A tetramethoxybenzophenone as efficient triplet photocatalyst for the transformation of diazo compounds

Article abstract of DOI:10.1021/jo062426n

(Chemical Equation Presented) The aromatic ketone 2,2′,4,4′- tetrarnethoxybenzophenone has a strong absorption band between 300 and 375 nm, and its π,π* triplet excited-state is selectively populated in methanol. Both facts make this aromatic ketone a ver

Full text of DOI:10.1021/jo062426n

SCHEME 1. Reaction Pathways for the Transformation of
Alkyl 2-Diazo-3-oxoalkenoates
A Tetramethoxybenzophenone as Efficient Triplet
Photocatalyst for the Transformation of
Diazo Compounds
Lourdes Pastor-Pe´rez, Christine Wiebe,
Julia Pe´rez-Prieto,* and Salah-Eddine Stiriba*
Instituto de Ciencia Molecular/ICMOL, UniVersidad de
Valencia, Pol´ıgono La Coma s/n, Apartado de Correos 22085,
46980 Valencia, Spain
julia.perez@uV.es; stiriba@uV.es
ReceiVed NoVember 24, 2006
diazoalkane transitions at longer wavelengths than those of BP.4
Moreover, due to its nπ* nature, the BP triplet easily abstracts
hydrogen from the solvent, which results in the photosensitizer
transformation into BP-derived alcohols and pinacols.5 Both
facts prevent the use of BP as an efficient triplet photocatalyst
for diazo compounds transformation.
Previous studies have shown that after substitution of electron-
donating groups, such as OCH3, onto the aromatic rings of BP
the relative position of nπ* and ππ* triplet states is largely
affected by the solvent polarity. Thus, in the case of 4-metoxy-
benzophenone (MBP), while its triplet has an n,π* configuration
in the nonpolar cyclohexane, the π,π* triplet predominates in
aqueous solutions.6 Transient absorption spectra due to n,π*
and π,π* being simultaneously populated are observed upon
laser excitation in polar solvents such as acetonitrile.7
Therefore, in principle, it could be possible to obtain a
selective π,π* triplet population in media less polar than aqueous
solutions by attaching a higher number of electron-donating
groups to the aromatic rings of BP, such as in the case of
2,2′,4,4′-tetramethoxybenzophenone, TMBP.8
We report here that it is possible to selectively populate the
π,π* triplet of TMBP in methanol. Both the lower capability
of π,π* triplets for direct hydrogen abstraction and the much
stronger absorption of TMBP than BP at wavelengths longer
The aromatic ketone 2,2′,4,4′-tetramethoxybenzophenone has
a strong absorption band between 300 and 375 nm, and its
π,π* triplet excited-state is selectively populated in methanol.
Both facts make this aromatic ketone a versatile and efficient
triplet photocatalyst for the transformation of R-diazo car-
bonyl compounds into mainly the cyclopropanation product.
R-Diazo carbonyl compounds give the Wolff rearrangement
as the paramount reaction pathway under direct irradiation (2
in Scheme 1).1 The [1,2] shift that gives rise to ketenes proceeds
in the singlet state, accompanying or following the loss of N2.
Thus, upon its excitation, methyl 2-diazo-3-oxoheptenoate (1a)2
leads mainly to the Wolff rearrangement product 2a. The O-H
insertion product 4a is also detected when using alcohols as
reaction media (Scheme 1). By contrast, benzophenone (BP)-
mediated photosensitization provides the diazo compound triplet,
which minimizes 2a (f9%) as well as 4a (f9%) and affords
mainly the intramolecular cyclopropanation product 3a (f88%).
It has been stressed that Wolff rearrangement is the major
reaction pathway of the singlet carbene, while CdC addition
of triplet carbene is fast relative to intersystem crossing.
