Original acyclic (E)-α,α-dialkylketonitrones bearing a chiral auxiliary on their nitrogen atom were synthesized and successfully employed for the asymmetric synthesis of α,α-disubstituted amino acids using regio- and stereocontrolled 1,3-dipolar cycloaddition reactions with vinyl ethers. N-Glycosyl chiral auxiliaries were found to provide excellent exo- and π-facial stereocontrol. The obtained enantiopure cycloadducts were selectively transformed into functional α,α-disubstituted amino acids and related β-peptides through the highly regioselective opening of an intermediate quaternary anhydride.

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Bicyclic isoxazolidines displaying one or two quaternary stereocenter(s) were formed starting from functional cyclic ketonitrones equipped with a phenyl glycinol chiral auxiliary. The products were engaged in stereocontrolled 1,3‐dipolar cycloaddition reactions with a range of electron‐rich and electron‐poor dipolarophiles. A new reductive removal of the phenyl glycinol chiral auxiliary was introduced and was shown to afford chemoselectively a quaternary isoxazolidine derivative (of oxaprolinol‐type) without cleaving the N–O isoxazolidine bond. Keeping the aldehyde function masked as a cyclic pseudo‐acetal, the liberated oxy‐amine function was shown to be available for a pseudo‐peptide coupling with various N‐protected amino acids. The isoxazolidine ring was opened by a reductive N–O bond cleavage, giving a pseudo‐dipeptide that was C‐terminated with an aldehyde function.