Photogeneration and reactivity of 1,n-diphenyl-1,n-azabiradicals

Article abstract of DOI:10.1021/jo0601967

The 1,5-diphenyl-1,5-azapentanediyl biradical Ia was generated by photolysis of 1,2-diphenylazacyclopentane (pyrrolidine 1a). Among the reaction pathways followed by Ia, C-N bond reformation with ring closure was found to be the predominating process, as determined by separate irradiation of either of the pure enantiomers of 1a. Disproportionation was a minor process and took place only via H abstraction by the C5 benzylic radical. Another minor pathway was C5-aryl coupling, with formation of 5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b] azepine (4a), which is equivalent to photo-Claisen rearrangement of 1a. Likewise, the 1,4-diphenyl-1,4-azabutanediyl biradical Ib was generated by photolysis of 1,2-diphenylazacyclobutane (azetidine 1b). This species underwent predominating C2-C3 cleavage, as indicated by the extensive styrene formation. Although NI-C4 bond reformation also took place, this is not the major pathway occurring from Ib. Besides, C4-aryl coupling to give 4-phenyl-1,2,3,4- tetrahydroquinoline (4b) was also observed. All the possible reaction pathways were theoretically studied at the UB3LYP/6-31G* computational level; the results were found to be in good agreement with the experimental observations.

Full text of DOI:10.1021/jo0601967

Photogeneration and Reactivity of 1,n-Diphenyl-1,n-azabiradicals
Edgar A. Leo,† Luis R. Domingo,‡ Miguel A. Miranda,*,† and Rosa Tormos†
Departamento de Qu´ımica-Instituto de Tecnolog´ıa Qu´ımica UPV-CSIC, UniVersidad Polite´cnica de
Valencia, Camino de Vera s/n, 46022 Valencia, Spain, and Departamento de Qu´ımica Orga´nica, Instituto
de Ciencia Molecular, UniVersidad de Valencia, Dr. Moliner 50 E-46100 -Burjassot, Valencia, Spain
mmiranda@qim.upV.es
ReceiVed January 30, 2006
The 1,5-diphenyl-1,5-azapentanediyl biradical Ia was generated by photolysis of 1,2-diphenylazacyclo-
pentane (pyrrolidine 1a). Among the reaction pathways followed by Ia, C-N bond reformation with
ring closure was found to be the predominating process, as determined by separate irradiation of either
of the pure enantiomers of 1a. Disproportionation was a minor process and took place only via H abstraction
by the C5 benzylic radical. Another minor pathway was C5-aryl coupling, with formation of 5-phenyl-
2,3,4,5-tetrahydro-1H-benzo[b]azepine (4a), which is equivalent to photo-Claisen rearrangement of 1a.
Likewise, the 1,4-diphenyl-1,4-azabutanediyl biradical Ib was generated by photolysis of 1,2-
diphenylazacyclobutane (azetidine 1b). This species underwent predominating C2-C3 cleavage, as
indicated by the extensive styrene formation. Although N1-C4 bond reformation also took place, this is
not the major pathway occurring from Ib. Besides, C4-aryl coupling to give 4-phenyl-1,2,3,4-
tetrahydroquinoline (4b) was also observed. All the possible reaction pathways were theoretically studied
at the UB3LYP/6-31G* computational level; the results were found to be in good agreement with the
experimental observations.
CHART 1. Structures of 1,n-Azabiradicals Ia and Ib and
Their All-Carbon Analogues IIa and IIb
Introduction
Biradical intermediates play an important role in many
thermal and photochemical processes. 1,n-Diaryl-1,n-alkanediyl
biradicals (as for example, IIa and IIb in Chart 1) have been
proposed as intermediates in a wide range of reactions such as
the geometric photoisomerization of cycloalkanes,1 the dimer-
ization of styrenes,2 and the photoextrusion of CO2, N2, SO2,
or CO in lactones,3 cyclic azoalkanes,4 sulfones,5 or ketones,6,7a,b
respectively. They have also been generated via two-photon two-
laser photolysis of 1,n-dichloro-1,n-diphenylalkanes.7,8
† Universidad Polite´cnica de Valencia.
‡ Universidad de Valencia.
(1) Jones, G., II; Chow, Y. L. J. Org. Chem. 1974, 39, 1447-1448.
(2) (a) Caldwell, R. A.; Diaz, J. F.; Hrncir, D. C.; Unett, D. J. J. Am.
