Diastereomeric differentiation in the quenching of excited states by hydrogen donors

Article abstract of DOI:10.1002/anie.200250442

Chiral dyads of (S)-ketoprofen and (S)- or (R)-tetrahydrofurfurylamine show diastereomeric differentiation in photoinduced hydrogen abstractions, which could be directly followed by time-resolved observation of the ketone triplet state. A unimolecular rat

Full text of DOI:10.1002/anie.200250442

Angewandte
Chemie
Photoinduced Hydrogen Abstraction
Diastereomeric Differentiation in the Quenching
of Excited States by Hydrogen Donors**
Uwe Pischel, Sergio Abad, Luis R. Domingo,
Francisco Boscµ, and Miguel A. Miranda*
Photoinduced hydrogen transfer and electron transfer to
excited states of carbonyl compounds are two of the most
intensively investigated fundamental processes in photo-
chemistry.[1–3] Numerous studies have been performed to
elucidate the mechanisms as well as to determine ways to
control these processes,and have involved variation of the
electronic nature of the excited state (n,p* versus p,p*)[4,5]
and its multiplicity,that is,singlet- versus triplet-state photo-
chemistry.[6,7] Electronic donor properties,such as bond
dissociation energies and ionization potentials,[1,4,7,8] struc-
tural features,namely,stereoelectronic and steric hindrance
effects,[9,10] and the influence of the chemical surrounding
(solvent polarity,hydrogen bonding) have also been inves-
tigated.[11–14]
However,relatively little is known about diastereomeric
differentiation in the intramolecular quenching of excited
states,which is basically related to the search for asymmetric
photoreactions,and is another phenomenon which could
control the kinetics of hydrogen- or electron-transfer pro-
cesses.[15–17] Recently,studies were performed on the intra-
molecular exciplex-mediated quenching of triplet states in
diastereomeric dyads consisting of 2-arylpropionic acid
derivatives and electron donors of biological importance,
[18,19]
namely,tyrosine and tryptophan.
Other studies focused
on the chiral control of intramolecular charge-transfer
quenching of ketone triplets in solution and in the solid
state.[20,21] Reports on related intermolecular quenching are
rather scarce and are also focused mainly on exciplex-
mediated processes.[22,23]
Although the possibility of conformational control of
photoinduced hydrogen abstractions in Norrish type II reac-
[*] Prof. Dr. M. A. Miranda, Dr. U. Pischel, Dipl.-Chem. S. Abad,
Dr. F. Boscµ
Instituto de Tecnología Química
Universidad PolitØcnica de Valencia, UPV-CSIC
Av. de los Naranjos s/n, 46022 Valencia (Spain)
Fax: (+34)96-3877-809
E-mail: mmiranda@qim.upv.es
Prof. Dr. L. R. Domingo
Departamento de Química Orgµnica
Facultad de Ciencias Químicas
Universidad de Valencia
Doctor Molliner 50, 46199 Burjassot, Valencia (Spain)
[**] Financial support by MCYT (Grant no. BQU2001-2725) is gratefully
acknowledged. U.P. thanks the Deutsche Forschungsgemeinschaft
for a research fellowship.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2003, 42, 2531 – 2534
DOI: 10.1002/anie.200250442
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2531

