β-Lactam-Forming Photochemical Reactions of N-Trimethylsilylmethyl- and N-Tributylstannylmethyl-Substituted α-Ketoamides

Article abstract of DOI:10.1021/jo030343q

Two mechanisms have been proposed for the β-lactam-forming photochemical reactions of α-ketoamides. One, suggested by Aoyama, involves excited-state H-atom abstraction while the other, put forth by Whitten, follows a sequential SET-proton-transfer route. The photochemical properties of N-trimethylsilylmethyl- and N-tributylstannylmethyl-substituted α-ketoamides were explored in order to gain information about the mechanism of this process and to develop a regioselective method for β-lactam formation. The results of this effort show that (1) photoreactions of N-trimethyl-silylmethyl-substituted α-ketoamides proceed by competitive H-atom abstraction and sequential SET-desilylation pathways and (2) a sequential SET-destannylation pathway is preferentially followed in photochemical reactions of the tributylstannylmethyl-substituted α-ketoamides.

Full text of DOI:10.1021/jo030343q

â-La cta m -F or m in g P h otoch em ica l Rea ction s of
N-Tr im eth ylsilylm eth yl- a n d N-Tr ibu tylsta n n ylm eth yl-Su bstitu ted
r-Ketoa m id es
Runtang Wang, Chuanfeng Chen,1 Eileen Duesler, and Patrick S. Mariano*
Department of Chemistry, University of New Mexico, Albuquerque, New Mexico 87131
Ung Chan Yoon
Department of Chemistry, Chemistry Institute for Functional Materials and
College of Natural Sciences, Pusan National University, Pusan 609-735, Korea
mariano@unm.edu
Received November 10, 2003
Two mechanisms have been proposed for the â-lactam-forming photochemical reactions of
R-ketoamides. One, suggested by Aoyama, involves excited-state H-atom abstraction while the other,
put forth by Whitten, follows a sequential SET-proton-transfer route. The photochemical properties
of N-trimethylsilylmethyl- and N-tributylstannylmethyl-substituted R-ketoamides were explored
in order to gain information about the mechanism of this process and to develop a regioselective
method for â-lactam formation. The results of this effort show that (1) photoreactions of N-trimethyl-
silylmethyl-substituted R-ketoamides proceed by competitive H-atom abstraction and sequential
SET-desilylation pathways and (2) a sequential SET-destannylation pathway is preferentially
followed in photochemical reactions of the tributylstannylmethyl-substituted R-ketoamides.
SCHEME 1
In tr od u ction
Far too seldom has the long-range goal of mechanistic
photochemical studies been the development of syntheti-
cally useful reactions. As a result, the synthetic potential
of exited-state reactions has often gone unnoticed. An
example of this is found in studies of photoinduced
reactions of R-ketoamides 1 that produce â-lactams 5
(Scheme 1). Following a number of earlier studies,2-6
Aoyama and co-workers7-10 conducted a series of explor-
atory investigations that focused on the scope and mech-
anism of this process. This group proposed that this
reaction is initiated by hydrogen atom abstraction by the
carbonyl oxygen of the excited ketone from an amide
R-carbon. The initially formed intermediate in this
pathway is either a triplet 1,4-biradical 3 or a singlet 1,4-
dipole 4, depending upon the multiplicity of the reacting
excited state of 1. Electrocyclic ring closure of the dipole
then produces the â-lactam 5 along with other products,
(1) Current address: Center for Molecular Science, Institute of
Chemistry, Chinese Academy of Sciences, Beijing 100080, China.
(2) Akermark, B.; J ohansson, N.-G. Tetrahedron Lett. 1969, 371.
(3) Henery-Logan, K. R.; Chen, C. G. Tetrahedron. Lett. 1973, 1103.
(4) Zhehavi, U. J . Org. Chem. 1977, 42, 2821.
(5) Shozaki, M.; Hiraoka, T. Synth. Commun. 1979, 9, 179.
(6) Shima, K.; Tanabe, K.; Furukawa, S.; Saito, J .; Shirahashi, K.
Bull. Hem. Soc. J pn. 1984, 57, 1515.
(7) Hasegawa, T.; Watabe, M.; Aoyama, H.; Omote, Y. Tetrahedron
1977, 33, 485.
(8) Aoyama, H.; Hasegawa, T.; Watabe, M.; Shirashi, H.; Omote, Y.
J . Org. Chem. 1978, 43, 419.
including oxazolidinone 6 that derives from intramolecu-
lar addition of the hydroxyl group to the iminium cation.
Additional evidence for the intermediacy of dipole 4 in
this process comes from the observation that R-hydrox-
amides 7 are produced by photoreactions conducted in
MeOH. As with other photochemical reactions promoted
by carbonyl H-atom abstraction, this process proceeds in
high yields when the amide nitrogen contains identical
alkyl substituents. Although an insufficient number of
examples exist8 to conclusively prove the point, one
expects that R-ketoamides which possess two different
(9) Aoyama, H.; Sakamoto, M.; Omote, Y. J . Chem. Soc., Perkin
Trans. 1 1981, 1357.
