Chemistry Reference
In-Depth Information
The hydroxy protective group has little effect on the diastereoselectivity of the
process, but it significantly influences the yield, probably by affecting the stability
of enolates, with silyl groups being most successful (Table 3.1). The alkylated
products
40
were generally obtained good yields and excellent diastereoselectivity
(up to 98%). The absolute configuration of the newly created chiral center
(R)
product was determined X-ray analysis and by chemical correlation of the free
hydroxy acids
41,
which was obtained without racemization in the saponification
step.
Compared to other approaches developed for the asymmetric synthesis
of
-hydroxy acids, the fructose auxiliary gave slightly lower yield and
stereoselectivity than Katsuki's pyrrolidine [17] and Wang's [18] and Pearson's [19]
dioxolane auxiliaries. It is not quite as selective as the Evans auxiliary [20], but it
gave good yields with various electrophiles, including many less reactive iodides
(Table 3.2).
α
Table 3.1
Diastereoselective methylation of the enolate derived from
39.
O
O
O
Me
1) LiHMDS
O
O
O
O
O
OR
OR
2) MeI
THF/ HMPA
-95 °C
O
O
O
O
O
O
40a-k
39a-k
Entry
Substrate
R
a)
Product
Yield (%)
de (%)
b)
1
39a
Bn
40a
73
86
2
39b
CH
2
C
6
H
4
NO
2
(
p
)
40b
19
89
3
39c
PMB
40c
66
91
4
39d
CH
2
C
6
H
4
F (
p
)
40d
75
93
5
39e
Me
40e
66
92
6
39f
MOM
40f
65
91
7
39g
BOM
40g
68
87
8
39h
TBS
40h
76
84
c)
89
c)
9
39i
TBDPS
40i
83
10
39j
TES
40j
77
88
c)
11
39k
TIPS
40k
70
84
a) PMB
=
p
-methoxybenzyl; MOM
=
methoxymethyl; BOM
=
benzyloxymethyl;
TBS
=
t
-butyldimethylsilyl; TBDPS
=
t
-butyldiphenylsilyl; TES
=
triethylsilyl; TIPS
=
tris(isopropyl)
silyl.
b)
Determined by 1H NMR.
c)
Reaction conducted at
−
78 °C.
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