The triplet-sensitized photolysis of R-diazo carbonyl com-
pounds has been performed in the presence of a high excess of
BP.2,3 But, even so, it is unlikely that complete sensitization is
achieved in each case, since it is known the existence of
(4) Bradley, J. N.; Cowell, G. W.; Ledwith, J. Chem. Soc. 1964, 353.
(5) (a) Li, J. T.; Yang, J. H.; Han, J. F.; Li, T. S. Green Chem. 2003, 5,
433. (b) Scaiano, J. C. J. Photochem. 1973, 2, 81. (c) Bachmann, W. E.
Organic Synthesis, Collect. Vol. II; John Wiley and Sons: New York, 1948;
p 71.
(6) Bosca´, F.; Cosa, G.; Miranda, M. A.; Scaiano, J. C. Photochem.
Photobiol. Sci. 2002, 1, 704.
(7) This is one of the few examples of solvent-dependent inversion of
configuration in BP derivatives: (a) Singh, A. K.; Bhasikuttan, A. C.; Palit,
D. K.; Mittal, J. P. J. Phys. Chem. A 2000, 104, 7002. (b) Bhasikuttan,
A. C.; Singh, A. K.; Palit, D. K.; Sarpre, A. V.; Mittal, J. P. J. Phys. Chem.
A 1998, 102, 3470.
* To whom correspondence should be addressed (J.P.P.). Phone: 34 96354
3050. Fax: 34 96354 3274.
(1) (a) Kirmse, W. Eur. J. Org. Chem. 2002, 2193. (b) Meier, H.; Zeller,
K. P. Angew. Chem., Int. Ed. 1975, 14, 32. (c) Wolff, L. Justus Liebigs
Ann. Chem. 1902, 325, 120.
(2) Fien, J.; Kirmse, W. Angew. Chem., Int. Ed. 1998, 37, 2232.
(3) Tomioka, H.; Okuno, H.; Kondo, S.; Izawa, Y. J. Am. Chem. Soc.
1980, 102, 7123.
(8) Shiraishi, Y.; Koizumi, H.; Hirai, T. J. Phys. Chem. B 2005, 109,
8580.
10.1021/jo062426n CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/18/2007
J. Org. Chem. 2007, 72, 1541-1544
1541

FIGURE 1. UV/vis absorption spectra of BP and TMBP in CH3CN
and MeOH. Sample concentration was 10-4 M.
TABLE 1. Photophysical Properties of TMBPa
CH3OH
CH3CN
dioxane
λ
abs (nm)
311
480
0.004
1.4
308
448
0.005
2.0
307
453
0.004
2.5
λ
em (nm)
b
Φf
1τ c (ns)
ES (kcal‚mol-1
)
75
76
78
a Parameters: absorption maximum of the longest π,π* transition (λabs),
emission maximum (λem) at λexc ) 355 nm, fluorescence quantum yield
(Φf), singlet lifetime (1τ), and energy of the singlet excited state (ES).
b Fluorescence quantum yields at λexc) 355 nm were determined using
quinine bisulfate (0.5 M) in sulfuric acid as described elsewhere.17 c Based
on the fluorescence decay monitored at 470 nm.
than 300 nm (see below) prompted us to study the versatility
of TMBP as photocatalyst for the transformation of diazo
compounds.
The photochemical and photophysical properties of TMBP
were studied by means of time-resolved measurements. Its
capability as photocatalyst for diazo compound transformation
was tested in two model compounds, tert-butyl 2-diazo-3-oxo-
6-heptenoate (1b) and tert-butyl 2-diazo-3-oxo-7-octenoate (1c),
using acetonitrile and methanol as polar solvents. For compari-
son purposes, the studies were also performed with BP.
Figure 1 shows the absorption spectra of TMBP in acetonitrile
and methanol. It exhibits two strong bands at λmax ) 278 nm
(log ꢀ ) 4.45) and 312 nm (log ꢀ ) 4.42) in methanol, plus a
long tail in the lowest energy region.9 The maximum at 312
nm could be assigned to the 2,4-dimethoxybenzoyl chro-
mophore, by comparison with absorption spectra of substituted
benzophenones.10 That maximum undergoes a small hypso-
chromic displacement in less polar solvents (from 312 nm in
methanol to 307 nm in dioxane), which is in agreement with
the π,π* character of this electronic transition (Table 1).
