Enantioselective Addition Reactions Catalyzed by Carbohydrate-Derived Organocatalysts - Carbohydrates: Tools for Stereoselective Synthesis - page 353

Table 16.6 Continued )

O 2 N

O

11f (15 mol%)

O

PhCO 2 H (5 mol%)

NO 2 +

*

H 2 O (2.0 equiv)
toluene, rt

Ph () n Ph

() n

Ketone Yield (%) syn / anti ee (%) ( syn)

Acetophenone 85 — 96

OAc

Cyclohexanone 89 71/29 95

S

O

Acetone 85 — 94

AcO
AcO

N N

NH 2

OAc

H
11f

H

S

S S

OR

N

H

OR OR

N

N -H 2 O N H

O

N N N

O O

NH 2 N

H

H

H H

H H

RO RO O

OR

RO RO O RO RO O

OR OR

OH 2

O

N O

N O N O

H

R'

R' R'

12

O

H 2 O+H +

-H +

Michael Donor
& Acceptor

O 2 N

R'

‡

S

S

OR

OR

N H

S N H

N

O N

N

O N

H

OR H

H

N

H

N

O

N

RO RO O

OR RO

O

H OR

H

RO

N O

N O

RO

OR

O 2 N

RO

si

R'

R'

R'

14 13

Figure 16.2 Plausible mechanism for bifunctional amine-thiourea catalysis.

A bifunctional catalytic mechanism was suggested in which the thiourea moiety
interacts through hydrogen bonding with the nitro group of the

unsaturated
nitroolefin enhancing its electrophilicity while the neighboring primary amine
activates ketones by formation of an enamine intermediate 13 which is promoted
by acid additives. Subsequently, the C-nucleophile attacks the Si -face of the

α - β

-
carbon at the nitroolefin to give the imine intermediate 14. Finally, the catalyst is
regenerated through hydrolysis of the imine 14 by water (Figure 16.2).

β