Photosensitized oxidations of substituted pyrroles: Unanticipated radical-derived oxygenated products

Article abstract of DOI:10.1021/jo9012942

(Chemical Equation Presented) Photooxidation of pyrrole adducts 7-10 has been investigated in order to establish a general reaction pattern andmechanism for the formation of the resulting oxygenated products. The reactions were performed in several solvents utilizing both type I and type II sensitizers. In most cases, photooxidations gave complex mixture of products. Among these products, 5,5- or 6,5-bicyclic lactams (11, 15, and 19), maleimide 12 unsaturated γ-lactams (16 and 20), 5-hydroxylactams (13, 17, and21), and 5-methoxylactams (14, 18, and22) wereisolated and characterized. Photooxidation of 2,5-dimethyl-substituted pyrrole 10 in aprotic solvents unexpectedly afforded aldehyde 23 as the major product. Moreover, photooxidation of pyrrole adduct 10 in protic solvents exclusively gave the unprecedented solvent-trapped products 24-27. The formation of products 11-22 was rationalized by the intermediacy of a commonendoperoxide intermediate, whichcould be formedby both type I and type II mechanisms. Compounds 23-27 were most probably formed via an electron-transfer mechanism. 2009 American Chemical Society.

Full text of DOI:10.1021/jo9012942

pubs.acs.org/joc
Photosensitized Oxidations of Substituted Pyrroles: Unanticipated
Radical-Derived Oxygenated Products
Mariza N. Alberti, Georgios C. Vougioukalakis,† and Michael Orfanopoulos*
Department of Chemistry, University of Crete, 71003 Voutes, Heraklion, Crete, Greece. †Present address:
Institute of Physical Chemistry, NCSR Demokritos, 15310 Agia Paraskevi, Attiki, Greece.
orfanop@chemistry.uoc.gr
Received June 17, 2009
Photooxidation of pyrrole adducts 7-10 has been investigated in order to establish a general reaction pattern
and mechanism for the formation of the resulting oxygenated products. The reactions were performed in several
solvents utilizing both type I and type II sensitizers. In most cases, photooxidations gave complex mixture of
products. Among these products, 5,5- or 6,5-bicyclic lactams (11, 15, and 19), maleimide 12 unsaturated
γ-lactams (16 and 20), 5-hydroxylactams (13, 17, and 21), and 5-methoxylactams (14, 18, and 22) were isolated
and characterized. Photooxidation of 2,5-dimethyl-substituted pyrrole 10 in aprotic solvents unexpectedly
afforded aldehyde 23 as the major product. Moreover, photooxidation of pyrrole adduct 10 in protic solvents
exclusively gave the unprecedented solvent-trapped products 24-27. The formation of products 11-22 was
rationalized by the intermediacy of a common endoperoxide intermediate, which could be formed by both type I
and type II mechanisms. Compounds 23-27 were most probably formed via an electron-transfer mechanism.
Introduction
pyrroles has been driven by the developments in photother-
apeutic methods treating neonatal jaundice.4 Recently, at-
tention has been focused on the role of porphyrins in the
so-called photodynamic action.5 One of the problems asso-
ciated with the photooxidation of pyrrole derivatives is the
Singlet oxygen (1O2)1,2-mediated oxidation of pyrroles is of
significant interest due to the widespread occurrence of pyrrole
derivatives in natural products and the well-established sensi-
tivity of these heterocyclic compounds under photooxidation
conditions.3 In this context, pyrrole derivatives often require
special handling in order to minimize their oxidative decom-
position. Initial interest in the photocatalytic oxidation of
(3) For review articles on 1O2 addition reactions to heterocycles, see:
(a) Wasserman, H. H.; Lipshutz, B. H. Reactions of Singlet Oxygen with Hetero-
cyclic Systems. In Singlet Oxygen; Wasserman, H. H., Murray, R. W., Ed.;
Academic Press: New York, 1979; pp 429-509. (b) Matsuura, T. Tetrahedron
1977, 33, 2869–2905. (c) George, M. V.; Bhat, V. Chem. Rev 1979, 79, 447–478.
(d) Feringa, B. L. Recl. Trav. Chim. Pays-Bas 1987, 106, 469–488. (e) Iesce,
M. R.; Cermola, F.; Temussi, F. Curr. Org. Chem. 2005, 9, 109–139. (f) Clennan,
E. L.; Pace, A. Tetrahedron 2005, 61, 6665–6691.
(4) (a) Lightner, D. A.; Quistad, G. B. Science 1971, 175, 324. (b) Lightner,
D. A.; Crandall, D. C. FEBS Lett. 1972, 20, 53–56. (c) Lightner, D. A.; Quistad,
G. B. FEBS Lett. 1972, 25, 94–96. (d) Odell, G. B.; Schaffer, R.; Simopoulos, A. P.
In Phototherapy in the Newborn: An Overview; National Academy of Sciences:
Washington, D.C., 1975.
(5) (a) Kuimova, M. K.; Botchway, S. W.; Parker, A. W.; Balaz, M.; Collins,
H. A.; Anderson, H. L.; Suhling, K.; Ogilby, P. R. Nature Chem. 2009, 1, 69–73.
For selected reviews of photodynamic therapy, see: (b) Dougherty, T. J.; Gomer,
C. J.; Henderson, B. W.; Jori, G.; Kessel, D.; Korbelik, M.; Moan, J.; Peng, Q.
J. Natl. Cancer Inst. 1998, 90, 889–905. (c) Dolmans, D. E.; Fukumura, D.; Jain,
R. K. Nature Rev. Cancer 2003, 3, 380–387.
*To whom correspondence should be addressed. Tel: +30 2810 545030.
Fax: +30 2810 545001.
(1) (a) Frimer, A. A. Chem. Rev. 1979, 79, 359–387. (b) Schweitzer, C.;
Schmidt, R. Chem. Rev. 2003, 103, 1685–1757. (c) Greer, A. Acc. Chem. Res.
2006, 39, 797–804.
(2) For reviews on 1O2 reactions, see: (a) Baumstark, A. L.; Rodriguez, A.
Photochemical Methods for the Synthesis of 1,2-Dioxetanes. In CRC Handbook
of Organic Photochemistry and Photobiology; Horspool, W. M., Song, P.-S.,
Ed.; CRC Press: Boca Raton, 1995; pp 335-345. (b) Adam, W.; Griesbeck, A. G.
Photooxygenation of 1,3-Dienes. In CRC Handbook of Organic Photohcemistry
and Photobiology; Horspool, W. M., Song, P.-S., Ed.; CRC Press: Boca Raton,
1995; pp 311-324. (c) Adam, W.; Prein, M. Acc. Chem. Res. 1996, 29, 275–283.
(d) Prein, M.; Adam, W. Angew. Chem., Int. Ed. Engl. 1996, 35, 477–494.