Communications
tions[24,25] or photoenol formation[26] has been reported,
diastereomeric differentiation of a hydrogen donor by an
excited chromophore remains unprecedented. Just recently
such an effect was observed in hydrogen abstractions in dyads
comprised of a chiral benzophenone derivative,namely,( S)-
ketoprofen (KP),and a chiral 1,4-cyclohexadiene. [27] Unfortu-
nately,the lifetime of the triplet state of ketoprofen in the
investigated dyads was too short for direct kinetic character-
ization. Thus,a hydrogen donor with lower interaction
efficiency,that is,a chiral tetrahydrofuran derivative,
seemed to be a promising choice to circumvent this problem.
The intermolecular rate constant for the triplet quenching of
benzophenone by this ether is known to be 30 times lower
than for 1,4-cyclohexadiene (9.6 ” 106 mꢀ1 sꢀ1 versus 2.9 ”
108 mꢀ1 sꢀ1) in benzene.[28] Furthermore,a higher selectivity
in the quenching reaction can be anticipated as a result of the
lower reactivity of tetrahydrofuran which might result in a
significant discrimination between both diastereomers (sim-
ilar to the reactivity-selectivity principle).
Ketoprofen is a known photosensitizer similar to benzo-
phenone which is photophysically well-characterized,[29] with
special emphasis devoted to its photobiological importance.[30]
Since benzophenone can be considered as the classical
carbonyl chromophore,our investigations regarding diaster-
eomeric differentiation during hydrogen-abstraction reac-
tions are expected to provide deeper insights into a photo-
chemical mechanism of general interest.
Figure 1. Transient decay for solutions of a) (S,S)-KP-THFFA and
b) (S,R)-KP-THFFA in acetonitrile (9.5”10ꢀ4 m) under nitrogen at
525 nm upon excitation at 355 nm. The inset shows the corresponding
transient spectrum of (S,S)-KP-THFFA 20–120 ns after the laser flash.
position of these bands and the ratio between their intensities
(A325/A530 ca. 1.6:1) lead to an unambiguous assignment of this
transient to the triplet–triplet absorption (the triplet state) of
the ketoprofen chromophore.[29–31] The ketyl radical of
ketoprofen has similar absorption maxima (330 and
540 nm),but with a much larger ratio of the intensities of
the two bands. The kinetics of the transient was measured at
lobs = 525 nm and shown to consist of a major fast component
and a minor slow component (lifetime ca. 3.4–3.8 ms). The
latter might be caused by the decay of biradicals formed as a
result of hydrogen abstraction. Based on the transient
spectrum,the major fast component can be ascribed to the
triplet decay,which is significantly different for the two
diastereomers: tT = 0.95 ms for (S,S)-KP-THFFA and 1.20 ms
for (S,R)-KP-THFFA. The corresponding decay traces are
shown in Figure 1. This result provides kinetic evidence for
diastereomeric differentiation in the photoinduced hydrogen-
transfer process. The triplet lifetime of ketoprofen itself under
the same experimental conditions is t0 = 1.32 ms. The intra-
molecular rate constant for hydrogen abstraction (kH) was
determined from the following relationship [Eq. (1)].
The dyads (S,S)-KP-THFFA and (S,R)-KP-THFFA were
synthesized from (S)-ketoprofen (KP) and (S)- or (R)-
tetrahydrofurfurylamine ((S)- or (R)-THFFA) by condensa-
O
Me
O
Me
O
O
H
H
HN
HN
H
O
H
O
(S,S)-KP-THFFA
(S,R)-KP-THFFA
kH ¼ 1=tTꢀ1=t0
ð1Þ
tion in the presence of 1-ethyl-3-(3-dimethylamino)propyl-
carbodiimide (EDC) in dichloromethane. Analysis of the
A unimolecular rate constant of kH = 3.0 ” 105 sꢀ1 is found
for the S,S diastereomer,while the S,R diastereomer reacts
four times slower (kH = 7.5 ” 104 sꢀ1).
1
products by H and 13C NMR spectroscopy confirmed their
identity. The UV/Vis absorption spectra of both isomers in
acetonitrile are characterized by a weak absorption at 338 nm,
which corresponds to the n,p* transition,and a much stronger
band at 254 nm,which is typical for the p,p* absorption.
These bands are similar to those obtained for the benzophe-
none chromophore.
Laser flash photolysis studies on the nanosecond time-
scale using the 355-nm output of a Nd:YAG laser (full width
of half maximum height: ca. 10 ns,10 mJpulse ꢀ1) were
performed to clarify the role of diastereomeric differentiation
in the primary step of the photoreduction of the carbonyl
function,namely,transfer of a hydrogen atom to the triplet-
excited chromophore. A transient with absorption maxima at
325 and 530 nm was formed immediately in both cases
(Figure 1,inset) upon excitation of nitrogen-bubbled solu-
tions of the diastereomers (9.5 ” 10ꢀ4 m) in acetonitrile. The
To rule out the possibility that the diastereomeric differ-
entiation found for the dyads simply reflects the result of
different conformational pre-organization of the diastereom-
ers,the intermolecular triplet quenching of ( S)-KP by the
acetamides of (S)- and (R)-THFFA was examined. Remark-
ably,true chiral recognition was actually observed in this
experiment. The respective bimolecular quenching rate con-
stants were 3.8 ” 107 and 2.0 ” 107 mꢀ1 sꢀ1,thus,the enantiose-
lectivity factor was 1.9. Although this value is smaller than
that found in the intramolecular case,as would be expected
from the higher degrees of freedom,it is still quite substantial
and deserves further investigation. This chiral recognition
could be associated with restricted approach geometries,
probably as
a
result of hydrogen-bonding interactions
2532
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 2531 – 2534

