The aza-type-B photochemical rearrangement: The role of a second carbonyl in heterocyclic photochemistry. Mechanistic and exploratory organic photochemistry

Article abstract of DOI:10.1021/jo0706372

(Chemical Equation Presented) In contrast to the photochemistry of monocyclic aza-cyclohexenones, their counterparts with a second carbonyl group undergo photochemical rearrangements which parallel those of the 4,4-disubstituted cyclohexenones.

Full text of DOI:10.1021/jo0706372

The Aza-Type-B Photochemical Rearrangement: The Role of a
Second Carbonyl in Heterocyclic Photochemistry. Mechanistic and
Exploratory Organic Photochemistry1,2
Howard E. Zimmerman* and Oleg D. Mitkin
Department of Chemistry, UniVersity of WisconsinsMadison, Madison, Wisconsin 53706
zimmerman@chem.wisc.edu
ReceiVed April 2, 2007
In contrast to the photochemistry of monocyclic aza-cyclohexenones, their counterparts with a second
carbonyl group undergo photochemical rearrangements which parallel those of the 4,4-disubstituted
cyclohexenones.
Introduction
carbonyl group leads to type-B type photochemistry, and it is
that chemistry which we now describe.
One of the better known organic photochemical rearrange-
ments is that of 4,4-disubstituted cyclohexenones.3 Note eq 1
Results
Synthesis of Photochemical Reactants. The three reactants
selected for study were diphenylpyridine-2,6-diones 7, 8, and
9. The first was prepared in a single step from the imide 10 as
noted in Scheme 1, and the second, 8, utilized the short sequence
in the same scheme using a modified Reich procedure for
introduction of the conjugation.4 Both synthetic reactants 10
and 11 were known.5,6
The third photochemical reactant 9 was prepared as outlined
in Scheme 2, utilizing photochemical cis-trans isomerization.
The ratio of 16/17 was 53:34 (360 nm light).
(1) This is Paper 283 of our general series.
(2) (a) For Paper 282, see: Zimmerman, H. E. Pure Appl. Chem. 2006,
2193-2203. Porter Award Address. (b) For Paper 281, see: Zimmerman,
H. E.; Mitkin, O. J. Am. Chem. Soc. 2006, 128, 12743-12749.
(3) (a) Zimmerman, H. E.; Wilson, J. W. J. Am. Chem. Soc. 1964, 86,
4036-4042. (b) Zimmerman, H. E.; Rieke, R. D.; Scheffer, J. R. J. Am.
Chem. Soc. 1967, 89, 2033-2047. (c) Zimmerman, H. E.; Hancock, K. G.
J. Am. Chem. Soc. 1968, 90, 3749-3760.
(4) Reich, H. J. Org. Synth. 1980, 59, 58-65.
which includes the mechanism. Surprisingly, replacement of the
C-6 carbon by an amino nitrogen has been found2 to effect quite
different reaction courses. One example is shown in eq 2.
Interestingly, it now has been found that introduction of a second
(5) Urech, E.; Tagmann, E.; Sury, E.; Hoffmann, K. HelV. Chim. Acta
1953, 36, 1809-1815.
(6) Bretschneider, H.; Deutscher, H.; Klotzer, W.; Sander, M. Monatsh.
Chem. 1958, 89, 288-300.
10.1021/jo0706372 CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/29/2007
J. Org. Chem. 2007, 72, 6091-6096
6091

Zimmerman and Mitkin
SCHEME 1. Synthesis of Two of the Photochemical
Reactants
configurations was based on an upfield shift of N-methyl group
protons to δ 2.33 in endo compound 28 compared to δ 2.99 in
exo-29.
SCHEME 2. Synthesis of the Third Photochemical Reactant 9
The Photochemistry. On photolysis of reactant 7 in metha-
nol, we observed two photoproducts, 30 and 31. Bicyclic product
31 is a known9a compound, and dimer 30 is assigned the anti
head-to-head structure 30 on the following grounds. Since the
13C NMR spectrum showed only eight signals, unsymmetrical
structures can be ruled out. Structures with two trans-cyclobu-
tane ring junctions can also be eliminated. On the basis of
excessive crowding a cis-syn-cis dimer appears to be unlikely.
In the protium NMR, a downfield signal at 3.41 pm (d, J ) 8.6
Hz) is assigned to bridgehead protons R to the carbonyl; a head-
to-tail structure would not be expected to give a sharp doublet.6
The photolysis of the heterocycle 8 in benzene afforded
SCHEME 3. Synthesis of Potential Photoproducts
exclusively the type-B rearrangement product 25, whereas in
methanol 27, a type-A structure9b was also formed. The structure
of 25 was established by X-ray.10
Synthesis of Potential Photochemical Products. In this
study, a number of bicyclic[3.1.0] heterocycles were encoun-
tered, and it was expedient to synthesize a number of potential
photoproducts independently. These syntheses are outlined in
Scheme 3. Where further photoproducts resulted, we dealt with
each structure individually.