(e) Stratakis, M.; Orfanopoulos, M. Tetrahedron 2000, 56, 1595–1615.
7274 J. Org. Chem. 2009, 74, 7274–7282
Published on Web 09/09/2009
DOI: 10.1021/jo9012942
r
2009 American Chemical Society

Alberti et al.
JOCArticle
SCHEME 1. Most Common Oxygenated Products Detected
from the Photooxidations of Pyrroles (Nuc = Nucleophile)
SCHEME 2. Photosensitized Oxidation of Homochiral 2-Methyl-
pyrroles
CHART 1
low chemoselectivity. Thus, their photosensitized oxidation
often gives rise to a complex mixture of oxygenated products.
This complexity has been mainly attributed to the multiple
available pathways for the decomposition of primary oxy-
genated products such as hydroperoxides, dioxetanes, and
endoperoxides. The most common isolated products are
shown in Scheme 1. Remarkably, reaction conditions and
the substitution pattern on the pyrrole ring play a significant
role in determining the nature of the oxygenated products.
Wasserman and Boger reported an interesting study on
the photooxidation of N-substituted6 and N-unsubstituted7
pyrroles. In particular, they showed that when the hetero-
cyclic ring is substituted by both electron-releasing and
electron-withdrawing groups, oxidation reactions can be
controlled. This unique behavior has been utilized to synthe-
size the d,l- and meso-isochrysohermidin8 as well as the A and
B rings of the prodigiosin.9 It is also worth mentioning that
the photooxidation of N-arylpyrroles has led to the forma-
tion of hydroxy- or methoxylactams.10 In the same work, it
was proposed that the oxygenated products of these reac-
tions may encompass features related to the mitomycin
antibiotics.
be converted into unsaturated γ-lactams 4 in high yields
(Scheme 2);11 note that lactams 3 and 4 are important
synthons for the preparation of a variety of biologically
active compounds.12 More recently, Demir and Aydoyan
showed that the 1O2-mediated oxidation of homochiral
2-methylpyrroles 5 produced chiral bicyclic lactams 6 in
good diastereoselectivity and moderate to high chemical
yields (Scheme 2).13 It should be also mentioned that chiral
bicyclic lactams are frequently used as synthons in the total
synthesis of certain natural products.14,15 The high chemo-
selectivity in the photooxidation of homochiral 2-methyl-
pyrrole derivatives 1 and 5 prompted us to study the photo-
sensitized oxidation of a family of related substrates. Herein,
we report the structure as well as the stereochemistry of a
series of novel products formed in the reactions of pyrrole
adducts 7-10 (Chart 1) with photoreactive molecular oxy-
gen species. We also thoroughly discuss mechanistic possi-
bilities in these photocatalytic oxidations.
Results and Discussion
Photosensitized Oxidation of Pyrrole Derivative 7. The
photooxidation of 7 (prepared by a known procedure)16
In 2002, Demir and co-workers showed that the photo-
oxidation of homochiral 2-methylpyrrole derivatives 1 can
(12) For selected examples, see: (a) Moloney, M. G. Nat. Prod. Rep.
1999, 16, 485–498. (b) Cuiper, A. D.; Kouwijzer, M. L. C. E.; Grootenhuis,
P. D. J.; Kellog, R. M.; Feringa, B. L. J. Org. Chem. 1999, 64, 9529–9537.
(c) Schieweck, F.; Altenbach, H. -J. J. Chem. Soc., Perkin Trans. 1 2001,
3409–3414. (d) Andrews, M. D.; Brewster, A. G.; Moloney, M. G. J. Chem.
Soc., Perkin Trans. 1 2002, 80–90.
(6) (a) Wasserman, H. H.; Frechette, R.; Rotello, V. M.; Schulte, G.
Tetrahedron Lett. 1991, 32, 7571–7574. (b) Boger, D. L.; Baldino, C. M.
J. Org. Chem. 1991, 56, 6942–6944.
(7) (a) Wasserman, H. H.; Powers, P.; Petersen, A. K. Tetrahedron Lett.
1996, 37, 6657–6660. (b) Wasserman, H. H.; Xia, M.; Wang, J.; Petersen,
A. K.; Jorgensen, M. Tetrahedron Lett. 1999, 40, 6145–6148. (c) Wasserman,
H. H.; Xia, M.; Wang, J.; Petersen, A. K.; Jorgensen, M.; Power, P.; Parr, J.
Tetrahedron 2004, 60, 7429–7425.
(8) (a) Wasserman, H. H.; DeSimone, R. W.; Boger, D. L.; Baldino, C. M.
J. Am. Chem. Soc. 1993, 115, 8457–8458. (b) Boger, D. L.; Baldino, C. M.
J. Am. Chem. Soc. 1993, 115, 11418–11425. (c) Wasserman, H. H.; Rotello,
V. M.; Frechette, R.; Desimone, R. W.; Yoo, J. U.; Baldino, C. M.
Tetrahedron 1997, 53, 8731–8738.
(13) Aydoyan, F.; Demir, A. S. Tetrahedron: Asymmetry 2004, 15, 259–
265.
(14) For a review article on the synthetic utility of chiral bicyclic lactams,
see: Meyers, A. I.; Brengel, G. P. Chem Commun. 1997, 1–8.
(15) For selected examples, see: (a) Meyers, A. I.; Garland, R. J. J. Am.
Chem. Soc. 1984, 106, 1146–1148. (b) Meyers, A. I.; Fleming, S. A. J. Am.
Chem. Soc. 1986, 108, 306–307. (c) Meyers, A. I.; Romine, J. L.; Fleming,
S. A. J. Am. Chem. Soc. 1988, 110, 7245–7247. (d) Meyers, A. I.; Berney, D.
J. Org. Chem. 1989, 54, 4673–4676. (e) Meyers, A. I.; Bienz, S. J. Org. Chem.
1990, 55, 791–798. (f) Armstrong, D. W.; He, L.; Yu, T.; Lee, J. T.; Liu, Y.
Tetrahedron: Asymmetry 1999, 10, 37–60.
(9) Wasserman, H. H.; Petersen, A. K.; Xia, M.; Wang, J. Tetrahedron
Lett. 1999, 40, 7587–7589.
(10) Basha, F. Z.; Franck, R. W. J. Org. Chem. 1978, 43, 3415–3417.
(11) Demir, A. S.; Aydoyan, F.; Akhmedov, I. M. Tetrahedron: Assyme-
try 2002, 13, 601–605.
(16) (a) Mecerreyes, D.; Pomposo, J. A.; Bengoetxea, M.; Grande, H.
Macromolecules 2000, 33, 5846–5849. (b) Trombach, N.; Hild, O.; Schlettwein,
€
D.; Wohrle, D. J. Mater. Chem. 2002, 12, 879–885.
J. Org. Chem. Vol. 74, No. 19, 2009 7275

Alberti et al.
