Asymmetric Syntheses of (−)-3-epi-Fagomine, (2R,3S,4R)‑Dihydroxypipecolic Acid, and Several Polyhydroxylated Homopipecolic Acids

A range of enantiopure polyhydroxylated piperidines, including (2R,3S,4R)-dihydroxypipecolic acid, (−)-3-epi-fagomine, (2S,3S,4R)-dihydroxyhomopipecolic acid, (2S,3R,4R)-dihydroxyhomopipecolic acid, and two trihydroxy-substituted homopipecolic acids, have been prepared using diastereoselective olefinic oxidations of a range of enantiopure tetrahydropyridines as the key step. The requisite substrates were readily prepared from tert-butyl sorbate using our diastereoselective hydroamination or aminohydroxylation protocols followed by ring-closing metathesis. After diastereoselective olefinic oxidation of the resultant enantiopure tetrahydropyridines and deprotection, enantiopure polyhydroxylated piperidines were isolated as single diastereoisomers (>99:1 dr) in good overall yield.