Stereoconvergent approach for synthesizing enantiopure 5, 6-dialkylpipecolic acids.
Investigating a general route for synthesizing pipecolic acid ) piperidine-2-carboxylic acid ( derivatives with substituents at the 3-, 4-, 5- and 6-position, we discovered a stereoconvergent process that provides an effective means for making 5, 6-dialkyl-epsilonpipecolate (Scheme 1, PhF = 9-phenylfluoren-9-yl). Hydrogenation of diastereomeric mixtures of gamma-oxo gamma-hydroxy and gamma-acetoxy alpha-N-(PhF)amino tert-butyl esters causes the eventual loss of the gamma-substituent to furnish an azadiene intermediate that can reduce diastereoselectively to 5, 6-dialkylpipecolate having the all cis relative stereoconfiguration. Five enantiopure (>94% ee) 5,6-dialkylpipecolic acids were synthesized, employing aspartic acid as an inexpensive chiral educt in this process.
Swarbrick
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ME
Departement de Chimie, Universite de Montreal, Montreal, Quebec, Canada.
Lubell
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WD
D001224:Aspartic Acid / Q000737:chemistry*; D002621:Chemistry / Q000379:methods; D007659:Ketones / Q000737:chemistry; D008956:Models, Chemical; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D007659:Ketones; D010875:Pipecolic Acids; D001224:Aspartic Acid