260
S. Breitenlechner, P. Selig, T. Bach
2
Stoichiometric Template-Based Enantioselectivity
The diastereoselective reaction using aldehyde 7 clearly showed that the
lactam motif was well capable of sterically fixing a second, prochiral
lactam in a defined fashion closely to the nearby benzaldehyde moiety. Replacing this photochemically active backbone of 7 by a photochemically inactive, yet bulky shield should enable the complexation of
a prochiral lactam substrate in a chemically unreactive though sterically
well-defined chiral environment, and lead to the efficient face differentiation between the two chiral planes of the substrate by simple sterical
shielding. In other words, such a complexing agent could reasonably be
seen as a non-covalently attached chiral auxiliary binding the substrate
in a sterically defined fashion by hydrogen bonds.
2.1
Properties and Synthesis of the Template
The synthesis of the as yet most successful, photochemically inactive
template is shown in Scheme 4. Starting from the known precursor
10 (Stack et al. 1992) derived from Kemp’s triacid, the introduction
of a bulky, photochemically unreactive shield into the backbone was
achieved by condensation of the acid chloride with a suited aminoalcohol to give the oxazole 11. Selective reduction of imide 11 using NaBH 4
and Et 3 SiH gave the corresponding lactam rac-12 as a racemic mixture
of enantiomers. These could be easily separated after conversion to their
N-menthyloxycarbonyl derivatives by simple flash-chromatography on
silica gel. N-defunctionalisation with trifluoroacetic acid finally regenerated both enantiomers of (+)-12 and (–)-12 in pure form (Bach et al.
2001b).
Complexing agents (+)-12 and (–)-12 proved to be excellently suited
for the purpose of enantioselective photochemical reactions in solution.
As expected from our experience with compound 7, the lactam motif
enables a strong and sterically defined complexation of other substrate
amides and lactams. In addition, the tetrahydronaphthalene shield in the
backbone is bulky enough to provide an efficient shielding of one enantiotopic face of the substrate while being photochemically unreactive at
wavelengths >300 nm and not interfering with the hydrogen bonding
of the substrate. Similar templates with a smaller, bicyclic shield or an
S. Breitenlechner, P. Selig, T. Bach
2
Stoichiometric Template-Based Enantioselectivity
The diastereoselective reaction using aldehyde 7 clearly showed that the
lactam motif was well capable of sterically fixing a second, prochiral
lactam in a defined fashion closely to the nearby benzaldehyde moiety. Replacing this photochemically active backbone of 7 by a photochemically inactive, yet bulky shield should enable the complexation of
a prochiral lactam substrate in a chemically unreactive though sterically
well-defined chiral environment, and lead to the efficient face differentiation between the two chiral planes of the substrate by simple sterical
shielding. In other words, such a complexing agent could reasonably be
seen as a non-covalently attached chiral auxiliary binding the substrate
in a sterically defined fashion by hydrogen bonds.
2.1
Properties and Synthesis of the Template
The synthesis of the as yet most successful, photochemically inactive
template is shown in Scheme 4. Starting from the known precursor
10 (Stack et al. 1992) derived from Kemp’s triacid, the introduction
of a bulky, photochemically unreactive shield into the backbone was
achieved by condensation of the acid chloride with a suited aminoalcohol to give the oxazole 11. Selective reduction of imide 11 using NaBH 4
and Et 3 SiH gave the corresponding lactam rac-12 as a racemic mixture
of enantiomers. These could be easily separated after conversion to their
N-menthyloxycarbonyl derivatives by simple flash-chromatography on
silica gel. N-defunctionalisation with trifluoroacetic acid finally regenerated both enantiomers of (+)-12 and (–)-12 in pure form (Bach et al.
2001b).
Complexing agents (+)-12 and (–)-12 proved to be excellently suited
for the purpose of enantioselective photochemical reactions in solution.
As expected from our experience with compound 7, the lactam motif
enables a strong and sterically defined complexation of other substrate
amides and lactams. In addition, the tetrahydronaphthalene shield in the
backbone is bulky enough to provide an efficient shielding of one enantiotopic face of the substrate while being photochemically unreactive at
wavelengths >300 nm and not interfering with the hydrogen bonding
of the substrate. Similar templates with a smaller, bicyclic shield or an