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intracomplex functionalization directed by the conformations of freely rotating units.
To overcome this flexibility, we studied the functionalization of dicarboxylic acids dou-
bly complexed with disubstituted benzophenones [154]. Two sorts of complexing were
used: benzophenone dication
75
ion-paired with substrate dicarboxylate ion
76
, and
benzophenone dicarboxylate
77
hydrogen bonded to substrate dicarboxylic acid
78
.We
saw high selectivities for attack at the two central (equivalent) carbons with a substrate
of the correct length to fit well across the benzophenone, while there was less selec-
tivity with a longer substrate with flexible conformations in the complexes. As de-
scribed later, such double complexing of substrates was of general interest and general
utility in other artificial enzymes.
1.4.3
Directed Halogenations
Irradiation of the benzophenone-linked steroids in the presence of CCl
4
solvent gave
some chlorination of the steroids. Also, irradiation in the presence of BrCCl
3
afforded
no benzophenone products, only bromosteroids from a free radical chain process in-
itiated by the irradiation [155]. In the presence of PhICl
2
we saw only chlorosteroids,
again by a radical chain process [155]. In both cases the rather selective hydrogen ab-
straction led to exclusive substitution of tertiary hydrogens of the steroids, in particular
at C-9 and C-14. C-9 bromo- and chlorosteroids
79
and
80
could be dehydrohaloge-
nated to form the 9(11) olefin
81
. This afforded an easy entry into corticosteroids,
which have an oxygen atom at C-11 and often, usefully, have a fluorine at C-9.
Such normal free-radical substitution processes might be geometrically directed to
otherwise unremarkable positions in substrates, as the benzophenone reactions had
been. Consequently, in our first example, we found that intramolecular chlorination
could be directed by attachment of a PhICl
2
group to the steroid [156], i.e., compound
82
directed chlorination exclusively to C-14 (
83
), while
84
directed halogenation exclu-
sively to C-9 (
85
). As shown in Scheme 1.1, an intramolecular hydrogen abstraction by
