Cyclopropyl building blocks in organic synthesis, 51 - An easy access to 1-azaspiropentane-2-carboxamides - The first derivatives of a new type of amino acids

Azaspiropentanecarboxamides 10 and 12 are formed with remarkable ease in two steps in a one-pot operation from methyl 2-chloro-2-cyclopropylideneacetate (4) by addition of a primary amine in tetrahydrofuran and subsequent treatment with sodium hydride/triethylamine in the presence of another equivalent of a primary amine or ammonia. Achievable yields of the amides 10, 12 were moderate to good (27-59%, 12-48%), while the corresponding esters 9 could only be obtained in poor yields (4-14%). The new alpha-amino acid amides are surprisingly stable, and they can be incorporated into small peptides as demonstrated with the preparation of the glycine 13e and the spirocyclopropaneoxazoline derivative 14e.