Directed Openings of 2,3-Epoxy Alcohols via Reactions with Isocyanates: Synthesis of (+)-erythro-Dihydrosphingosine

Article abstract of DOI:10.1021/jo00220a015

Two methods for the synthesis of 2-(N-alkylamino) 1,3-diols from 2,3-epoxy alcohols are described.In one procedure (method A) an epoxyurethane (5, 8, 11, 14, 16) prepared from the corresponding epoxy alcohol by standard procedures is cyclized to a 2-oxazolidinone derivative (6, 9, 12, 15, 17) in 81-90percent yield by treatment with NaH in THF or NaOMe in MeOH.The second procedure (method B) involves treatment of the epoxy alcohol (4, 7, 10, 13, 24) with benzyl isocyanate, an NH3 synthetic equivalent, and NaH in THF at reflux.Hydrolysis of the crude isoxazolidinones by exposure to LiOH in EtOH at reflux smoothly affords 2-(N-benzylamino) 1,3-diols (22, 23, 30, 31) in 68-72percent overall yield.These procedures are highly regioselective; products resulting from intramolecular addition of the urethane nitrogen atom to the epoxide β-position were not detected.This methodology was applied to a short, highly stereoselective synthesis of (+)-erythro-dihydrosphingosine (26) from palmitic aldehyde ( 47-54percent overall yield).