JOCArticle
TABLE 1. Photooxidations of Pyrrole Derivative 7a
entry
solvent (radical scavenger)
εb (20 °C)
sensc
TPP
TPP
TPP
RB
RB
RB
TPP
RB
11d
12d
13d
14d
1
2
3
4
5
6
7
8
9
10
CCl4
benzene
CH2Cl2
(CH3)2CO
CH3CN
MeOH
CH2Cl2 (galvinoxyl)
MeOH (galvinoxyl)
CH3CN
2.24
2.28
9.14
17
14
16
24
24
<5
18
<5
23
6
24
38
43
46
45
26
40
26
51
76
59
48
41
30
31
19
42
24
26
18
21.0
36.64
33.0
9.14
33.0
36.64
36.64
∼50
∼45
DCA
W10O32
4-
CH3CN
aAll photooxidations were run up to 70-80% conversion of pyrrole 7. bDielectric constant.17 cSens = sensitizer. dRelative product yield (%) was
determined by 1H NMR analysis of the crude reaction mixtures (average of four runs, error ( 4%).
was initially carried out in oxygen-saturated CH2Cl2, at 0 °C
in the presence of tetraphenylporphyrin (TPP, principally a
type II sensitizer) with a 300 W xenon lamp (>300 nm) as the
light source (Table 1 , entry 3). The reaction was monitored
SCHEME 3. Type I and Type II DCA-Sensitized Photooxida-
tion Mechanisms (R = Unsaturated Substrate)
1
by H NMR spectroscopy, while the product distribution
was found to be independent of the conversion. In particular,
irradiation of 7 for 2 min (78% conversion) exclusively gave
three products: 5,5-bicyclic lactam 11, maleimide 12, and
5-hydroxylactam 13 (Table 1, entry 3). Surprisingly, unlike
the previously reported formation of lactam 6 (Scheme 2) as
the major isolated product,13 in our case 5,5-bicyclic lactam
11 was the minor product. When the photooxidation of 7 was
performed using identical conditions with those described
previously11,13 (i.e., in oxygen-saturated CH2Cl2 solution, at
rt, in the presence of TPP under irradiation with a 100 W
sodium lamp), the product distribution was again identical
with our first run. Next, three control experiments were
carried out: (1) irradiation of 7 in the presence of TPP under
anaerobic conditions; (2) irradiation of 7 in the absence of
TPP under aerobic conditions; and (3) a solution of 7 was left
in the dark in the presence of TPP and molecular oxygen. In
all cases, pyrrole derivative 7 remained unreacted. These
results clearly indicate that products 11-13 are formed via a
photosensitized process.
In order to explore the mechanism of adduct formation we
then performed the same photosensitized oxidation in a
variety of solvents and sensitizers. As can be seen in Table 1,
photooxidation of pyrrole 7 in the presence of TPP (entries
1-3) and Rose Bengal (RB) (entries 4 and 5) in polar
and nonpolar solvents afforded adducts 11-13. In all cases,
5,5-bicyclic lactam 11 was the minor product. Note that for
the first four runs as the solvent polarity increases the relative
yield of product 13 decreases with simultaneous increase of
product 12. When methanol was used as the solvent, apart
from oxygenated products 11-13, 5-methoxylactam 14 was
also obtained (Table 1, entry 6). Furthermore, the presence
of galvinoxyl as a radical scavenger/inhibitor in the photo-
oxidation of pyrrole 7 in CH2Cl2 or MeOH did not signifi-
cantly affect the product distribution (Table 1, compare
entries 3 and 6 with 7 and 8, respectively). Therefore, it seems
reasonable to assume that the formation of products 11-14
and their distribution are independent of the presence of a
radical scavenger.
Control experiments showed that product 13 does not
interconvert to 11, 12, or 14, either photochemically or in the
dark. In addition, when we used pyridine as cosolvent
(along with CH2Cl2 as solvent), we found that the yield of
pyrrolinone products decreased compared to the reaction in
the absence of pyridine. Therefore, taking into account
previous findings,18 it appears logical to assume that the
endoperoxide, between pyrrole 7 and 1O2, is precursor to the
isolated photoproducts 11-14.
Previous studies have shown that the photooxidation of
pyrroles in the presence of molecular oxygen and type II
sensitizers produces 5-hydroxy or 5-methoxylactams and
maleimides. Specifically, these products are obtained when
a hydrogen atom18a,19 or an alkyl group19c,20 is placed at
the R-position of the reactant pyrrole.19c,20 Furthermore,
the oxygenation of organic compounds photosensitized by
9,10-dicyanoanthracene (DCA) has been extensively studied
(18) (a) Lightner, D. A.; Bisacchi, G. S.; Norris, R. D. J. Am. Chem. Soc.
1976, 98, 802–807. (b) Franck, R. W.; Auerbach, J. J. Org. Chem. 1971, 36,
31–36.
(19) (a) De Mayo, P.; Reid, S. T. Chem. Ind. (London) 1962, 1576–1577.
(b) Quistad, G. B.; Lightner, D. A. J. Chem. Soc. D, Chem. Commun 1971,
1099–1100. (c) Lightner, D. A.; Pak, C.-S. J. Org. Chem. 1975, 40, 2724–2728.
(20) (a) Quistad, G. B.; Lightner, D. A. Tetrahedron Lett. 1971, 21, 4417–
4420. (b) Lightner, D. A.; Quistad, G. B. Angew. Chem., Int. Ed. 1972, 11,
215–216. (c) Lightner, D. A.; Crandall, D. C. Tetrahedron Lett. 1973, 21,
1799–1802. (d) Lightner, D. A.; Crandall, D. C. Experentia 1973, 29, 262–
264. (e) Lightner, D. A.; Norris, R. D.; Kirk, D. I.; Key, R. M. Experentia
1974, 30, 587–588. (f) Li, H. -Y.; Drummond, S.; DeLucca, I.; Boswell,
G. A. Tetrahedron 1996, 52, 11153–11162.
(17) Dean, J. A. In Lange’s Handbook of Chemistry; 15th ed., McGraw-Hill,
Inc.: New York, 1999; pp 464-488.
7276 J. Org. Chem. Vol. 74, No. 19, 2009

Alberti et al.
