results of Table 5 are consistent with a unimolecular hybrid catalysis
mechanism, whereby the Lewis acid and Lewis base are present
in the same molecule (Fig. 1). To benchmark the performance of
18ceZn(OTf)2, and to confirm our HPLC peak assignments, we
compared it to L-proline, tested under the same conditions (entry
14). 18ceZn(OTf)2 performs very similarly to generate the anti
product selectively with good, but not excellent, enantioselectivity
(76% ee under these conditions).
To determine the potential utility of our catalyst system, alternative
aldol reactions were investigated (Table 7). Unfortunately,
little practical substrate scope was observed with our
optimal conditions. No reaction was observed between
propionaldehyde and the less activated acceptors 4-
chlorobenzaldehyde (entry 2) and benzaldehyde (entry 3), even
at 70 C. The use of isobutyraldehyde (31b) as donor also failed
with all substrates (entries 4e6). Pleasingly, cyclohexanone gave
reactions with all 3 acceptors, albeit in low yield. Moderately good
anti enantioselectivity (73% ee) was observed with 4-
nitrobenzaldehyde as acceptor (entry 7).