Chemistry Reference
In-Depth Information
Br
Br
CO
2
Me
CO
2
Me
NaH, DMF
Cr(CO)
3
Cr(CO)
3
10.214
10.215
Scheme 10.54
NaH, BnBr,
DMF
Bn
NaH, BnBr,
DMF
CO
2
Me
CO
2
Me
CO
2
Me
Cr(CO)
3
Cr(CO)
3
Cr(CO)
3
trans-
10.216
10.217
cis-
10.216
Scheme 10.55
complex
10.210
could then be attacked by a second nucleophile, even a modest nucleophile such as the anion
of a
-ketoester or a malonate. An improved yield of addition could be obtained by a second ligand change,
from a carbonyl to a phosphorus ligand. This appears to reduce by-product formation from direct attack on the
CO ligands. The metal-free product
10.213
were be obtained by mild oxidation. As both nucleophilic attacks
were
trans
to the metal, the two substituents are
cis
to each other, in contrast to the nucleophile/electrophile
sequence with Cr(CO)
3
(see Scheme 10.50).
10.3.2 Deprotonation
A simple demonstration of the ability of the Cr(CO)
3
unit to stabilize a negative charge in the benzylic
position is in the alkylation behaviour of methyl phenylacetate (Scheme 10.54).
73
Treatment of the uncom-
plexed ester with sodium hydride and 1,3-dibromopropane gave no product as the benzylic protons are not
sufficiently acidic to be removed. Under the same conditions, the Cr(CO)
3
complex
10.214
gave the expected
cyclobutane
10.215
.
In addition, the stereochemistry of alkylation is controlled by the Cr(CO)
3
group. For the indane complexes,
cis
- and
trans
-
10.216
, alkylation occurred exclusively
trans
to the metal, regardless of the original stereo-
chemistry of the ester (Scheme 10.55), both giving the same isomer
10.217
of the product, via a common
enolate.
74
An extreme example of benzylic alkylation is provided by the hexamethyl benzene complex
10.218
with
the more strongly electron-withdrawing FeCp
+
unit (Scheme 10.56). Hexa-allylation can be achieved, albeit
slowly, using a base as mild as KOH, giving a product
10.219
described as a “tentacled sandwich”.
75
Even
more prolonged reaction times result in formation of the dodeca-allylation product
10.220
.
The Cr(CO)
3
unit also activates the ring protons towards removal. Ring deprotonation can be made easier
and be directed if a substituent with lone pairs is present on the ring. A lone pair can coordinate to the
lithium of the incoming base and direct deprotonation to the
ortho
position. In many cases this reaction -
ortho
-metallation - is already possible without metal complexation, but complexation makes it easier. Not
all substituents show this behavior equally.
76
A fluorine substituent is particularly effective, even more
effective than a methoxy substituent in a competition experiment (Scheme 10.57),
77
while, amongst ethers,
the methoxymethoxy substituent proved best.
78
