Chemistry Reference
In-Depth Information
An intereresting aspect of the Takemoto system is the possibility of preparing both
diastereoisomeric products selectively, depending on the cation provided by the base:
With a lithium amide the (
R
,
S
)- and with KOH the (
S
,
S
) - diastereoisomer, respectively,
was preferentially formed. The authors proposed for rationalization of this remarkable
reversal, that with LiNR
2
an N,O - chelated
syn
- and with KOH an
anti
- enolate is formed.
The procedure also allowed the preparation of
α
,
α
- disubstituted amino acids.
8B.7.3. Allylic Substitutions with Nonstabilized Enolates, Enamines, Indole
Derivatives, and Organozinc Compounds
8B.7.3.1. Silyl Enol Ethers as Pronucleophiles
Nonstabilized enolates have been
thoroughly studied as nucleophiles in Pd-catalyzed allylic substitution [147]. Lithium
enolates, because of their comparatively strong basicity, can induce side reactions such
as enolate equilibration, elimination, and cleavage of carbonates. Improved results have
been obtained with Zn and Cu enolates. Graening and Hartwig reported highly regio-
and enantioselective reactions of allylic carbonates with enolates generated
in situ
from
trimethylsilyl enol ethers (Scheme 8B.87) [325]. Use of cesium fl uoride as standard desi-
lylation reagent was unsatisfactory because of low degrees of regioselectivity and dial-
lylation as side reaction. Diallylation could be suppressed by desilylation with a
combination of CsF and ZnF
2
. Explicit catalyst activation was not necessary as C- H
activation occurred
in situ
(
31
P NMR).
OSi(CH
3
)
3
OCO
2
t
-Bu
O
O
R
2
+
R
1
[Ir(COD)Cl]
2
/
ent-
L59
Additives: CsF/ZnF
2
1:3
DME, 50°C
R
2
R
1
R
2
R
1
b
l
R
1
=2-furyl, R
2
=Ph
R
1
= 4-(F
3
C)C
6
H
4
,R
2
=Ph
R
1
=Ph,
b
/
l
= 99:1, 96% ee (74%)
b
/
l
= 94:6, 95% ee (81%)
b
/
l
= 95:5, 91% ee (46%)
b
/
l
= 85:15, 94% ee (75%)
R
2
=
i
-Pr
R
1
=
i
-Pr,
R
2
=Ph
Scheme 8B.87.
Alkylations with ketone enolates generated from silyl enol ethers.
Rate and selectivity of the reaction were strongly infl uenced by the substituent R
2
of the silyl enol ether. Good results were obtained for compounds with R
2
= aryl.
However, reactions were slow and yields moderate for cases with R
2
= alkyl. The abso-
lute confi guration of one of the products was determined and found to be in accordance
with the general rule presented in Section 8B.7.1.5.2. The question of diastereoselectiv-
ity, arising upon use of silyl enol ethers with a substituent at the
α
- position, has not
been addressed so far.
8B.7.3.2. Decarboxylative Allylic Alkylation
The technique of allylic substitution
via decarboxylative
in situ
generation of an enolate was introduced by Saegusa and Tsuji
