Chemistry Reference
In-Depth Information
A high-yield access to cyanides from isocyanides is given by the isocyanide-
cyanide rearrangement [1215, 1216]. Isocyanides are converted to cyanides by flash
thermolysis in excellent yields (often near 100%) under strict retention of configu-
ration. The employed isocyanides were prepared by standard procedures from the
corresponding formamides by the use of phosphoryl chloride. A 1-homocubyl iso-
cyanide was synthesized in 51% yield [1216].
A total synthesis of the marine indole alkaloids (
G
)-hapalindoles, e.g. 1629, has
been described, in which the isocyanide function is formed in the last step by de-
hydration of a formamide precursor with phosphoryl chloride; yields are 73-85%
[1217, 1218].
H
NC
H
Hapalindole U
1629
H
20
C) solution of
the formamide (6.5 mg) in pyridine (0.4 mL) under Ar atmosphere was added
phosphoryl chloride (11
Typical procedure. (
)-Hapalindole U 1629 [1218]:
To a cooled (
G
L) and the mixture was stirred at the same temperature
for 40 min. Addition of saturated aq. NaHCO
3
, extraction with 10% MeOH/
CH
2
Cl
2
, standard work-up, and PTLC (hexane/EtOAc, 4:1) afforded (
G
)-hapa-
lindole U 1629 (4.5 mg, 73%) as colorless needles; mp 240-242
C (CH
2
Cl
2
/
hexane).
During the synthesis and evaluation of a series of arachidonate epoxy inhibitors,
1631 was prepared in 85% yield by dehydration of the formamide 1630 with phos-
phoryl chloride [1219].
The synthesis of 1,6-di-O-(2-isocyano-3-methylcrotonyl)-d-mannit (antibiotic A
32390 A) required diisocyano compounds as intermediates, which were prepared
from the corresponding formamides by dehydration with phosphoryl chloride in
yields of 54-74% [1220].
m
O
O
POCl
3
Et
3
N
OMe
OMe
Et
2
O/petrol
ether
40°C, 1 h
MOMO
NHCHO
MOMO
NC
85 %
1631
1630
Another type of isocyanide reaction is the facile reductive removal of the amino
group in 1632, via the formamide and the isocyanide. It is exploited in a synthesis
