268
S. Breitenlechner, P. Selig, T. Bach
(+)-12 (2.5 equivalents) resulted in high ee values both at 25 °C
(d.r. = 63/37) and at 0 °C (d.r. = 87/13) for the predominant transdiastereoisomer trans-29 (80% ee and 96% ee). Changing the solvent
to trifluorotoluene at 0 °C increased the enantioselectivity to 99% ee
while the diastereomeric ratio remained unchanged (d.r. = 88/12). The
chiral complexing agent (+)-12 could be recovered in yields over 90%
in all cases. By reducing the amount of chiral complexing agent at 0 °C
to catalytic amounts, a chirality multiplication could be detected. With
0.1 equivalents of (+)-12 a chirality turnover could be achieved resulting
in an ee of 55%. The diastereomeric ratio dropped to an almost 1:1 mixture, the reaction mixture being heterogeneous throughout the course of
the reaction. We assume that the chiral complexing agent (+)-12 can dissolve the substrate and that the radical reaction proceeds under homogeneous conditions. This allows faster reaction rates and the substrates
can pass through more than one catalytic cycle until full conversion is
achieved.
The model in Scheme 11 explains the regioselectivity, enantioselectivity and diastereoselectivity of the reaction. In the radical cyclisation
step the endo radical 28 is formed exclusively due to the high stability of the resulting benzyl radical. The approach of the alkyl radical in
the complex 27·(+)-12 occurs from the sterically unhindered re face
whereas the attack of the radical from the si face is blocked by the
tetrahydronaphthalene shield. For the same reason the hydrogen abstraction step in the complex 28·(+)-12 takes place at the same face
to form product trans-29 predominantly with high enantioselectivity.
Introducing two geminal methyl groups into the butyl side chain
changed the regioselectivity of the reaction (Scheme 12). Without chiral
complexing agent the regioisomeric ratio 31/32 was 65/35, whereas in
the presence of template (+)-12 the exo-product 31 was the exclusive
product. The exo-regioselectivity can be explained by enhanced stereoelectronic factors, which favour the chair-type transition state of the
exo-cyclisation. The increase of regioselectivity in the presence of the
chiral complexing agent is not fully understood, but it is shown by models that the interaction between 1
-H of the alkyl chain of substrate 30
and the tetrahydronaphthalene of the chiral complexing agent (+)-12 is
higher in the transition state of the endo-cyclisation.
S. Breitenlechner, P. Selig, T. Bach
(+)-12 (2.5 equivalents) resulted in high ee values both at 25 °C
(d.r. = 63/37) and at 0 °C (d.r. = 87/13) for the predominant transdiastereoisomer trans-29 (80% ee and 96% ee). Changing the solvent
to trifluorotoluene at 0 °C increased the enantioselectivity to 99% ee
while the diastereomeric ratio remained unchanged (d.r. = 88/12). The
chiral complexing agent (+)-12 could be recovered in yields over 90%
in all cases. By reducing the amount of chiral complexing agent at 0 °C
to catalytic amounts, a chirality multiplication could be detected. With
0.1 equivalents of (+)-12 a chirality turnover could be achieved resulting
in an ee of 55%. The diastereomeric ratio dropped to an almost 1:1 mixture, the reaction mixture being heterogeneous throughout the course of
the reaction. We assume that the chiral complexing agent (+)-12 can dissolve the substrate and that the radical reaction proceeds under homogeneous conditions. This allows faster reaction rates and the substrates
can pass through more than one catalytic cycle until full conversion is
achieved.
The model in Scheme 11 explains the regioselectivity, enantioselectivity and diastereoselectivity of the reaction. In the radical cyclisation
step the endo radical 28 is formed exclusively due to the high stability of the resulting benzyl radical. The approach of the alkyl radical in
the complex 27·(+)-12 occurs from the sterically unhindered re face
whereas the attack of the radical from the si face is blocked by the
tetrahydronaphthalene shield. For the same reason the hydrogen abstraction step in the complex 28·(+)-12 takes place at the same face
to form product trans-29 predominantly with high enantioselectivity.
Introducing two geminal methyl groups into the butyl side chain
changed the regioselectivity of the reaction (Scheme 12). Without chiral
complexing agent the regioisomeric ratio 31/32 was 65/35, whereas in
the presence of template (+)-12 the exo-product 31 was the exclusive
product. The exo-regioselectivity can be explained by enhanced stereoelectronic factors, which favour the chair-type transition state of the
exo-cyclisation. The increase of regioselectivity in the presence of the
chiral complexing agent is not fully understood, but it is shown by models that the interaction between 1
-H of the alkyl chain of substrate 30
and the tetrahydronaphthalene of the chiral complexing agent (+)-12 is
higher in the transition state of the endo-cyclisation.