Electronic effects of ring substituents on triplet benzylic biradicals

Article abstract of DOI:10.1021/ol0528383

UV irradiation of α-(o-alkylphenyl)acetophenones with a methoxy or cyano substituent para to the o-alkyl group of the α-aryl ring has revealed that a methoxy group slightly increases the stereoselectivity but not the quantum yield of indanol formation, whereas a cyano group greatly lowers both diastereoselectivity and quantum efficiency, confirming the likelihood that hydrogen-bonding of the hydroxy group to the α-phenyl ring plays an important role in the cyclization of the photogenerated triplet 1,5-biradical intermediates.

Full text of DOI:10.1021/ol0528383

ORGANIC
LETTERS
2006
Vol. 8, No. 4
645-647
Electronic Effects of Ring Substituents
on Triplet Benzylic Biradicals
Peter J. Wagner* and Lingling Wang
Department pf Chemistry, Michigan State UniVersity, East Lansing, Michigan 48864
wagnerp@mail.msu.edu
Received November 23, 2005
ABSTRACT
UV irradiation of
r-(o-alkylphenyl)acetophenones with a methoxy or cyano substituent para to the o-alkyl group of the r-aryl ring has revealed
that a methoxy group slightly increases the stereoselectivity but not the quantum yield of indanol formation, whereas a cyano group greatly
lowers both diastereoselectivity and quantum efficiency, confirming the likelihood that hydrogen-bonding of the hydroxy group to the
ring plays an important role in the cyclization of the photogenerated triplet 1,5-biradical intermediates.
r-phenyl
When we first began studies of δ-hydrogen abstraction by
excited ketones,1 we were surprised to find a quantum yield
of 100% for indanol formation from R-(o-tolyl)acetophenone,
since quantum yields for product formation in photoreactions
that proceed via a biradical intermediate often are quite low
because of competing reversion of the biradical to ground-
state reactant via intramolecular radical-radical reactions.
In the case of the hydroxyl-substituted biradicals formed via
hydrogen abstraction by a carbonyl, an internal dispropor-
tionation reaction occurs in which the remote benzyl radical
site abstracts a hydrogen atom from the hydroxyl-substituted
radical site, forming the original ketone (Scheme 1) and thus
phenyl groups trans, but in methanol only a 2:1 trans/cis ratio
of isomers.2 Computational study of the various minimum
energy 1,5-biradical conformations (see the Supporting
Information) indicated that the conformer that can most easily
rotate to form the major product is significantly lower in
energy than the conformer that is more likely to rotate into
the minor product (see Scheme 2). This energy difference
Scheme 2
Scheme 1
minimizing formation of distinct photoproducts.
A later study revealed remarkable diastereoselectivity in
the photocyclization of R-(o-ethylphenyl)acetophenone: in
hydrocarbon solvents a 95% preference for formation of the
3-methyl-2-phenyl-2-indanol isomer with the methyl and
appeared to be due to hydrogen bonding of the biradical OH
group to the R-phenyl ring, since rotation of the C-OH bond
(2) Wagner, P. J.; Meador, M. A.; Zhou, B.; Park, B.-S. J. Am. Chem.
Soc. 1991, 113, 9630.
(1) Meador, M. A.; Wagner, P. J. J. Am. Chem. Soc. 1983, 105, 4484.
10.1021/ol0528383 CCC: $33.50
© 2006 American Chemical Society
Published on Web 01/14/2006