JOCArticle
TABLE 2. Photooxidations of Pyrroles 8 and 9a
15, n = 1c
19, n = 2c
16, n = 1c
20, n = 2c
17, n = 1c
21, n = 2c
18, n = 1c
22, n = 2c
entry
n
solvent (1O2 quencher or radical scavenger)
sensb
TPP
TPP
TPP
RB
RB
RB
TPP
TPP
RB
DCA
DCA
DCA
W10O32
TPP
RB
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
CCl4
Benzene
CH2Cl2
(CH3)2CO
CH3CN
MeOH
CH2Cl2 (DABCO)
CH2Cl2 (galvinoxyl)
MeOH (galvinoxyl)
CCl4
9
15
11
10
10
8
17
19
<5
11
11
17
18
36
14
35
16
41
47
70
46
57
15
55
49
15
26
43
31
48
45
9
50
38
19
44
33
15
28
32
25
63
46
52
34
19
17
13
24
62
∼55
CH3CN
CH3CN (DABCO)
CH3CN
CH2Cl2
MeOH
CH2Cl2 (galvinoxyl)
MeOH (galvinoxyl)
4-
60
50
TPP
RB
52
10
c
aAll photooxidations were run up to 70-80% conversion of pyrrole 8 or 9. bSens = sensitizer. Relative product yield (%) was determined by
1H NMR analysis of the crude reaction mixtures (average of four runs, error ( 4%).
and has been shown to occur by two competing mechanisms:
type I and II (Scheme 3).21 The relative contribution of these
two pathways depends on solvent polarity and the nature of
the substrate. It is generally accepted that, in polar solvents,
ion pairs diffuse apart to give solvent-separated radical ions,
which can react further.22 On the other hand, in the presence
transient, which is designated as wO.26 In general, wO
reactivity provides an interesting mechanistic tool for studies
of light-induced oxidations, since it proceeds exclusively via
free-radical pathways (electron or hydrogen transfer).27
In this context, and in order to get further information on the
reaction mechanism, we examined the photooxidation of 7
under type I conditions (electron and/or hydrogen transfer). In
particular, the photooxidation reactions of 7 were carried out in
1
of O2-acceptors and nonpolar solvents, the corresponding
1O2-adducts appear to be the mainly formed products.23
Moreover, photocatalyzed reactions induced by polyoxo-
metalates such as decatungstate (W10O324-) have been ex-
plored extensively over the past several years.24,25 It is
4-
CH3CN, at 0 °C, with either DCA or W10O32 as photo-
sensitizers. In this case, products 11-13 were exclusively
formed, and their relative yields are shown in Table 1 (entries
9 and 10). Note that these entries show an increased relative
yield of maleimide 12 in comparison to that of entry 5 (with
CH3CN as the solvent).
4-
generally accepted that illumination of W10O32 leads to
4-
the formation of a charge-transfer excited state W10O32 *
that decays in less than 30 ps to an extremely reactive
Photosensitized Oxidations of 2-Methylpyrroles 8 and 9.
Compounds 1-(2-hydroxyethyl)-2-methylpyrrole (8) and
1-(3-hydroxypropyl)-2-methylpyrrole (9) were prepared
from the reactions of 5-chloro-3-penten-2-one with the
corresponding amino alcohols.28 The photooxidation reac-
tions of 8 (under mainly type II conditions) were carried out
in several solvents, at 0 °C, in the presence of molecular
oxygen and TPP or RB (Table 2, entries 1-5). The conver-
sion and product distribution in these reactions were mea-
sured by integrating the appropriate peaks in the 1H NMR
spectra. It was again found that the product distribution was
independent of the conversion. In all cases, three oxygenated
products were formed (Table 2, entries 1-5). In particular,
irradiation of 8 gave 5,5-bicyclic lactam 15, unsaturated
(21) For two related reviews, see: (a) Foote, C. S. In Free Radicals
in Biology; Pryor, W. A., Ed.; Academic Press: New York, 1976; pp 85-133.
(b) Foote, C. S. Tetrahedron 1985, 41, 2221–2227.
(22) For some selected examples, see: (a) Eriksen, J.; Foote, C. S. J. Am.
Chem. Soc. 1980, 102, 6083–6088. (b) Lewis, F. D.; Bedell, A. M.; Dykstra,
R. E.; Elbert, J. E.; Gould, I. R.; Farid, S. J. Am. Chem. Soc. 1990, 112, 8055–
8064. (c) Kanner, R. C.; Foote, C. S. J. Am. Chem. Soc. 1992, 114, 678–681.
(23) For some selected examples, see: (a) Steichen, D. S.; Foote, C. S.
Tetrahedron Lett. 1979, 20, 4363–4366. (b) Santamaria, J. Tetrahedron Lett.
1981, 22, 4511–4514. (c) Araki, Y.; Dobrowolski, D. C.; Goyne, T.; Hanson,
D. C.; Jiang, Z. Q.; Lee, K. J.; Foote, C. S. J. Am. Chem. Soc. 1984, 106, 4510–
4575.
(24) For three related reviews, see: (a) Hill, C. L. Chem. Rev. 1998, 98,
1–390. (b) Tanielian, C. Coord. Chem. Rev. 1998, 178-180, 1165–1181.
(c) Tzirakis, M. D.; Lykakis, I. N.; Orfanopoulos, M. Chem. Soc. Rev. 2009,
38, 2609-2621.
(25) For some recent examples, see: (a) Lykakis, I. N; Vougioukalakis,
G. C.; Orfanopoulos, M. J. Org. Chem. 2006, 71, 8740–8747. (b) Esposti, S.;
Dondi, D.; Fagnoni, M.; Albini, A. Angew. Chem., Int. Ed. 2007, 46, 2531–
2534. (c) Tzirakis, M. D.; Orfanopoulos, M. Org. Lett. 2008, 10, 873–876.
(d) Tzirakis, M. D.; Orfanopoulos, M. J. Am. Chem. Soc. 2009, 131, 4063–
4069.
(26) (a) Duncan, D. C.; Netzel, T. L.; Hill, C. L. Inorg. Chem. 1995, 39,
4640–4646. (b) Tanielian, C.; Duffy, K.; Jones, A. J. Phys. Chem. B 1997,
101, 4276–4282. (c) Duncan, D. C.; Fox, M. A. J. Phys. Chem. A 1998, 102,
4559–4567.
(27) Tanielian, C.; Schweitzer, C.; Seghrouchni, R.; Esch, M.; Mechin, R.
Photochem. Photobiol. Sci. 2003, 2, 297–305.
(28) (a) Barbry, D.; Faven, C.; Ayana, A. Synth. Commun. 1993, 23,
_
2647–2658. (b) Demir, A. S.; Akhmedov, I. M.; Tanyeli, C.; Gerc-ek, Z.;
Gadzhili, R. A. Tetrahedron: Asymmetry 1997, 8, 753–757. (c) Demir, A. S.;
€
Akhmedov, I. M.; S-es-enoglu, O.; Alpturk, O.; Apaydin, S.; Gerc-ek, Z.;
_
ꢀ
Ibrahimzade, N. J. Chem. Soc., Perkin Trans. 1 2001, 1162–1167.
€
_
J. Org. Chem. Vol. 74, No. 19, 2009 7277

Alberti et al.
