Chemistry Reference
In-Depth Information
Pd(II)
EtO
2
C
EtO
2
C
EtO
2
C
EtO
2
C
CO
2
Me
CO
2
Me
1
1
1
1
.
2
3
Scheme 11.72
Ph
CoBr
2
L, Zn, ZnI
2
+
Ph
Ph
Ph
11.214
11.215
L = dppp
L = dppe
98:2
25:75
Scheme 11.73
This cyclization has been used in an efficient synthesis of chokol A
11.219
, an anti-fungal compound
(Scheme 11.74).
99
The acetal
11.216
, in which the tartrate moiety functions as an economical chiral auxiliary,
cyclized using palladium acetate to give an 8.5:1 mixture of stereoisomers. Acidic hydrolysis removed the
acetal to give a ketone
11.217
, which could be taken through to the natural product
11.219
by selective
reduction of the electron-poor alkene, stereoselective addition of a methyl group, allylic oxidation and
desilylation.
Ene-yne cycloisomerization was used as a key step in a synthesis of hamayne
11.225
, a crinane alkaloid
and acetylcholineesterase inhibitor (Scheme 11.75).
100
The cyclisomerization, which creates a quaternary
centre was challenging. As a thermal Alder-ene reaction, without palladium, the reaction of
11.220
did
not proceed. It was successful employing a palladium(II) catalyst with a bis-imine ligand, providing that
microwave heating was used. Further, the alkyne could not be terminal. If a terminal alkyne was employed
(R
=
H), intermolecular alkyne-alkyne coupling was observed (see Schemes 11.90-11.94), and a substituted
1. Pd(OAc)
2
2. H
3
O
+
O
(Ph
3
PCuH)
6
EtO
2
C
O
O
SiMe
3
SiMe
3
EtO
2
C
11.216
11.217
1. MeCeCl
2
2. SeO
2
,
t
-BuOOH
3. KO
t
-Bu, DMSO
OH
O
OH
SiMe
3
11.218
11.219
Scheme 11.74
