Chemistry Reference
In-Depth Information
TsCl, pyr.,
DMAP, CH
2
Cl
2
(quant.)
R
1
HO
HO
HO
1) MesCOOH,
TFAA, CH
2
Cl
2
2) 80% aq. AcOH
(62% for 2 steps)
Ph
O
O
O
O
HO
MesCOO
MesCOO
OMe
MesCOO
HO
OMe
MesCOO
OMe
Methyl 4,6-
O
-
benzylidene- -D-
glucopyranoside
43
:R
1
=Ts
44
:R
1
=I
42
MaI, 2-butanone,
reflux (83%)
MesCO : 2,4,6-(CH
3
)
3
C
6
H
2
CO
O
Me
Me
(CH
3
CH=CHCO)
2
O,
Et
3
N, DMAP, CH
2
Cl
2
(99%)
Xc
Raney-Ni W4,
EtOH
Me
O
O
O
HO
MesCOO
MesCOO
MesCOO
OMe
MesCOO
OMe
(85%)
45
46
R
1
I, Bu
3
SnH,
Et
3
B/O
2
,Et
2
AlCl,
CH
2
Cl
2
, -78 °C
1) 4M KOH-MeOH,
reflux, then 1M HCl
R
1
R
1
O
O
Xc
Ph
Me
O
Me
H
46
2) aniline, EDCI•HCl,
DMAP, CH
2
Cl
2
(quant. for 2 steps)
(quant.)
47
48
R
1
=
i
-Pr, 90%
de
R
1
= Et, 72%
de
R
1
=
t
-Bu, 90%
de
Scheme 2.9
Synthesis of the 2,3-
O
-mesitoyl-type auxiliary
45
and the 1,4-additions of some
alkyl radicals to its 4-
O
-crotonyl esters
46.
adducts
46,
followed by treatment of the resulting
-alkylated butanoic acids
47
with aniline in the presence of
N
-(3-dimethylamino)propyl-
N
β
′
-ethylcarbodiimide
(EDCI).
The glycopyranoside-based diastereoselective 1,4-additions were further devel-
oped by the Tadano group using other hexopyranosides, such as
α
-d-manno-
and
-d-galactopyranosides. Scheme 2.10 shows representative examples
for the d-mannopyranose-based approach [18]. Thus, two 3-
O
-crotylated-
α
-d-
mannopyranosides,
50
and
52,
were synthesized from known methyl
4,6-
O
-benzyl-
α
-d-mannopyranoside.
Selective
O
-benzylation of the 4,6-di-
O
-benzyl derivative provided
49,
which was
acylated with crotonic anhydride to provide the 3-
O-
crotonyl ester
50.
On the other
hand, treatment of the 4,6-
O
-benzyl derivative with crotonic anhydride in the pres-
ence of CuCl
2
provided preferentially the 3-
O
-crotonyl ester
51,
which was then
acylated with pivaloyl (Piv) chloride to provide
52.
The 1,4-addition of a vinyl cuprate, prepared from vinylmagnesium bromide and
cuprous bromide, to
50
preferentially provided the 1,4-adduct
53
possessing the
(R)
-configuration at the new stereogenic center, in 84% yield. Alkaline hydrolysis
of
53
to remove the carbohydrate auxiliary and successive alkylation of the result-
ing carboxylate benzyl bromide provided
α
-vinylated butanoic acid benzyl ester
54
in 76% ee. On the other hand, 1,4-addition of vinyl cuprate to
52
provided the
1,4-adduct
55,
possessing a new stereogenic center with
(S)
-configuration, in 78%
β
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