Chem. Soc. 1994, 116, 8138-8145. (b) Brown, W. G. J. Am. Chem. Soc.
1968, 90, 1916-1917. (c) Li, T.; Padias, A. B.; Hall, H. K., Jr.
Macromolecules 1990, 23, 3899-3904. (d) Kaufmann, K. F. Makromol.
Chem. 1979, 180, 2649-2663.
(3) (a) Givens, R. S. Org. Photochem. 1981, 5, 227-346. (b) Budac,
D.; Wan, P. J. Photochem. Photobiol., A 1992, 67, 135-166.
(4) (a) Kopecky, K. R.; Soler, J. Can. J. Chem. 1974, 52, 2111-2118.
(b) Kohmoto, S.; Yamada, K.; Joshi, U.; Kawatuji, T.; Yamamoto, M.;
Yamada, K. J. Chem. Soc., Chem. Commun. 1990, 127-129.
(5) Zimmt, M. B.; Doubleday, C., Jr.; Turro, N. J. Chem. Phys. Lett.
1987, 134, 549-552.
Comparatively little is known about the analogous aza
biradicals (Ia and Ib in Chart 1). A related precedent was
published by Platz and Burns.9 They were able to generate the
1-imino-8-naphthoquinomethane biradical (together with 1-methyl-
8-nitrenonaphthalene) upon photolysis of 1-azido-8-methyl-
(7) (a) Banks, J. T.; Garc´ıa, H.; Miranda, M. A.; Perez-Prieto, J.; Scaiano
J. C. J. Am. Chem. Soc. 1995, 117, 5049-5054. (b) Perez-Prieto, J.; Miranda,
M. A.; Garc´ıa, H.; Ko´nya, K.; Scaiano, J. C. J. Org. Chem. 1996, 61, 3773-
3777. (c) Miranda, M. A.; Font-Sanchis, E.; Perez-Prieto, J.; Scaiano, J. C.
J. Org. Chem. 1999, 64, 7842-7845.
(6) (a) Peyman, A.; Beckhaus, H. D.; Ru¨chardt, C. Chem. Ber. 1998,
121, 1027-1031. (b) Zimmt, M. B.; Doubleday, C., Jr.; Gould, I. R.; Turro,
N. J. J. Am. Chem. Soc. 1985, 107, 6724-6726. (c) Tarasov, V. F.;
Klimenok, B. B.; Askerov, D. B.; Buchachenko, A. L. Bull. Acad. Sci. USSR,
DiV. Chem. Sci. (Engl. Transl.) 1985, 34, 330-332.
(8) (a) Perez-Prieto, J.; Miranda, M. A.;. Font-Sanchis, E.; Ko´nya, K.;
Scaiano, J. C. Tetrahedron Lett. 1996, 37, 4923-4926. (b) Miranda, M.
A.; Perez-Prieto, J.; Font-Sanchis, E.; Ko´nya, K.; Scaiano, J. C. J. Org.
Chem. 1997, 62, 5713-5719.
(9) Platz, M. S.; Burns, J. R. J. Am. Chem. Soc. 1979, 101, 4425-4426.
10.1021/jo0601967 CCC: $33.50 © 2006 American Chemical Society
Published on Web 05/11/2006
J. Org. Chem. 2006, 71, 4439-4444
4439

Leo et al.
CHART 2. Structural Formulas of Compounds 1-6
naphthalene in a 2-methyltetrahydrofuran matrix at 77 K; the
structure was assigned by means of ESR. Nitrogen-centered
biradicals have also been proposed as intermediates in the
photochemistry of pyrrolidones and bichromophoric styrene-
amine systems.10 However, a systematic study on the formation
and behavior of this type of biradical has not yet been carried
out.
We became interested in the chemistry of 1,5-diphenyl-1,5-
azapentanediyl biradical (Ia) as a logical extension of our
previous studies on the C-centered analogue IIa, which is known
to undergo cyclization to 1,2-diphenylcyclopentanes or dispro-
portionation to 1,5-diphenylpentenes.7a,c
FIGURE 1. Chiral HPLC analysis of (a) racemic 1a, (b) and (d) its
two pure enantiomers, and (c) and (e) separate irradiation of each
enantiomer.
