Organocatalytic Asymmetric Michael Addition of Aliphatic Aldehydes to Indolylnitroalkenes: Access to Contiguous Stereogenic Tryptamine Precursors

Because
of the importance of the indole framework and the versatile
transformation of nitro and formyl groups, the efficient synthesis
of optically pure 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanals,
one type of tryptamine precursors are of great interest for pharmaceutical
and biological research. Herein, the Michael addition of aliphatic
aldehydes to indolylnitroalkenes has been developed using (S)-diphenylprolinol trimethylsilyl ether as an organocatalyst,
which provides the desired optically pure syn 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanal derivatives in up to 98% yield
with up to >99:1 dr and >99% ee. To show the
synthetic
usefulness of this methodology, optically active 2-alkyl-4-nitro-3-(1-tosyl-1H-indol-3-yl)­butan-1-ol and tryptamine derivatives are readily
obtained by stepwise systematic transformations.