314
M. Benaglia
Proline-promoted condensation to hydroxyacetone as the aldol donor
gave access to synthetically relevant syn-α-hydroxy-β-aminoketones,
that were obtained in moderate to good yields, and good to high diastereo- and enantioselectivities (equation b, Scheme 6). Exploiting its
solubility properties, the PEG–Pro catalyst was easily recovered and recycled to promote all of the above-mentioned reactions that occurred in
slowly diminishing yields but virtually unchanged enantioselectivities.
4.2
MacMillan’s Catalyst
Another chiral organic catalyst of major success is MacMillan’s catalyst, 18, that has found widespread use in a number of relevant processes (MacMillan 2000). Immobilized versions of these catalysts for
the enantioselective Diels–Alder cycloaddition of dienes with unsaturated aldehydes were developed on soluble (Benaglia et al. 2002) and
insoluble supports (equation a, Scheme 7) (Benaglia 2006).
The PEG-supported imidazolidinone 19 (Scheme 7) was later used in
1,3-dipolar cycloadditions (Puglisi et al. 2004). By reacting N-benzylC-phenylnitrone with acrolein, it was shown that the outcome of the
reaction was strongly dependent on the nature of the acid employed to
generate the catalyst, and that only the use of HBF 4 as in the case of
19 allowed reproducible results to be obtained. Under the best reaction
conditions (20 mol% of catalyst, DCM, –20 °C, 120 h) the product was
obtained in 71% yield as a 85:15 trans/cis mixture of isomers, the trans
isomer having 87% ee (equation b, Scheme 7).
A comparison of the results obtained with catalyst 19 with those obtained by MacMillan indicates that the major difference between the
PEG-supported and the non-supported catalyst resides in the chemical
rather than in the stereochemical efficiency. Indeed, while the supported
catalyst gave trans/cis ratios almost identical to and ee only 3%–6%
lower than those obtained with the non-supported catalyst, the difference in chemical yields was larger, ranging from 9% to 27%.
The PEG-supported catalyst was recycled twice to afford the product
with constant level of diastereo- and enantio-selectivity but in chemical
yields diminishing from 71% to 38%. In order to explain this behaviour
several experiments were carried out. First, after each recovery the supported catalyst was examined by
1 H NMR that showed degradation,
M. Benaglia
Proline-promoted condensation to hydroxyacetone as the aldol donor
gave access to synthetically relevant syn-α-hydroxy-β-aminoketones,
that were obtained in moderate to good yields, and good to high diastereo- and enantioselectivities (equation b, Scheme 6). Exploiting its
solubility properties, the PEG–Pro catalyst was easily recovered and recycled to promote all of the above-mentioned reactions that occurred in
slowly diminishing yields but virtually unchanged enantioselectivities.
4.2
MacMillan’s Catalyst
Another chiral organic catalyst of major success is MacMillan’s catalyst, 18, that has found widespread use in a number of relevant processes (MacMillan 2000). Immobilized versions of these catalysts for
the enantioselective Diels–Alder cycloaddition of dienes with unsaturated aldehydes were developed on soluble (Benaglia et al. 2002) and
insoluble supports (equation a, Scheme 7) (Benaglia 2006).
The PEG-supported imidazolidinone 19 (Scheme 7) was later used in
1,3-dipolar cycloadditions (Puglisi et al. 2004). By reacting N-benzylC-phenylnitrone with acrolein, it was shown that the outcome of the
reaction was strongly dependent on the nature of the acid employed to
generate the catalyst, and that only the use of HBF 4 as in the case of
19 allowed reproducible results to be obtained. Under the best reaction
conditions (20 mol% of catalyst, DCM, –20 °C, 120 h) the product was
obtained in 71% yield as a 85:15 trans/cis mixture of isomers, the trans
isomer having 87% ee (equation b, Scheme 7).
A comparison of the results obtained with catalyst 19 with those obtained by MacMillan indicates that the major difference between the
PEG-supported and the non-supported catalyst resides in the chemical
rather than in the stereochemical efficiency. Indeed, while the supported
catalyst gave trans/cis ratios almost identical to and ee only 3%–6%
lower than those obtained with the non-supported catalyst, the difference in chemical yields was larger, ranging from 9% to 27%.
The PEG-supported catalyst was recycled twice to afford the product
with constant level of diastereo- and enantio-selectivity but in chemical
yields diminishing from 71% to 38%. In order to explain this behaviour
several experiments were carried out. First, after each recovery the supported catalyst was examined by
1 H NMR that showed degradation,