Chemistry Reference
In-Depth Information
P
t
-Bu
2
P
t
-Bu
2
PhCl, NaO
t
-Bu, Pd(OAc)
2
Fe
Fe
Ph
Ph
Ph
Ph
Ph
3.15
1.24
Scheme 3.18
Sonogashira
reaction
MeO
NHAc
MeO
MeO
C-H activation
and coupling
3.16
O
O
MeO
MeO
(Ph
3
P)
2
PdCl
2
,
CuI, Et
3
N
Cl
Br
+
MeO
MeO
Br
MeO
3
1
3
1
MeO
3.17
OMOM
1. (
S
)-pinene, 9-BBN
2. NaH, MOMCl
3. H
2
NNHTs, AcONa
MeO
Pd(OAc)
2
, K
2
CO
3
,
Davephos
1.20
,
Δ
MeO
Br
MeO
3.20
MeO
MeO
1. HCl, MeOH
2. Zn(N
3
)
2
.Py
2
,
DIAD, PPh
3
OMOM
N
3
MeO
MeO
MeO
MeO
3
3
.
MeO
1. LiAlH
4
, THF
2. Ac
2
O, Et
3
N, DMAP
NHAc
MeO
MeO
3.16
Scheme 3.19
achieved using a palladium catalyst with the Davephos ligand
1.20
. Other ligands were much less effective.
The synthesis could then be completed by deprotection of the alcohol and installation of the nitrogen as an
azide in a Mitsunobu reaction, followed by reduction and acetylation.
Two C-H catalytic activation reactions were employed in a synthesis of rhazinal
3.23
(Scheme 3.20).
17
The
starting material was prepared from a readily available aldehyde
3.24
. An aldol reaction installed a methylene
group
to the carbonyl. This was followed by addition of methyl lithium and a Johnson-Claisen rearrangment