JOCArticle
TABLE 3. Photosensitized Oxidations of 10 in Aprotic Solventsa
entry
solvent (1O2 quencher or radical scavenger)
sensb
TPP
TPP
TPP
RB
15c
16c
17c
23c
1
2
3
4
5
6
7
8
9
CCl4
benzene
CH2Cl2
(CH3)2CO
CH3CN
CH2Cl2 (galvinoxyl)
CH2Cl2 (DABCO)
CCl4
CH3CN
CH3CN (DABCO)
CH3CN
<5
8
8
8
8
∼25
ndd
9
10
32
<5
33
30
20
9
40
25
25
33
18
12
65
59
53
62
51
15
63
66
56
69
45
RB
TPP
TPP
DCA
DCA
DCA
W10O32
10
5
35
7
9
ndd
11
ndd
13
15
10
11
ndd
28
4-
aAll photooxidations were run up to 70-80% conversion of pyrrole 10. bSens = sensitizer. cRelative product yield (%) was determined by 1H NMR
analysis of the crude reaction mixtures (average of four runs, error ( 4%). dNot detected.
γ-lactam 16, and 5-hydroxylactam 17. It is worth mentioning
that the addition of a catalytic amount of p-TsOH to a
solution of 17 in toluene/CH3CN (3:1, v/v) at 70-80 °C led
after 1 h to the formation of compound 16. This observation
further confirms the structure of compound 17.
pyrroles 7 and 8, demonstrate that the formation of the
6,5-bicyclic lactam is generally preferred compared to the
5,5-bicyclic lactam. When methanol was used as the solvent,
5-methoxylactam 22 was obtained in 60% relative yield
(Table 2, entry 15) besides oxygenated products 19-21.
Ultimately, when galvinoxyl was used as radical inhibitor
in the photooxidation of pyrrole 9 in CH2Cl2 or MeOH,
products 19-21 or 19-22 were observed, respectively
(Table 2, entries 16 and 17).
Photosensitized Oxidations of Pyrrole 10. 1-(2-Hydroxy-
ethyl)-2,5-dimethylpyrrole (10) was prepared by the Pall-
Knorr condensation of 2,5-hexanedione and ethanol-
amine.30,31 The photooxidations of 10 were initially carried
out in several aprotic solvents under conditions similar to
that for pyrroles 7 and 8 (Table 3, entries 1-5), while the
conversion and the product distribution were measured as
described above. It was once again found that the product
distribution was independent of the conversion; in parti-
cular, irradiation of 10 in CH2Cl2 furnished a complex
mixture of four oxygenated products: 5,5-bicyclic lactam
15, unsaturated γ-lactam 16, 5-hydroxylactam 17, and alde-
hyde 23. Solvent polarity did not have a considerable impact
on product distribution (Table 3, entries 1-5). Interestingly,
aldehyde 23 was the major product (51-65%), whereas
oxygenated products 15-17 were generally detected in small
quantities. On the basis of what is known for the photo-
oxidation products of substituted pyrroles,3c,e,f,11,13 the for-
mation of 23 was completely unprecedented.
In the aforementioned cases (Table 2, entries 1-5), solvent
polarity did not have any considerable effect on the product
distribution; 5,5-bicyclic lactam 15 was the minor product
(9-15%), whereas unsaturated γ-lactam 16 and 5-hydro-
xylactam 17 were the major products (85-91% combined
yield). When the solvent was methanol, methanol-trapped
compound 18 was obtained as the major product (Table 2,
entry 6). When TPP was used as the photosensitizer in
CH2Cl2 and in the presence of a catalytic amount of DAB-
1
CO, a well-established O2 physical quencher,29 products
15-17 were exclusively formed (Table 2, entry 7) suggesting
that their formation is independent of the presence of O2
1
quenchers. Moreover, we examined the photooxidation of
pyrrole 8 in CH2Cl2 or MeOH in the presence of galvinoxyl
as a radical inhibitor (Table 2, entries 8 and 9). In accordance
with our previous findings (Table 1, entries 7 and 8), pro-
ducts 15-18 were mainly observed.
As an extension of our studies we also performed the
photosensitized oxidations of 8 with DCA in both polar and
nonpolar solvents (Table 2, entries 10 and 11). In addition,
we carried out the photooxidation of 8 in CH3CN with either
DCA in the presence of DABCO or with W10O324- (Table 2,
entries 12 and 13). In these cases, 5,5-bicyclic lactam 15 was
the minor product (11-18%), whereas unsaturated γ-lactam
16 and 5-hydroxylactam 17 were the major adducts
(82-89% combined yields).
The photooxidation of pyrrole 9 in CH2Cl2 at 0 °C with
TPP as the sensitizer afforded 6,5-bicyclic lactam 19, un-
saturated γ-lactam 20, and 5-hydroxylactam 21 (Table 2,
entry 14). Note that 6,5-bicyclic lactam 19 was formed in
36% relative yield, and in this case, the minor product was
5-hydroxylactam 21 (19% relative yield). These findings, in
conjunction with our results on the photooxidation of
In order to understand the origin of aldehyde 23, we
performed the photooxidation of 10 in CH2Cl2 using TPP
as sensitizer, along with a catalytic amount of either galvin-
oxyl, a radical scavenger, or DABCO, a 1O2 quencher
(Table 3, entries 6 and 7). The photooxidation of 10 in
CH2Cl2 in the presence of galvinoxyl furnished aldehyde 23
in 15% relative yield (entry 6), while, in the absence of
galvinoxyl, aldehyde 23 was formed in 53% relative yield
(entry 3). This result strongly supports a free-radical process
(30) (a) Paal, C. Chem. Ber. 1884, 17, 2756–2767. (b) Knorr, L. Chem. Ber.
1884, 17, 1635–1642.
(31) Zhu, M.; Spink, D. C.; Bank, S.; Chen, X.; DeCaprio, A. P.
J. Chromatogr. 1993, 628, 37–47.
(29) (a) Ouannes, C.; Wilson, T. J. Am. Chem. Soc. 1968, 90, 6527–6528.
(b) Foote, C. S. In Quenching of Singlet Oxygen; Wasserman, H. H., Murray,
R. W., Ed.; Academic Press: New York, 1979; pp 139-173.
7278 J. Org. Chem. Vol. 74, No. 19, 2009

Alberti et al.
JOCArticle
TABLE 4. Photooxidations of Pyrrole 10 in Protic Solvents (MeOH
and EtOH)
To the best of our knowledge, there are no reports regarding
the formation of such trapped products (24-27) in the photo-
oxidation of substituted furans3d-f,32 or pyrroles. In fact,
the photooxidation of 2,5-dimethylpyrrole in methanol has
been reported to afford 5-methoxy-5-methyl-3-pyrrolin-2-one,
5-methoxy-5-methoxymethyl-3-pyrrolin-2-one, and 2-formyl-
2-methoxy-5-methylidene-3-pyrroline.33
Mechanistic Considerations. As we already mentioned, it is
generally accepted that type I and type II photooxida-
tion mechanisms (Scheme 3) are often competitive. When
RB, DCA, or W10O324- are used in polar solvents, the type I
mechanism predominates, whereas in the case of TPP as the
sensitizer in nonpolar solvents, the type II process (energy
transfer) is more likely to occur. Consistent to this hypo-
thesis, the photooxidation of 7-10 in CH2Cl2 in the presence
or in the absence of galvinoxyl (Tables 1-3) gave rise to the
same oxygenated products and in similar relative yields.