(10) Aoyama, H.; Sakamoto, M.; Kuwabara, K.; Yoshida, K.; Omote,
Y. J . Am. Chem. Soc. 1983, 105, 1958.
10.1021/jo030343q CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/28/2004
J . Org. Chem. 2004, 69, 1215-1220
1215

Wang et al.
SCHEME 2
SCHEME 3
alkyl groups on nitrogen would be transformed to mix-
tures of â-lactams by this pathway.
In a later discussion of this novel photochemical
process, Chesta and Whitten11 suggested that a single
electron transfer (SET) mechanism is operable. In the
SET pathway, intramolecular proton transfer from the
amide cation radical in zwitterionic biradical 2 to the
ketone anion radical generates the same intermediates,
3 and 4, that are produced by the H-atom abstraction
route. However, Chesta and Whitten’s proposal11 was not
supported by any conclusive experimental observations,
and consequently, it cannot be used reliably to predict
the behavior of unsymmetric and/or structurally complex
systems.
The interrelated issues of mechanism and synthetic
application of the â-lactam forming photoreactions of
R-ketoamides were of interest to us as result of earlier
investigations carried out in our laboratories in the area
of SET photochemistry. In particular, our earlier studies
focusing on the kinetics of aminium radical reactions12,13
and the excited-state reactions of N-silylmethylimides14,15
seemed to be related to these issues. By using a combina-
tion of product distribution and laser flash photolysis
methods, we showed that the rates of silophile induced
desilylation of R-silylamide cation radicals far exceed
those of base-induced R-deprotonation.12,13 An example
of this kinetic preference is found in the photochemical
generation of azomethine 10 from the N-silymethyl-
maleimide 8, formed by a pathway involving the inter-
mediacy of zwitterionic biradical 9 (Scheme 2). In this
process, transfer of trimethylsilyl group to the oxyanion
center occurs more rapidly than does proton transfer.
Other efforts in our laboratories demonstrated that the
rates of R-destannylation reactions of cation radicals
exceeds those of R-desilylation.16,17 In another pertinent
investigation, Yoshida and co-workers18,19 observed that
R-trialkylsilyl and R-tributylstannyl substitution dra-
matically increases the thermodynamic stability of amine
and amide cation radicals. These effects, seen in the
oxidation potentials of the corresponding nitrogen con-
taining electron donors, makes SET from R-silyl- and
R-stannylamines and R-silyl- and R-stannylamides ther-
modynamically/kinetically more favorable.
SCHEME 4
Based on these observations, we anticipated that
zwitterionic biradicals 12, formed by intermolecular SET
in the excited states of N-trimethysilylmethyl- or N-
tributylstannylmethyl-substituted R-ketoamides 11 would
preferentially participate in either intermolecular or
intermolecular silyl or stannyl group transfer rather than
proton-transfer processes (Scheme 3). In addition, we
believed that this selectivity might serve as the founda-
tion for regioselective and, thus synthetically useful,
â-lactam-forming photochemical reactions.
The proposal presented above guided the current
studies, in which product distributions, arising from
photoreactions of R-silyl- and R-stannyl-substituted R-
ketoamides, were determined and translated into conclu-
sions about the mechanism(s) for â-lactam formation.
Results emanating from this effort demonstrate that (1)
â-lactam forming photoreactions of R-silyl-substituted
R-ketoamides are not regioselective because they occur
by competitive H-atom abstraction and sequential SET-
desilylation pathways and (2) N-tributylstannylmethyl-
substituted R-ketoamides undergo regioselective photo-
reactions to produce â-lactams through the near exclusive
operation of a sequential SET- destannylation route.
Resu lts a n d Discu ssion
Four R-ketoamides, containing N-trimethylsilylmethyl
or N-tributylstannylmethyl substituents, were pre-
pared in order to investigate the issues discussed above.
Reactions of the in situ prepared benzoylformic acid
chloride with commercially available N-benzyl- (13) and
N-methyl-N-trimethylsilylmethylamine (14) were used to
produce the corresponding R-silylketoamides 15 and 16
(Scheme 4). An alternate approach, involving N-alkyl-
ation of the anion, formed by sodium hydride treatment
of the secondary ketoamides 17 and 18, with tributyl-
stannylmethyl iodide,20 was employed to prepare the
analogous tin-containing substrates 19 and 20 (Scheme
5).
(11) Chesta, C. A.; Whitten, D. G. J . Am. Chem. Soc. 1992, 114, 2188.
(12) Zhang, X.; Yeh, S.-R.; Hong, S.; Freccero, M.; Albini, A.; Falvey,
D. E.; Mariano, P. S. J . Am. Chem. Soc. 1994, 116, 4211.
(13) Su, Z.; Mariano, P. S.; Falvey, D. E.; Yoon, U. C.; Oh, S. W. J .
Am. Chem. Soc. 1998, 120, 10676.