SCHEME 1. Mechanistic Pathways Available for the
1,5-Azabiradical Ia
Likewise, the 1,4-diphenyl-1,4-azabutanediyl biradical Ib is
the aza analogue of IIb, which produces a mixture of 1,2-
diphenylcyclobutane, styrene, and 1-phenyl-1,2,3,4,-tetrahy-
dronaphthalene as a result of cyclization, cleavage, and ortho
coupling processes, respectively.7b
In this context, we report here on the unambiguous generation
of 1,n-azabiradicals by photolysis of the 1,2-diphenylazacy-
cloalkanes, as well as on their fate, as revealed by the analysis
of the final products. Theoretical calculations on the possible
reaction pathways have also been performed to rationalize the
experimental data.
Results and Discussion
1,5-Azabiradical. Biradical Ia was generated by 254 nm
photolysis of pyrrolidine 1a (Chart 2), which was obtained
following a literature procedure.10b After homolytic C-N bond
cleavage, the possible pathways available for Ia are (i) C-N
bond reformation with ring closure leading back to the starting
material, (ii or iii) disproportionation, and (iv or v) C-C or
C-N coupling with intramolecular rearrangement (see Scheme
1). Chemical evidence for the pathways actually occurring from
Ia was obtained by analysis of the final product distribution.
As stated above, C-N bond reformation along route (i) would
lead back to pyrrolidine 1a. In this context, it is worth
mentioning that even after prolonged irradiation most of the
starting 1a remained apparently “unreacted”. To determine
whether (and if so, to what extent) retrocyclization was actually
occurring, racemic 1a was resolved into the two pure enanti-
omers by means of HPLC equipped with a semipreparative
chiral column. Then parallel irradiation of the two enantiomers
was conducted until the degree of conversion into other products
was about 5%. Analysis of the pyrrolidine fraction by chiral
HPLC revealed that the extent of inversion from either of the
two 1a enantiomers was about 10% (Figure 1). If one assumes
that pathway (i) occurs without any significant enantioselectivity
under the employed reaction conditions, 10% inversion of the
configuration would be equivalent to 20% reformation of 1a
after C-N bond homolysis. In other words, route (i) would
represent about 80% of all the processes actually occurring from
Ia.
In any case, retrocyclization must be by far the major reaction
pathway; thus, even if it ensues with complete inversion of
configuration, it would still represent two-thirds (10% vs 10 +
5%) of all the processes occurring from Ia. However, if there
is some “memory of chirality” during ring closure, more than
80% of biradical Ia would be following this pathway. In this
context, the multiplicity of the biradical (singlet vs triplet) would
play an important role. Although no experimental evidence was
obtained by means of transient absorption measurements,
calculations showed that the two states are nearly degenerate
(see below). This suggests that the most feasible situation is
retrocyclization with a high degree of racemization.
In regard to the two possible disproportionation processes,
no evidence was obtained for route (ii), because not even traces
of alkene 2a were detected. Conversely, route (iii) seems to
(10) (a) Miriam, B. S.; Maitland, J., Jr. J. Am. Chem. Soc. 1972, 94,
8281-8282. (b) Lewis, F. D.; Wagner-Brennan, J. M.; Miller, A. M. Can.
J. Chem. 1999, 74, 595-604.
4440 J. Org. Chem., Vol. 71, No. 12, 2006

Azabiradicals
SCHEME 2. Mechanism Proposed by Lewis Explaining
Photoproducts Formation by Irradiation of 2a
SCHEME 4. Main Photoproducts Resulting from
Irradiation of 2b
SCHEME 3. Mechanistic Pathways Available for the
1,4-Azabiradical Ib
stressed that compound 1b reacted about 10 times faster than
its higher homologue 1a under the same irradiation conditions.
As for 1a, the extent of retrocyclization was determined in this
case by parallel irradiation of the two enantiomers of 1b. After
20% conversion, analysis of the azetidine fraction by chiral
HPLC showed that the degree of configuration inversion from
either of the two 1b enantiomers was about 5%. Taking into
account the above discussion, route (i) would represent about
one-third of all the processes actually occurring from Ib.
Disproportionation to compounds 2b or 3b was not detected
in the reaction mixture. Likewise, not even traces of 5b were
observed. However, a small amount of the Claisen rearrange-
ment product 4b was indeed found in the photolyzate. By far,
the predominating process for the 1,4-azabiradical Ib was
cleavage of the C2-C3 bond, as indicated by the extensive
formation of styrene (process vi in Scheme 3).