However, similar oxygenated products were observed (a)
when the photooxidation of 7-10 in polar solvents (using
RB, DCA, or W10O324- as sensitizers) was carried out in the
presence or in the absence of galvinoxyl (Tables 1-3) and (b)
when the photooxidation of 8 or 10 in CH2Cl2 (using TPP as
sensitizer) was examined in the presence or in the absence of
DABCO (Tables 2 and 3). Taking into account the data
obtained from the TPP-sensitized photooxidations of pyr-
roles 8 and 10 in CH2Cl2, it seems likely that these reactions
proceed with both type I and type II mechanisms. Consider-
ing the reduction potential of 1TPP* (Ered = 0.81 V vs
SCE),34 an electron-transfer mechanism35 should be possible
for substrates with negative oxidation potentials. Although
there are no literature data available, we believe that pyrroles
8 and 10 comply with this requirement. More generally, on
the basis of our results (from the sensitized photooxidations
of pyrroles 7-10), we suggest that oxygenated products
11-22 can be formed by either of the two mechanisms or,
most probably, by both of them operating simultaneously:
(a) a type I electron transfer (ET) or hydrogen abstraction
transfer (HAT) process and (b) a type II energy-transfer
process via 1O2. The distinction between these two mechan-
istic pathways is not always straightforward.
The formation of oxygenated products 11-22 under
energy-transfer conditions (type II) is outlined in Scheme 4.
It is known that in the 1O2 reactions of pyrroles, the
oxygenated products are derived from a common reactive
endoperoxide intermediate. Lightner and co-workers ob-
served the formation of this endoperoxide intermediate by
using low-temperature 1H NMR spectroscopy.18a,19c The
origin of the oxygenated products can be then explained by
ground- and excited-state reactions of these unstable endo-
peroxides. In the present case, we suggest that the initially
formed endoperoxide A can be followed by five different
mechanistic pathways (Scheme 4, pathways a-e). Hydro-
lysis of endoperoxide A affords hydroperoxide B, a proper
precursor to 5-hydroxylactams 13, 17, and 21 (pathway a);
irradiation conversion 24, R = Mea 25, R = Mea
entry
R
time
(%)a
26, R = Eta 27, R = Eta
1
2
3
4
5
6
7
8
9
Me 1 min
Me 1.5 min
Me 2 min
Me 2.5 min
Me 4 min
Me 5 min
20
40
50
68
100
100
25
40
48
100
79
73
59
ndb
21
27
41
16
84
ndb
100
100
100
84
100
ndb
ndb
ndb
16
Et
Et
Et
Et
Et
Et
40 s
1.5 min
2 min 40 s
3 min
10
11
12
72
3.5 min
4.5 min
100
100
59
ndb
41
100
aConversion and relative product yield (%) were determined by
1H NMR analysis of the crude reaction mixtures (average of three runs,
error ( 4%). bNot detected.
for the formation of aldehyde 23. On the other hand, the
photooxidation of 10 in the presence of DABCO furnished
aldehyde 23 in 63% relative yield (entry 7). Moreover, we
performed the photosensitized oxidation of 10 with DCA in
both polar and nonpolar solvents (Table 3, entries 8 and 9).
Additionally, we carried out the photooxidation of 10, in
CH3CN, with DCA in the presence of DABCO as well as
with W10O324- (Table 3, entries 10 and 11). In all these cases,
aldehyde 23 was the major product (45-69%).
When pyrrole 10 was photooxidized in MeOH using RB
as sensitizer, at 0 °C for 1 min, an unprecedented, methanol-
trapped product (24) was formed quantitatively (Table 4,
entry 1). Product 24 is very reactive and, under the photoox-
idation conditions, can be readily transformed into diether 25.
Indeed, when 10 was photooxidized in MeOH for 5 min (in the
presence of a catalytic amount of RB, at 0 °C), diether 25 was
formed quantitatively (Table 4, entry 6). The relative yields of
these adducts in various irradiation times are shown in Table 4
(entries 2-5). In order to be certain that compounds 24 and 25
are indeed derived through photosensitized oxidations, we
performed two control experiments: (1) irradiation of 10 under
oxygen but in the absence of a sensitizer and (2) irradiation of
10 with a sensitizer under anaerobic conditions. Both experi-
ments failed to afford either 24 or 25. Furthermore, we
performed the photooxidation of 10 in MeOH with a catalytic
1
amount of galvinoxyl. In this case, H NMR analysis of the
crude photooxidation mixtures (obtained after 1, 2 and 4 min)
showed consumption of starting material and formation of
unidentified highly polar side products. These results clearly
demonstrate that methanol-trapped products, 24 and 25, are
formed through a radical-mediated process.
In a similar manner, we performed the photooxidation of
pyrrole 10 in EtOH. In accordance to the findings obtained
using MeOH as a solvent, we were able to isolate and
characterize ethanol-trapped products 26 and 27. The rela-
tive yields of these compounds were dependent on the
pyrrole conversion (Table 4, entries 7-12).
(32) Foote, C. S.; Wuesthoff, M. T.; Wexler, S.; Burstain, I. G.; Denny,
R.; Schenck, G. O.; Schulte-Elte, K. -H. Tetrahedron 1967, 23, 2583–2599.
(33) Low, L. K.; Lightner, D. A. J. Chem. Soc., Chem. Commun. 1972,
116–117.
(34) Darwent, J. R.; Douglas, P.; Harriman, A.; Porter, G.; Richoux,
M.-C. Coord. Chem. Rev. 1982, 44, 83–126.
(35) (a) Kavarnos, G. J.; Turro, N. J. Chem. Rev. 1986, 86, 401–449.
(b) Kavarnos, G. J. Fundamental Concepts of Photoinduced Electron-Transfer. In
Top. Curr. Chem.; Springer: Berlin-Heidelberg, 1990; Vol. 156, pp 21-58.
J. Org. Chem. Vol. 74, No. 19, 2009 7279

Alberti et al.
