Stereoselectivity in the triplet decay of chiral benzophenone–naphthalene bichromophoric systems

Abstract

Chiral recognition in the intramolecular induced quenching of the methoxynaphthalene triplet by benzophenone has been observed by using diastereomeric bichromophores

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Chiral recognition is a crucial phenomenon in biochemical systems as well as in technological applications. It enables the rational design of pharmaceuticals, chiral sensors and molecular devices.¹ In asymmetric organic photochemistry, chiral recognition in the excited state is important to achieve enantioselectivity during photosensitization and quenching processes.² Our group has recently succeeded in proving the existence of enantioselective discrimination in the intramolecular quenching of benzoylthiophene-derived triplets by phenols and indoles.³ In view of the current interest on stereoselectivity in photophysical/photochemical processes we decided to look for a possible chiral discrimination in systems where triplet decay is controlled by induced quenching (IQ). This has been defined as a type of quenching different from energy or electron transfer and does not lead to any photochemical product;⁴ it is inherent to photoreactions via triplet exciplexes^4–9 They can compete with other events such as electron transfer (ET); actually, using benzophenone–anisole systems it has been demonstrated that the relationship between IQ rate constants and oxidation potentials follows Rehm–Weller behavior. This implies involvement of the same intermediate for IQ and ET processes.⁴

Bichromophoric compounds containing benzophenone and naphthalene units constitute classical textbook systems, that have been used to study singlet–singlet and triplet–triplet energy transfer processes.⁶ In this respect, Shizuka and co-workers have studied benzophenone–methoxynaphthalene bichromophores BP–(CH₂)₃–NPOMe. They suggested that deactivation of the methoxynaphthalene triplet, generated by intramolecular benzophenone photosensitization, occurs by interaction with the ground-state BP-moiety through triplet exciplexes with loose sandwich-like structures and weak charge transfer character.^7–10

This appeared to be an adequate model system in order to investigate the possible stereoselectivity in the process by introducing chirality in the bichromophores. To this end, enantiomerically pure compounds were obtained by condensation of (R)- and (S)-naproxol† [NPX, 2-(6-methoxy-2-naphthyl)propan-1-ol] with (S)-ketoprofen [KP, (2S)-2-(3-benzoylphenyl)propanoic acid] in the presence of dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine, using dry methylene chloride as solvent (Scheme 1).

Scheme 1 Processes involved in the photoexcitation-deactivation of KP-NPX bichromophores.

The UV spectra of the bichromophoric compounds were merely the sum of the spectra of the individual chromophores, indicating little electronic interaction between the chromophores in the ground state (Fig. 1).

Fig. 1 Absorption spectra of ketoprofen (A), naproxol (B) and (S,S)-KP-NPX (C). Inset: Magnification of the spectra above 340 nm.

All the processes involved in the photoexcitation–deactivation of the obtained KP-NPX bichromophores are summarized in Scheme 1. Fluorescence spectra were obtained at λ_exc = 318 nm for (S,R)- and (S,S)-KP-NPX (2.5 × 10⁻⁴ M) in argon-saturated acetonitrile solutions and compared to those of naproxen [2-(6-methoxy-2-naphthyl)propanoic acid] under the same conditions (Fig. 2). As expected, the shapes of the three emision spectra were identical due to the nonemissive nature of the benzophenone singlet state. However, the emission intensity was considerably lower for the bichromophoric compounds, although the concentrations were adjusted to match the same absorption by the methoxynaphthalene chromophore. Thus, in the bichromophoric compounds the naphthalene singlet state is quenched by the benzophenone group, due to singlet–singlet energy transfer.¹¹

Fig. 2 Fluorescence emission spectra of naproxen, (S,R)-KP-NPX and (S,S)-KP-NPX, in nitrogen-saturated acetonitrile at λ_exc = 318 nm. The intensities of the KP-NPX bichromophores have been multiplied by ten.