From the known reactant 20,7 isomers 22 and 23 were
obtained and distinguished based on their cyclopropane ring
proton 1H NMR splitting constants: 8.4 Hz for the endo bicyclic
22 and 3.5 Hz for the exo bicyclic 23, which is in agreement
with an earlier study of similar systems.3a Also, the protons of
the N-methyl group of endo-22 exhibit an upfield shift to δ
2.44 compared with δ 3.00 in exo-23 due to shielding by the
phenyl group.
The photolysis of reactant 9 in benzene afforded endo and
exo type-B photoproducts. See eq 7. However, again, in
methanol, type-A rearrangement also resulted to give 27 (eq
8).
Using diphenyldiazomethane 24 with the imide 26,8 bicyclic
27 was obtained. Bicyclic products 28 and 29 were obtained
from the known7 20. The assignment of exo and endo
6092 J. Org. Chem., Vol. 72, No. 16, 2007

The Aza-Type-B Photochemical Rearrangement
TABLE 1. Energies and Densities for Triplet Eigenvalues 1 and 2a
Eigenvalue 1
Eigenvalue 2
Energy:
Densities:
C5
O-p π
py
-513.49722
-513.49511
1.02229
1.91036
0.99535
1.01204
1.05782
1.86219
a NBO densities are occupancies from natural orbitals as a basis.
Contrast eqs 1 and 2. The bond scission chemistry was shown
to arise from the singlet excited states2 while it is the triplet
which is responsible for the chemistry of the present research,
even without the use of a triplet sensitizer. It is clear that the
second carbonyl enhances intersystem crossing as a result of
greater spin-orbit coupling. While the monocarbonyl com-
pounds are amides with diminished spin-orbit coupling, the
imide structure of the dicarbonyl compounds reverses this effect
and partially restores the individual carbonyl π-bond orders,
thus increasing the spin-orbit coupling and hence the rapid
conversion to triplets.
The formation of both diastereomers from 9 contrasts with
the formation of only endo-25 from irradiation of 8. Compare
eqs 6 and 7. This appears to result from the reluctance of 25 to
isomerize. In a further search for bicyclic stereoisomerization,
22 was photolyzed and smoothly led reversibly to its stereoi-
somer 23. See eq 9.
A related observation is the appearance of the oxa-di-π-
methane rearrangement when the solvent is methanol. Structur-
ally, the reaction is analogous to the type-A rearrangement.
However, oxa-di-π-methane rearrangements occur via the π-π*
excited state, and here, methanol is seen to raise the energy of
the n-π* state, thus permitting intervention of π-π* reactivity.
Computational Aspects and Methodology. In parallel with
our experimental efforts, and in order to better understand the
reaction course, we turned to ab initio computations. CASSCF-
(8,8)/6-31G(d) computations and NBO analyses on compound
7 showed that the lowest Franck-Condon triplet excited state
formed (i.e., with S0 geometry) is π-π*. Such triplets are known
to result in [2 + 2] additions.5 The second excited state and
relatively close in energy is an n-π* triplet, which is usually
responsible for aryl migration. Interestingly, in another set of
computations, with T1 optimized geometry, T2 exhibited two
roots, both with odd-electron densities at carbon-5. Note Table
1. The matching odd-electron density was at oxygen-7, either
in the π-system or in the py-orbital, depending on the state.
Conclusion
The course of the photochemistry of the nitrogen heterocycles
has proven to be dependent on the number of carbonyl groups.
With one carbonyl, singlet photochemistry has been shown to
result. In contrast, with a second carbonyl, intersystem crossing
is enhanced and triplet chemistry is observed. In addition, the
reaction course is solvent dependent. This dependence controls
whether it is the n-π* or the π-π* triplet which reacts.
Computationally, the two states were determined to be close-
lying. In benzene, the type-B rearrangement, common in
cyclohexenone photochemistry, resulted from the n-π* triplet.
In methanol, there is competitive oxa-di-π-methane rearrange-
ment which occurs as expected from the π-π* triplet.