Similarly to the analogous BP transition with maximum at 253
nm in methanol, it displays a hyperchromic effect in the proton-
donating solvent (compare methanol vs acetonitrile in Figure
1). On the other hand, the absorption at longer wavelengths,
partially overlapped by the high-intensity band at 312 nm, can
be assigned to the carbonyl n,π* transition. Overall, TMBP has
a much higher molar extinction coefficient than BP in the 300-
375 nm wavelength range (Figure 1).9
FIGURE 2. Triplet-triplet transient absorption spectra of (A) BP in
CH3CN, (B) TMBP in cyclohexane, (C) TMBP in CH3CN, and (D)
TMBP in MeOH. Spectra A were taken 40 (s) and 400 ns (--) after
the laser pulse (λexc ) 355 nm). Spectra B-D were taken 10 (s) and
70 ns (--) after the laser pulse (λexc ) 355 nm).
quantum yield (Φf) are similar for all the solvents, with values
in the range of 1.4-2.5 ns and 0.004-0.005, respectively. The
excitation spectra (λem) emission maximum) shows that the
emission band is not related to the strong absorption at λmax
)
310 nm (of π,π* nature) but to a weak absorption located at
ca. 350 nm, partially overlapped by the high-intensity π,π* band
(Figure S1). This absorption can be safely assigned to the n,π*
transition by comparison with that of BP (maximum at 340 nm
in methanol). The intersection between the normalized emission
and excitation traces allowed us to locate the 0-0 transition
and to estimate the singlet excited-state energy (ES); see Table
1. The lowest value was found in methanol, which could indicate
the stabilization of this excited state by solvation and/or
formation of a hydrogen-bonded complex in the hydrogen-bond-
forming solvent.
For deactivation of the S1 singlet excited state, one route is
via intersystem crossing. In order to detect the TMBP T-T
absorption, laser flash photolysis (LFP) experiments were carried
out on solutions of TMBP in cyclohexane, methanol, and
acetonitrile, employing a 355 nm laser as the excitation source.
For comparison, the typical spectrum of benzophenone triplet
(n,π* nature) is also included (Figure 2A). In methanol, the
transient absorption bands of TMBP are located at λmax ) 470
nm and close to 700 nm (Figure 2D). These absorptions could
be assigned to the 3TMBP of π,π* character by similarity with
TMBP shows very small fluorescence in different solvents
(Table 1, Figure S1 in the Supporting Information). The
emission maximum is located at 480 nm in methanol but moves
to ca. 450 nm in other solvents. Fluorescence lifetime (1τ) and
(9) VanAllan, J. A. J. Org. Chem. 1958, 23, 1679.
(10) Arnold, D. R.; Birtwell, R. J. J. Am. Chem. Soc. 1973, 95, 4599.
1542 J. Org. Chem., Vol. 72, No. 4, 2007

TABLE 2. Photocatalytic Studies.
ratiod (%)
run
D
S
S/D molar ratio
λ a
solvent
2
3
5
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
1c
1c
1c
A
B
A
A
A
B
C
B
B
B
A
A
A
B
C
B
B
B
CH3CN
CH3CN
CH3OHb
CH3CN
CH3CN
CH3CN
CH3CN
CH3OH
CH3OH
CH3OH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3OH
CH3OH
CH3OH
83
87
64
64
4
17
16
0
17
13
20
36
90
70
70
65
73
86
7
38
66
70
69
36
71
60
BPc
0.10
0.10
0.10
0.10
0.25
0.50
1.00
TMBPc
TMBPc
TMBPc
TMBP
TMBP
TMBP
6
13
14
35
27
14
0
0
93
43
18
24
25
39
17
26
BPc
0.10
0.10
0.10
0.10
0.05
0.10
0.05
19
15
6
6
12
4
TMBPc
TMBPc
TMBPc
BPb,c
TMBPb
TMBPb
4
a Deaerated solutions irradiated for 5 h. Excitation: A, λ > 300 nm; B, 400 < λ < 320 nm; C, λ > 350 nm. b Compound 4 is formed in e10%.