(14) Yoon, U. C.; Kim, D. U.; Lee, C. W.; Choi, Y. S.; Lee, Y. J .;
Ammon, H. L.; Mariano, P. S. J . Am. Chem. Soc. 1995, 117, 2698.
(15) Yoon, U. C.; Cho, S. J .; Lee, Y. J .; Mancheno, M. J .; Mariano,
P. S. J . Org. Chem. 1995, 60, 2353.
(16) Borg, R. M.; Mariano, P. S. Tetrahedron Lett. 1986, 2821.
(17) Yoon, U. C.; J in, Y. X.; Oh, S. W.; Cho, D. W.; Park, K. H.;
Mariano, P. S. J . Photochem. Photobiol. Chem. A 2002, 150, 77.
(18) Yoshida, J .; Maekawa, T.; Murata, T.; Matsunaga, S.; Isoe, S.
J . Am. Chem. Soc. 1990, 112, 1962.
Preparative photochemical reactions of the ketoamides
were explored next. Solutions of 15, 16, 19, and 20 in
MeOH and MeCN were irradiated with Pyrex glass
filtered light (λ > 290 nm) for time periods required to
(19) Yoshida, J .; Itoh, M.; Isoe, S. J . Chem. Soc., Chem. Commun.
1993, 547.
(20) Ahman, J .; Somfai, P. Synth. Commun. 1994, 24, 1117.
1216 J . Org. Chem., Vol. 69, No. 4, 2004

â-Lactam-Forming Photochemical Reactions of R-Ketoamides
SCHEME 5
SCHEME 6
TABLE 1. P r od u cts a n d Yield s of P h otor ea ction s of
r-Ketoa m id es 15, 16, 19, a n d 20
keto-
amide
Solvent
MeOH
products (% yield)
15
21 (6), 22 (14), 23 (3), 27 (3), 28 (10), 29 (7),
32 (11), 33 (5), 37 (10)
15
MeCN
21 (10), 22 (22), 23 (6), 27 (3), 38 (8), 39 (4),
40 (22)
16
16
19
19
20
20
MeOH
MeCN
MeOH
MeCN
MeOH
MeCN
24 (4), 25 (3), 30 (5), 35 (6), 35 (10) 36 (23)
24 (14), 25 (7), 31 (6), 41 (6), 42 (22)
21 (37), 26 (3), 27 (10), 32 (25), 37 (8)
21 (42), 26 (3), 27 (7)
24 (40, 31 (9), 36 (3)
24 (44), 31 (5)
promote >90% conversion of the substrates. Products
were separated from each of the mixtures by using
preparative TLC. Structural assignments to all previ-
ously uncharacterized photoproducts were made by using
a combination of spectrophotometric and X-ray crystal-
lographic techniques. As can be seen by viewing the data
in Table 1, the mass balances of products generated in
these photochemical reactions are less than 100%. In
each case, the remaining material is comprised of a
mixture of very minor (<1%), uncharacterized sub-
stances.
The results of the preparative photochemical studies
are summarized in Table 1 and Scheme 6. Irradiation of
the N-benzyl-N-trimethylsilylmethyl ketoamide 15 in
MeOH results in the generation of a highly complex
mixture of products, including substances which do (â-
lactams 22 and 23, oxazolidinones 28 and 29) and do not
contain TMS groups (â-lactam 21, oxazolidinone 27,
R-hydroxyamides 22 and 23, ester 37). Photoreaction of
15 in MeCN also produces a complex product mixture
comprised of TMS-containing (22, 23, 38) and non-TMS-
containing (21, 27, 39, 40) substances. Similar observa-
tions were made in studies of the N-methyl-substituted
R-silylketoamide 16. Irradiation of 16 in MeOH or MeCN
brings about formation of products that contain (in MeOH
25, 30, 35; in MeCN 25) and do not contain TMS groups
(in MeOH 24, 34, 36; in MeCN 24, 31, 41, 42).
SCHEME 7
In contrast to the behavior of the TMS-substituted
substrates, photoreactions of the tributylstannyl-keto-
amides 19 and 20 produce less complex product mixtures.
For example, irradiation of the N-benzyl analogue 19 in
both MeOH and MeCN leads to formation of the tin-
containing product 26 along with those that do not
contain the tributyl-stannyl group (in MeOH 21, 27, 32;
in MeCN 21, 27). The N-methyl-N-tributylstannylmethyl
ketoamide 20 participates in the most chemoselective
photoreactions observed in this series. Irradiation of
MeOH and MeCN solutions of 20 in each case leads to
exclusive production of the nontributylstannyl containing
â-lactam 24, oxazolidinone 31, and R-hydroxyamide 36.
It seems reasonable to conclude that the major prod-
ucts generated in the photoreactions described above
arise by secondary reactions of 1,4-dipolar intermediates,
produced by H-atom abstraction and/or SET pathways.
