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(R)
-configuration in the dehydropiperidine ring [26]. The conversion of
68
into
69
involved an initial Mannich reaction between the glycosylimine
68
and the siloxy
diene, followed by 1,4-addition of the intermediate glycosylamine to the resulting
conjugate enone and subsequent elimination of MeOH. For construction of
2,6-disubstituted 4-piperidone skeletons, a second 1,4-addition to the enone moiety
in
69
was explored. A combination of the organocuprate, prepared from PrMgCl
and CuCl, and boron trifluoride worked well for this purpose. Thus
cis
-2,6-di-
alkylated piperidin-4-one
70,
which incorporates the carbohydrate template at
nitrogen, was obtained with high diastereoselectivity (dr
10 : 1) and in an accept-
able yield of 81%. The Kunz group further demonstrated the synthetic utility of
piperidinone
70
for the synthesis of decahydroquinoline alkaloids. Pumiliotoxin
C, a representative of the
cis
-annulated decahydroquinoline alkaloids, was isolated
from a glandular secretion of a South American frog of the genus
Dendrobates
.
Some
trans
-annulated decahydroquinoline alkaloids are also known. The Kunz
group completed the total synthesis of
trans
-annulated 4a-epi-pumiliotoxin C (
74
)
from
70:
Oxidative cleavage of the vinyl group in the side chain in
70,
followed by
base-mediated intramolecular aldol condensation of the resulting aldehyde, pro-
duced octahydroquinoline derivative
71.
The 1,4-addition of Me
2
CuLi to the bicy-
clic enone
71
in the presence of TMSCl efficiently provided
72
(dr
>
15 : 1) after
cleavage of the intermediate silyl enol ether. From
trans
-annulated decahydroqui-
noline
72,
trans
-4a-epi-pumiliotoxin C (
74
) was synthesized in a five-step reaction
sequence, including removal of the d-galactosyl moiety and removal of the carbo-
nyl functionality in the resulting
73
via hydrogenolytic desulfurization of the cor-
responding dithiolane. More recently, the Kunz group applied these 1,4-additions
based on the 4-dihydropyridone scaffold attached at the anomeric carbon of the
d-galactopyranose to solid-phase synthesis [27, 28]. Furthermore, the Kunz group
has extended this glycosylamine-based synthesis of piperidine alkaloids to a d-
arabinosylamine-derived auxiliary, which was prepared from 2,3,4-tri-
O
-pivaloyl-
α
>
-d-arabinopyranosylamine by a reaction sequence analogous to that used for
67.
This compound acts as a pseudo enantiomer to galactosyl amine
67
and thus the
reaction with the Danishefsky-Kitahara diene leads to carbohydrate-bound dehy-
dropiperidine derivatives with stereocentres in opposite configuratiion compared
to those in galactose-bound dehydropiperidines
69.
The 1,4-addition of various
organocopper reagents to these 2-alkylated (or -arylated)
N
-arabinopyranosyl
5,6-dehydropiperidin-4-ones provided various 2,6-
cis
-substituted piperidines [29].
Desymmetrization of prochiral compounds is one of the most convenient strate-
gies for supplying enantioenriched chiral compounds. The Kunz group reported
desymmetrization of a 4-pyridone tethered to a carbohydrate unit by the nitrogen
atom. For this purpose, per-
O
-pivaloylated
-d-galactopyranosyl fluoride
75,
which
was conveniently prepared from d-galactose [24], was reacted with 4-(trimethylsi-
loxy)pyridine in the presence of a Lewis acid (TiCl
4
), which provided
N
-(
α
-d-
galactopyranosyl)-4-pyridone
76
quantitatively (Scheme 2.14) [30, 31]. The
4-pyridone
76.
This compound was subsequently treated with
i
Pr
3
SiOTf and
2,6-lutidine to form the corresponding
N
-glycosyl 4-siloxypyridinium salt, which
was reacted with organomagnesium halides (R
1
β
Me, Pr, and Ph). The expected
1,4-addition proceeded with good to excellent diastereoselectivities (80-100% de),
=
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