Chemistry Reference
In-Depth Information
9
Related Organocatalysts (2):
Urea Derivatives
Waka Nakanishi
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi,
Inage, Chiba 263-8522, Japan
9.1
Introduction
Activity in a living organism could be, in a chemical sense, managed by a variety of catalytic
reactions [1]. A typical example is an enzyme-participating reaction, in which a highly
controlled hydrogen bonding network plays an important role. In general, an enzyme
specifically recognizes a substrate (in some cases, also a reactant) and then catalyses a variety
of reactions (Figure 9.1a). A metal catalysed reaction is artificially developed in which a
metal ion serves as a Lewis acid catalyst (Figure 9.1b). On the other hand, urea, thiourea and
guanidine have been shown to serve as metal-free organocatalysts through double hydrogen
bonding [2,3] (Figure 9.1c), in which they could act as either Lewis acids (type I) or proton
donors in chelation binding (type II). Phosphate and nitro groups are activated in the latter
bidentate fashion. In Figure 9.1c, highly asymmetric induction could be expected when the
substrate is fixed under an effective chiral environment after tuning of its side chains.
A vast number of valuable metal catalysed reactions has been developed to date.
However, metal-free organocatalysis attracts much attention due not only to green chemical
but also to economic demands. An organosuperbase has generally a highly conjugated
system stabilized in the protonated form, and the resultant conjugated acid could act as a
Brønsted acid and/or a Lewis acid catalyst in organic synthesis. In fact, the Lewis acid type
of catalysis activation has been reported in reactions in which guanidine or amidine
