Chemistry Reference
In-Depth Information
4
Guanidines in Organic Synthesis
Tsutomu Ishikawa
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage,
Chiba 263-8522, Japan
4.1
Introduction
Guanidines can be categorized as organic superbases [1] due to the resonance stability of
their conjugated acids [2] and, thus, are expected to catalyse various types of base-
participated organic reactions. Among guanidine compounds, 1,1,3,3-tetramethylguani-
dine (or N,N,N
0
,N
0
-tetramethylguanidine; TMG) (1) is regarded as a typical and funda-
mental guanidine compound and, in fact, has been used in many kinds of base-catalysed
reaction. Barton et al. [3] reported the preparation of pentaalkylguanidines 2 and their
application to organic synthesis as sterically-hindered organic bases, which are called
. Bicyclic guanidines 3, 1,5,7-triazabicycle[4.4.0]dec-5-ene (TBD) and the
N-methyl analogue (MTBD) were introduced by Schwesinger [4] (Figure 4.1).
Guanidine participating organic reactions could be schematically classified into two
types of reactions: catalytic and stoichiometric, in which a guanidinium salt composed of
guanidine like 2 and either an acid or nucleophile plays an important role as a common
active complex. In the former type of reaction, 2 is repeatedly used as a free base catalyst,
whereas a guanidinium salt is formed in the latter (Figure 4.2).
As expected from a Barton
Barton
s bases
s base (2), the guanidine skeleton can be widely and easily
modified to a chiral base by introducing chirality into the molecule, in which five chiral
centres can be theoretically incorporated in the three nitrogen atoms, indicating that the
TMG (1) participating organic reactions could be theoretically expanded to asymmetric