Laser excitation‡ at 355 nm of (S,R)- and (S,S)-KP-NPX (3.0 × 10⁻³ M) in N₂-saturated acetonitrile solutions led to the excited KP singlet state which undergoes fast intersystem crossing (isc) to the KP triplet. Intramolecular^4,7,10,11 triplet–triplet energy transfer from ³KP (E_T = 69 kcal mol⁻¹)¹² to the NPX moiety (E_T = 62 kcal mol⁻¹)⁹ results in the NPX triplet (λ_abs = 430 nm). This must occur within the laser pulse duration, as evidenced by the transient absorption spectrum that corresponds to the triplet naphthalene-like chromophore (Fig. 3). No absorption for triplet benzophenone was observed at 525 nm, even at short delays. The resulting triplets, KP-³NPX*, decay to the ground state; the triplet decay traces measured at 430 nm showed that the (R) and (S) NPX triplets were quenched differently by the (S)-KP moiety (Fig. 4). Thus, the 430 nm band decayed with first-order rate constants k_d of 8.5 × 10⁵ and 5.3 × 10⁵ s⁻¹ for (S,R)- and (S,S)-KP-NPX, respectively.¹³

Fig. 3 (A) Transient absorption spectrum recorded 20 ns after laser excitation (355 nm) of (S,S)-KP-NPX (3 × 10⁻³ M) in deaerated acetonitrile. (B) Transient absorption spectrum recorded 120 ns after laser excitation (355 nm) of (S,R)-KP-NPX (3 × 10⁻³ in deaerated acetonitrile.

Fig. 4 Triplet decay traces (λ_exc = 355 nm, λ_obs = 430 nm) of (S,R)-KP-NPX and (S,S)-KP-NPX in acetonitrile

The stereoselectivity, as shown by the ratio between the decay rate constants, was 1.6. The sensitivity to pair configuration is a strong evidence for the involvement of intermediate (KP-NPX)* exciplexes in the NPX deactivation (steps (4) and (5), Scheme 1). Furthermore, it is indicative of specific structural requirements in the formation of the sandwich-like intermediates involved in the induced quenching processes. Diastereomeric discrimination, though associated with charge transfer quenching (rather than exciplex formation) has been previously reported for 1,2,3,4-tetraphenyl-1,4-diketones.¹⁴

In summary, we have synthesized two new chiral bichromophoric diastereomers, which are good models to demonstrate the involvement of through-space methoxynaphthalene–benzophenone interactions in the decay of the NPX triplet. This process has been found to be stereoselective.

Acknowledgements

We thank Generalitat Valenciana and the Spanish Government (Projects GV01-272, BQU2001-2725, BQU2002-00377) for generous support of this work. S. E. S. is indebted to “Ramón y Cajal” program (MCyT, Spain) for financial support.

Notes and references

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7. T. Sekiguchi, M. Yamaji, H. Tatemitsu, Y. Sakata and H. Shizuka, Laser flash photolysis studies on intramolecular hydrogen atom transfer of [(hydroxynaphthyl)propyl]benzophenone and intramolecular proton-induced electron transfer of [(methoxynaphthyl)propyl]benzophenone via triplet exciplexes, J. Phys. Chem., 1993, 97, 7003–7010.
8. M. Yamaji, Y. Aihara, T. Itoh, S. Tobita and H. Shizuka, Thermochemical profiles on hydrogen atom transfer from triplet naphthol and proton-induced electron transfer from triplet methoxynaphthalene to benzophenone via triplet exciplexes studied by laser flash photolysis, J. Phys. Chem., 1994, 98, 7014–7021.
9. T. Tanaka, M. Yamaji and H. Shizuka, Solvent dependence of triplet energy transfer from triplet benzophenone to naphtols and methoxynaphthalenes, J. Chem. Soc., Faraday Trans, 1998, 94, 1179–1187.
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Footnotes