Experimental Section
Discussion
1-Methyl-5,5-diphenylpyridine-(1H,5H)-2,6-dione (7). A 230
mg (5.8 mmol) portion of sodium hydride (60% in mineral oil)
was washed free of oil with hexane and THF and suspended in
15.0 mL of DMF. Then 1.022 g (3.9 mmol) of imide5 10 was added
with stirring. After the hydrogen evolution was complete (15 min),
0.40 mL (6.4 mmol) of methyl iodide was added and stirring
continued overnight. The mixture was diluted with water, extracted
with benzene, washed, dried, concentrated in vacuo, and crystallized
from heptane to give 963 mg (89.5%) of 1-methyl-5,5-diphenylpy-
ridine-(1H,5H)-2,6-dione (7): mp 125.5-126.5 °C; 1H NMR
(CDCl3, 300 MHz) δ 7.32-7.39 (m, 6H), 7.21-7.26 (m, 4H), 7.01
Contrast of the Triplet Chemistry with the Second
Carbonyl Present. A first item to be noted is the contrast
observed between the photochemistry encountered in the present
dicarbonyl systems and the photochemistry of the monocarbonyl
compound counterparts we had investigated in our earlier
studies.2b Thus we now see phenyl migration occurring as the
prevailing reaction in the dicarbonyl systems in contrast to the
bond scission found in the earlier monocarbonyl systems.
(7) Izzo, P. T. J. Org. Chem. 1963, 28, 1713-1715.
(8) Gill, G. B.; James, G. D.; Oates, K. V.; Pattenden, G. J. Chem. Soc.,
Perkin Trans. 1 1993, 21, 2567-2580.
(9) (a) Baltzly, R.; Mehta, N. B.; Russell, P. B.; Brooks, R. E.; Grivsky,
E. M.; Steinberg, A. M. J. Org. Chem. 1962, 27, 213-218. (b) The bicyclic-
[3.1.0] photoproduct, geminally substituted with two substituents originally
at C-4, is structurally parallel to the type-A photoproducts of 2,5-
cyclohexadienones. However, mechanistically, these arise from an oxa-di-
π-methane rearrangement as subsequently noted.
(d, J ) 10.2 Hz, 1H), 6.34 (d, J ) 10.2 Hz, 1H), 3.31 (s, 3H); 13
C
NMR (CDCl3, 75.4 MHz) δ 173.45, 164.48, 148.07, 140.88, 128.57,
128.40, 127.85, 199.02, 59.26, 26.40. HRMS calcd for C18H15NO2
300.1000 (M + Na), found 300.0996 (M + Na).
5-Methyl-3,3-diphenylpiperidine-2,6-dione (11). A mixture of
3.84 g (13.1 mmol) of methyl 4-cyano-2-methyl-4,4-diphenylbu-
tanoate6 and 2.30 g (16.7 mmol) of potassium carbonate was boiled
in a mixture of 5.5 mL of water and 37.0 mL of methanol for 2 h.
Methanol was removed under reduced pressure, and the residue
was diluted with water, neutralized with hydrochloric acid, extracted
(10) The diffractometry was performed by Dr. Ilia Guzei, and we
gratefully acknowledge helpful advice from Dr. Ilia Guzei on our Shelxtl
computations.
J. Org. Chem, Vol. 72, No. 16, 2007 6093

Zimmerman and Mitkin
with dichloromethane, dried, and concentrated in vacuo. The residue
was dissolved in 15 mL of acetic acid treated with 5.0 mL of
sulfuric acid and refluxed for 2 h. After cooling to ambient
temperature, the mixture was poured onto crushed ice, and the crude
product was filtered and dried. Crystallization from ethanol afforded
2.56 g (70.0%) of 5-methyl-3,3-diphenylpiperidine-2,6-dione: mp
(E)-Methyl 4-Cyano-3-methyl-4,4-diphenylbut-2-enoate 16.
To 3.73 g (19.3 mmol) of diphenylacetonitrile in 30 mL of dry
dioxane were added 2.1 mL (21.2 mmol) of methyl tetrolate at 50-
70 °C and then 1.1 mL of Triton B (benzyltrimethylammonium
hydroxide 40% solution in methanol). The mixture was refluxed
for 2 h, and dioxane was removed under reduced pressure, diluted
with water, extracted with ether, washed with diluted hydrochloric
acid and brine, dried, and concentrated in vacuo to give 5.518 g
(98%) of (E)-methyl 4-cyano-3-methyl-4,4-diphenylbut-2-enoate
1
184-186 °C (lit.6 183-186 °C); H NMR (CDCl3, 300 MHz) δ
8.00 (br s, 1H), 7.25-7.45 (m, 8H), 7.06-7.09 (m, 2H), 2.66 (d,
J ) 9.6 Hz, 2H), 2.45 (m, 1H), 1.31 (d, J ) 6.3 Hz, 3H); 13C
NMR (CDCl3, 75.4 MHz) δ 138.69, 129.30, 128.37, 128.00, 63.83,
21.42. HRMS calcd for C18H15NO2 300.1000 (M + Na), found
300.1007 (M + Na).
