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Kultur Dokumente
R. B. WOODWARD
Meo
NHCOCH3
Meo
Meo
Meo
Meo
C)
Meo
OH
II III
34 R. B. WOODWARD
IV v
MeOOC c� MeOOC � S
I
Cl Cl
VI VII
VIII
the initial union of the molecules had taken place to give the ex
pected (VI), and in a general way it was clear that a kind of in
ternal oxidation-reduction must have occurred-that is, that the
carbon-chlorine bond of (VI) had been reduced, at the expense
of the oxidation of the skeleton of the molecule, with concomitant
transformation of the latter to the stable aromatic isothiazole sys
tem. In detail, one might postulate that the unshared electron
pair on the nitrogen atom attacks the sulfur atom directly, to give
the fugitive intermediate (IX) , from which one might imagine a
36 R. B. WOODWARD
H H
CH3 :Q N CH3 N
'\ '
MeOOC
I //':)
GCl
MeOOC D
I s
IX x
XI
XII XIII
A TOTAL SYNTHESIS OF COLCHICINE 37
stable aromatic ring, and we could now begin to build upon this
firm base. At the very outset we were able to take advantage of
one of the positive fruits which we had hoped for in the pres
ence of the isothiazole ring. The methyl group of our intermedi
ate, situated as it is a to the carbon-nitrogen double bond of the
isothiazole system, would be expected to be activated by that s itu
ation, and such was indeed found to be the case. When (VIII)
was treated with N-bromosuccinimide in carbon tetrachloride so
lution in the presence of light, it was readily transformed into
the corresponding bromo compound (XIV) , which in its turn re-
XIV xv
¢3P=CHx:; �\
s
Meooc �
XVI
38 R. B. WOODWARD
Meo Meo
Me o Meo
Meo Meo
XVII XVllI
Meo Meo
Meo Meo
Meo
XIX xx
XXI
aldehyde (XX) . The stage was now set for a further Wittig reac
tion, in this case with the phosphorane ( XXI ) . The combination
of these two molecules gave a mixture of stereoisomeric
a, {3,y, o unsaturated esters, which was hydrolyzed by aqueous
sodium hydroxide, and irradiated with visible light in the pres
ence of iodine, in order to convert each of the substances contain
ing one or more cis-oriented double bonds to the same /rans
isomer ( XXII) .
M eo
Meo
XXII
Meo
Meo
HOOC
XX III XXIV
Meo Meo
Meo Meo
xxv XXVI
Meo Meo
MeO Meo
COOH
COOH COO Me
XX VII XXVIII
Meo
Meo
XXIX
Meo Meo
Meo MeO
CHOH
xxx XXXI
Meo MeO
Meo Meo
OAc
0
XX XII XXXIII
Meo Meo
Meo Meo
AcO
OH
XX XIV xx xv
Meo MeO
MeO Meo
XXXVI XXXVII
Meo
Meo
0
OH
XX XVIII
REFERENCES