ENANTIOSPECIFIC SYNTHESIS OF THE (4R)-1-AZABICYCLO[2.2.1]HEPTANE RING-SYSTEM

An enantioselective synthesis of (4R)-1-azabicyclo[2.2.1]heptane derivatives is described commencing from readily available trans-4-hydroxy-L-proline which is converted into the key intermediate (3R)-N-(tert-butoxycarbonyl)-3-methylsulfonyloxypyrrolidine 4. Reaction of the sulfonate ester 4 with an enolate anion yields a mixture of (3R)-pyrrolidinylacetic esters 8 and 9 which are reduced to the corresponding alcohols 10 and 11. Conversion of the alcohols into the sulfonate esters 12 and 1 3 followed by deprotection of the pyrrolidine nitrogen leads to cyclisation yielding the (4R)-1-azabicyclo [2.2.1] heptane derivatives 14 and 15.