New Concepts for Organocatalysis
3
time, the perfect enantioselectivities often observed in enzymatic reactions were considered beyond reach for non-biological catalysts. Such
biological catalysis is increasingly used on an industrial scale and is
particularly favored for hydrolytic reactions. However, it became evident that high levels of enantioselectivity can also be achieved using
synthetic metal complexes as catalysts. Transition metal catalysts are
particularly useful for asymmetric hydrogenations, but may leave possibly toxic traces of heavy metals in the product.
In contrast, in organocatalysis, a purely organic and metal-free small
molecule is used to catalyze a chemical reaction. In addition to enriching chemistry with another useful strategy for catalysis, this approach
has some important advantages. Small organic molecule catalysts are
generally stable and fairly easy to design and synthesize. They are often
based on nontoxic compounds, such as sugars, peptides, or even amino
acids, and can easily be linked to a solid support, making them useful for industrial applications. However, the property of organocatalysts
most attractive to organic chemists may be the simple fact that they are
organic molecules. The interest in this field has increased spectacularly
in the last few years (Berkessel and Gröger 2005; List and Yang 2006).
Organocatalysts can be broadly classified as Lewis bases, Lewis acids, Brønsted bases, and Brønsted acids (for a review, see Seayad and
List 2005). The corresponding (simplified) catalytic cycles are shown
in Scheme 1. Accordingly, Lewis base catalysts (B:) initiate the catalytic cycle via nucleophilic addition to the substrate (S). The resulting
complex undergoes a reaction and then releases the product (P) and the
catalyst for further turnover. Lewis acid catalysts (A) activate nucleophilic substrates (S:) in a similar manner. Brønsted base and acid catalytic cycles are initiated via a (partial) deprotonation or protonation,
respectively.
2
Enamine Catalysis
Enamine catalysis involves a catalytically generated enamine intermediate that is formed via deprotonation of an iminium ion and that reacts
with various electrophiles or undergoes pericyclic reactions. The first
example of asymmetric enamine catalysis is the Hajos–Parrish–Eder–
3
time, the perfect enantioselectivities often observed in enzymatic reactions were considered beyond reach for non-biological catalysts. Such
biological catalysis is increasingly used on an industrial scale and is
particularly favored for hydrolytic reactions. However, it became evident that high levels of enantioselectivity can also be achieved using
synthetic metal complexes as catalysts. Transition metal catalysts are
particularly useful for asymmetric hydrogenations, but may leave possibly toxic traces of heavy metals in the product.
In contrast, in organocatalysis, a purely organic and metal-free small
molecule is used to catalyze a chemical reaction. In addition to enriching chemistry with another useful strategy for catalysis, this approach
has some important advantages. Small organic molecule catalysts are
generally stable and fairly easy to design and synthesize. They are often
based on nontoxic compounds, such as sugars, peptides, or even amino
acids, and can easily be linked to a solid support, making them useful for industrial applications. However, the property of organocatalysts
most attractive to organic chemists may be the simple fact that they are
organic molecules. The interest in this field has increased spectacularly
in the last few years (Berkessel and Gröger 2005; List and Yang 2006).
Organocatalysts can be broadly classified as Lewis bases, Lewis acids, Brønsted bases, and Brønsted acids (for a review, see Seayad and
List 2005). The corresponding (simplified) catalytic cycles are shown
in Scheme 1. Accordingly, Lewis base catalysts (B:) initiate the catalytic cycle via nucleophilic addition to the substrate (S). The resulting
complex undergoes a reaction and then releases the product (P) and the
catalyst for further turnover. Lewis acid catalysts (A) activate nucleophilic substrates (S:) in a similar manner. Brønsted base and acid catalytic cycles are initiated via a (partial) deprotonation or protonation,
respectively.
2
Enamine Catalysis
Enamine catalysis involves a catalytically generated enamine intermediate that is formed via deprotonation of an iminium ion and that reacts
with various electrophiles or undergoes pericyclic reactions. The first
example of asymmetric enamine catalysis is the Hajos–Parrish–Eder–