JOCArticle
SCHEME 4. Suggested Mechanism for the Formation of 11-22 under Type II Conditions
SCHEME 5. Proposed Mechanistic Pathways for the Forma-
tion of 11-22 under Type I Conditions
however, it has been reported that in nonaqueous sol-
vents the major pathway for the formation of 5-hydroxy-
lactams is a-H abstraction either intramolecularly, from
biradical C (pathway b), or by other agents (e.g., an ex-
cited molecule of the sensitizer).18a Also note that the
role of the pyrrole a-hydrogen is very important in the
mechanism of endoperoxides decomposition via nonhydro-
lytic pathways.11,18a,19c,20a,c-e We believe that in case of the
photooxidation of pyrrole 10, 5-hydroxylactam 17 origi-
nates from the hydrolysis of the corresponding endoperoxide
followed by the loss of one a-methyl group. A similar dealky-
lation reaction was reported in 1972.20b
Oxygenated products 17 and 21 can undergo elimination
of H2O to form unsaturated γ-lactams 16 and 20, respec-
tively. 1-(Hydroxyethyl)maleimide 12, on the other hand,
may originate from biradical B, formed either by thermal or
photochemical O-O homolysis of A followed by hydrogen
loss from the alkoxy radicals (pathway b).36 The formation
of bicyclic hydroperoxide E from A involves the intramole-
cular nucleophilic attack of the hydroxyl group either di-
rectly or through an open dipolar D1,37 shown in pathway c
(Scheme 4).13 The bicyclic hydroperoxide E decomposes
yielding bicyclic lactams 11, 15, and 19 (pathway d). In a
similar manner, methanolysis of the endoperoxide A, either
directly or via pathway c, gives hydroperoxide F, a precursor
to 5-methoxylactams 14, 18, and 22 (pathway e).
A reasonable mechanistic rationalization for the sensitized
photooxidation of pyrroles 7-10 under ET conditions (type I)
is presented in Scheme 5. Initially, an electron is transferred
from the pyrrole to the photoexcited sensitizer to form the
radical ions. Subsequent oxidation of sens•- by ET to mole-
cular oxygen furnishes the superoxide radical anion (O2•-).
Reaction of the latter with [7-10]•þ gives rise to dipolar or
biradical D1 or D2, respectively. The intermediate or transition
state D1,2 is expected to yield endoperoxide A (Scheme 5,
pathway a).38 Eventually, oxygenated products 11-22 are
generated according to the mechanism shown in Scheme 4.
Alternatively, dipolar species D1 is intramolecularly attacked
by the hydroxyl moiety, forming the bicyclic hydroperoxide
which decomposes to bicyclic lactams 11, 15, and 19
(Scheme 5, pathway b).
(36) Storey, P. R.; Morrison, W. H.; Butler, J. M. J. Am. Chem. Soc. 1969,
91, 2398–2400.
(37) In the case that the exciplex has a zwitterionic character, the bicyclic
lactams and the 5-methoxylactams could also be formed without the inter-
mediacy of the endoperoxide B. Also note that 1,4-dipolars and 1,4-biradi-
cals are often suggested as intermediates in singlet oxygen [4
þ
2]
cycloaddition reactions. For some representative examples, see: (a) Clennan,
E. L.; Nagraba, K. J. Org. Chem. 1987, 52, 294–296. (b) O’Shea, K. E.; Foote,
C. S. J. Am. Chem. Soc. 1988, 110, 7167–7170. (c) Kwon, B.-M.; Foote, C. S.;
Khan, S. I. J. Org. Chem. 1989, 54, 3378–3382. (d) McCarrick, M. A.; Wu,
Y.-D.; Houk, K. N. J. Org. Chem. 1993, 58, 3330–3343. (e) Motoyoshiya, J.;
Okuda, Y.; Matsuoka, I.; Hayashi, S.; Takaguchi, Y.; Aoyama, H. J. Org.
Chem. 1999, 64, 493–497. (f) Bobrowski, M.; Liwo, A.; Oldziej, S.; Jeziorek,
D.; Ossowski, T. J. Am. Chem. Soc. 2000, 122, 8112–8119. (g) Sevin, F;
McKee, M. L. J. Am. Chem. Soc. 2001, 123, 4591–4600.
(38) For the formation of endoperoxides via an electron-transfer path-
way, see: (a) Eriksen, J.; Foote, C. S.; Parker, T. L. J. Am. Chem. Soc. 1977,
99, 6455–6456. (b) Santamaria, J. Tetrahedron Lett. 1981, 22, 4511–4514.
(c) Jianxin, C.; Yi, C.; Baowen, Z.; Yangfu, M. Acta Chim. Sin. 1985, 43,
601–602.
7280 J. Org. Chem. Vol. 74, No. 19, 2009

Alberti et al.
JOCArticle
SCHEME 6. Suggested Mechanism for the Formation of 23 under
Type I Conditions
SCHEME 7. Suggested Mechanism for the Formation of 24-27
under Type I Conditions
According to the data in Table 3, aldehyde 23 is generated
to a greater extent in aprotic solvents via an ET process. The
suggested mechanism for this novel photooxidation reaction
is shown in Scheme 6. Electron transfer from pyrrole 10 to
the excited state of the sensitizer affords radical cation 10•þ
and sens•-. Oxidation of sens•- via ET to molecular oxygen
furnishes the superoxide radical anion (O2•-), while a simul-
taneous proton loss from 10•þ affords radical G. The pre-
ferential site for radical recombination between G and the
superoxide radical anion is the a-carbon atom given that the
aromaticity is restored in species G2. This radical intermedi-
ate leads to hydroperoxy anion H, the protonation of which
affords hydroperoxide I. At the last step, I undergoes
dehydration to yield aldehyde 23.
RB is a well-known photosensitizing dye of xanthine origin.
This powerful photosensitizer is known for its high efficiency in
generating singlet oxygen.39 However, it has been reported that
it can also form radicals in the presence of many electron-
donating molecules.40 Considering the data obtained from the
RB-sensitized photooxidations of pyrrole 10 in MeOH in the
presence or in the absence of galvinoxyl, we strongly suggest
that solvent-trapped products 24-27 are formed via an ET
mechanism. This mechanism is outlined in Scheme 7. In
particular, ET from 10 to the excited state of RB leads to the
formation of the radical ions 10•þ and RB•-. Since the radical
anion of RB is a reducing species, it can form superoxide radical
anion (O2•-) under aerobic conditions. Superoxide radical
anion may then abstract a hydrogen atom from 10•þ, affording
cation J. The possibility of a hydrogen atom abstraction from
10•þ, by the excited stated of RB, cannot be excluded. The
a-carbon atom should be the preferential site for methanol or
ethanol attack (the resonance structure J2 predominates). This
leads to the formation of products 24 and 26, which are even
better electron donors than 10. Further ET from 24 or 26 to the
excited stated of RB and subsequent HAT of 24•þor 26•þ
affords cation K. This cation can be trapped by methanol or
ethanol to form products 25 and 27, respectively.
Conclusion
In this work, we studied the photooxidation of N-substituted
pyrroles 7-10 using either type I or type II conditions. In all
cases, bicyclic lactams 11, 15, and 19 were the minor products.
