The morpholine substructure is quite common in nature and has many pharmacological attributes including antiviral (moroxydine, morazine), analgesic (morpheridine), antitussive (pholcodine), musche relaxant (flumetramide), antiolytic (molindine), and antiparasitic (minorazole) applications. Additional examples include Largorce's report that morpholines and iodine form charge-transfer complexes with applications in novel thyroid-targeting drugs~1 and Bianchi's report that morpholine-based fungicides control Helminthosporium teres with excellent selectivity.~2 Morpholines can also play a significant role in modern organic synthesis. For example, Enders et al. recently reported that (S,S)-3,5-dimethylmorpholine imparts good to excellent diastereoselectivity when employed as a C2-symmetric auxiliary in Diels-Alder reactions.~3 In light of these valuable biological and synthetic uses, we undertook a study targeting optically active 3-hydroxymethyl-5-alkylmorpholines from amino acids and report here a concise route to 5 (Scheme 1).
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