c Important photochemical degradation of the sensitizer is observed. d Isolated yields are reported in the Experimental Section (see SMI).
those of MBP in acetonitrile-water mixtures.6,11 The spectra
obtained in cyclohexane show the presence of a new band
located at λmax ) 580 nm (Figure 2B), which could be ascribed
nied by a small amount of a new compound, unsaturated ketone
5b (run 5).13 An appreciable degradation of the photosensitizer
is also observed in this case. Results are wavelength-dependent,
as shown by an enhanced yield of 2b and 5b combined with a
decrease of the cyclopropanation product yield when exciting
at 400 > λ > 320 and λ > 350 nm (compare runs 5-7). In
addition, the product distribution changes with the solvent and
the S/D molar ratio; thus, 2b is not detected in methanol and
the 3b/5b ratio increases with the photosensitizer concentration
(compare run 6 with runs 8-10).
Similar studies were performed with diazo compound 1c.
Direct irradiation of 1c leads also mainly to the Wolff rear-
rangement product (93%, run 11). Results for the photosensitized
reactions are analogous to those for 1b; cyclopropanation is the
main process when using TMBP (runs 12-15, 17, and 18). It
is remarkable that compound 3c is the major product even when
using a TMBP/1c molar ratio of 0.05 (compare runs 17 and
18). In good agreement with LFP experiments, insignificant
photochemical degradation of the TMBP is observed in metha-
nol;14 meanwhile important decomposition is detected for TMBP
in acetonitrile and for BP in both solvents. As shown above,
the product distribution was affected by the wavelength, the
solvent, and the photosensitizer concentration. As these findings
could indicate secondary photoreactions of primary products,
control experiments were performed to determine the photo-
stability of 3 to direct or photosensitized irradiation. However,
no new products are detected in either case. For example, 3b
and 3c do not undergo any transformation after direct irradiation
at 400 > λ > 320 nm (CH3CN, 5 h). Under the same conditions,
TMBP does not photosensitize the transformation of 3c.
3
to the TMBP with n,π* nature6,11 (compare with Figure 2A
for BP).
In acetonitrile, transient absorption spectra due to n,π * and
π,π* being simultaneously populated are observed upon laser
excitation (Figure 2C). These results demonstrate that a higher
number of electron-donating groups on the aromatic rings of
the TMBP provokes a better proximity of the two lowest triplet
states, and a small π,π* triplet population is observed even in
a low polar solvent such as cyclohexane.
The capability of TMBP to act as triplet photocatalyst was
tested in the transformation of diazo compounds 1b and 1c.
The influence of the sensitizer/diazo (S/D) molar ratio, the use
of either acetonitrile or methanol as solvent, and the excitation
wavelengths (λ > 300 nm, 400 > λ > 320 nm, and λ > 350
nm) was explored (Table 2). The deaerated solutions were
irradiated for 5 h in the presence and in the absence of the
aromatic ketone.
In both solvents, the direct photolysis (λ > 300 nm 12 or
400 > λ > 320 nm) of 1b leads mainly to 2b (runs 1-3). The
intramolecular addition to the double bond is a minor reaction
(3b f 20%). In methanol, formation of the O-H insertion
product is also detected (run 3). On the other hand, the
cyclopropanation yield increases after excitation at λ > 300 nm
in the presence of a small amount of BP (BP/1b ) 0.1), though
2b still predominates (run 4).