Angewandte
Chemie
between the carboxy group of (S)-KP and the NH group of
the acetamides of (S)- and (R)-THFFA.
NH
H
H
O
O
The ketyl radicals formed (biradicals in the case of an
intramolecular hydrogen transfer) remain difficult to assign in
the transient spectrum for the following reasons: 1) the ketyl
radical is generated only in a relatively small amount
(maximum 30% quenching effect for (S,S)-KP-THFFA) and
2) a significant amount of long-lived light-absorbing transi-
ents (LAT) is formed during irradiation of the dyads,as
evidenced by an increase in the absorbance at approximately
330 nm (Figure 2).[32] However,although LAT complicate the
H
CH3
HO
Scheme 1. Diastereomeric photoproducts of (S,S)-KP-THFAF.
In conclusion,kinetic evidence for diastereomeric differ-
entiation is presented for a classical textbook example of a
hydrogen-abstraction process. The concept is supported by
photoproduct studies and quantum-chemical calculations.
Received: October 25,2002
Revised: March 13,2003 [Z50442]
Keywords: diastereoselectivity · hydrogen transfer · ketones ·
.
laser chemistry · photochemistry
[1] J. C. Scaiano, J. Photochem. 1973, 2,81 – 118.
[2] S. G. Cohen,A. Parola,G. H. Parsons, Chem. Rev. 1973, 73,141 –
161.
[3] W. M. Nau, Ber. Bunsen-Ges. 1998, 102,476 – 485.
[4] P. J. Wagner,R. J. Truman,A. E. Puchalski,R. Wake,
J. Am.
Figure 2. Steady-state irradiation of a solution of (S,R)-KP-THFFA in
nitrogen-bubbled acetonitrile at lexc =254 nm. The UV/Vis spectra
were taken in time intervals of 10 s. The inset shows the respective
plots for the decrease of the absorbance at 254 nm for a) (S,S)-KP-
THFFA and b) (S,R)-KP-THFFA.
Chem. Soc. 1986, 108,7727 – 7738.
[5] W. J. Leigh,E. C. Lathioor,M. J. S. Pierre, J. Am. Chem. Soc.
1996, 118,12339 – 12348.
[6] W. M. Nau,F. L. Cozens,J. C. Scaiano, J. Am. Chem. Soc. 1996,
118,2275 – 2282.
[7] U. Pischel,W. M. Nau, J. Am. Chem. Soc. 2001, 123,9727 – 9737.
[8] J. B. Guttenplan,S. G. Cohen, J. Am. Chem. Soc. 1972, 94,4040 –
4042.
analysis of the transient spectra,they provide clear-cut
evidence for the hydrogen-transfer process.
[9] D. Griller,J. A. Howard,P. R. Marriott,J. C. Scaiano,
J. Am.
The influence of stereochemistry on the decomposition of
the dyads under steady-state irradiation was tested in an
additional experiment. The decay of the band at 254 nm in
nitrogen-saturated solutions was followed during the irradi-
ation time (Figure 2). Significant differences were noted
between the two diastereomers,similar to the situation for the
analogous ketoprofen–cyclohexadiene dyad,[27] with (S,R)-
KP-THFFA being more photostable than the S,S diaster-
eomer. Logarithmic plots of absorbance versus irradiation
time yielded straight lines (Figure 2,inset),whose slopes
point to a difference factor of 2. Again,similar to the kinetic
observation of the triplet,the S,S compound reacts more
efficiently,although with a somewhat lower differentiation.
Finally,isolation of the major photoproducts was accom-
plished by means of preparative HPLC. The NMR data (see
Supporting Information) confirm the unambiguous formation
of biradical recombination products,as reported for other
benzophenone–hydrogen-donor dyads.[27,33] Hydrogen is sur-
prisingly not abstracted from the more highly substituted
OCHR group,but from the OCH 2 group. Molecular modeling
studies (ab initio B3LYP6-31G* DFTand semiempirical AM1
calculations; see Supporting Information) on the transition
states for both pathways revealed a higher activation energy
(by 1.8 kcalmolꢀ1) for hydrogen abstraction from the methine
group,presumably as a result of a higher ring strain in the
resulting cyclophane-like photoproduct (Scheme 1).
Chem. Soc. 1981, 103,619 – 623.
[10] M. von Raumer,P. Suppan,E. Haselbach, Helv. Chim. Acta
1997, 80,719 – 724.
[11] P. J. Wagner,A. E. Kemppainen, J. Am. Chem. Soc. 1969, 91,
3085 – 3087.
[12] A. A. Gorman,C. T. Parekh,M. A. J. Rodgers,P. G. Smith,
Photochem. 1978, 9,11 – 17.
[13] J. D. Simon,K. S. Peters, J. Am. Chem. Soc. 1982, 104,6542 –
6547.
[14] W. M. Nau,U. Pischel, Angew. Chem. 1999, 111,3126 – 3129;
Angew. Chem. Int. Ed. 1999, 38,2885 – 2888.
[15] H. Rau, Chem. Rev. 1983, 83,535 – 547.
[16] Y. Inoue, Chem. Rev. 1992, 92,741 – 770.
[17] A. G. Griesbeck,U. J. Meierhenrich, Angew. Chem. 2002, 114,
3279 – 3286; Angew. Chem. Int. Ed. 2002, 41,3147 – 3154.
[18] M. A. Miranda,A. Lahoz,R. Martꢀnez-Mꢁnez,F. Boscꢁ,J. V.
Castell,J. Pꢂrez-Prieto, J. Am. Chem. Soc. 1999, 121,11569 –
11570.
[19] M. A. Miranda,A. Lahoz,F. Boscꢁ,M. R. Metni,F. B. Abde-
louahab,J. V. Castell,J. Pꢂrez-Prieto, Chem. Commun. 2000,
2257 – 2258.
[20] R. Boch,C. Bohne,J. C. Scaiano, J. Org. Chem. 1996, 61,1423 –
1428.
[21] J. N. Moorthy,S. L. Monahan,R. B. Sunoj,J. Chandrasekhar,C.
Bohne, J. Am. Chem. Soc. 1999, 121,3093 – 3103.
[22] T. Yorozu,K. Hayashi,M. Irie, J. Am. Chem. Soc. 1981, 103,
5480 – 5484.
[23] T. Nishiyama,K. Mizuno,Y. Otsuji,H. Inoue, Chem. Lett. 1994,
2227 – 2228.
J.
Angew. Chem. Int. Ed. 2003, 42, 2531 – 2534
www.angewandte.org
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2533

