For molecules with a singlet ground state, the population of triplet states is mainly possible (a) by direct excitation and subsequent intersystem crossing or (b) by energy transfer from an appropriate sensitizer. The latter scenario enables a catalytic photochemical reaction in which the sensitizer adopts the role of a catalyst undergoing several cycles of photon absorption and subsequent energy transfer to the substrate. If the product molecule of a triplet-sensitized process is chiral, this process can proceed enantioselectively upon judicious choice of a chiral triplet sensitizer. An enantioselective reaction can also occur in a dual catalytic approach in which, apart from an achiral sensitizer, a second chiral catalyst activates the substrate toward sensitization. Although the idea of enantioselective photochemical reactions via triplet intermediates has been pursued for more than 50 years, notable selectivities exceeding 90% enantiomeric excess (ee) have only been realized in the past decade. This review attempts to provide a comprehensive survey on the various photochemical reactions which were rendered enantioselective by triplet sensitization.
The photochemical deracemization of 2,4-disubstituted 2,3-butadienamides (allene amides) was investigated both experimentally and theoretically. The reaction was catalyzed by a thioxanthone which is covalently linked to a chiral 1,5,7-trimethyl-3-azabicyclo[3.3.1]nonan-2-one skeleton providing a U-shaped arrangement of the sensitizing unit relative to a potential hydrogen-bonding site. Upon irradiation at λ = 420 nm in the presence of the sensitizer (2.5 mol %), the amides reached at −10 °C a photostationary state in which one enantiomer prevailed. The enantioenriched allene amides (70–93% ee) were isolated in 74% to quantitative yield (19 examples). Based on luminescence data and DFT calculations, energy transfer from the thioxanthone to the allene amides is thermodynamically feasible, and the achiral triplet allene intermediate was structurally characterized. Hydrogen bonding of the amide enantiomers to the sensitizer was monitored by NMR titration. The experimental association constants (K a) were similar (59.8 vs 25.7 L·mol–1). DFT calculations, however, revealed a significant difference in the binding properties of the two enantiomers. The major product enantiomer exhibits a noncovalent dispersion interaction of its arylmethyl group to the external benzene ring of the thioxanthone, thus moving away the allene from the carbonyl chromophore. The minor enantiomer displays a CH−π interaction of the hydrogen atom at the terminal allene carbon atom to the same benzene ring, thus forcing the allene into close proximity to the chromophore. The binding behavior explains the observed enantioselectivity which, as corroborated by additional calculations, is due to a rapid triplet energy transfer within the substrate-catalyst complex of the minor enantiomer.
A photochemical deracemization of 5-substituted 3-phenylimidazolidine-2,4-diones (hydantoins) is reported (27 examples, 69%-quant., 80–99% ee). The reaction is catalyzed by a chiral diarylketone which displays a two-point hydrogen bonding site. Mechanistic evidence (DFT calculations, radical clock experiments, H/D labeling) suggests the reaction to occur by selective hydrogen atom transfer (HAT). Upon hydrogen binding, one substrate enantiomer displays the hydrogen atom at the stereogenic center to the photoexcited catalyst allowing for a HAT from the substrate and eventually for its conversion into the product enantiomer. The product enantiomer is not processed by the catalyst and is thus enriched in the photostationary state.
3‐Substituted quinoxalin‐2(1H)‐ones and various aryl‐substituted or tethered olefins underwent an enantioselective, inter‐ or intramolecular aza Paternò–Büchi reaction upon irradiation at λ=420 nm in the presence of a chiral sensitizer (10 mol %). For the intermolecular reaction with 1‐arylethenes as olefin components, the scope of the reaction was studied (14 examples, 50–99 % yield, 86–98 % ee). The absolute and relative configuration of the products were elucidated by single‐crystal X‐ray crystallography. The reaction is suggested to occur by triplet energy transfer in a hydrogen‐bonded 1:1 complex between the imine substrate and the catalyst. The intramolecular cycloaddition, consecutive reactions of the product azetidines, and an alternative reaction mode of quinoxalinones were investigated in preliminary experiments.
Upon irradiation in the presence of a chiral benzophenone catalyst (5 mol %), a racemic mixture of a given chiral imidazolidine-2,4-dione (hydantoin) can be converted almost quantitatively into the same compound with high enantiomeric excess (80−99% ee). The mechanism of this photochemical deracemization reaction was elucidated by a suite of mechanistic experiments. It was corroborated by nuclear magnetic resonance titration that the catalyst binds the two enantiomers by two-point hydrogen bonding. In one of the diastereomeric complexes, the hydrogen atom at the stereogenic carbon atom is ideally positioned for hydrogen atom transfer (HAT) to the photoexcited benzophenone. Detection of the protonated ketyl radical by transient absorption revealed hydrogen abstraction to occur from only one but not from the other hydantoin enantiomer. Quantum chemical calculations allowed us to visualize the HAT within this complex and, more importantly, showed that the back HAT does not occur to the carbon atom of the hydantoin radical but to its oxygen atom. The achiral enol formed in this process could be directly monitored by its characteristic transient absorption signal at λ ≅ 330 nm. Subsequent tautomerization leads to both hydantoin enantiomers, but only one of them returns to the catalytic cycle, thus leading to an enrichment of the other enantiomer. The data are fully consistent with deuterium labeling experiments and deliver a detailed picture of a synthetically useful photochemical deracemization reaction.
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