Handbook of Functionalized Organometallics Applications in S

14.5 Examples of the Use of Electrophilic Multihapto-Complexes in Organic Synthesis
14.5.3
Aryl Substituents with x-Directing Effects in Synthetic Applications of
Multihapto-Complexes
As indicated in Section 14.3.4, the directing effects of aryl substituents are complicated
by the need to consider the orientation of the arene, which itself can be
influenced by electronic effects in the arene, or the metal complex. There are
examples of 1-Ar substituents directing either ipso or x, and perhaps because of
this uncertainty, there are no examples yet of target molecule syntheses planned
to start from a simple 1-aryl substituted multihapto-complex (but see Section
14.5.5 for 1-aryl-4-methoxycyclohexadienyl examples). The x-directing 2-aryl substitution
pattern on cyclohexadienyliron complexes has been used in work directed
towards unnatural amino acid side-chain features (Table 14.1: entry 9). Addition
of the Shiffs base nucleophile (MeO 2C)Ph 2N=CH ± [78] and an aminomalonate
derivative (H 2N)(CO 2Et)(Me 3SiCH 2CH 2O 2C)C ± [80] 70 to have been used to introduce
a glycine moiety to a side-chain that after decomplexation and aromatization
would produce a biaryl feature in 69. In the silylalkyl ester case, desilylation and
concomitant decarboxylation afforded the unbranched amino acid.
14.5.4
Electron-donating Groups with Ipso-Directing Effects in Synthetic Applications of
Multihapto-Complexes
A synthesis of isopiperitone (71) in Rosenblum's group provides an early synthetic
example where the power of the C-1donor substituent in 72 was employed
[16]. Although it only produced one carbon±carbon bond, the metal featured twice
in this synthesis (Table 14.1: entry 10), and the strategy can be classed as iterative
(g 2 ® g 1 ® g 2 ). Similarly in 74, the metal moves to the least-hindered end, and the
relatively large size of the organic group in the donor does not present a problem
for ipso addition [297]. This is a key step (Table 14.1: entry 11) in the enantioselective
synthesis of ent-sitophilate (73).
Our own work in Norwich (Table 14.1: entries 15, 17±19) addressing the alkaloid
targets has also made use of ipso-directed nucleophile addition followed by
removal of the electron-donating directing group to establish an iterative approach
to key aryl-substituted quaternary centers (entries 17±19) and ring junctions
(entries 15, 31) in the targets. The reactions that produce the electrophilic functionalized
multihapto-complexes 84 [4], 86 [128] and 88 [106] provide good examples,
and again, the regiocontrol at this stage of the synthesis was on a secure
basis because of the mutually reinforcing directing effects of the unsymmetrically
placed substituents in 19. This work is discussed in more detail later (see Section
14.5.5) where the use of C-2 x-directing donor substituents in the creation of quaternary
centers is described.
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