As mentioned above, a drawback of using BP as photocatalyst
is its important photochemical degradation by reaction with the
solvent. In fact, analysis of the photolyzate by NMR revealed
an important degradation due to the n,π* nature of the BP low-
lying triplet excited state. Interestingly enough, under the same
conditions, the TMBP-photosensitized transformation of 1b
mainly affords the cyclopropanation product (90%), accompa-
(13) The formation of these types of products in BP-photosensitized
transformation of diazo compounds has not been previously reported. The
structure of 5b was assigned by comparison with 5a, which has been
synthesized (in a 55% yield) by Pd(II)-mediated cyclization of 1a (Taber,
D. F.; Amedio, J. C., Jr.; Sherrill, R. G. J. Org. Chem. 1986, 51, 3382). No
similar studies have been done for 1b,c.
(14) It has been reported that, upon photoexcitation of TMBP in
methanol, a transient absorption attributed to ketyl radical is observed.8
However, lamp irradiation of this ketone in methanol revealed its photo-
stability (less than 5% of decomposition, 2 h of irradiation).
(11) Baral-Tosh, S.; Cattopadhyay, S. K.; Das, P. K. J. Phys. Chem.
1984, 88, 1404. Shizuka, H.; Obuchi, H. J. Phys. Chem. 1982, 86, 1297.
(12) Pyrex filtered. Lamp with a broad emission band between 280 and
380 nm (λmax ) 320 nm). Other sharp emissions are ca. 400, 440, and
540 nm.
J. Org. Chem, Vol. 72, No. 4, 2007 1543

tert-butyl 3-oxohept-6-enoate (2 g, 10.31 mmol), prepared by the
method of Weiler,19 in 20 mL of acetonitrile. After stirring for 3 h
at room temperature, 10 mL of 10% aqueous NaOH (10 mL) was
added and the product was extracted with CH2Cl2 (3 × 30 mL).
The combined organic extracts were dried over Na2SO4 and
concentrated under vacuum. The crude product was purified by
chromatography on silica gel with hexane/ethyl acetate (15:1) as
the eluent to give 1.79 g (80%) of pure 1b as yellow oil. Rf (hexane/
Analysis of the data summarized in Table 2 reveals that both
3b/3c and 5b/5c 15 are formed in the triplet-sensitized processes.
Therefore, the presence of 3 upon direct photolysis could agree
with spin equilibration of the carbene, which would allow
generating the triplet carbene and leading to the cyclopropana-
tion product. Meanwhile, the absence of 5 in the direct
photolysis of 1 could be due to the low efficient intersystem
crossing yielding the diazo triplet excited state. However, since
formation of 5 is enhanced when decreasing the photosensitizer
concentration (compare runs 8-10), it must be obtained upon
direct excitation of its precursor,16 which should arise from the
diazo triplet excited state. It also should be noted that irradiation
of compound 3 either in the presence or in the absence of a
catalytic amount of TMBP does not afford the cyclic enone 5.
Finally, a TMBP/1b molar ratio of 0.25 is enough to avoid direct
diazo compound irradiation, as shown by the absence of 2b
under such conditions (run 8).
In summary, experimental data indicate that it is possible to
selectively populate the π,π* triplet of TMBP in methanol. Its
low capability for direct hydrogen abstraction from methanol
together with the strong absorption band of TMBP (300-375
nm range) make this aromatic ketone a versatile and efficient
triplet photocatalyst for diazo compounds transformation in such
a polar solvent. In addition, 2-methyl-5-oxocycloalk-1-enecar-
boxylates are generated (up to 35% yield) in the triplet-
photosensitized transformation. The present study offers useful
guidelines for the design of aromatic ketones with the desirable
photophysical characteristics to act as cheap triplet photocata-
lysts.
1
EtOAc, 1:1) 0.81. H NMR (300 MHz, CDCl3) δ 5.74-5.89 (m,
1H), 4.95-5.07 (m, 2H), 2.91 (t, J ) 9 Hz, 2H), 2.33-2.40 (m,
2H), 1.51 (s, 9H); 13C NMR (75.4 MHz, CDCl3) δ 192.5, 160.5,
137.0, 115.3, 83.1, 50.9, 39.3, 28.2, 28.1.
