Hetero-Diels–Alder and pyroglutamate approaches to (2S,4R)-2-methylamino-5-hydroxy-4-methylpentanoic acid

The stereoselective syntheses of fully protected (2S,4R)-2-methylamino-5-hydroxy-4-methylpentanoic acid, a non-coded amino acid of cyclomarin A, and its diastereomer are reported. A pyroglutamate template was employed in the key diastereoselective alkylation used for introducing the 4-methyl stereochemistry. In addition, the first diastereoselective intramolecular hetero-Diels–Alder of a 2-cyano-1-azadiene with an electron deficient dienophile is described.