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A. Berkessel
1
Introduction
The term organocatalysis refers to the use of low-molecular weight and
metal-free catalysts for the selective, in most cases enantioselective,
transformation of organic substrates (Berkessel and Gröger 2005). The
mechanisms by which metal-free enzymes (more than half of all enzymes known to date do not contain catalytically active metals) effect
dramatic rate accelerations have been a major field of research in bioorganic chemistry for decades, dating back to the first half of the twentieth
century (Langenbeck 1949). In many instances, organocatalysts can be
considered as ‘minimal versions’ of metal-free enzymes, and the mechanisms and the categorizations of enzymatic catalysis apply to the action
of organocatalysts as well. In both cases, the accelerations observed depend on the typical interactions of organic molecules with one another.
A general distinction can be made between processes that involve the
formation of covalent adducts between catalyst and substrate(s) within
the catalytic cycle, and processes that rely on non-covalent interactions
such as hydrogen bonding or the formation of ion pairs. The former
type of interaction has been termed ‘covalent catalysis’, whereas the latter situation is usually called ‘noncovalent catalysis’. The formation of
covalent substrate–catalyst adducts may occur e.g. by single-step Lewisacid – Lewis-base interaction, or by multi-step reactions such as the formation of enamines from aldehydes and secondary amines. The catalysis of aldol reactions by the formation of enamines is a striking example
of common mechanisms in enzymatic catalysis and organocatalysis. In
class I aldolases, lysine provides the catalytically active amine group,
whereas typical organocatalysts for this purpose are secondary amines,
the most simple one being proline (List and Seayad 2005). Noncovalent
catalysis in many instances rests on the formation of hydrogen-bonded
adducts between substrate and catalyst, or on protonation/deprotonation
processes. Phase-transfer catalysis (PTC) by organic phase-transfer catalysts falls into the category ‘noncovalent catalysis’. The latter is mechanistically unique because PTC promotes reactivity, not only by altering the chemical properties of the reactants, but also involves a transport
phenomenon.
This chapter discusses four cases of organocatalysis effected by multiple hydrogen bonding. It should be pointed out at the very beginning
A. Berkessel
1
Introduction
The term organocatalysis refers to the use of low-molecular weight and
metal-free catalysts for the selective, in most cases enantioselective,
transformation of organic substrates (Berkessel and Gröger 2005). The
mechanisms by which metal-free enzymes (more than half of all enzymes known to date do not contain catalytically active metals) effect
dramatic rate accelerations have been a major field of research in bioorganic chemistry for decades, dating back to the first half of the twentieth
century (Langenbeck 1949). In many instances, organocatalysts can be
considered as ‘minimal versions’ of metal-free enzymes, and the mechanisms and the categorizations of enzymatic catalysis apply to the action
of organocatalysts as well. In both cases, the accelerations observed depend on the typical interactions of organic molecules with one another.
A general distinction can be made between processes that involve the
formation of covalent adducts between catalyst and substrate(s) within
the catalytic cycle, and processes that rely on non-covalent interactions
such as hydrogen bonding or the formation of ion pairs. The former
type of interaction has been termed ‘covalent catalysis’, whereas the latter situation is usually called ‘noncovalent catalysis’. The formation of
covalent substrate–catalyst adducts may occur e.g. by single-step Lewisacid – Lewis-base interaction, or by multi-step reactions such as the formation of enamines from aldehydes and secondary amines. The catalysis of aldol reactions by the formation of enamines is a striking example
of common mechanisms in enzymatic catalysis and organocatalysis. In
class I aldolases, lysine provides the catalytically active amine group,
whereas typical organocatalysts for this purpose are secondary amines,
the most simple one being proline (List and Seayad 2005). Noncovalent
catalysis in many instances rests on the formation of hydrogen-bonded
adducts between substrate and catalyst, or on protonation/deprotonation
processes. Phase-transfer catalysis (PTC) by organic phase-transfer catalysts falls into the category ‘noncovalent catalysis’. The latter is mechanistically unique because PTC promotes reactivity, not only by altering the chemical properties of the reactants, but also involves a transport
phenomenon.
This chapter discusses four cases of organocatalysis effected by multiple hydrogen bonding. It should be pointed out at the very beginning