Reaction of Enolates - Carbohydrates: Tools for Stereoselective Synthesis - page 50

process was around 5-10 : 1, with an intriguing reversal of the asymmetric induc-
tion by changing the R group from an aliphatic to an aromatic group. The authors
proposed that their aliphatic imides formed lithium-chelated (Z) -enolates 22,
which were alkylated on the exposed Si -face to yield adducts 24. By an undeter-
mined stereoelectronic effect between the carbohydrate auxiliary's oxygen and the
aromatic ring of the imide, aryl substituted imides seem to form preferentially
the (E) enolates 23, leading to the alkylated products 25 through Re- face attack
(Scheme 3.10).

R 2 O

O O

O

R 1

O

R 1 = alk y l

O

1

R

R 2 X

N

N

O O

O O

O

Li

D- xylo 24

O

22

O

O

O LiHMDS

R 1

N

O O

R 1

O

O

R 2

O O

O

21

R 1 = ar y l

O

N

R 2 X O

1

R

O O

Li

N

O O O

25

O

23

Scheme 3.10 Aldol reaction using a xylose-derived oxazolidinone as chiral auxiliary.

More recently, Tadano's group has successfully used carbohydrate auxiliaries in
several stereoselective C-C bond formations, such as 1,4-additions of organocop-
per reagents, conjugate additions of alkyl radicals, and Diels-Alder reactions [12].
In the case of enolate alkylation, they have found that d-glucopyranoside 26 gave
the best results. Alkylation of the sodium enolate derived from 4- O -acyl derivative
27 with alkyl halides provided the desired compounds 29 with excellent yield and
90-96% de (Scheme 3.11) [13].
The high stereoselectivity observed was explained by invoking the formation of
(Z) -enolate 28, as a consequence of an unfavorable steric interaction between the
R 1 group and the carbohydrate framework and an effective blockade of the front
side of the enolate by the TBS ( t -butyldimethylsilyl) group on O3.
The same explanation was invoked for the high diastereoselectivity obtained
during the asymmetric synthesis of compounds with an all-carbon stereogenic
center through a double alkylation of the -carbon of 4- O -acetoacetyl derivative 30,

which was also prepared by acylation of 26 (Scheme 3.12) [14]. The acetoacetate
30 exists as a 3 : 1 mixture of the diketo and keto-enol forms. The C-methylation
at the

α

-carbon of this mixture occurred on using K 2 CO 3 with methyl iodide at
40 °C. NMR analysis of the mixture indicated that the mono C-methylated product
31 exists as a 5 : 2 : 2 mixture of three tautomeric forms. The second alkylation
reaction of this mixture using sodium methoxide as base and benzyl bromide or

α