Biomedical Engineering Reference
In-Depth Information
4.2.1.2. From Alkynes Not only allenes but also alkynes can be activated by an
electrophilic gold species for the addition of oxygen nucleophiles.
As in the case of allenes, various furan or pyran derivatives can be obtained
depending on the cyclization mode (Scheme 4.12).
A fantastic example of a
g
-hydroxyalkyne cycloisomerization was reported by
Trost and Dong in their total synthesis of the anticancer agent bryostatin 16,
[10b]
(Scheme 4.13). As a proof of the mildness of the reaction conditions and the
compatibility of gold catalysis with a wide range of other oxygenated functionalities,
the cycloisomerization was performed at a very late stage of the synthesis. The Au(I)-
catalyzed transformation of the
g
-hydroxyalkyne
35
33
was selective toward the
formation of compound
that results from a 6-
endo
cyclization mode. Notably,
other electrophilic metals such as palladium afforded mixtures of five- and six-
membered cycles.
34
n
= 1
endo
n
= 2
endo
O
O
Au(I)
or
Au(III)
n
= 3-4
2,3-Dihydrofuran
3,4-Dihydropyran
n
OH
n
= 1-3
Hydroxyalkyne
n
= 2
exo
n
= 3
exo
O
O
exo
-Methylene-
tetrahydropyran
exo
-Methylene-
tetrahydrofuran
SCHEME 4.12
MeO
HO
OH
OH
H
3
COOC
H
3
COOC
O
O
O
O
OTES
O
(Ph
3
P)AuCl (20 mol%)
OTES
O
AgSbF
6
(20 mol%)
HO
O
O
O
NaHCO
3
CH
2
Cl
2
/CH
3
CN
OTBS
OTBS
0°C to rt
73%
COOCH
3
COOCH
3
33
34
1. Piv
2
O, DMAP
CH
2
Cl
2
, 50°C (62%)
2. TBAF, THF (50%)
HO
OPiv
H
3
COOC
O
O
OH
O
O
O
Bryostatin 16
35
OH
COOCH
3
SCHEME 4.13
Synthesis of the anticancer agent bryostatin 16 by Trost and Dong.
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