TheN-Benzylirninederivedfrom2,3-di-O-benzyl-D-glyceraidehyde reactswithDanishefsky's diene to afford the correspondinghetero Diels-Alder adductwith a high diaatereoaelectivity. This compoundcanbe.transformed to enantiomerically pure(2R)40xopipecolicacid 01997 EIsevierScienceLtd.
The piperidine ringis oneof the mostabundantmolecularfragmentsin bothnaturalproductsandsynthetic compoundswithbiologicalactivity.1Forthisreason,the development of methodsforthe asymmetricsynthesis of homochirslpipendinebuildingblockshas recentlyreceivedconsiderableattention.zThe asymmetrichetero Diels-Aldercycloadditionusingiminesas dienophileshas givenaccessto a widevarietyof possibilitiesforthe synthesisof the piperidinering.The lowreactivityof commondeactivatediminesis counteractedby the useof electron-richbutadienederivativessuch as Brsssard'sdiene and Dsnishefsky'sdiene and/orthe use of Lewis acids. The diastereoselectivityof this reactionhas been investigatedwith chiral imines derivedfrom chirrd amines,qchid aminoslcohols,dchirrtlaminosugars,sor chirrdaminoacidderivatives,cas well as withthe use of chiral Lewis acids,7 and more recently with the use of chiral dienes.gNevertheless,to the best of our knowledgeandexcludingthe workof Akibaet al.?a thatdescribesthe useof thebenzyliminederivedform(S')lactaldehydeas the startingmaterial,andthe workof MidlandrmdMcLoughlin,9b that studiesthe cycloaddition reaction of a chiral imine derived from (2R,3S)-2,3-O-cyclohexylidene-2,3-dihy&oxybutyrddehyde with Brassard'sdiene,therearenoexamplesin theliteratureof heteroDiels-Alder cycloaddition reactionsusingchid iminesas dienophilesin whichthe chid matrixis thecsrbonylmoiety.
Ourrecentworkhas beendirectedtowardsthe synthesisof highlytimctionalisedaminoacidsfromchid iminesderivedfromconvenientlyprotectedD-glyceraldehyde,lo a usefulstartingmaterialfromthe chirslpool. Duringthe courseof this resewchwe havestudiedthe behaviourof imine 1,preparedfrom2,3-di-O-benzyl-Dglycerrddehyde andbenzylsminein the presenceof anhydrousmagnesiumsulphate,10btowardsDanishefsky's diene.