Although the photochemistry of N-cinnamylaniline 2b (Chart
2) has not been the subject of previous studies, we wondered
whether its behavior could be analogous to that of its higher
homologue 2a. If so, photolysis of 2b should occur via H
transfer in an intramolecular exciplex, leading to the 1,4-
azabiradical Ib and providing an alternative entry to this
intermediate. However, in this case, the only observed process
was C-N cleavage to afford a radical pair and all the coupling
products (in-cage and out-of-cage) derived therefrom. This is
summarized in Scheme 4.
play some role, as indicated by the formation of 4-phenylbutanal
and aniline, the obvious hydrolysis products of imine 3a.
Finally, of the two possible products of intramolecular
rearrangement, only 4a was obtained. Its formation occurs
through route (iv), which involves the typical Claisen rear-
rangement with 1,3-benzyl migration.11 The alternative rear-
rangement product with C-N coupling (5a) was not formed.
In a previous work, Lewis studied the photochemistry of N-(4-
phenylbut-3-enyl)aniline 2a.10b After irradiation, this bichro-
mophoric aniline/styrene system was found to undergo an
intramolecular photocyclization process (Scheme 2), with
formation of 1a as major photoproduct. Besides, GC-MS
analysis revealed the formation of 2-benzyl-1-phenylazetidine
(6a) and several other unidentified minor products. As this
constitutes an alternative generation of the 1,5-diphenyl-1,5-
azabiradical Ia, all the compounds obtained by irradiation of
2a and indicated in Scheme 1 should also be found in the
photolysis mixture from 1a. As a matter of fact, when we
irradiated N-(4-phenylbut-3-enyl)aniline (2a) under the same
conditions as 1a, minor amounts of compound 4a were actually
obtained.
Theoretical Studies. The possible reaction channels were
theoretically studied at the UB3LYP/6-31G* computational
level. For the 1,5-azabiradical Ia, five reaction channels were
considered (see Scheme 1) involving five transition states,
TS1a-TS5a, two intermediates, IN4a and IN5a, and three
products, 1a-3a, which were located and characterized. The
total and relative energies are summarized in Table 1, while
the geometries of the transition structures (TSs) are given in
Figure 2.
1,4-Azabiradical. Biradical Ib was generated by the irradia-
tion of azetidine 1b (Chart 2), which was also synthesized
following a known method.12 As in the case of Ia, several
pathways are available for Ib after homolytic C-N bond
cleavage: (i) C-N bond reformation with ring closure leading
back to the starting material, (ii or iii) disproportionation, (iv
or v) C-C or C-N coupling with intramolecular rearrangement,
and (vi) C2-C3 cleavage to afford olefin and imine units (see
Scheme 3).
The most favorable reactive channel corresponds to cycliza-
tion, to give pyrrolidine 1a via TS1a. The process is almost
barrierless and strongly exothermic (-50.9 kcal/mol). For the
disproportionation reactions, hydrogen abstraction by the C5-
centered radical via TS3a is 3.3 kcal/mol more favorable than
by the N1-centered radical via TS2a. Both reactions are also
very exothermic processes, -46.7 and -41.8 kcal/mol. Finally,
for intramolecular radical attack to the two aromatic rings, the
energy of TS4a is 5.5 kcal/mol lower than that of TS5a. In
addition, formation of IN4a is also 7.0 kcal/mol more exother-
mic than that of IN5a. These results indicate that the most
favorable reaction channels are those proceeding through TS1a,
TS3a, and TS4a, in clear agreement with the experimental
findings. Thus, processes involving attack by the C-centered
radical (channels iii and iv) are clearly favored over those
The first pathway, C-N bond reformation along route (i),
would lead back to azetidine 1b. In this context, it has to be
(11) Galindo, F. J. Photochem. Photobiol., C: Photochem. ReV. 2005,
6, 123-138.
(12) Jackson, M. B.; Mander, L. N.; Spotswood, T. M. Austr. J. Chem.
1983, 36, 779-788.
J. Org. Chem, Vol. 71, No. 12, 2006 4441

Leo et al.