† Naproxol enantiomers were obtained from (R)-(+)- or (S)-(−)-naproxen by reduction with LiAlH₄ in tetrahydrofuran. ¹H and ¹³C NMR spectra were recorded in a 300 MHz spectrometer; chemical shifts (δ) are reported in ppm relative to TMS. The coupling constants (J) are in hertz (Hz).(S,R)-KP-NPX: ¹H NMR (300 MHz, CDCl₃): δ (ppm) 1.26 (3H, d, J = 7.1 Hz, CH₃ NPX), 1.45 (3H, d, J = 7.2 Hz, CH₃ KP), 3.15 (1H, m, CH NPX), 3.75 (1H, q, J = 7.2 Hz, CH KP), 3.85 (3H, s, OCH₃), 4.20 (1H, dd, J₁ = 10.9, J₂ = 7.1 Hz, CH₂ NPX), 4.30 (1H, dd, J₁ = 10.9, J₂ = 7.1 Hz, CH₂ NPX), 7.05 (2H, m, arom. CH), 7.22 (2H, m, arom. CH), 7.30–7.71 (8H, m, arom. CH), 7.72–7.75 (3H, m, arom. CH). ¹³C NMR (75 MHz, CDCl₃): δ 18.3 (CH₃), 18.6 (CH₃), 39.2 (CH NPX), 45.8 (CH KP), 55.7 (OCH₃), 70.1 (CH₂ NPX), 106.0 (arom. CH_. NPX), 119.2 (arom. CH NPX), 125.9 (arom. CH), 126.6 (arom. CH), 127.3 (arom. CH), 128.7 (arom. CH), 128.8 (arom. CH), 129.3 (arom. CH), 129.5 (arom. CH), 130.4 (arom. CH), 131.9 (arom. CH), 132.8 (arom. CH), 133.9 (arom. C), 137.9 (arom. C), 138.1 (arom. C), 138.4 (arom. C), 141.1 (arom. C), 157.8 (arom. C NPX), 174.3 (C=O ester), 196.8 (C=O ketone). IR (NaCl) ν/cm⁻¹: 1732 (C=O, ester).(S,S)-KP-NPX: ¹H NMR (300 MHz, CDCl₃): δ 1.29 (3H, d, J = 7.1 Hz, CH₃ NPX), 1.45 (3H, d, J = 7.2 Hz, CH₃ KP), 3.15 (1H, m, CH NPX), 3.74 (1H, q, J = 7.2 Hz, CH KP), 3.89 (3H, s, OCH₃), 4.25 (2H, d, J = 7.1 Hz, CH₂ NPX), 6.95 (2H, m, arom. CH), 7.10–7.60 (10H, m, arom CH), 7.70 (3H, m, arom. CH). ¹³C NMR (75 MHz, CDCl₃): δ 18.4 (CH₃), 18.6 (CH₃ ), 39.2 (CH NPX), 45.8 (CH KP), 55.7 (OCH₃), 70.2 (CH₂ NPX), 106.0 (arom. CH NPX), 119.2 (arom. CH NPX), 125.9 (arom. CH), 126.6 (arom. CH), 127.3 (arom. CH), 128.7 (arom. CH), 128.8 (arom. CH), 129.4 (arom. CH), 129.5 (arom. CH), 129.7 (arom. CH), 130.4 (arom. CH), 131.9 (arom. CH), 132.9 (arom. CH), 133.9 (arom. C), 137.9 (arom. C), 138.2 (arom. C), 138.5 (arom. C), 141.2 (arom. C), 157.8 (arom. C_. NPX), 174.3 (C=O ester), 196.8 (C=O ketone). IR (NaCl) ν/cm⁻¹: 1731 (C=O, ester).

‡ Laser Flash Photolysis experiments. Laser flash photolysis experiments were carried out by using the third harmonics (355 nm) of a pulsed Nd:YAG laser. The pulse duration was 10 ns and the energy of the laser beam was 10 mJ pulse⁻¹. A Lo255 Oriel xenon lamp was employed as the detecting light source. The laser flash photolysis apparatus consisted of the pulsed laser, the Xe lamp, a 77200 Oriel monochromator, an Oriel photomultiplier (PMT) system made up of 77348 side-on PMT tube, 70680 PMT housing and a 70705 PMT power supply. The oscilloscope was a TDS-640A Tektronix. The output signal was transferred to a personal computer for data analysis.

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