Enantioselective Photochemistry
273
cient complexation and due to a lack of enantioface differentiation. The
search for a catalyst/substrate combination which was suited to demonstrate the general principle of enantioselective photochemical reaction
eventually led to the development of a catalytic photoinduced electron
transfer (PET) reaction, which is discussed in the next section.
4.2
PET-Catalysed Reaction
Benzophenones have been described as useful sensitisers for PET catalysed conjugate addition reactions of α-amino alkyl radicals to enones
(Bertrand et al. 2000). We tried to modify this reaction and synthesised the pyrrolidinylethyl-substituted quinolone 35 from the known
bromide (Bauer et al. 2005). Upon electron transfer from the pyrrolidine
to a given acceptor, a radical cyclisation occurs (Scheme 15), which
after electron and proton transfer generates a pyrrolizidine. We found
4,4
-dimethoxybenzophenone to be a suitable catalyst for this reaction.
Remarkably, the reaction proceeded with excellent simple diastereoselectivity and a single diastereoisomeric product rac-36 was obtained.
With 10 mol% of the catalyst, a chemical yield of 71% was achieved.
In order to install a benzophenone at the bicyclic scaffold we relied
on the previously used oxazole linkage. To this end, the known aminohydroxybenzophenone 37 (Aichaoui et al. 1990) was coupled to the free
acid rac-38, which is available from Kemp’s triacid in five synthetic
steps. Remarkably, an O-acylation instead of the expected N-acylation
was observed resulting in ester rac-39. As a consequence, oxazole formation was less straightforward but could eventually be achieved under
more forceful conditions. The reaction sequence led to the racemic benzophenone rac-40, i.e. to a 1/1 mixture of the enantiomers (+)-40 and
(–)-40, which was separated by chiral HPLC (Daicel Chiralpak AD).
It is important to mention that a separation of enantiomers at an earlier stage is not sensible. While carboxylic acid 38 can be obtained in
enantiomerically pure form, racemisation occurs upon activation, presumably due to a bridged symmetrical intermediate (Kirby et al. 1998)
(Scheme 16).
The assignment of the absolute configuration to the individual enantiomers of 40 was conducted by a molecular recognition experiment
(Bauer and Bach 2004) with the related 3-aza-bicyclo[3.3.1]nonan-2-
273
cient complexation and due to a lack of enantioface differentiation. The
search for a catalyst/substrate combination which was suited to demonstrate the general principle of enantioselective photochemical reaction
eventually led to the development of a catalytic photoinduced electron
transfer (PET) reaction, which is discussed in the next section.
4.2
PET-Catalysed Reaction
Benzophenones have been described as useful sensitisers for PET catalysed conjugate addition reactions of α-amino alkyl radicals to enones
(Bertrand et al. 2000). We tried to modify this reaction and synthesised the pyrrolidinylethyl-substituted quinolone 35 from the known
bromide (Bauer et al. 2005). Upon electron transfer from the pyrrolidine
to a given acceptor, a radical cyclisation occurs (Scheme 15), which
after electron and proton transfer generates a pyrrolizidine. We found
4,4
-dimethoxybenzophenone to be a suitable catalyst for this reaction.
Remarkably, the reaction proceeded with excellent simple diastereoselectivity and a single diastereoisomeric product rac-36 was obtained.
With 10 mol% of the catalyst, a chemical yield of 71% was achieved.
In order to install a benzophenone at the bicyclic scaffold we relied
on the previously used oxazole linkage. To this end, the known aminohydroxybenzophenone 37 (Aichaoui et al. 1990) was coupled to the free
acid rac-38, which is available from Kemp’s triacid in five synthetic
steps. Remarkably, an O-acylation instead of the expected N-acylation
was observed resulting in ester rac-39. As a consequence, oxazole formation was less straightforward but could eventually be achieved under
more forceful conditions. The reaction sequence led to the racemic benzophenone rac-40, i.e. to a 1/1 mixture of the enantiomers (+)-40 and
(–)-40, which was separated by chiral HPLC (Daicel Chiralpak AD).
It is important to mention that a separation of enantiomers at an earlier stage is not sensible. While carboxylic acid 38 can be obtained in
enantiomerically pure form, racemisation occurs upon activation, presumably due to a bridged symmetrical intermediate (Kirby et al. 1998)
(Scheme 16).
The assignment of the absolute configuration to the individual enantiomers of 40 was conducted by a molecular recognition experiment
(Bauer and Bach 2004) with the related 3-aza-bicyclo[3.3.1]nonan-2-