As shown in Scheme 7, H-atom transfer from R-positions
of the N-alkyl or N-trialkylmetal groups to the phenone
excited state gives rise to Si- or Sn-containing dipolar
intermediates 43. Electrocyclic ring closure of these
intermediates leads to â-lactams 44 while oxazolidinones
arise by intramolecular addition of the alcohol group to
the iminium cation moiety in 43. Also, hydrolysis (by
adventitious water) and MeOH addition reactions of 43
yield R-hydroxyamide products. We suggest that in
contrast sequential SET-demetalation pathways are
responsible for formation of the â-lactams, oxazolidinones
and R-hydroxyamide that do not contain either Me3Si or
J . Org. Chem, Vol. 69, No. 4, 2004 1217

Wang et al.
SCHEME 8
Exp er im en ta l Section
N-(Tr im eth ylsilyl)m eth yl-N-ben zyl R-Ketoa m id e 15. To
the in situ prepared benzoylformic acid chloride (2.5 g, 15
mmol) in CH2Cl2 was added triethylamine (1.1 g, 11 mmol)
followed by dropwise addition of N-(trimethylsilylmethyl)-
benzylamine (2.0 g, 10.3 mmol) at 0 °C. The resulting mixture
was warmed to 25 °C, stirred overnight, washed with water,
dried, and concentrated in vacuo, giving a residue which was
subjected to flash chromatography (silica gel, 1:9 EA-hexane)
to yield 15 (2.8 g, 83%) as a solid: mp 66-69 °C; 1H NMR
(mixture of rotamers) 7.93-7.90 (m, 2H), 7.50-7.45 (m, 1H),
7.39-7.33 (m, 2H), 7.29-7.16 (m, 5H), 4.67 (s, 0.33H), 4.28
(s, 1.67H), 2.86 (s, 1.67H), 2.64 (s, 0.33H), 0.05 (s, 7.5H), -0.02
(s, 1.5H); 13C NMR 191.2, 191.0, 166.2, 166.0, 135.5, 134.8,
134.1, 133.0, 129.2, 129.1, 128.5, 128.4, 128.3, 128.0, 127.7,
127.6, 53.0, 48.5, 37.5, 35.6, -1.6, -2.0; IR 1679, 1630; HRMS
(FAB) m/z 326.1587 (calcd for C19H24NO2Si, 326.1576).
N-(Tr im et h ylsilyl)m et h yl-N-m et h yl R-Ket oa m id e 16.
To the in situ prepared benzoylformic acid chloride (3.4 g, 20
mmol) in CH2Cl2 was added N-(trimethylsilylmethyl)-N-
methylamine (1.17 g, 10 mmol) at 0 °C. The temperature was
raised to 25 °C, and the resulting mixture was stirred
overnight and concentrated in vacuo affording a residue which
was subjected to flash chromatography (silica gel, 1:3 EA-
hexane) giving 16 (1.7 g, 71%): 1H NMR (mixture of rotamers)
7.94-7.90 (m, 2H), 7.66-7.58 (m, 1H), 7.50-7.45 (m, 2H), 3.08
(s, 2H), 2.93 (s, 2.4H), 2.77 (s, 0.6H), 0.15 (s, 6.2H), 0.05 (s,
2.8H); 13C NMR 191.9, 166.0, 134.5, 133.3, 129.6, 128.9, 41.4,
39.0, 37.5, 34.1, -1.5, -1.8; IR 1674, 1634; HRMS (FAB) m/z
250.1275 (calcd for C13H20NO2Si 250.1263).
TABLE 2. Tota l Yield s of P r od u cts Con ta in in g a n d Not
Con ta in in g Me3Si or Bu 3Sn Gr ou p s fr om P h otor ea ction s
of r-Ketoa m id es 15, 16, 19, a n d 20
total yield of
MR3-containing
products (%)
total yield of
non-MR3-containing
products (%)
ketoamide
solvent
15
15
16
16
19
19
20
20
MeOH
MeCN
MeOH
MeCN
MeOH
MeCN
MeOH
MeCN
34
36
18
7
3
3
25
39
33
48
61
49
52
49
0
0
N-(Tr i-n -b u t ylst a n n yl)m et h yl-N-b en zyl R-Ket oa m id e
19. Sodium hydride (95%, 280 mg, 11.1 mmol) was added to a
solution of R-oxo-N-benzylbenzeneacetamide (2.66 g, 11.1
mmol) in DMF (25 mL). When evolution of hydrogen ceased
(ca.15-30 min), tri-n-butylstannylmethyl iodide20 (4.7 g, 10.8
mmol) was added, and the resulting mixture was stirred for 1
h at room temperature, poured into water, and extracted with
ethyl ether. The organic layers were washed with water, dried,
and concentrated in vacuo giving a residue which was sub-
jected to flash chromatography (silica gel, 1:10 EA-hexane)
to give 19 (4.94 g, 84%): 1H NMR (mixture of rotamers) 7.99-
7.95 (m, 2H), 7.62-7.58 (m, 1H), 7.51-7.44 (m, 2H), 7.35-
7.24 (m, 5H), 4.63 (s, 0.23H), 4.37 (s, 1.77H), 2.91 (s, 0.23H),
2.88 (m, J ) 14.3 Hz, 1.77H), 1.41-1.51 (m, 7H), 1.20-1.35
(m, 7H), 0.81-0.94 (m, 13H); 13C NMR 191.4, 166.3, 136.1,
135.4, 134.5, 133.6, 129.8, 129.7, 129.0, 128.9, 128.7, 128.2,
128.1, 128.0, 54.7, 49.9, 33.4, 31.0, 29.0, 27.3, 13.7, 10.6; IR
1679, 1630; HRMS (FAB) m/z 550.2307 (calcd for C28H41NO2-
Li120Sn 550.2319), m/z 548.2297 (calcd for C28H41NO2Li118Sn
548.2313), m/z 546.2304 (calcd for C28H41NO2Li116Sn 546.2315).