Seventeen different products from both protic and polar or
nonpolar aprotic solvents were isolated and fully characterized.
The formation of products 11-22 could be rationalized by both
type I and type II mechanisms; the distinction between these
mechanistic pathways is not trivial. On the other hand, un-
precedented compounds 23-27 were most probably formed
through an electron-transfer mechanism.
Experimental Section
General Procedures for the Photosensitized Oxidations of
Pyrrole Adducts 7-10. A solution of the pyrrole (0.27 mmol)
in solvent (50 mL) containing a catalytic amount of sensitizer
(10-4 M) was placed in a flask, and oxygen was gently bubbled
through it. The solution was cooled to 0 °C and irradiated with a
xenon 300 W lamp. All photooxidations were stopped at
70-80% pyrrole conversion. When TPP and RB were used as
sensitizers, irradiation time varied between 1 and 5 min. On the
other hand, when DCA and W10O324- were used as sensitizers,
irradiation time varied between 30 min and 2 h. When DABCO
or galvinoxyl were used in the photooxidation, their concentra-
tion was 1.2 ꢀ 10-3 and 10-2 M, respectively. In most cases,
photooxidations gave complex mixtures of oxygenated pro-
ducts. These adducts were purified by flash column chromatog-
raphy using silica gel.
Photosensitized Oxidations of 7. Photolysis of 7 in several
solvents and sensitizers (Table 1) gave complex mixtures of
oxygenated products 11-14. These adducts were purified by
flash column chromatography over silica gel (hexanes/EtOAc
= 4:1 f EtOAc/acetone = 3:1 v/v). The spectroscopic data of
products 11-14 are as follows:
(39) (a) Gollnick, K.; Schenck, G. O. Pure Appl. Chem. 1964, 9, 507–525.
(b) Murasecco-Suardi, P.; Gassmann, E.; Broun, A. M.; Oliveros, E. Helv.
Chim. Acta 1987, 70, 1760–1766.
(40) For some selected examples, see: (a) Lambert, C.; Sarna, T.;
Truscott, G. T. J. Chem. Soc., Faraday Trans. 1990, 86, 3879–3882.
(b) Sarna, T.; Zajac, J.; Bowman, M. K.; Truscott, T. G. J. Photochem.
2,3-Dihydropyrrolo[2,1-b]oxazol-5(7aH)-one (11): 1H NMR
(500 MHz, CDCl3) δ 7.15 (d, 1H, J = 6.0 Hz), 6.16 (d, 1H, J =
6.0 Hz), 5.45 (br s, 1H), 4.27 (m, 1H), 4.19 (t, 1H, J = 7.0 Hz),
ꢁ
Photobiol. A: Chem 1991, 60, 295–310. (c) Rozanowska, M.; Ciszewska, J.;
Korytowski, W.; Sarna, T. J. Photochem. Photobiol. B: Biol 1995, 29, 71–77.
(d) Lambert, C. R.; Kochevar, I. E. Photochem. Photobiol. 1997, 66, 15–25.
J. Org. Chem. Vol. 74, No. 19, 2009 7281

Alberti et al.
JOCArticle
3.75 (m, 1H), 3.28 (m, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ
177.0, 146.0, 131.3, 93.4, 71.0, 42.8 ppm; MS m/z = 125 (100,
m/z = 95).
chromatography over silica gel (hexanes/EtOAc = 4:1 f
EtOAc/acetone = 1:1 v/v).
Photosensitized Oxidations of 10. Photolysis of 8 and 9 in
several solvents and sensitizers (Tables 3 and 4) gave mixtures of
oxygenated products 15-17 and 23-27, respectively. These
adducts were purified by flash column chromatography over
silica gel (hexanes/EtOAc = 4:1 f EtOAc/acetone = 2:1 v/v).
1-Hydroxyethylmaleimide (12): 1H NMR (500 MHz, CDCl3)
δ 6.74 (s, 2H), 3.78 (m, 2H), 3.73 (m, 2H), 2.10 (br s, 1H, OH)
ppm; 13C NMR (125 MHz, CDCl3) δ 171.3, 134.4, 61.0, 40.8
ppm; ESI-MS m/z = 164.3 [M þ Na]þ.
5-Hydroxy-1-(2-hydroxyethyl)-1H-pyrrol-2(5H)-one (13): 1H
NMR (500 MHz, CDCl3) δ 6.96 (d, 1H, J = 6.0 Hz), 6.11 (d, 1H,
J = 6.0 Hz), 5.45 (br s, 1H), 5.26 (br s, 1H, OH), 3.91 (br s, 1H,
OH), 3.76 (m, 3H), 3.39 (m, 1H) ppm; 13C NMR (75 MHz,
CDCl3) δ 170.8, 146.5, 128.0, 84.8, 61.6, 43.5 ppm; MS m/z =
125 (100, m/z = 40).
Acknowledgment. The Foundation for Education and
European Culture is acknowledged for providing a one year
fellowship to M.N.A. The financial support of the University
of Crete (ELKE K.A. 2750) is also acknowledged. We are
grateful to Prof. T. Drewello at the University of Erlangen-
1-(2-Hydroxyethyl)-5-methoxy-1H-pyrrol-2(5H)-one
(14):
1H NMR (500 MHz, CDCl3) δ 6.94 (d, 1H, J = 6.0 Hz), 6.29
(d, 1H, J = 6.0 Hz), 5.47 (br s, 1H), 3.80 (m, 2H), 3.56 (t, 2H, J =
5.0 Hz), 3.18 (s, 3H), 3.00 (br s, 1H, OH) ppm; 13C NMR
(75 MHz, CDCl3) δ 170.8, 144.0, 130.5, 89.6, 61.8, 51.1, 43.7
ppm; ESI-MS m/z = 180.2 [M þ Na]þ.
€
Nuremberg for performing the ESI-HRMS analyses.
Supporting Information Available: General experimental
considerations and experimental procedures for the synthesis of
pyrroles 7-10. Analytical and spectroscopic data for com-
pounds 7-10 and 15-27. Copies of 1H and 13C NMR spectra
for pyrroles 7-10 and the photooxidation products. Copies of
HMQC and HMBC spectra for compounds 17 and 23. Copies of
DEPT 135 and HMQC spectra for compounds 24 and 25. This
material is available free of charge via the Internet at http://
pubs.acs.org.
Photosensitized Oxidations of 8 and 9. Photolysis of 8 and 9 in
several solvents and sensitizers (Table 2) gave complex mix-
tures of oxygenated products 15-18 and 19-22, respectively.
Compounds 15-18 were purified by flash column chromato-
graphy over silica gel (hexanes/EtOAc = 4:1 f EtOAc/acetone
= 2:1 v/v). Compounds 19-22 were purified by flash column
7282 J. Org. Chem. Vol. 74, No. 19, 2009