1
16: mp 89-89.5 °C (methanol); H NMR (CDCl3, 300 MHz) δ
7.26-7.44 (m, 10H), 5.54 (d, J ) 1.2 Hz, 1H), 3.71 (s, 3H), 2.33
(d, J ) 1.2 Hz, 3H); 13C NMR (CDCl3, 75.4 MHz) δ 166.42,
155.27, 137.11, 129.20, 128.91, 128.84, 122.47, 121.48, 61.07,
51.62, 18.66.
1,5-Dimethyl-3,3-diphenylpiperidine-2,6-dione (12). A 0.55 g
(13.8 mmol) portion of sodium hydride (60% in mineral oil) was
washed free of oil with hexane and THF and suspended in 20.0
mL of DMF. Then 2.56 g (9.2 mmol) of 5-methyl-3,3-diphenylpi-
peridine-2,6-dione was added with stirring. After the evolution of
hydrogen was complete (0.5 h), 0.86 mL (13.8 mmol) of methyl
iodide was added and the stirring continued overnight. The mixture
was diluted with water, extracted with benzene, washed, dried,
concentrated in vacuo, and crystallized from ethanol to give 1.93
g (71.7%) of 1,5-dimethyl-3,3-diphenylpyridine-(1H,3H)-2,6-di-
one: mp 150-151 °C; 1H NMR (CDCl3, 300 MHz) δ 7.24-7.41
(m, 6H), 7.17-7.20 (m, 2H), 7.07-7.10 (m, 2H), 3.28 (s, 3H),
2.59-2.65 (m, 2H), 2.38-2.50 (m, 1H), 1.32 (d, J ) 6.9 Hz, 3H);
13C NMR (CDCl3, 75.4 MHz) δ 175.36, 174.98, 143.58, 140.23,
129.29, 128.80, 128.15, 128.02, 127.81, 127.45, 57.84, 38.83, 34.64,
27.89, 16.70. HRMS calcd for C19H19NO2 316.1313 (M + Na),
found 316.1322 (M + Na).
1,3-Dimethyl-5,5-diphenyl-3-(phenylselenyl)piperidine-2,6-di-
one (13). To a solution of 0.90 mL (6.42 mmol) of diisopropylamine
in 5.0 mL of THF was added 2.6 mL (6.5 mmol) of 2.5 M
n-butyllithium in hexane at -70 °C, and the mixture was stirred at
-70 °C for 15 min. Then a solution of 1.50 g (5.11 mmol) of the
imide in 20 mL of THF was slowly added, and the mixture was
stirred for 10 min at -70 °C followed by the addition of preprepared
solution of phenylselenyl bromide (obtained by addition of 0.165
mL (3.20 mmol) of bromine to 1.00 g (3.20 mmol) of diphenyl-
diselenide in 5.0 mL of THF). The mixture was allowed to warm
up to room temperature, quenched with saturated ammonium
chloride solution, extracted with benzene, washed with brine, dried
with sodium sulfate, and concentrated in vacuo. Column chroma-
tography (eluent ) hexane/ether 7:1) afforded 2.064 g (90.0%) of
1,3-dimethyl-5,5-diphenyl-3-(phenylselenyl)piperidine-2,6-dione: 1H
NMR (CDCl3, 300 MHz) δ 7.54-7.57 (m, 2H), 7.26-7.45 (m,
9H), 7.03-7.12 (m, 4H), 3.28 (s, 3H), 3.23 (d, J ) 15.0 Hz, 1H),
3.05 (d, J ) 15.0 Hz, 1H), 1.22 (s, 3H); 13C NMR (CDCl3, 75.4
MHz) δ 174.66, 173.83, 142.32, 141.90, 138.33, 130.09, 129.17,
129.14, 128.86, 128.36, 128.33, 127.90, 127.82, 57.08, 45.38, 43.55,
28.87, 26.44. HRMS calcd for C25H23NO2Se 472.0792 (M + Na),
found 472.0805 (M + Na).
(Z)-Methyl 4-Cyano-3-methyl-4,4-diphenylbut-2-enoate 17.