N-(Tr i-n -bu tylsta n n yl)m eth yl-N-m eth yl R-Ketoa m id e
20. Sodium hydride (95%, 96 mg, 3.8) was added to the solution
of R-oxo-N-methylbenzeneacetamide (615 mg, 3.8 mmol) in
DMF (15 mL). When the evolution of hydrogen ceased (ca. 10-
20 min), tri-n-butylstannylmethyl iodide (1.3 g, 3 mmol) was
added and the resulting mixture was stirred for 1 h, poured
into water, and extracted with ethyl ether. The organic layers
were washed with water, dried, and concentrated in vacuo
affording a residue which was subjected to flash chromatog-
raphy (silica gel, 1:10 EA-hexane) giving 20 (1.3 g, 93%): 1H
NMR (mixture of rotamers) 7.90-7.87 (m, 2H), 7.60-7.53 (m,
1H), 7.45-7.39 (m, 2H), 3.06 (s, 2H), 3.01 (s, 0.4H), 2.91 (s,
2.6H), 1.54-1.44 (m, 7H), 1.40-1.19 (m, 7H), 1.00-0.79 (m,
13H); 13C NMR 191.5, 165.6, 134.3, 133.3, 129.5, 128.7, 38.3,
35.8, 34.3, 33.6, 28.9, 27.3, 13.5, 10.4; IR: 1687, 1630; HRMS
(FAB) m/z 470.1964 (calcd for C22H37NO2Li116Sn 470.2002),
472.2034 (calcd for C22H37NO2Li118Sn 472.2000), 474.2026
(calcd for C22H37NO2Li120Sn 474.2006).
Bu3Su groups. In these cases, SET from the amide
nitrogen to the excited ketone carbonyl gives rise to
zwitterionic biradicals 46 (Scheme 8), which undergo
nucleophile (H2O or MeOH) induced demetalation to form
the dipolar intermediates 47.
On the basis the mechanistic proposals made above,
the relative contributions of the H-atom abstraction and
sequential SET-demetalation pathways to photoreactions
of the Si- and Sn-substituted R-ketoamides can be ap-
proximated by evaluating the ratios of products that
contain Me3Si and Bu3Sn groups to those in which these
groups are absent. The ratios (Table 2) clearly demon-
strate that (1) H-atom abstraction and SET-demetalation
routes operate with nearly equal efficiencies in photo-
reactions of the N-benzyl-N-trimethylsilylmethyl sub-
strate 15, (2) the SET-demetalation pathway is favored
over the H-atom abstraction route in the reaction of the
N-methyl TMS-containing ketoamide 16, and (3) photo-
chemical reactions of the Bu3Sn-substituted substrates
19 and 20 follow the SET-demetalation route nearly
exclusively.
Several interesting conclusions come from the observa-
tions summarized above. First, since H-atom abstraction
is competitive with sequential SET-desilylation (as ex-
pected, more so in reactions of the N-benzyl substrate)
in substrates where the latter pathway is facilitated by
lower oxidation potentials of the R-silyl amide moiety, it
is reasonable to conclude that the photoreactions of N,N-
dialkyl-substituted R-ketoamides studied earlier by
Aoyama7-10 are also initiated by ketone carbonyl H-atom
abstraction. Thus, Aoyama’s original mechanistic expla-
nation11 of these photoreactions appears to be correct.
Second, photoreactions of the Bu3Sn-substituted sub-
strates, which follow the SET-destannylation pathway
nearly exclusively, are highly regioselective because a
single dipolar intermediate is selectively formed in these
processes.
Ir r a d ia tion of 15 in MeOH. A solution of 15 (400 mg, 1.23
mmol) in 100 mL of MeOH was irradiated for 4 h (100%
conversion). Concentration of the photolysate in vacuo followed
by preparative TLC of the resulting residue gave 21 (19 mg,
1218 J . Org. Chem., Vol. 69, No. 4, 2004

â-Lactam-Forming Photochemical Reactions of R-Ketoamides
6%), 27 (6 mg, 3%), 22 (58 mg, 14%), 23 (13 mg, 3%), 28 (39
mg, 10%), 29 (28 mg, 7%), 32 (38 mg, 11%), 33 (15 mg, 5%),
and 37 (20 mg, 10%).