TABLE 1. UB3LYP/6-31G* Total (in au) and Relative (in kcal/
mol) Energies of the Stationary Points Involved in the Reactions of
the 1,5- and 1,4-Azabiradicals Ia and Ib
E
∆E
Ia
-674.612 038
-674.609 753
-674.591 593
-674.596 918
-674.601 312
-674.592 697
-674.693 157
-674.678 661
-674.686 381
-674.644 664
-674.633 548
TS1a
TS2a
TS3a
TS4a
TS5a
1a
2a
3a
IN4a
IN5a
1.4
12.8
9.5
6.7
12.1
-50.9
-41.8
-46.7
-20.5
-13.5
Ib
TS1b
TS2b
TS3b
TS4b
TS6b
1b
2b
-635.299 171
-635.288 351
-635.264 134
-635.267 275
-635.297 475
-635.294 029
-635.355 189
-635.362 715
-635.370 033
-635.342 536
-635.334 448
6.8
23.7
20.0
FIGURE 3. Energy profile (in kcal/mol) for all the possible reaction
channels of Ia.
1.1
3.2
forming bonds are 2.491 Å (C5-C(Ar)) at TS4a and 2.209 Å
(N1-C(Ar)) at TS5a.
-35.2
-39.9
-44.5
-27.2
-22.1
The extent of bond formation along a reaction pathway is
provided by the concept of bond order (BO).13 The BO value
of the N1-C5 forming bond at TS1a is 0.01, a very low value
indicating that bond formation is not yet initiated. Note that
this TS has been associated with the C2-C3 bond rotation. At
the TSs corresponding to the disproportionation reactions, the
BO values of the forming and breaking bonds are 0.23 (N1-
H) and 0.60 (C4-H) at TS2a, as compared with 0.23 (C5-H)
and 0.64 (C2-H) at TS3a. These values point to asynchronous
bond-forming and bond-breaking processes, where the latter are
slightly more advanced than the former. Finally, at the TSs
associated with radical attack to the aromatic rings, the BO
values of the forming bonds are 0.21 (C5-C(Ar)) at TS4a and
0.32 (N1-C(Ar)) at TS5a. Bond formation at the more
favorable TS4a is more delayed than at TS5a.
3b
IN4b
iminea + styrene
a The imine of aniline with formaldehyde.
The initial S2 values for the singlet biradical Ia (1.04)
became 0.49 after spin annihilation. These deviations of S2
from zero indicate that the biradical species are not pure singlet
spin states.14 A value of the unity for S2 indicates a 1:1 mixture
of singlet and triplet states.15 Analysis of the total atomic spin
density in biradical Ia indicated that it is mainly located at the
nitrogen atom (-0.63) and at the benzylic carbon (0.76). At
the UB3LYP/6-31G* level, the triplet biradical Ia, with S2
)
2.06, lies only 0.1 kcal/mol above the singlet biradical. However,
the atomic spin density at the nitrogen atom now has a positive
value (0.63), indicating that both electrons have R spin.
Otherwise, both degenerated singlet and triplet biradicals have
identical geometrical and electronic structures.
FIGURE 2. Geometries of the 1,5-azabiradical Ia and the transition
structures TS1a-TS5a involved in the reactions of Ia. Bond lengths
between the atoms directly involved in the reaction are given in
angstroms.
For the 1,4-azabiradical Ib, five reaction channels were also
considered (see Scheme 3) involving five transition states
(TS1b-TS4b and TS6b), one intermediate (IN4b), and five
products (1b-3b, styrene, and the imine of aniline with
formaldehyde), which were located and characterized. The total
and relative energies are summarized in Table 1, while the
geometries of the TSs are given in Figure 4.
According to DFT calculations, coupling of the C4-centered
radical of Ib with the aromatic carbon ortho to the nitrogen
atom (ultimately leading to 4b after 1,3-H migration) is a
associated with the less-reactive N-centered radical (channels
ii and v). This is schematically shown in Figure 3.
In regard to the geometries of the TSs involved in the
reactions of Ia given in Figure 2, analysis of the atomic
movement at the unique imaginary frequency of TS1a (28.9i
cm-1) indicates that this TS is mainly associated with the C2-
C3 bond rotation. Intramolecular biradical coupling with forma-
tion of the N1-C5 bond is nearly barrierless. For the TSs
corresponding to the disproportionation reactions, the lengths
of the forming and breaking bonds are: 1.574 Å (N1-H) and
1.222 Å (C4-H) at TS2a or 1.683 Å (C5-H) and 1.227 Å
(C2-H) at TS3a. Finally, at the TSs corresponding to intramo-
lecular radical attack to the aromatic rings, the lengths of the
(13) Wiberg, K. B. Tetrahedron 1968, 24, 1083-1096.