The solution of 5.518 g (18.9 mmol) of the E isomer in 250 mL of
benzene was purged with nitrogen for 1 h. Irradiation was carried
out with the 0.2 M CuSO4 filter solution for 24 h. Separation by
column chromatography (column 15.0 cm × 2.5 cm, eluent )
hexane/ether 19:1) afforded 2.905 g (52.6%) of the starting E isomer
and 1.864 g (33.8%) of the desired (Z)-methyl 4-cyano-3-methyl-
4,4-diphenylbut-2-enoate 17: mp 91-92 °C (methanol); 1H NMR
(CDCl3, 300 MHz) δ 7.33-7.39 (m, 10H), 6.15 (d, J ) 1.5 Hz,
1H), 3.28 (s, 3H), 1.90 (d, J ) 1.2 Hz, 3H); 13C NMR (CDCl3,
75.4 MHz) δ 165.44, 146.50, 138. 20, 128.87, 128.85, 128.54,
123.19, 121.87, 57.35, 51.53, 25.42.
4-Methyl-5,5-diphenylpyridine-(1H,5H)-2,6-dione (19). A mix-
ture of 1.864 g (6.4 mmol) of (Z)-methyl 4-cyano-3-methyl-4,4-
diphenylbut-2-enoate and 1.100 g (8.0 mmol) of potassium
carbonate was refluxed in 2.7 mL of water and 18.0 mL of methanol
for 2 h. Methanol was removed under reduced pressure, and the
mixture was diluted with water, neutralized with hydrochloric acid,
extracted with dichloromethane, dried, and concentrated in vacuo.
The residue was dissolved in 15 mL of acetic acid treated with 5.0
mL of sulfuric acid and refluxed for 2 h. After cooling to ambient
temperature, the mixture was poured onto crushed ice, and the crude
product was filtered and dried. Crystallization from propanol-2
afforded 0.753 g (42.4%) of 4-methyl-3,3-diphenylpyridione-2,6:
1
mp 243-246 °C; H NMR (CDCl3, 300 MHz) δ 8.02 (br s, 1H),
7.29-7.39 (m, 10H), 6.28 (s, 1H), 1.74 (s, 3H); 13C NMR (CDCl3,
75.4 MHz) δ 174.91, 163.90, 159.21, 138.69, 129.30, 128.37,
128.00, 63.83, 21.42. HRMS calcd for C18H15NO2 300.1000 (M +
Na), found 300.1007 (M + Na).
1,4-Dimethyl-5,5-diphenylpyridine-(1H,5H)-2,6-dione (9). A
0.66 g (16.5 mmol) portion of sodium hydride (60% in mineral
oil) was washed free of oil with hexane and THF and suspended
in 25.0 mL of DMF, and 4.189 g (15.1 mmol) of 4-methyl-3,3-
diphenylpiperidine-2,6-dione 19 was added with stirring. After the
evolution of hydrogen was complete (15 min), 1.03 mL (16.5 mmol)
of methyl iodide was added and the stirring continued overnight.
The mixture was diluted with water, extracted with benzene,
washed, dried, concentrated in vacuo, and crystallized from
propanol-2 to give 3.802 g (86.4%) of 1,4-dimethyl-5,5-diphen-
ylpyridine-(1H,5H)-2,6-dione 9: mp 104-105 °C; 1H NMR
(CDCl3, 300 MHz) δ 7.26-7.37 (m, 10H), 6.32 (d, J ) 1.5 Hz,
1H), 3.22 (s, 3H), 1.70 (d, J ) 1.5 Hz, 3H); 13C NMR (CDCl3,
75.4 MHz) δ 175.87, 164.48, 157.00, 139.78, 129.68, 128.71,
128.25, 120.40, 64.14, 26.94, 21.48. HRMS calcd for C19H17NO2
314.1157 (M + Na), found 314.1147 (M + Na).
endo,exo-3-Methyl-1,6-diphenyl-3-azabicyclo[3.1.0]hexane-
2,4-diones 22 and 23. To a stirred solution of 506 mg (2.71 mmol)
of 1-methyl-3-phenylmaleimide,7 820 mg (3.52 mmol) of dimeth-
ylbenzylsulfonium bromide, and 37 mg (0.14 mmol) of triethyl-
benzylammonium bromide in 10.0 mL of dichloromethane was
added 2.5 mL of 50% sodium hydroxide solution at 0 °C, and the
stirring continued overnight. The mixture was diluted with water,
extracted with ether, washed with brine, dried over sodium sulfate,
concentrated in vacuo, and chromatographed on silica gel (column
1,3-Dimethyl-5,5-diphenylpyridine-(1H,5H)-2,6-dione (8). To
a stirred solution of 1.658 g (3.70 mmol) of 1,3-dimethyl-5,5-
diphenyl-3-(phenylselenyl)piperidine-2,6-dione and 311 mg (3.70
mmol) of sodium bicarbonate in 55 mL of ethanol was added a
solution of 3.166 g (14.8 mmol) of sodium periodate in 18 mL of
water with external cooling in an ice bath. The mixture was stirred
overnight at ambient temperature, diluted with water, extracted with
chloroform, washed with diluted sodium sulfite solution, then with
water, dried over sodium sulfate, and the solvent was removed in
vacuo to give 0.956 g (88.8%) of 1,3-dimethyl-5,5-diphenylpyri-
dine-(1H,5H)-2,6-dione 8 after crystallization from ethanol: mp
1
211-213 °C; H NMR (CDCl3, 300 MHz) δ 7.30-7.38 (m, 6H),
7.19-7.22 (m, 4H), 6.75 (dd, J1 ) 3.0 Hz, J2 ) 1.5 Hz, 1H), 3.31
(s, 3H), 2.08 (d, J ) 1.5 Hz, 3H); 13C NMR (CDCl3, 75.4 MHz) δ
174.15, 165.94, 143.50, 142.03, 128.88, 128.84, 128.07, 126.22,
59.90, 27.20, 16.97. HRMS calcd for C19H17NO2 314.1157 (M +
Na), found 314.1162 (M + Na).
