Biomedical Engineering Reference
In-Depth Information
Ph
Ph
OH
Propargyl bromide
NaHCO
3
, DMF, 70°
C
Ph
EtOH, rt
Ph
(HO)
2
B
HN
CO
2
Me
N
CO
2
Me
O
O
85%
86%
H
2
N
2
Me
Ph
Ph
OH
OH
45
46
47
48
(de > 99%)
49
[Pd] (10 mol%)
PhH, 80°C
(81%)
Grubbs-Hoveyda
(10 mol%)
CH
2
Cl
2
, reflux
(89%)
[Ru] (10 mol%)
acetone, rt
(85%)
[Au] (10 mol%)
MeOH, rt
(80%)
[Co], Me
3
NO
NH
4
Cl, PhH, rt
(85%)
NaH, PhMe, rt
(88%)
m
-CPBA, THF
-78 to 0°C
(87%)
Ph
Ph
Ph
Ph
CO
2
Me
MeO
2
C
N
MeO
2
C
N
MeO
2
C
N
N
O
Ph
Ph
H
H
Ph
H
O
OH
H
OH
Ph
OH
OH
50
51
52
(dr > 10:1)
56
Ph
Ph
Ph
O
N
CO
2
Me
N
MeO
2
C
N
MeO
Grubbs-Hoveyda
(10 mol%)
CH
2
Cl
2
, reflux
(90%)
O
O
Ph
H
H
H
OH
Ph
Ph
53
(
trans
/
cis
= 6.7:1)
54
55
CH
2
Cl
2
, rt
(72% from
trans
-
53
)
Grubbs-Hoveyda
(10 mol%)
CH
2
Cl
2
, reflux
(87%)
[Co], Me
3
NO
PhH, rt
(85%)
[Ru] (10 mol%)
acetone, rt
(91%)
[Pd] (10 mol%)
PhH, 80°C
(70%)
Ph
Ph
Ph
Ph
Ph
CO
2
Me
Ph
O
MeO
2
C
N
O
O
N
N
O
N
N
O
N
O
Ph
O
O
H
O
N
N
H
OH
H
H
O
H
H
O
Ph
Ph
N
O
Ph
Ph
Ph
62
61
(
trans
/
cis
= 6.4:1)
60
59
58
OH
57
(
trans
/
cis
= 3:1)
Me
CH
2
Cl
2
, rt
(65% from
trans
-
61
)
CH
2
Cl
2
, rt
(80% from
57
)
Ph
Ph
CO
2
Me
S
O
CO
2
Me
N
N
H
H
N
O
O
N
CO
2
Me
N
H
N
N
O
Ph
Ph
N
Ph
O
O
Ph
N
N
O
OH
OH
OH
N
Me
O
Me
64
65
66
63
SCHEME 15.6
diastereomeric ratio (dr
via a Pauson-Khand
reaction [40] catalyzed by Co
2
(CO)
8
. Ene-yne metathesis catalyzed by the Grubbs-
Hoveyda catalyst [41] provided diene
10:1) into the cyclopentenone
52
H
53
with moderate diastereoselectivity (
trans
/
cis
in methanol following
an electrophilic activationof the alkynemoiety in the presence ofNaAuCl
4
[42].Under
basic conditions, compound
¼
6.7:1). The morpholine scaffold
54
was obtained from
49
55
without epimerization. A Meisenheimer rearrangement promoted by
m
-CPBA led to
the allylic
N
-oxide
49
underwent a transesterification to give lactone
56
, which after ene-yne metathesis provided diene
57
in excellent
yield, yet with moderate diastereoselectivity (
trans
/
cis
was sub-
jected to a second round of differentiation that led to additional skeletal diversity
represented by structures
¼
3:1). Lactone
55
58
-
61
obtained from similar metal-catalyzed processes.
Dienes
were reacted with 4-methyl-1,2,4-triazoline-3,5-dione to afford
the corresponding Diels-Alder adducts
53
,
57
, and
61
, obtained independently as
major products. This outstanding exampleof abranchingpathway involvingonly three
to five synthetic steps led to 15 structurally different molecular skeletons bearing very
62
,
63
, and
64
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