Cycloadditions - Carbohydrates: Tools for Stereoselective Synthesis - page 65

which the acryloyl moiety adopts an s -trans conformation and the attack of the
diene is directed to the upper face of the acrylic double bond. Per-silylation prior
to the addition of the Lewis acid proved to be essential as otherwise the formation
of HCl and chlorotitanate salts severely hampered the Diels-Alder reaction. For
fully protected dienophiles 16 and 20, the milder Lewis acid TiCl 2 (O i Pr) 2 was suf-
ficient and the reaction was conducted at 30 to 0 °C. Both auxiliary-modified

dienophiles offered high yields of the endo -products in excellent values of dr but
even more importantly they led to a complete reversal of the asymmetric induction
of the reaction. The Diels-Alder products attached to the carbohydrate backbones
of endo - 25 and endo - 26 were obtained in opposite configuration and thus dien-
ophiles 16 and 20 act as efficient pseudo-enantiomer s. Again the authors offer a
plausible explanation of the stereochemical outcome for both dienophiles. Unlike
in the case of 21 and 23, which act as chelate ligands for one Ti(IV) center, 16 and
20 presumably do not form chelates. Instead, the pivalates and the acrylate
coordinate to one Ti(IV) center each, making the activated dienophiles very bulky
species. In the favored transition states TS-3 and TS-4 the acrylic ester moiety
exists in an s -trans conformation and is preferentially attacked by the diene from
the face opposite to the bulky pivalate at C4.
Using 16 and 20 Diels-Alder reactions of an impressive range of cyclic
and acyclic dienes were performed (Scheme 4.4), giving products in moderate to

−

O

R 4 =

CH 3
H 2
C

27

D- gluco L- arabino

L- rhamno D- arabino

O

O

H 3 C
H 3 C

PivO
PivO

R 4 =

28

O H 3 C O O

O

16

31

O

20

PivO

OMe

O O

O O

H 2
C

O O

OR 4

R 4 =

O

29 CH 3

O

Lewis acid
TiCl 2 (O i Pr) 2 or TiCl 4

H C

R 4 = 30 CH 3

Et 2 AlCl TiCl 4

TiCl 2 (O i Pr) 2 or TiCl 4

Cr(CO) 3

R 1

O

O

a

R 1 = R 2 = R 3 = H

R 2

∗

∗ ∗

Aux O Aux O

b R 1 = Me R 2 = R 3 = H

∗

∗

c

R 1 = R 2 = H R 3 = Me

R 3

d

R 1 = H R 2 = R 3 = Me

Aux O O

Aux O O endo- 11

endo- 7

endo- 9

endo- 10

dr (2R):(2S) dr (2R):(2S) dr (2R):(2S) dr (1R):(1S)

16 94% dr 95:5

16 92% dr 98:2 16 88% dr 90:10 16 87% dr 99:1 16 90% dr 92:8

20 80% dr 6:94 20 88% dr 7:93 20 52% dr 1:99 20 68% dr 5:95 20 60% dr 10:90

58% dr 64:36 40% dr 64:36

27 37% dr 75:25 27 27

a

c

28 68% dr 73:27 28 56% dr 81:19

28 48% dr 85:15

29 60% 56%de

29 65% 54%de

29 71% 66%de 30 77% 90%de

30 63 70%de

30 89% 84%de

31 65% dr 19:81

31 71% dr 0:100

27 50% dr 68:32 27 39% dr 55:45

b d

28 65% dr 79:21 28 51% dr 66:34

31 49% dr 0:100

Scheme 4.4 Diels-Alder reactions of various dienes with auxiliary-modified dienophiles by
Kunz, ( 16, 20 ), Shing ( 27-30 ), and Nouguier ( 31 ).