Chemistry Reference
In-Depth Information
Scheme 1 Synthesis of Gabriel's [1,2-
a
]IF dione 9 [
16
]
Scheme 2 Syntheses of parent [1,2-
a
]IF dione 12 [
27
]
Scheme 3 Asymmetric synthesis of 12 and [2,1-
b
]IF dione 17 [
38
-
40
]
1.2 Early Research
The first reported synthesis of an IF scaffold dates to 1884 when Gabriel condensed
2 equiv. phthalic anhydride (6) with ethyl acetoacetonate (7) to form carboxylic
acid 8 and later ethyl ester 9 (Scheme
1
)[
16
].
In 1955, Chardonnens and Ritter isolated the parent [1,2-
a
]dione 12 through
oxidative cleavage of benzo[
e
]acephenanthrylene (10) using sodium dichromate to
generate 2-fluorenonylbenzoic acid (11)
followed by ring closure using
concentrated sulfuric acid (Scheme
2
)[
27
].
Chardonnens and coworkers later devised a more general pathway to 12 by
condensing either indenyl ketone 13a or 13b, respectively, with quinoline and NaOH
in a stainless steel autoclave at 250
C to give 7-keto-12-hydroindeno[1,2-
a
]fluorenone
(14) in 30% yield (Scheme
3
)[
38
-
40
]. Incidentally, 9-keto-12-hydroindeno[2,1-
b
]
