Chemistry Reference
In-Depth Information
2.2.1 Halogenation at C-2. As above described monobromo exo-
glycals are suitable substrates for palladium catalysed cross-coupling
reactions. The direct reaction of monobrominated phosphoranes
with lactones is not straightforward. However, the facile addition of
chlorine to dichloroolefins 1 has been described some years ago.
25
Thus
halogenation of anomeric double seemed a viable process and bromi-
nation of compounds 3 was examined. Considerable experimentation led
to find the proper conditions which allowed the formation of brominated
exo-glycals from 3 (Scheme 5).
Simple treatment of an activated exo-glycal with 1.6 equivalent of
bromine in carbon tetrachloride in the presence of triethylamine gave
excellent yield of the expected brominated compounds 12 and 13 as a Z/E
mixture (Scheme 5). The stereochemistry of each compound was
determined by
1
H NMR, the allylic proton being shifted to lower field in
the Z isomer (about 5.7 ppm) than in the E isomer (about 5.4 ppm).
12,24
The reaction worked equally well with pyranosidic exo-glycal 14 pro-
viding a 1 : 1.5 Z/E mixture of 15 and 16 in 62% yield. The observed results
were rationalized in terms of bromonium formation occurring mainly
trans to the O-isopropylidene ring followed by opening with bromide ion.
The subsequent step is the non-stereospecific base-catalyzed elimination
of hydrobromic acid to yield the bromo exo-glycal as a Z/E mixture. The
Z/E ratio was found to depend on the configuration of the starting
exo-glycal and on the carbohydrate configuration. In spite of the low
stereoselectivity, the bromination of activated exo-glycals was indeed a
true advance in the functionalization of these compounds. The reactivity
of these bromo esters was next investigated.
2.2.2 Formation of C-C bond at C-2. On the basis of previous results
on the cross-coupling reaction of dibromo-exo-glycals, obviously the
same reaction with compounds 12, 13, 15 and 16 was explored.
24
However, the use of the previous conditions (Pd(PPh
3
)
4
,DME,851C, 24 h)
COOMe
Br
COOMe
O
O
O
Br
2
(1.6 eq.)
Br
COOMe
+
CCl
4,
Et
3
N
0°Cthenrt
O
O
O
O
O
O
12
Z
13
E
Z/E
Zisomer
86%
1:1.5
gulo
E
isomer
91%
1.5:1
1.5:1
1.5:1
Zisomer
70%
manno
E
isomer
81%
Zisomer
55%
1:1.5
1:2.3
ribo
E
isomer
77%
O
O
O
O
COOMe
O
Br
O
COOMe
O
O
O
Br
2
(1,6 eq.)
CCl
4,
Et
3
N
0 °C then RT
COOMe
+
Br
OO
OO
OO
14
Z
isomer
15
Z
16
E
62%
Z/E
1/1.5
Scheme 5 Bromination of activated exo-glycals.
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