Chemistry Reference
In-Depth Information
O
Pd(OAc)
2
, K
3
PO
4
,
SPhos
1.16
B
O
I
NO
2
[Ir(cod)Cl]
2
, dtbpy, B
2
pin
2
Me
3
Si
Me
3
Si
N
N
Boc
3.93
Boc
3.94
Pd(O
2
CCF
3
),
t
-BuOOBz
NO
2
NO
2
Me
3
Si
Me
3
Si
N
N
Boc
CO
2
TSE
3
9
3
.
9
O
1. H
2
, Pd/C
2. AlCl
3
3. Mukaiyama's reagent,
Et
3
N
NH
O
NO
2
CO
2
TSE
Me
3
Si
N
N
3
.
9
3
9
Scheme 3.43
PdCl
2
, AcOH,
MnO
2
, BQ
OAc
3.99
3.100
Scheme 3.44
2
-alkene complexes (Chapter 6), the process can be
made catalytic by the inclusion of an oxidizing agent. An example is the use of a carboxylate ion
as the nucleophile,
45
palladium is reduced to palladium(0). As with
giving an alternative to singlet oxygen and selenium dioxide for allylic oxidation
(Scheme 3.44).
The most ambitious application of this chemistry is in the ring closure to form 6-deoxyerythronolide B
3.104
(Scheme 3.45).
46
Macrolides are most commonly prepared by lactonization of a hydroxy acid, so there
is a need to carry the hydroxy functional group through the synthesis. The allylic CH activation method avoids
this need, requiring just an alkene. Controlled by the conformation of the substrate, allylic oxidation of the
precursor
3.101
provided a single diastereoisomer of the macrolide
3.103
. A bis-sulfoxide
3.102
was found
to be the optimum ligand for palladium. The macrolide
3.103
could be converted to 6-deoxyerythronolide
B
3.104
by simultaneous reduction of the alkene and the PMP acetal, selective oxidation of one hydroxyl
group, and acetonide removal.
