Cycloadditions - Carbohydrates: Tools for Stereoselective Synthesis - page 68

asymmetric induction in the presence of a Lewis acid was opposite to that
observed under thermal conditions and a dr of 90 : 10 in favor of the (2 R )-prod-
uct was obtained (cf. entries 2 and 5). The authors explain this switch in the
stereoselectivity by a conformational change within the acrylic ester moiety,
which is triggered by complexation by the Lewis acid (cf. Scheme 4.6 below).
The d- manno -configured dienophiles 37a-d were tested under thermal condi-
tions (not shown) and in the presence of EtAlCl 2 (entries 7-10). While thermal
conditions did not give any stereoselectivity, good to high yields and endo:exo
selectivities were observed for 37a-d in the presence of EtAlCl 2 but again the
steric bulk of the C3 substituent had strong impact on stereoselectivity. A dr of
91 : 9 in favor of the (2 R )-product was obtained for R 1 Bz ( 37c ), while smaller

and larger groups led to reduced stereoselectivity ( 37a,b and 37d ).
The alternative d-gluco configured dienophile 38 carrying the acrylic ester on
C2 was also explored under thermal conditions and Lewis acid catalysis (Table 4.1,
entries 11, 12) [5b]. High yields were obtained in both cases, but the endo:exo
selectivity was rather low under thermal conditions. As in case of dienophile 36b,
thermal conditions and Lewis acid catalysis led to opposite stereochemistry in
the Diels-Alder addition products, which were obtained in good drs in both
cases. Thus, the change in reaction conditions can be used to obtain both product
enantiomers with the same carbohydrate dienophile.
Finally, Tadano used dienophiles 37b and 38 in the asymmetric Diels-Alder
reaction with furan ( 3 ) [6]. In the presence of EtAlCl 2 good yields and high endo:exo
selectivities were observed; 37b and 38 yielded the product in opposite configura-
tion and are therefore efficient pseudo-enantiomers in this reaction (Table 4.1
entries 13, 14).
After chromatographic purification, which removed the exo -diastereomers, the
Diels-Alder products were cleaved off the carbohydrate auxiliaries by DIBALH
reduction, as exemplified for the product of dienophile 36c (Scheme 4.5). Upon
reduction (2 S )- 39c yielded norbornylmethanol, (2 S )- 40, in 94% ee, while the car-
bohydrate scaffold 41c was isolated in 76% yield and may be re-used [5b].

=

O

H 3 C H 3 C

DIBALH, CH 2 Cl 2

O O

O HO

+

TBSO TBSO

TBSO TBSO

OMe OMe

HO

(2S) -39c (2S) -40 41c

76% re-isolated

94%ee

dr (2R):(2S) = 5:95

Scheme 4.5 Cleavage of the product from the carbohydrate scaffold and re-isolation of the

auxiliary.

Scheme 4.6 presents a rationale explaining the diastereoselectivities observed
with 36b under thermal conditions and Lewis acid catalysis. The authors suggest
that the acrylic ester moiety predominantly adopts an s-cis conformation in
the absence of a Lewis acid, while coordination of a Lewis acid triggers a