such that the O-H bond points away from the R-phenyl ring
raises the conformer’s energy close to that of the conformer
that can form the cis indanol. Thus, the internal hydrogen
bonding could be the source of the high stereoselectivity,
whereas H-bonding to solvent alters selectivity. To test this
notion further, we decided to study some R-(o-ethylphenyl)-
and R-(o-tolyl)acetophenones with conjugating substituents
on the R-aryl groups. We presumed that these substituents
would alter the Lewis basicity of the R-aryl rings and thus,
by altering the strength of any hydrogen bonding, also alter
biradical behavior and product ratios.
to undergo more reversion to reactant than cyclization to
indanol. The methoxy group does not enhance quantum
yields even though it should enhance benzyl radical basicity;
a different electronic effect on biradical behavior may well
be involved (see below).
To determine the stereoselectivity of cyclization, com-
pounds 2-om and 2-cn, 0.1 M in benzene-d6, were irradiated
at 300-360 nm and different temperatures in sealed,
deaerated NMR tubes. The only products from each ketone
were two isomeric 2-indanols, easy to distinguish because
of the 0.44 ppm difference in the chemical shifts of their
methyl groups. Preparative-scale irradiation at higher con-
centrations followed by column chromatography provided
isolation and identification of the two isomers.
Table 2 lists the variations in isomeric indanol ratios as a
Table 2. Indanol Isomer Ratios from 2-cn and 2-om
Ring-substituted versions of R-tolyl- and R-(o-ethylphen-
yl)acetophenone, 1 and 2, were synthesized by Pd(II)-
catalyzed coupling of para-substituted o-bromoalkylbenzenes
with acetophenone.3 Details of the syntheses of both of the
substituted 2-bromoalkylbenzenes and the reactant ketones
are included in the Supporting Information.
% cis
2-om
% trans
trans/cis
ratio
T, °C
2-cn
2-cn
2-om
2-cn
2-om
0
25
45
75
9.9
10.4
11.9
14.1
4.5
5.5
5.9
6.0
89.3
89.2
87.6
85.6
95.5
94.0
93.7
93.4
9.0
8.6
7.4
6.1
21.
17.2
15.8
15.6
The four ring-substituted R-aryl ketones, 0.1 M in benzene-
d6 solutions containing varying amounts (or none) of a diene
quencher, were irradiated at 313 nm in parallel with an
actinometer. Measurements of product concentrations pro-
vided the quantum yield and triplet reactivity data in Table
1. The slopes of linear Stern-Volmer plots of quantum yields
function of temperature and para-substituent X. Figure 1
contains Arrhenius plots of the trans/cis indanol ratios from
Table 1. Kinetics of Photocyclization
ketone
Φcyc
kqτ, M-1
kH, 108 s-1
1a
1-om
1-cn
2a
2-om
2-cn
1.0
31.0
14.9
53.0
5.4
2.5
14.5
1.6
4.0
0.1
10.8
23.6
4.1
0.98
0.34
0.64
0.61
0.29
a References 2 and 5.
Figure 1. Temperature effects on trans/cis indanol ratios for 2 (4),
2-om (O), and 2-cn (0).
as a function of quencher concentrations provided the kqτ
values from which kH and 1/τ values were derived, with kq
known to be 5 × 109 M-1 s-1.
2-cn, 2-om, and 2, the latter from an earlier paper.5 Table 3
lists the enthalpic and A-factor differences between cis and
trans cyclization of the biradicals formed from the three
The two substituents had the expected effect on reaction
kinetics, the methoxy group speeding up δ-hydrogen abstrac-
tion (kH) and the cyano group slowing it down, neither by
large amounts. This behavior is in accord with the known
charge-transfer nature of benzylic hydrogen abstraction by
triplet ketones.4 Quantum yields depend on biradical behav-
ior, and the large negative cyano effect suggests little OH
hydrogen bonding to the R-phenyl ring, allowing the biradical
Table 3. Activation Parameters for Cyclization
a
ketone
∆∆E* (c-t) kcal/mol
Atrans/Acis
2
2-mo
2-cn
0.67
0.74
1.00
4.5
5.5
1.5
(3) Palucki, M.; Buchwald, S. L.J. Am. Chem. Soc. 1997, 119, 11108.
Culkin, D. A., Hartwig, J. F. Acc. Chem. Res. 2003, 35, 234.
(4) Wagner, P. J.; Truman, R. J.; Puchalski, A. E.; Wake, R. J. Am.
Chem. Soc., 1986, 108, 7727.
a Arrhenius preexponential factors: exp(∆Sq/R).
646
Org. Lett., Vol. 8, No. 4, 2006

