Photochemical Deracemization of Primary Allene Amides by Triplet Energy Transfer: A Combined Synthetic and Theoretical Study

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 (Ka) 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.