6094 J. Org. Chem., Vol. 72, No. 16, 2007

The Aza-Type-B Photochemical Rearrangement
12.0 cm × 2.5 cm, eluent ) hexane/ether 7:1, then 4:1) to give the
following products:
Fraction 1. 2.6 mg unidentified.
7.30-7.47 (m, 16H), 3.41 (d, J ) 8.7 Hz, 2H), 3.15 (d, J ) 8.4
Hz, 2H), 2.44 (s, 6H); 13C NMR (CDCl3, 75.4 MHz) δ 173.46,
172.81, 132.52, 132.42, 128.84, 128.75, 128.71, 128.28, 128.04,
42.36, 41.39, 31.98, 23.55. HRMS calcd for C36H30N2O4 577.2103
(M + Na), found 577.2130 (M + Na).
Fraction 2. 56 mg (74.6%). endo-3-Methyl-1,6-diphenyl-3-
azabicyclo[3.1.0]hexane-2,4-dione 22: mp 126.5-127 °C (heptane);
1H NMR (CDCl3, 300 MHz) δ 7.53-7.58 (m, 2H), 7.26-7.48 (m,
8H), 3.42 (d, J ) 8.4 Hz, 1H), 3.15 (d, J ) 8.4 Hz, 1H), 2.44 (s,
3H); 13C NMR (CDCl3, 75.4 MHz) δ 173.86, 173.21, 132.99,
132.87, 129.27, 129.18, 129.15, 129.12, 128.67, 128.46, 42.79,
41.82, 32.43, 23.96. HRMS calcd for C18H15NO2 300.1000 (M +
Na), found 300.1013 (M + Na).
Fraction 3. 27 mg (3.6%). exo-3-Methyl-1,6-diphenyl-3-azabicyclo-
[3.1.0]hexane-2,4-dione 23: mp 197.5-199 °C (heptane; lit.7 196-
198 °C); 1H NMR (CDCl3, 300 MHz) δ 7.24-7.25 (m, 5H), 7.09-
7.12 (m, 3H), 6.82-6.85 (m, 2H), 3.30 (d, J ) 3.6 Hz, 1H), 3.12
(d, J ) 3.6 Hz, 1H), 3.00 (s, 3H).
endo,exo-3,6-Dimethyl-1,6-diphenyl-3-azabicyclo[3.1.0]hexane-
2,4-diones 28 and 29. To a stirred solution of 159 mg (0.85 mmol)
of 1-methyl-3-phenylmaleimide,7 390 mg (1.33 mmol) of dimethyl-
(1-phenylethyl)sulfonium iodide, and 12 mg (0.044 mmol) of
triethylbenzylammonium bromide in 5.0 mL of dichloromethane
was added 1.0 mL of 50% sodium hydroxide solution at 0 °C, and
the stirring continued overnight. The mixture was diluted with water,
extracted with ether, washed with brine, dried over sodium sulfate,
concentrated in vacuo, and chromatographed on silica gel (column
40.0 cm × 2.5 cm, eluent ) hexane/ether 6:1) to give the following
products:
Fraction 1. 11 mg (4.6%). exo-3,6-Dimethyl-1,6-diphenyl-3-
azabicyclo[3.1.0]hexane-2,4-dione 29: mp 174-175 °C (heptane);
1H NMR (CDCl3, 300 MHz) δ 7.24-7.29 (m, 2H), 7.02-7.18 (m,
8H), 3.47 (s, 1H), 2.99 (s, 3H), 1.61 (s, 3H); 13C NMR (CDCl3,
75.4 MHz) δ 174.46, 173.82, 139.75, 130.63, 129.13, 128.71,
128.49, 128.22, 127.75, 127.45, 48.98, 45.71, 34.09, 24.52, 19.90.