Communications
[24] J. C. Dalton,K. Dawes,N. J. Turro,D. S. Weiss,J. A. Barltrop,
J. D. Coyle, J. Am. Chem. Soc. 1971, 93,7213 – 7221.
[25] F. D. Lewis,R. W. Johnson, J. Am. Chem. Soc. 1972, 94,8914 –
8916.
[26] J. C. Netto-Ferreira,J. C. Scaiano, J. Am. Chem. Soc. 1991, 113,
5800 – 5803.
[27] M. A. Miranda,L. A. Martꢀnez,A. Samadi,F. Boscꢁ,I. M.
Morera, Chem. Commun. 2002,280 – 281.
[28] W. Adam,J. N. Moorthy,W. M. Nau,J. C. Scaiano, J. Org. Chem.
1997, 62,8082 – 8090.
[29] L. J. Martꢀnez,J. C. Scaiano, J. Am. Chem. Soc. 1997, 119,
11066 – 11070.
[30] F. Boscꢁ,M. L. Marin,M. A. Miranda, Photochem. Photobiol.
2001, 74,637 – 655.
[31] R. V. Bensasson,J.-C. Gramain, J. Chem. Soc. Faraday Trans. 1
1980, 76,1801 – 1810.
[32] N. Filipescu,F. L. Minn, J. Am. Chem. Soc. 1968, 90,1544 – 1547.
[33] R. Breslow,P. Kalicky, J. Am. Chem. Soc. 1971, 93,3540 – 3541.
2534
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 2531 – 2534