N
N O
O
O
HO
HNO 3
H 2 SO 4
N
N O
O
O
HO
O 2 N
114 115
The production by total synthesis of an analogue that incorporates an
additional fused ring, by way of contrast, includes a good many more
steps. The lengthy synthesis starts with the aluminum chloride-catalyzed
acylation of fluorotoluene ( 116 ) with succinic anhydride to afford the
acid ( 117 ). The ketone group is then reduced to methylene by means of
hydrogen over palladium; the acid is then esterified with methanol to
yield 118. Reaction with nitric acid proceeds in a straightforward manner
to afford the nitro derivative ( 119 ). The ester grouping is then saponified.
Heating the resulting acid in polyphosphoric acid results in ring closure
and thus formation of a tetralone ring ( 120 ). The next few steps establish
the requisite functionality in this newly added ring. This sequence includes
formal transfer of the carbonyl group to the alternate benzylic position.
O
O
O
HO
F
116
O
O
O
AlCl 3 F
CO 2 H
O
- H 2
- MeOHF
CO 2 CH 3
117 118
HNO 3
F
CO 2 CH 3
119
NO 2
- NaOH
- PPA
F NO 2
O
- NaBH 4
2. TsOH
F NH 3. H^2
121 2 120 - Ac 2 O
- KMnO 4
F NHCOCH 3
122
BuONO O
F NHCOCH 3
123
O
NOH
Zn/Ac 2 O
F NHCOCH 3
124
O
NHCOCH 3
- OH2. CFâ
3 COCl
F NH 2
125
O
NHCOCF 3
O
O
O
HO
O
126
F
NHCOCF 3
base
127
tBuOK
N
N
N
- COMPOUNDS WITH FIVE OR MORE FUSED RINGS: CAMPTOTHECINS 231