HRMS calcd for C19H17NO2 314.1157 (M + Na), found 314.1165
(M + Na).
Fraction 3. 44.3 mg (22.3%). 3-Methyl-6,6-diphenyl-3-azabicyclo-
[3.1.0]hexane-2,4-dione 31: mp 156-157 °C (propanol-2; lit.9 157
1
°C); H NMR (CDCl3, 300 MHz) δ 7.39-7.43 (m, 2H), 7.20-
7.34 (m, 8H), 3.17 (s, 2H), 2.35 (s, 3H); 13C NMR (CDCl3, 75.4
MHz) δ 173.34, 141.40, 136.40, 129.54, 129.31, 129.11, 128.45,
127.94, 127.14, 50, 46, 34.11, 23.89. HRMS calcd for C18H15NO2
300.1000 (M + Na), found 300.1002 (M + Na).
Fraction 4. 15.3 mg (7.7%). Unidentified.
Irradiation of 1,3-Dimethyl-5,5-diphenylpyridine-(1H,5H)-
2,6-dione (8) in Benzene. A solution of 400 mg (1.37 mmol) of
1,3-dimethyl-5,5-diphenylpyridine-(1H,5H)-2,6-dione 8 in 250 mL
of benzene was purged with nitrogen for 1 h. The irradiation was
then carried out with the 0.2 M CuSO4 filter solution for 1 h. TLC
indicated one new spot. The irradiation was continued for 3 more
hours, achieving practically complete conversion of the starting
material. The solution was concentrated in vacuo and crystallized
from propanol-2 to give 320 mg (80%) of 1,3-dimethyl-5,6-
diphenyl-3-azabicyclo[3.1.0]hexane-2,4-dione 25: mp 130-131 °C;
1H NMR (CDCl3, 300 MHz) δ 7.26-7.49 (m, 10H), 3.33 (s, 1H),
2.45 (s, 3H), 1.47 (s, 3H); 13C NMR (CDCl3, 75.4 MHz) δ 175.91,
174.78, 133.65, 131.68, 130.49, 129.23, 129.08, 129.06, 128.87,
128.29, 46.06, 45.86, 38.11, 24.02, 12.09. HRMS calcd for
C19H17NO2 314.1157 (M + Na), found 314.1172 (M + Na).
Irradiation of 1,3-Dimethyl-5,5-diphenylpyridine-(1H,5H)-
2,6-dione 8 in Methanol. A solution of 300 mg (1.03 mmol) of
1,3-dimethyl-5,5-diphenylpyridine-(1H,5H)-2,6-dione 8 in 250 mL
of methanol was purged with nitrogen for 1 h. The irradiation was
then carried out with the 0.2 M CuSO4 filter solution for 6 h. TLC
indicated two new distinctive spots. The solution was concentrated
in vacuo and separated by chromatography (column 12.0 cm ×
2.5 cm, eluent ) hexane/ether 4:1) to give the following prod-
ucts:
Fraction 2. 192 mg (77.8%). endo-3,6-Dimethyl-1,6-diphenyl-
3-azabicyclo[3.1.0]hexane-2,4-dione 28: mp 134-135 °C (hep-
1
tane); H NMR (CDCl3, 300 MHz) δ 7.55-7.58 (m, 2H), 7.27-
Fraction 1. 13.1 mg. Starting material.
Fraction 2. 155.3 mg (54.1%). 1,3-Dimethyl-5,6-diphenyl-3-
azabicyclo[3.1.0]hexane-2,4-dione 25.
Fraction 3. 77.5 mg (27.0%). 1,3-Dimethyl-6,6-diphenyl-3-
azabicyclo[3.1.0]hexane-2,4-dione 27.
7.50 (m, 8H), 3.00 (s, 1H), 2.33 (s, 3H), 1.20 (s, 3H); 13C NMR
(CDCl3, 75.4 MHz) δ 174.39, 173.84, 138.98, 130.45, 130.33,
129.24, 129.00, 128.68, 128.40, 128.14, 48.65, 48.84, 36.74, 25.45,
23.95. HRMS calcd for C19H17NO2 314.1157 (M + Na), found
314.1156 (M + Na).