Photosensitized Transformation of tert-Butyl 2-Diazo-3-oxo-
hept-6-enoate (1b). General Procedure. To a solution of tert-
butyl 2-diazo-3-oxo-6-heptenoate (300 mg, 1.32 mmol) dissolved
in deaerated CH3CN, BP(OMe)4 (42 mg, 0.13 mmol) was added,
and the solution was irradiated for 5 h. The solvent was evaporated
under vacuum, and the crude product was purified by chromatog-
raphy on silica gel with hexane/ethyl acetate (15:1) as the eluent
to yield a mixture of 234 mg (90%) of 3b as yellow oil and 30 mg
(6%) of 5b as yellow oil. cis-tert-Butyl 2-oxo-bicyclo[3.1.0]hexane-
1
1-carboxylate (3b): Rf (hexane/EtOAc, 3:1) 0.47. H NMR (400
MHz, CDCl3) δ 2.43-2.48 (m, 1H), 2.09-2.17 (m, 3H), 1.87-
1.91 (m, 2H), 1.55 (s, 9H), 1.22 (t, J ) 4 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ 206.3, 166.2, 80.5, 37.2, 32.7, 31.4, 27.0, 20.7,
19.8. MS EI (m/z) 196 (M+, 25), 181 (100), 161 (5). IR (film, cm-1
)
2978, 1739, 1712, 1369, 1324, 1305, 1272, 1158, 1032. tert-Butyl
2-methyl-5-oxocyclopent-1-enecarboxylate (5b):Rf (hexane/EtOAc,
3:1) 0.28. 1H NMR (400 MHz, CDCl3) δ 2.58-2.60 (m, 2H), 2.40-
2.43 (m, 2H), 2.31 (s, 3H), 1.52 (s, 9H). 13C NMR (100 MHz,
CDCl3) δ 203.7, 181.9, 162.5, 134.0, 81.8, 34.9, 32.4, 28.2, 19.1.
MS EI (m/z) ) 196 (M+, 2), 181 (3), 141 (100). IR (film, cm-1
2977, 2925, 1738, 1705, 1633, 1368, 1354, 1254, 1251.
)
Experimental Section
Preparation of tert-Butyl 2-Diazo-3-oxohept-6-enoate (1b).
General Procedure. Mesyl azide18 (1.24 g, 9.28 mmol) and
triethylamine (1.40 mL, 19.0 mmol) were added to a solution of
Acknowledgment. We thank the Spanish Government
(Grant CTQ2005-00569), the Generalitat Valenciana (Grants
ACOMP06/134, GV06/234), and Universidad de Valencia
(Grant UV-AE-20050209) for generous support of this work.
(15) Compound 5c has been obtained in a 21% yield from 6-methyl-
3,4-dihydropyran-2-one: Hird, A. W.; Hoveyda, A. H. J. Am. Chem. Soc.
2005, 127, 14988.
(16) Further studies will be pursued to determine the structure of the
precursor affording 5.
(17) Dawson, W. R.; Windsor, M. W. J. Phys. Chem. 1968, 72, 3251.
(18) For the preparation of mesyl azide, see: Boyer, J. H.; Mack, C. H.;
Goebel, N.; Morgan, L. R., Jr. J. Org. Chem. 1958, 23, 1051.
(19) Weiler’s method for the preparation of â-keto esters: Huckin, S.
N.; Weiler, L. J. Am. Chem. Soc. 1974, 96, 1082.
Supporting Information Available: Synthesis and character-
ization data and NMR spectra for compounds 1b,c, 2b,c, 3b,c, and
5b,c, UV/vis spectra of 1b and TMBP, and emission and excitation
spectra of TMBP. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO062426N
1544 J. Org. Chem., Vol. 72, No. 4, 2007