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.
Spirocyclic oxindoles undergo an enantioselective oxygenation reaction (nine examples; e.r. up to 97:3) upon catalysis by a chiral ruthenium porphyrin complex (1 mol %). The catalyst exhibits a lactam ring, which is responsible for substrate association through hydrogen bonds, and an active ruthenium center, which is in a defined spatial relationship to the oxygenation substrate. DFT calculations illustrate the perfect alignment of the active site with the reactive C-H bond and suggest--in line with the kinetic isotope effect--an oxygen rebound mechanism for the reaction.
A chiral manganese porphyrin complex with a two-point hydrogen-bonding site was prepared and probed in catalytic C-H oxygenation reactions of 3,4-dihydroquinolones. The desired oxygenation occurred with perfect site selectivity at the C4 methylene group and with high enantioselectivity in favor of the respective 4S-configured secondary alcohols (12 examples, 29-97 % conversion, 19-68 % yield, 87-99 % ee). Mechanistic studies support the hypothesis that the reaction proceeds through a rate- and selectivity-determining attack of the reactive manganese oxo complex at the hydrogen-bound substrate and an oxygen transfer by a rebound mechanism.
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.
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