Chemistry Reference
In-Depth Information
3.3 Formation of C-N bond at the anomeric centre
The 1,4 addition of nitrogen nucleophiles on activated double bond is a
well known process.
39
This reaction has been exploited with exo-glycals 3
and benzylamine was found to be the reagent of choice for this purpose.
Simple dissolution of the exo-glycal as a Z/E mixture in benzylamine for a
few days cleanly gave the expected adduct 40 in excellent yield as a single
anomer, the N-benzyl group being trans to the 2,3-O-isopropylidene group
as shown by nOe difference spectroscopy.
40
The reaction worked
well with furanose-exo-glycals but was more complex with pyranose exo-
glycals. As an example, exo-glycal 14 reacted with benzylamine in 44 h to
give the expected the adduct 44 together with the open-chain form
enaminoester 45 in a 1 : 5 ratio (Scheme 12).
These sugar b-amino esters are of great interest since this new class of
compounds developed by several groups is a growing field in rapid
emergence.
41
The adducts 40 were thus involved in several constructions.
For that purpose, the N-benzyl group was removed by catalytic hydro-
genation giving the free amine 41 as a mixture of anomers because of
mutarotation. Fortunately, on reaction with acylating reagents, only one
amide was formed probably because the N-acylation reaction is faster on
the a anomer of 41. It was not possible to remove the ester group on the
N-benzyl adduct without rapid decarboxylation of the corresponding
carboxylic acid but this reaction can be easily carried out on N-acylated
derivatives. Protection of the free amine 41 as a carbamate, Boc or Cbz
like compound 42 followed by ester saponification gave access to the free
acid 43. This allowed the coupling of the two sugar b amino acid building
blocks 41 and 43 with different a-amino acids
40
opening the way to new
chiral species such as spironucleosides.
42
The interest in b-amino acids relies in part to the tendency of their
short oligomers, the so-called foldamers, to adopt well defined spatial
arrangement like helix.
43
Several carbohydrate derived amino acids have
COOMe
COOMe
COOMe
NH
2
O
O
R
O
R
R
PhCH
2
NH
2
H
2
Pd/C 10%
EtOAc
NHBn
neat, rt, 2-4 days
O
O
O
O
O
O
50-90%
O
35 + 38
40
41
R=
O
COOMe
COOH
O
O
R
R
K
2
CO
3
CbzCl, Me
OH
NaHCO
3
NHCbz
NHCbz
MeOH/H
2
O
O
O
O
O
95%
75%
42
43
O
O
O
O
NHBn
OH
O
COOMe
NHBn
PhCH
2
NH
2
neat, rt, 44h
O
O
O
COOMe
+
COOMe
OO
OO
OO
73%
14
Z
44
45
1:5
Scheme 12 Benzylamine addition on activated exo-glycals.
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