Ir r a d ia tion of 15 in MeCN. A solution of 15 (400 mg, 1.23
mmol) in 100 mL of MeCN was irradiated for 3 h (100%
conversion). Concentration of the photolysate in vacuo followed
by preparative TLC of the resulting residue gave 21 (30 mg,
10%), 22 (89 mg, 22%), 23 (23 mg, 6%), 27 (9 mg, 3%), and 38
(30 mg, 8%), 39 (9 mg, 4%), 40 (68 mg, 22%).
Ir r a d ia tion of 16 in MeOH. A solution of 16 (300 mg, 1.21
mmol) in 100 mL of MeOH was irradiated for 3 h (100%
conversion). Concentration of the photolysate in vacuo followed
by preparative TLC of the resulting residue gave 24 (8 mg,
4%), 25 (9 mg, 3%), 30 (15 mg, 5%), 35 (34 mg, 10%), 36 (58
mg, 23%) 34 (11 mg, 6%), and 37 (14 mg, 7%).
Ir r a d ia tion of 16 in MeCN. A solution of 16 (353 mg, 1.42
mmol) in 100 mL of MeCN was irradiated for 2 h (100%
conversion). Concentration of the photolysate in vacuo followed
by preparative TLC of the resulting residue gave 24 (35 mg,
14%), 25 (24 mg, 7%), 31 (15 mg, 6%), 41 (29 mg, 6%), and 42
(6 mg, 2%).
Ir r a d ia tion of 19 in MeOH. A solution of 19 (400 mg, 0.74
mmol) in 100 mL of MeOH was irradiated for 3 h (100%
conversion). Concentration of the photolysate in vacuo followed
by preparative TLC of the resulting residue gave 21 (70 mg,
37%), 26 (11 mg, 3%), 27 (18 mg, 10%), 32 (52 mg, 15%), and
37 (10 mg, 8%).
Ir r a d ia tion of 19 in MeCN. A solution of 19 (310 mg, 0.57
mmol) in 100 mL of MeCN was irradiated for 2.5 h (100%
conversion). Concentration of the photolysate in vacuo followed
by preparative TLC of the resulting residue gave 21 (60 mg,
42%), 26 (10 mg, 3%), and 27 (10 mg, 7%).
Ir r a d ia tion of 20 in MeOH. A solution of 20 (393 mg, 0.84
mmol) in 100 mL of MeOH was irradiated for 4 h (100%
conversion). Concentration of the photolysate in vacuo followed
by preparative TLC of the resulting residue gave 24 (60 mg,
40%), 31 (13 mg, 9%), and 36 (54 mg, 31%).
Ir r a d ia tion of 20 in MeCN. A solution of 20 (385 mg, 0.83
mmol) in 100 mL of MeCN was irradiated for 4 h (100%
conversion). Concentration of the photolysate in vacuo followed
by preparative TLC of the resulting residue gave 24 (65 mg,
44%) and 31 (8 mg, 5%).
128.5, 128.3, 125.5, 86.1, 59.3, 28.4; IR 1736; HRMS (FAB)
m/z 177.0779 (calcd for C10H11NO2 177.0790).
1
25: mp 135-137 °C; H NMR 7.41-7.27 (m, 5H), 3.88 (s,
1H), 3.10 (s, 1H), 2.90 (s, 3H), 0.19 (s, 9H); 13C NMR 169.7,
140.7, 128.6, 128.0, 125.2, 87.9, 63.1, 28.3, -2.1; IR 3305, 1732;
HRMS (FAB) m/z 250.1257 (calcd for C13H20NO2Si 250.1263).
26: 1H NMR 7.54-7.10 (m, 10H), 4.65 (s, 1H), 3.05, 2.53
(ABq, J ) 13.3 Hz, 2H), 1.48-1.21 (m, 14H), 0.96-0.82 (m,
13H); 13C NMR 169.5, 139.2, 133.8, 129.0, 128.7, 128.5, 127.9,
127.4, 125.7, 87.5, 73.7, 29.0, 27.3, 23.1, 13.6, 10.5. The
instability of this compound prevented the accumulation of
additional spectroscopic data.
27. The spectroscopic data accumulated for this substance
matched those previously reported:25 1H NMR 7.45-7.24 (m,
10H), 5.29 (s, 1H), 5.10, 5.04 (ABq, J ≈ 15.0 Hz, 2H), 4.55,
4.50 (ABq, J ) 15.0 Hz, 2H); 13C NMR 169.6, 136.3, 135.0,
128.9, 128.6, 128.5, 128.1, 127.9, 126.2, 79.9, 79.3, 44.5; IR
HRMS (FAB) m/z 254.1189 (calcd for C16H16NO2 254.1181).
28. The spectroscopic data accumulated for this substance
matched those previously reported:26 1H NMR 7.50-7.33 (m,
10H), 5.96 (d, J ) 2.0 Hz, 1H), 5.35 (d, J ) 1.8 Hz, 1H), 2.87,
2.21 (ABq, J ) 15.2 Hz, 2H), 0.03 (s, 9H); 13C NMR 169.5,
136.4, 136.3, 130.3, 129.0, 128.5, 128.4, 128.1, 126.7, 92.3, 79.3,
32.1, -1.3; IR 1699; HRMS (FAB) m/z 324.1407 (calcd for
C
19H22NO2Si 324.1420), m/z 326.1561 (calcd for C19H24NO2Si
326.1576).
