Biomedical Engineering Reference
In-Depth Information
Me
O
NO
2
H
N
Ph
Ph
N
Ph
N
CO
2
Et
1. Ac
2
O
Pyridine
EtO
2
C
EtO
2
C
NO
2
129
AgOAc
Et
3
N
51%
NO
2
2. Triton B
N
Me
CO
2
Me
N
Me
CO
2
Me
N
Me
63%
128
130
131
1. Zn, HCl
2. LiAlH
4
58%
Et
Et
1. TBSCl,
DBU
2.
Ph
OMe
N
N
Ph
I
HO
HO
N
HO
HN
3. Bu
4
NF/SiO
2
N
O
N
52%
N
Me
N
Me
O
133
132
Cephalotaxine
SCHEME 13.29
a sequence of alcohol protection, reaction of the indole with Eschenmoser's salt, and
deprotection of the alcohol produced
133
in 52% yield.
The
cis
-relationship between carboxyl and aryl groups in
130
stems from the
specific configuration of the ylide that results from the preferred
trans
disposition of
the substituents in imine
129
. As a result, the selective synthesis of 2,5-
trans
-
substituted pyrrolidines using amino acid-derived ylides in 1,3-dipolar cycloadditions
is difficult. Williams and coworkers developed an approach for overcoming this
limitation by condensing the glycine equivalent
134
with sterically hindered
aldehydes to generate the ylide (Scheme 13.30) [59]. For example,
134
was
condensed with propionaldehyde, generating ylide
135a
that underwent cycloaddi-
tion with dimethyl maleate to afford a 1.33:1 mixture of diastereomers predominating
in
136a
, though in only 32% yield. Using isobutyraldehyde, however, produced
136b
as a single isomer in 52% yield. Each of the products results from
endo
mode of
cycloaddition. Hydrogenolysis of
136a
and
136b
over catalytic amounts of Pd/C gave
137a
and
137b
in 93% and 99%, respectively.
This strategy for selectively fashioning 2,5-
trans
-disubstituted pyrrolidines
was applied toward the asymmetric synthesis of themanzamine alkaloid nakadomarin
A. Here, condensation of
134
with chiral aldehyde
138
in the presence of
139
Ph
Ph
OH
Ph
Ph
N
O
Ph
H
2
Pd/C
RCHO
p-
TsOH
MeO
2
C
CO
2
M
e
R
Ph
O
O
N
O
R
O
N
H
HN
O
MeO
2
C
CO
2
Me
O
R
CO
2
Me
MeO
2
C
134
135a
(R =
n
-Pr)
135b
(R =
i
-Pr)
136a
(R =
n
-Pr; 32%)
136b
(R =
i
-Pr; 52%)
137a
(R =
n
-Pr; 93%)
137b
(R =
i
-Pr; 99%)
SCHEME 13.30
Search WWH ::
Custom Search