PARADIGM AND ADVANTAGE OF CARBOHYDRATE CLICK CHEMISTRY STRATEGY FOR FUTURE DECOUPLING - Click Chemistry in Glycoscience: New Developments and Strategies - page 22

O

O

DIAD

NHBn

NH 3 + Cl -

93%

O

O

OBn NHTs

OBn NHTs

O

O

DIAD

N 3

N 3

91%

O

O

OBn NHBn

NH 3 Cl - OBn

FIGURE 1.21 Selective N-debenzylation of benzylamines by DIAD according to Kroutil

et al. [37].

Kroutil and collaborators [37] developed conditions enabling chemoselective
cleavage of benzylamines in the presence of such functionalities as azide, O -benzyl,
and N -tosyl using diisopropyl azidodicarboxylate (DIAD). Figure 1.21 shows some
examples of this high-yielding methodology.
Spencer et al. [38] compared the rate of hydrogenation of benzyl ethers containing
different substituents in the aromatic ring. The differences are significant. For exam-
ple, the reaction of the compound with the benzyl group containing trifluoromethyl
group in the para position is about five times slower than the reaction of a com-
pound with unsubstituted benzyl group. Introduction of t -butyl group into the para
position of the benzyl ether increases the rate of hydrogenation about 25 times. The
researchers found that the naphthylmethyl (NAP) group is exceptionally selective.
Figure 1.22 shows the carbohydrate examples.
It is worth adding that the NAP group can be introduced either using NAP bro-
mide [38, 39] or by forming the cyclic naphthyl acetal followed by hydrogenation

ONAP
BnO

OH
BnO

O

O

H 2
Pt/C
8h

Bn BnO

Bn BnO

OMe

OMe

90%

ONAP

OH

O

O

Bn BnO

H 2
Pt/C
8.5h

Bn BnO

BnO

OMe

BnO

OMe

89%

FIGURE 1.22 Selective removal of the NAP group in the presence of benzyl ethers according
to Spencer et al. [38].