Chemistry Reference
In-Depth Information
As the typical carbon-carbon bond-forming reaction using carbohydrate tem-
plates, the Tadano group explored the 1,4-conjugate additions of organometallic
species to
-unsaturated esters, such as crotonyl or cinnamoyl esters incorpo-
rated at the C4 of methyl 6-iodo-, 6-deoxy-2,3-di-
O
-protected, or 2,3,6-tri-
O
-
protected or at C6 of 2,3,4-tri-
O
-proteced
α
,
β
-d-glucopyranosides [17, 18]. As one
example, the synthesis of methyl 2,3-di-
O
-benzyl-6-deoxy-
α
-d-glucopyranoside
20
and the 1,4-addition of an organocopper reagent to its 4-crotonyl ester
21
are
depicted in Scheme 2.5. The carbohydrate auxiliary
20
was synthesized efficiently
from known methyl 2,3-di-
O
-benzyl-
α
-d-glucopyranoside by a two-step reaction
sequence, that is, hydride reduction of the corresponding 6-
O
-tosylate. The
crotonyl ester formation of the hydroxyl group at C4 in
20
provided
21.
The
1,4-addition of a vinylcopper reagent, prepared by mixing vinylmagnesium
bromide and cuprous bromide-dimethyl sulfide complex in THF-Me
2
S (2 : 1),
provided preferentially the 1,4-adduct
22
in 90% yield with 74% de.
α
1) TsCl, pyridine (quant.)
2) LiAlH
4
, THF , reflux
(81%)
OH
(MeCH=CHCO)
2
O, Et
3
N,
DMAP, CH
2
Cl
2
(99%)
Me
O
O
HO
HO
BnO
BnO
BnO
OMe
BnO
OMe
20
Methyl 2,3-di-
O
-benzyl-
-D-glucopyranoside
CH=CHMgBr,
CuBr•Me
2
S,
THF-Me
2
S (2:1),
—78 °C
O
O
Me
Me
O
O
Me
O
Me
O
BnO
BnO
(90%)
BnO
OMe
BnO
OMe
21
22 (
74%
de
)
Scheme 2.5
Synthesis of 2,3-di-
O
-benzyl-6-deoxy-
α
-d-glucopyranoside
20
and subsequent
1,4-addition of a vinyl cuprate to its 4-
O
-crotonyl ester
21.
-
d-glucopyranoside
26
as the most effective chiral auxiliary to date for the 1,4-
conjugate addition of organocuprates to an unsaturated ester incorporated in a
hexopyranoside derivative. Compound
26
was prepared efficiently staring from
methyl 4,6-
O
-benzylidene-
The Tadano group introduced 6-deoxy-2,3-di-
O
-(
t
-butyldimethylsilyl)-
α
-d-glucopyranoside [19] (Scheme 2.6):
O
-Silylation of
the 4,6-
O
-benzylidene derivative with
t
-butyldimethylsilyl (TBS) chloride, followed
by removal by hydrogenolysis of the benzylidene acetal in the resulting
23,
and
successive mono-
O
-sulfonyl ester formation provided the 6-
O
-tosyl derivative
24.
After substitution of the
O
-tosyl group by an iodo group, the resulting iodide
25
was treated with Raney nickel in EtOH to provide the auxiliary
26.
To introduce
an unsaturated ester as the reaction site for the planned 1,4-addition,
26
was
treated with crotonic acid in the presence of trifluoroacetic anhydride (TFAA) to
provide the 4-
O
-crotonyl derivative
27.
The 1,4-additions of three organocuprates
to
27
provided the 1,4-addcuts
28
in high yields with useful levels of diastereose-
lectivity (90% de) (Scheme 2.6) [20]. All the 1,4-adducts
28
(R
2
α
vinyl, ethyl, and
phenyl) possess the same configuration at the newly introduced stereocenter at
=
Search WWH ::
Custom Search