Chemistry Reference
In-Depth Information
O
O
O
Cl
O
O
t
-Bu
t
-Bu
CpRu
1
.
8
1
0
.
8
CpRu
Scheme 10.48
could also be intercepted by alkylating agents. Alkylation of the chromium is followed by CO insertion
leading to a dearomatized product
10.194
after reductive elimination. As the initial alkylation occurs
trans
to the metal and alkylation is on the metal, the product has
trans
stereochemistry. A similar stereochemical
outcome was observed using
4
-diene complexes (see Scheme 10.16)
The nucleophilic attack-electrophilic trapping sequence has been applied to the synthesis of the cytotoxic
acetoxytubipofuran
10.201
, isolated from a Japanese coral. A valine-derived chiral auxiliary was employed
to deliver the sensitive lithium ethoxyalkene nucleophile with control of both the regiochemistry -
ortho
-
and the stereochemistry (Scheme 10.51).
70
A chiral bidentate ligand for the lithium atom was also able to
exert control over the absolute stereochemistry, although a little less effectively. The
trans
stereochemistry
was then lost on enolate alkylation to install a methyl group. The second ring could be formed by an aldol
reaction in tandem with hydrolysis of enol ether
10.197
. After stereoselective reduction of the ketone, the
carbon atoms required for the third ring could be installed by a Johnson-Claisen reaction. Iodocyclization,
followed by a series of functional group interconversions then gave the natural product
10.201
with its
furan moiety.
Nucleophilic attack may also be intramolecular and can be used to make a variety of bicyclic, including
spiro, systems (Scheme 10.52).
71
Treatment of the chromium complex
10.202
, which has a nitrile on the side
chain, with LDA gave an anion
10.203
that cyclizes to give the
5
-intermediate
10.204
. Protonation gave a
mixture of enol ether isomers,
10.205
and
10.206
, which yielded the same enone
10.207
on acidic hydrolysis.
Double functionalization with dearomatization can also be achieved by a double nucleophilic attack. This
requires that the
5
-intermediate is reactivated by a ligand substitution in a similar way to methods for diene
complexes (Scheme 10.19). For the
5
-complex
10.209
that could be reactivated by substitution of a CO ligand by NO
+
(Scheme 10.53).
72
The second cationic
6
-complex
10.208
, addition of a Grignard reagent gave a
CN
CN
RT
CN
Cl
Cl
Cl
-78 °C
(OC)
3
Cr
5
(OC)
3
Cr
η
(OC)
3
Cr
5
η
10.170
10.185
10.183
- Cl
I
2
, -78 °C
CN
Cl
CN
(OC)
3
Cr
10.184
10.186
Scheme 10.49