29: 1H NMR 7.50-7.23 (m, 10H), 5.18 (d, J ) 2.8 Hz, 1H),
4.96 (d, J ) 2.9 Hz, 1H), 5.04, 4.13 (ABq, J ) 15.5 Hz, 2H),
0.13 (s, 9H); 13C NMR 171.7, 136.5, 135.7, 128.7, 128.4, 128.1,
127.8, 127.6, 126.9, 85.9, 79.3, 44.9, -3.8; IR 1695; HRMS
(FAB) m/z 324.1424 (calcd for C19H22NO2Si 324.1420).
30: 1H NMR 7.43-7.30 (m, 5H), 5.20-5.09 (m, 3H), 2.89,
2.72 (ABq, J ) 15.4 Hz, 2H), 0.10 (s, 9H); 13C NMR 168.9,
136.7, 128.6, 128.4, 126.3, 82.0, 79.0, 31.5, -1.8; IR 1699;
HRMS (FAB) m/z 250.1270 (calcd for C13H20NO2Si 250.1263).
31. 1H NMR spectroscopic data has been reported previously
for this compound:27 1H NMR 7.44-7.27 (m, 5H), 5.20-5.10
(m, 3H), 2.89 (s, 3H); 13C NMR 169.6, 136.3, 128.5, 128.4, 126.2,
81.7, 78.9, 26.5; IR 1707; HRMS (FAB) m/z 248.1112 (calcd.
for C13H18NO2Si 248.1107), m/z 250.1270 (calcd for C13H20
-
NO2Si 250.1263).
32: 1H NMR (mixture of rotamers) 7.34-6.95 (m, 10H), 5.34
(d, J ) 6.5 Hz, 0.5H), 5.19 (d, J ) 6.4 Hz, 0.5H), 5.09-4.95
(m, 1H), 4.61-4.20 (m, 4H), 3.26 (s, 1H), 3.08 (s, 2H); 13C NMR
174.4, 173.6, 129.2, 129.1, 128.9, 128.9, 128.7, 128.6, 128.1,
127.8, 127.6, 127.4, 127.4, 126.6, 77.5, 76.1, 72.0, 71.8, 56.3,
55.3, 48.6, 47.7; IR 3415, 1646; HRMS (FAB) m/z 286.1448
(calcd for C17H20NO3 286.1443).
Sp ectr oscop ic Da ta for P h otop r od u cts.
1
21: mp 107-109 °C; H NMR 7.46-7.22 (m, 10H), 5.22 (s,
1H), 4.47, 4.38 (ABq, J ) 15.0 Hz, 2H), 3.50, 3.38 (ABq, J )
5.5 Hz, 2H); 13C NMR 170.0, 138.5, 134.7, 128.8, 128.5, 128.2,
128.0, 127.8, 125.4, 85.4, 57.0, 45.8; IR 3338, 1724; HRMS
(FAB) m/z 254.1194 (calcd for C16H16NO2 254.1181).
22: 1H NMR 7.52-7.25 (m, 10H), 4.63 (s, 1H), 4.05 (s, 1H),
3.06, 2.35 (ABq, J ) 15.4 Hz, 2H), 0.06 (s, 9H); 13C NMR 169.5,
139.5, 133.6, 128.8, 128.6, 128.5, 128.2, 128.1, 125.5, 87.5, 72.9,
31.8, -1.7; IR 3305, 1728; HRMS (FAB) m/z 326.1570 (calcd
for C19H24NO2Si 326.1576).
35: 1H NMR (mixture of rotamers) 7.33-7.29 (m, 5H), 5.27,
4.69 (ABq, J ) 6.6 Hz, 1H), 4.59, 4.18 (ABq, J ) 10.7 Hz, 2H),
3.21, 2.83 (ABq, J ) 15.1 Hz, 2H), 3.22 (s, 0.8H), 3.12 (s, 2.2H),
0.01 (s, 6.5H), -0.07 (s, 2.5H); 13C NMR 172.4, 139.6, 129.0,
128.6, 127.4, 79.7, 77.8, 71.9, 71.7, 56.2, 55.2, 38.2, 36.1, -1.5,
-1.9; IR 1646; HRMS (FAB) m/z 282.1537 (calcd for C14H24
NO3Si 282.1525).
-
23: 1H NMR 7.43-7.19 (m, 10H), 4.99, 4.02 (ABq, J ) 15.3
Hz, 2H), 3.51 (s, 1H), 3.13 (s, 1H), 0.12 (s, 9H); 13C NMR 169.8,
140.5, 135.5, 128.7, 128.7, 128.1, 128.1, 127.7, 125.2, 87.8, 61.2,
45.8, -1.9; IR 3305, 1728; HRMS (FAB) m/z 326.1586 (calcd
for C19H24NO2Si 326.1576).
