Handbook of Functionalized Organometallics Applications in S

14.5 Examples of the Use of Electrophilic Multihapto-Complexes in Organic Synthesis
with 61 in the stereocontrolled synthesis (Table 14.1: entry 3) of the Prelog±
Djerassi lactone (60) [290]. Here two methyl groups are introduced in sequence
via an iterative approach (g 5 ® g 4 ® g 5 ® g 4 ). The same approach in the g 5 series
of electrophiles has been used towards tylosin, employing Fe(CO) 2P(OPh) 3 complexes
to minimize the internal addition of nucleophiles (see Section 14.3.8) that
tends to complicate the use of cycloheptadienyliron complexes.
Turning to directing effects from 2-alkyl substituents, the best examples are in
the g 5 series. Such groups tend to be only weakly x directing (see Section 14.3.4),
but if easily directed nucleophiles are used, then good control is sometimes possible.
Thus while early approaches to a-phellandrene [87] and carvone [291] required
the separation of regioisomers, a route towards bilobanone was shown to
be capable of good regiocontrol because of the use of a stabilized enolate as the
nucleophile [292,293]. Nonetheless, even the synthesis of a-phellandrene was sufficiently
effective for it to serve to define the absolute configuration of the electrophilic
multihapto-complex tricarbonyl[(2R)-(±)-(1,2,3,4,5-g)-2-methylcyclohexadienyl]iron
hexafluorophosphate [87]. A larger functionalized 2-C alkyl substituent
gave effective introduction of a cyclopentenone at the x position in a reaction that
was aiming to establish access to prostaglandin analogs with interphenylene features
in the upper (carboxylate-terminating) side-chain [294]. An unusual iridium
complex in a steroid A ring has also been elaborated using the x direction available
from the carbon±carbon bonds of the A/B ring junction of estradiol [140].
14.5.2
Electron-withdrawing Groups with x-Directing Effects in Synthetic Applications of
Multihapto-Complexes
To gain strong x-directing effects from C-1substituents, it is better to employ electron-withdrawing
substituents (Table 14.1: entries 4±8) such as ketones and esters.
Once again, the early stoichiometric studies with palladium provide good examples
in the steroid series [18]. Enantioselective stereocontrolled syntheses of gabaculine
(62) [114], shikimic acid (64) [115] from 63 by Birch's group, and 5-HETE
(65) [116] from 51 by Donaldson's group, utilizing optically pure g 5 tricarbonyliron
complexes, however, provide the best examples. These target structures suit the
selection of an x-directing ester group at one end of the p system. A 1-pentyl-pentadienyliron(1+)
complex has also been examined in work motivated by HETE
synthesis [62,63]. An organoiron route (Table 14.1: entry 7) to sections of macrolactin
A (66) cleverly exploits reversible addition of nucleophiles to the
Fe(CO) 2PPh 3 complex 67 [262] to switch from a addition to the required x product
exploiting thermodynamic control (see Section 14.4). There have been substantial
efforts made to address macrolactin synthesis using organoiron methodology
[295,296]. In the electrophile 22, C-1esters and 2-C methoxy groups (see below,
and Section 14.5.5) mutually reinforce their x-directing effects. This places the
approach [118] to analogs of SK&F L94901 (68) on a secure footing. Both electronic
effects, and the natural steric effects, were favoring the required product
(Table 14.1: entry 8).
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