ketones. The two substituents clearly have dramatically
opposite effects on stereoselectivity.
by minimizing OH H-bonding. The differences among the
Scheme 2 displays the computed minimum energy biradi-
cal conformers involved in this cyclization process, with BRt
able to undergo least motion radical coupling (rotations of
bonds a and b) easier than the higher energy BRc (rotation
of bond c also), as mentioned above. Our original study of
temperature effects on the diastereoselectivity of photocy-
clization by 25 revealed that the large trans/cis indanol ratio
is due to both enthalpic and entropic factors, which clearly
affect both 2-om and 2-cn as well. The fact that there are
both enthalpic and nonenthalpic cis/trans preferences is in
accord with there being at least two separate biradical
conformers that cyclize to diastereomers. We have suggested5
that the measured enthalpic differences most likely reflect
the thermodynamically controlled proportions of separate
biradical conformers as well as varied activation energies
for the bond rotations that allow cyclization of different
conformers to different isomers. The nonenthalpic differences
probably reflect different alignments of the two singly
occupied p orbitals in each of the biradical conformers that
presumably cyclize to different isomers. In the world of
ground states, intramolecular cyclization has a relatively fixed
negative activation entropy whether stereoisomers are formed
and regardless of reacting conformers with differing geom-
etries. But in the world of triplet biradicals, the nonenthalpic
spin-orbit induced conversion to singlet multiplicity required
for product formation does depend on biradical geometry.6
With two biradical conformers, rates of direct intersystem
crossing (isc) before cyclization would differ because of
different distances between the two radical sites and different
orientations of the singly occupied p orbitals. Rates of isc
coupled with radical-radical coupling would differ as the
two radical sites approach each other and as the p orbitals
realign for σ-bond formation.
Ketone 2 displays a 670 cal enthalpic preference and a
nearly 5:1 (28 eu) nonenthalpic (or entropic) preference for
trans cyclization.3 Both the enthalpic and nonenthalpic trans
preferences are slightly greater for 2-om, perhaps indicating
a small electron-donating effect by the methoxy group. The
cyano group in 2-cn has a larger electronic effect; the
enthalpic trans preference is 50% greater than it is in 2,
whereas the nonenthalpic trans preference is only 1/3 that
for 2. The enthalpic increase may reflect diminution of OH
H-bonding, which removes one impediment to the bond
rotation required for cyclization, while the nonenthalpic
decrease is likely due to partial electron withdrawal from
the benzylic carbon.
There are two ways that the para substituents’ electronic
effects can affect biradical behavior. The simpler one is that
the electron donor enhances the phenyl ring’s basicity, thus
favoring a large BRt/BRc ratio via OH H-bonding as
suggested above, while the strong electron withdrawer
reduces the ring’s basicity and thus lowers the BRt/BRc ratio
three reactants in quantum yields and stereoselectivity of
cyclization could well be due largely to this effect. However,
the substituents being para to the benzylic radical site adds
a factor to biradical behavior that has not received much
attention, namely the ionic effect of π conjugation. As Arnold
and co-workers have reported,7 both p-methoxy- and p-
cyanobenzyl radicals have delocalized spin, with the benzyl
carbon becoming either somewhat negative or positive,
respectively. With the spin density at the benzyl site of the
biradical lowered, spin-orbit coupling could be very dif-
ferent from that for a simple 1,5-pentanediyl biradical. This
could well explain why the nonenthalpic factor for 2-cn
displays the lowest trans/cis cyclization preference. Likewise,
the lack of any increase in indanol quantum yield that could
have been afforded by the methoxy group on 2-om may be
caused by the partial negative charge on each radical site
discouraging radical-radical coupling.
A possible cause of the low diastereoselectivity for 2-cn
and the low quantum yields for 1-cn and 2-cn may be the π
conjugation-induced opposite partial charges on the two
benzylic carbons of the biradical intermediates. Salem’s
original analysis of biradical multiplicity and spin-orbit
coupling6 suggested that opposite charges at the two radical
sites would favor primarily singlet multiplicity and thus
enhance the rate of cyclization by BRc and possibly enhance
the rate of disproportionation by the no-longer hydrogen-
bonding BRt. The low quantum yields may also result from
kH values being so low that significant CT quenching of the
triplet ketones by solvent benzene8 can compete and lower
the overall triplet lifetime, whereas triplet δ-hydrogen
abstraction by keones 1 and 2 is some three orders of
magitude faster than solvent quenching. In any event, these
results tend to verify our belief that internal hydrogen
bonding promotes both high quantum yields and diastereo-
selectivity in the photocyclization of R-aryl ketones via
δ-hydrogen abstraction from ortho substituents on the R-aryl
ring.
Finally, the significant effects that the two π-conjugating
substituents had on 1,5-biradical intermediates suggest that
additional studies, both experimental and computational, be
performed on how such substituents can affect triplet
biradical behavior.
Acknowledgment. This work was partially supported by
NSF Grant No. CHE98-11570.
Supporting Information Available: Synthesis of reactant
ketones, photochemical procedures, identification of indanol
photoproducts, and computational methods. This material is
available free of charge via the Internet at http://pubs.acs.org.
(5) Wagner, P. J.; Zand, A.; Park, B.-S. J. Am. Chem. Soc. 1996, 118,
12856.
(6) Salem, L. and Rowland, C., Angew. Chem., Int. Ed. Engl. 1972, 11,
92; Michl, J. J. Am. Chem. Soc. 1996, 118, 3568.
(7) Nicholas, A.; de martin, P.; Arnold, D. R. Can. J. Chem. 1986, 64,
270.
(8) Wagner, P. J., Leavitt, R. A. J. Am. Chem. Soc. 1973, 95, 3669.
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