(14) Goldstein, E.; Beno, B.; Houk K. N. J. Am. Chem. Soc. 1996, 118,
6036-6043.
(15) Cramer, C. J.; Dulles, F. J.; Giesen, D. J.; Almlo¨f, J. Chem. Phys.
Lett. 1995, 245, 165-170.
4442 J. Org. Chem., Vol. 71, No. 12, 2006

Azabiradicals
The geometries of the TSs involved in the reactions of 1,4-
azabiradical Ib are given in Figure 4. In TS1b, the N1-C4
distance is 2.371 Å and the N1-C2-C3-C4 dihedral angle is
only -24.8 degrees, pointing to a nearly planar arrangement.
Analysis of the atomic movement at the unique imaginary
frequency of TS1b (265.5i cm-1) indicates that this TS is mainly
associated with N1-C4 bond formation. For the TSs corre-
sponding to the disproportionation reactions, the lengths of the
forming and breaking bonds are 1.529 Å (N1-H) and 1.288 Å
(C3-H) at TS2b or 1.755 Å (C4-H) and 1.227 Å (C2-H) at
TS3b. In TS4b, associated with C4 radical attack to the aromatic
ring, the length of the C4-C(Ar) forming bond is 2.568 Å;
this value is larger than that found for C-C bond formation at
TS4a.
In regard to the BOs, the N1-C4 BO value at TS1b is 0.21;
this points to an early bond formation.16 At the TSs associated
with the disproportionation reactions, the BO values of the
forming and breaking bonds are 0.27 (N1-H) and 0.53 (C3-
H) at TS2b or 0.15 (C4-H) and 0.70 Å (C2-H) at TS3b. At
TS4b, corresponding to C4 radical attack to the aromatic ring,
the BO value of the C-C forming bond is 0.13 (C4-C(Ar)).
Thus, bond formation at TS4b is less advanced than at TS4a.
Finally, at TS6b, the C2-C3 BO value is 0.63; hence, bond
cleavage has already started.
The initial S2 values for the singlet biradical Ib (1.04)
became 0.49 after spin annihilation. Analysis of the total atomic
spin density in biradical Ib indicated that it is mainly located
at the nitrogen atom (-0.63) and at the benzylic carbon (0.76).
At the UB3LYP/6-31G* level, the triplet biradical Ib, with S2
) 2.06, lies 0.5 kcal/mol above the singlet biradical. However,
the atomic spin density at the nitrogen atom has a positive value
(0.64), indicating that both electrons have a R spin. Otherwise,
both species have identical geometrical and electronic structures.
For biradicals Ia and Ib, both singlet and triplet states are
degenerated. However, as a result of the fact that products and
intermediates of Scheme 3 have closed-shell configurations, the
reaction paths associated with the triplet state are very disfavored
due to the formation of triplet excited species.16,17
FIGURE 4. Geometries of the 1,4-azabiradical Ib and the transition
structures TS1b-TS4b and TS6b involved in its reactions. Bond
lengths between the atoms directly involved in the reaction are given
in angstroms.
FIGURE 5. Energy profile (in kcal/mol) for all the possible reaction
channels of Ib.
Conclusion
The chemistry of 1,5-diphenyl-1-azapentanediyl biradical Ia
is dominated by intramolecular N-C coupling, to give the five-
membered ring product (i.e., pyrrolidine 1a). Disproportionation
is a minor process and takes place only in one sense: abstraction
of the H atom R to the N center by the C5 benzylic radical.
Another minor pathway is C5-C(Ar) coupling, with formation
of 4a (equivalent to the photo-Claisen rearrangement of 1a).
This behavior is analogous to that of the 1,5-diphenyl-1,5-
pentanediyl biradical, although in the all-carbon case, the extent
of disproportionation is much higher,6a,7a and no C5-aryl
coupling with formation of a seven-membered ring is observed.
