Abstract
The direct α-amination of carbonyl compounds using organocatalysts represents a powerful
and atom-economical tool for asymmetric C–N bond formation. We describe a complete
account of α-functionalization of carbonyl compounds, through iterative sequential
α-aminoxylation/amination using electrophilic O and N sources, as well as sequential
α-amination/HWE reaction for enantio- and diastereoselective synthesis of both syn- and anti-1,3-aminoalcohols and 1,3-diamines. Additionally this protocol is further extended
for the easy construction of alkaloids such as indolizidine, pyrrolizidine, and quinolizidine
fused-ring systems just by tuning the chain length of the aldehyde used as a starting
material. This methodology provides further scope to extrapolate it for a variety
of naturally occurring hydroxylated monocyclic and fused bicyclic pyrrolidine and
piperidine based alkaloids such as lentiginosine, epi-lentiginosine, dihydroxypyrrolizidine, (+)-deoxoprosophylline and (–)-deoxoprosopinine
alkaloids. Furthermore, we have also uncovered proline-catalyzed anti-selectivity for the synthesis of 1,2-amino alcohols in α-amination of aldehyde and
one-pot indium-mediated Barbier type allylation of α-hydrazino aldehydes to accomplish
the total synthesis of clavaminols, sphinganine and spisulosine with reduced number
of steps and with high overall yields.
1 Introduction
2 Application in the Total Synthesis of Alkaloids
3 Conclusion
Key words
natural products - alkaloids - organocatalysts - α-amination - C–N and C–O bond formation