Irradiation of 1,4-Dimethyl-5,5-diphenylpyridine-(1H,5H)-
2,6-dione 9 in Benzene. A solution of 200 mg (0.69 mmol) of
1,4-dimethyl-3,3-diphenylpyridione-(1H,3H)-2,6 in 250 mL of
benzene was purged with nitrogen for 1 h. The irradiation was then
carried out with the 0.2 M CuSO4 filter solution for 2 h. TLC
indicated 2 new spots and practically complete conversion of the
starting material. The mixture was separated by chromatography
(column 40.0 cm × 2.5 cm, eluent hexane-ether 6:1) to give the
following products:
Fraction 1. 52.2 mg (26.1%). exo-3,6-Dimethyl-1,6-diphenyl-3-
azabicyclo[3.1.0]hexane-2,4-dione 29.
Fraction 2. 133.5 mg (66.8%). endo-3,6-Dimethyl-1,6-diphenyl-
3-azabicyclo[3.1.0]hexane-2,4-dione 28.
Irradiation of 1,4-Dimethyl-5,5-diphenylpyridine-(1H,5H)-
2,6-dione (9) in Methanol. A solution of 200 mg (0.69 mmol) of
1,4-dimethyl-3,3-diphenylpyridione-(1H,3H)-2,6 in 250 mL of
methanol was purged with nitrogen for 1 h. The irradiation was
then carried out with the 0.2 M CuSO4 filter solution for 1 h. TLC
indicated three new spots. The solution was concentrated in vacuo
and separated by chromatography (column 40.0 cm × 2.5 cm, eluent
) hexane/ether 6:1) to give the following products:
1,3-Dimethyl-6,6-diphenyl-3-azabicyclo[3.1.0]hexane-2,4-di-
one 27. A solution of 1.065 g (5.43 mmol) of diphenyldiazomethane
in 10.0 mL of benzene was added to a refluxed solution of 453 mg
(3.62 mmol) of 1,3-dimethylmaleimide in 10 mL of benzene during
3 h by a syringe pump. The mixture was refluxed for 12 h, cooled,
concentrated in vacuo, and chromatographed on silica gel (column
12.0 cm × 2.5 cm, eluent ) hexane/ether 4:1) to give 897 mg
(85.1%) of 1,3-dimethyl-6,6-diphenyl-3-azabicyclo[3.1.0]hexane-
1
2,4-dione 27: mp 116.5-118 °C (propanol-2); H NMR (CDCl3,
300 MHz) δ 7.15-7.38 (m, 10H), 3.10 (s, 1H), 2.33 (s, 3H), 1.38
(s, 3H); 13C NMR (CDCl3, 75.4 MHz) δ 177.03, 174.11, 138.90,
138.75, 129.19, 129.11, 128.90, 128.65, 127.98, 127.89, 54.26,
37.32, 35.81, 23.88, 11.73. HRMS calcd for C19H17NO2 605.2416
(2M + Na), found 605.2423 (2M + Na) (most intense peak,
monomer peak weaker).
Irradiation of 1-Methyl-3,3-diphenylpyridine-2,6-(1H,3H)-
dione in Methanol. A solution of 400 mg (1.44 mmol) of 1-methyl-
3,3-diphenylpyridine-2,6-(1H,3H)-dione in 250 mL of methanol was
purged with nitrogen for 1 h. The irradiation was then carried out
with the 0.2 M CuSO4 filter solution for 6 h. TLC indicated two
new distinctive spots. The solution was concentrated in vacuo and
separated by chromatography (column 12.0 cm × 2.5 cm, eluent
) hexane/ether 4:1) to give the following products:
Fraction 2. 50.3 mg. Starting material.
Fraction 2. 27.2 mg (18.2%). exo-3,6-Dimethyl-1,6-diphenyl-3-
azabicyclo[3.1.0]hexane-2,4-dione 29.
Fraction 1. 201 mg. Reactant.
Fraction 2. 73.4 mg (36.9%). [2 + 2] Adduct 30; mp 126-127.5
Fraction 3. 53.7 mg (35.9%). endo-3,6-Dimethyl-1,6-diphenyl-
3-az-bicyclo[3.1.0]hexane-2,4-dione 28.
1
°C (heptane); H NMR (CDCl3, 300 MHz) δ 7.54-7.57 (m, 4H),
J. Org. Chem, Vol. 72, No. 16, 2007 6095

Zimmerman and Mitkin
Fraction 3. 46.8 mg (31.3%). 1,3-Dimethyl-6,6-diphenyl-3-
azabicyclo[3.1.0]hexane-2,4-dione 27.
Supporting Information Available: Experimental procedures,
NMR spectra, X-ray data, and computational files. This material
is available free of charge via the Internet http://pubs.acs.org.
Acknowledgment. Support of this research by the National
Science Foundation is gratefully acknowledged with special
appreciation for its support of basic research.
JO0706372
6096 J. Org. Chem., Vol. 72, No. 16, 2007