36. This substance has been reported previously,28 but no
spectroscopic data was given: 1H NMR (mixture of rotamers)
7.42-7.30 (m, 5H), 5.26 (d, J ) 6.1 Hz, 0.5H), 5.18 (d, J ) 5.8
Hz, 0.5H), 4.85, 4.76 (ABq, J ) 9.9 Hz, 1H), 4.67-4.60 (m,
1H), 4.58, 4.24 (ABq, J ) 10.7 Hz, 1H), 3.18 (s, 1.7H), 3.05 (s,
1.3H), 3.00 (s, 1.3H), 2.72 (s, 1.7H); 13C NMR 173.9, 173.3,
139.2, 138.6, 128.9, 128.6, 128.4, 127.5, 127.3, 126.1, 79.7, 78.5,
71.7, 71.6, 55.9, 55.1, 33.5, 32.6; IR 1711, 1650; HRMS (FAB)
m/z 210.1143 (calcd for C11H16NO 210.1130).
24. Three earlier reports21-23 of this compound exist in which
no spectroscopic data is given. The spectroscopic data for this
substance given in a more recent publication matches the data
accumulated in this effort:24 mp 107-108 °C (lit.24 mp 102-
1
103 °C); H NMR 7.45-7.27 (m, 5H), 4.85 (s, 1H), 3.56, 3.47
(ABq, J ) 5.3 Hz, 2H), 2.85 (s, 3H); 13C NMR 170.3, 138.5,
38: 1H NMR 7.49-7.21 (m, 5H), 4.49 (s, 1H), 3.03 and 2.36
(ABq, J ) 15.3 Hz, 2H), 0.06 (s, 9H); 13C NMR 168.4, 134.6,
(21) Wehrli, H. Helv. Chim. Acta 1980, 7, 1915.
(22) Kaftory, M.; Yagi, M.; Tanaka, K.; Toda, F. J . Org. Chem. 1988,
53, 4391.
(23) Toda, F.; Miyamoto, H.; Kanemoto, K. J . Chem. Soc. Chem.
Commun. 1995, 1719.
(25) Kametani, T.; Kigasawa, M.; Wagatsuma, N.; Kohagisawa, T.;
Inoue, H. Heterocycles 1977, 7, 919.
(26) Novikov, M. S.; Khlebnikov, A. F.; Krebs, A.; Kostikov, R. R.
Eur. J . Org. Chem. 1998, 133.
(24) Berckmoes, K.; De Clercq, P. J .; Viterbo, D. J . Am. Chem. Soc.
1995, 117, 5859.
(27) Polonski, T. Tetrahedron 1983, 39, 3143.
(28) Schollkopf, V. U.; Beckhaus, H. Angew. Chem. 1976, 88, 296.
J . Org. Chem, Vol. 69, No. 4, 2004 1219

Wang et al.
128.5, 127.5, 126.0, 73.2, 31.9, 0.9, -1.6. The instability of this
compound prevented the accumulation of additional spectro-
scopic data.
Ack n ow led gm en t. Financial support for this re-
search provided to P.S.M. by the ACS (35546-AC1) and
NSF (CHE-0130943 and INT-0121510) and to U.C.Y.
by the Korea Science and Engineering Foundation
through the program of International Cooperative Re-
search (2002-5-123-01-2) is gratefully acknowledged.
40: mp 134-135 °C; 1H NMR 8.01 (s, 1H), 4.93, 4.65 (ABq,
J ) 2.7 Hz, 2H), 3.39, 3.13 (ABq, J ) 13.9 Hz, 2H); 13C NMR
174.6, 139.5, 135.4, 130.5, 128.7, 128.2, 127.8, 126.7, 125.2,
83.8, 75.5, 44.9; IR 3207, 1703; HRMS (FAB) m/z 254.1175
(calcd for C16H16NO2 254.1181)
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for all previously uncharacterized or not fully charac-
terized compounds prepared in this study and Chem-3D plots
of X-ray crystallographically determined atomic coordinates
for and a summary of crystallographic parameters of 40-42.
This material is available free of charge via the Internet at
http://pubs.acs.org.
41: mp 244-246 °C; 1H NMR 7.60-7.20 (m, 10H), 4.79, 4.68
(ABq, J ) 2.2 Hz, 4H), 2.62 (s, 6H); 13C NMR 167.7, 134.5,
128.3, 127.6, 127.2, 82.7, 80.4, 26.5; IR 1699; HRMS (FAB)
m/z 353.1490 (calcd for C20H21N2O4 353.1501).
42: 1H NMR 7.68-7.36 (m, 5H), 5.20, 5.05 (ABq, J ) 3.2
Hz, 2H), 2.90 (s, 3H); 13C NMR 167.7, 135.3, 129.7, 128.4,
126.0, 99.5, 79.3, 27.1; IR 3297, 1695; HRMS (FAB) m/z
194.0815 (calcd for C10H12NO3 194.0817).
J O030343Q
1220 J . Org. Chem., Vol. 69, No. 4, 2004