Highly substituted amino alcohols or N‐hydroxyamino alcohols can be prepared in good yield through a novel reductive cross‐coupling of nitrones with aldehydes or ketones (see scheme). The reactions are fast and highly chemoselective, that is, no homocoupling or reduction products are formed.
We have performed a detailed study of the title reaction, which is the key step of one of the most
realistic processes suggested for the prebiotic synthesis of amino acids. From a methodological point of view,
our results confirm the reliability of the integrated computational tool formed by the B3LYP density functional
model and the polarizable continuum model for the description of solvent effects. From a more chemical point
of view, the reaction is quite unlikely in the gas phase due to the presence of significant reaction barriers,
whereas the aqueous medium leads to a more feasible mechanism thanks to the preferential solvation of
zwitterionic transition structures. Both specific and bulk solvent effects play a role in determining the overall
mechanism.
[reaction: see text] A concise total synthesis of (+)-hyacinthacine A(2), a polyhydroxylated pyrrolizidine alkaloid, is described using our recently discovered inversion of the C-N bond polarity in nitrones. In the key step, the diastereoselective reductive coupling of a L-xylose-derived cyclic nitrone with ethyl acrylate allowed the assembly of the bicyclic core of the target molecule, by way of a tandem formation of the C-C and C-N bonds. The method opens a novel, short, and general route for the synthesis of other pyrrolizidine alkaloids.
Enantioselektive Synthese von γ‐Aminosäure‐Derivate: Die Umpolung der CN‐Bindung von Nitronen gelingt durch Reduktion mit SmI2. Auf diese Weise gebildete Spezies addieren unter milden Bedingungen mit exzellenter Stereoselektivität an α,β‐ungesättigte Ester. Man erhält γ‐N‐Hydroxyaminoester (siehe Schema).
The zinc-mediated reduction of nitroalkanes and nitroarenes in the presence of aldehydes is an efficient method to synthesize a wide range of nitrones. This method is mild enough to accommodate a variety of functional groups. It is particularly useful when the intermediate hydroxylamines are unstable and/or watersoluble. We used it to prepare several aromatic, aliphatic and highly functionalized sugar-derived nitrones.
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