The asymmetric synthesis
of novel 3-substituted isoindolinones
is herein reported. A new cascade reaction was developed that consisted
of the asymmetric nitro-Mannich reaction of suitable α-amido
sulfones designed from 2-formyl benzoates, followed by the
in situ
cyclization of the adducts. Very high enantioselectivities,
up to 98% ee, and very good yields were obtained in the presence of
the readily available neutral bifunctional organocatalyst derived
from
trans
-1,2-diaminocyclohexane, which is known
as Takemoto’s catalyst. The investigation of the reactivity
of the obtained products allowed either the selective Boc-deprotection
or reduction of the nitro group, leading to further functionalized
3-substituted isoindolinones without affecting the enantiomeric purity.