In regard to the 1,4-derivatives, the behavior of the 1,4-diphenyl-
1,4-butanediyl biradical is very similar to that of its 1-aza
analogue; the predominating process is C2-C3 cleavage
(detected through the formation of styrene), although C1-C4
(or N1-C4) coupling to give the four-membered rings also takes
place to a significant extent. C4-aryl coupling is in both cases
a minor process. A good correlation is observed between the
feasible reactive channel. At this computational level, the process
(channel iv) appears to be barrierless. The favorable boat
arrangement of the six-membered TS4b accounts for its low
activation energy. On the other hand, C2-C3 bond cleavage
via TS6b (channel vi) also presents a very low barrier, 3.2 kcal/
mol. The ring-closure process via TS1b (channel i), with the
formation of azetidine 1b, presents an activation energy of 6.8
kcal/mol, somewhat higher than that calculated for the formation
of pyrrolidine 1a; the higher strain associated with closure of a
four-membered ring accounts for this difference. By contrast,
the disproportionation reactions ii and iii present large activation
energies. The four-membered cyclic arrangements required for
this intramolecular hydrogen abstraction reaction account for
the large energy of TS2b and TS3b. This is schematically shown
in Figure 5.
All the possible reactions shown in Scheme 3 are exothermic
(between -22 and -45 kcal/mol). Again, formation of the four-
membered azetidine 1b is 15.7 kcal/mol less exothermic than
formation of five-membered pyrrolidine 1a, in clear agreement
with the larger ring strain associated with the four-membered
ring.
(16) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334-338.
(17) Domingo, L. R.; Pe´rez-Prieto, J. Chem. Phys. Chem. 2006, 7, 614-
618.
J. Org. Chem, Vol. 71, No. 12, 2006 4443

Leo et al.
were carried out using the Berny analytical gradient optimization
method.25 The stationary points were characterized by frequency
calculations to verify that the TSs have one and only one imaginary
frequency. The intrinsic reaction coordinate26 path was traced to
check the energy profiles connecting each TS with the two
associated minima of the proposed mechanism by using the second-
order Gonza´lez-Schlegel integration method.27 The electronic
structures of stationary points were analyzed by the natural bond
orbital method.28 All calculations were carried out with the Gaussian
03 suite of programs.29
experimental results and the theoretical calculations at the
UB3LYP/6-31G* computational level.
Experimental Section
Chemicals. Compounds 1a,10b 1b,12 2a,10b and 2b18 (see struc-
tures in Chart 1) were prepared following the literature methods.
Isolation and purification were done by conventional column
chromatography on silica gel, using hexane/dichloromethane as
eluent. Isolation of the pure enantiomers of 1a and 1b was
performed by semipreparative HPLC equipped with a chiral column,
employing 2-propanol/hexane as eluent.
Acknowledgment. Financial support from the Spanish
Goverment (Grant No. CTQ2004-03811), the Generalitat Va-
lenciana (Grupos 03/82), and the Universidad Polite´cnica de
Valencia (Grant 20060286 and fellowship to E.A.L.) is gratefully
acknowledged.
Photoproducts 4a,19 4b,20 7,21 8,18 9,18 10,22 and 1122 were known
and their structures were confirmed by comparison of their
spectroscopic data with those reported in the literature. Aniline,
4-phenylbutanal, and styrene were identified by comparison with
authentic samples.
Supporting Information Available: The (U)B3LYP/6-31G*
computed total energies, S2 values, unique imaginary frequency
of the TSs, and Cartesian coordinates of the stationary involved in
the reactions of the 1,5- and 1,4-azabiradicals Ia and Ib (23 pages).
This material is available free of charge via the Internet at
http://pubs.acs.org.
General Irradiation Procedure. Solutions of 1 mg/mL of the
substrate in HPLC grade acetonitrile were irradiated at room
temperature through quartz, with a multilamp photoreactor equipped
with eight lamps emitting at 254 nm (monochromatic). The
1
photoreaction course was followed by means of GC/MS and H
NMR.
JO0601967
The photoproducts obtained upon irradiation of the different
substrates are given below; the product distributions are indicated
in parentheses.
Irradiation of 1a (4 h, 24% conversion): 4-phenylbutanal +
aniline (57%) and 4a (43%).
Irradiation of 1b (30 min, 30% conversion): styrene (93%) and
4b (7%).
Irradiation of 2b (2h, 55% conversion): 7 (25%), 8 (11%), 9
(6%), 10 (33%), and 11 (25%).
Computational Methods. DFT calculations were carried out
using the B3LYP23 exchange-correlation functionals, together with
the standard 6-31G* basis set.24 For all DFT calculations, the
unrestricted formalism (UB3LYP) was employed. Optimizations
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4444 J. Org. Chem., Vol. 71, No. 12, 2006