysis of ketene 6.
Me
O
Me
Ph
Me
Ph
Me
O
Me
O
Me
Ph
+ MeOH/H2O/Me2NH
(1:1:1 )
O
O
hv, THF
O
C
Nu
- N2
N2
Ph
Ph
Ph
2b
2a + 2c
+
1a
6
0.3% 4%
51%
Scheme 8. The concurrent action of different nucleophiles with ketene 6.

2716
V. A. Nikolaev et al. / Tetrahedron Letters 51 (2010) 2713–2716
the photochemical reactor at certain time intervals. The solvent and
nucleophile were removed at 25–35 °C in vacuo (initially at 10–15 mmHg,
then at 1–0.5 mmHg), and the residue was immediately analyzed by 1H NMR
spectroscopy using dichloroethane as the internal standard. The reaction
products were isolated by recrystallization (2a–c) and/or by column
chromatography (3, 4, 5, 7, 8, 10a and 11) using as the eluents: light
petroleum ether (40–65 °C) and Et2O (or MTBE) in different ratios, or were
identified in the reaction mixture by IR spectroscopy and GC–MS analysis (6
and 9).
adjacent to the diazo group, but results from secondary photo-
chemical processes which give rise to the appearance in the reac-
tion mixture of the sensitizer, benzophenone. The latter, under
continued UV irradiation, initiates sensitized photolysis of the dia-
zoketones 1a,b (in parallel with the direct photochemical reaction),
which ultimately give rise to the formation of the C–H insertion
products 3, and presumably the monoketones 5.
Further investigation of the primary and secondary photochem-
ical reactions of diazotetrahydro-furanones 1, as well as their tet-
raphenyl- and tetraalkyl-substituted analogues is currently in
progress in our laboratories.
11. GC–MS analyses were performed using a Chromato-masspectrometer GCMS-
QP2010 Plus. The authors thank Dr. V. Utsal for this work.
12. The formation of benzophenone (7) in the reaction mixture was confirmed
from the 1H and 13C NMR spectra of the isolated compound, together with
identification of the corresponding hydrazone (mp 97–98 °C), which was
prepared by refluxing the isolated compound with hydrazine-hydrate in EtOH.
The presence of benzophenone (7) can be easily determined qualitatively and
quantitatively from the low-field doublet due to the ortho-protons at 7.79–
7.82 ppm in the 1H NMR spectra, which normally does not interfere with the
signals of other reaction products.
Acknowledgements
The authors are grateful to Professors Matthew S. Platz (OSU,
USA) and Thomas Bally (University of Fribourg, Switzerland) for
their sincere interest in this study and friendly discussions on
the obtained results.
13. Monitoring of ketene 6 formation and its disappearance from the reaction
mixture was achieved using IR spectroscopy which indicated the presence of
absorption bands at 2127 and 790 cmÀ1
.
14. Following 60 min of irradiation of diazoketone 1a in THF (without NuH) the
reaction mixture contained (according to 1H NMR with the internal standard):
benzophenone (7) (5%), C–H insertion product 3a (13%), Ph-group migration
product 4a (2%), monoketone 5a (1.6%), phenanthrene derivative 11 (2%), along
with oxetanecarboxylic acid 3a (6%).
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