Stanley H. B. Wright

Intramolecular 1,3-dipolar additions in 4-O-allyl pyranoside 6-nitrones: An approach to chiral pyrano-pyrans and pyrano-oxepans

Abstract Treatment of the easily prepared 6-aldehydo-glucopyranoside allyl ether (5) with N-benzylhydroxylarnine gave nitrone (6), which underwent a 1,3-dipolar addition to the 4-O-allyl group giving after deprotection and hydrogenolysis the chiral pyrano-pyran (11) and the pyrano-oxepan (13).

A synthesis of 1-azabicyclo[2.2.1]heptane-3-carboxylic acid esters in enantiomerically pure form

A novel synthesis of ethyl 1-azabicyclo[2.2.1]heptane-3-carboxylate via 1-benzylperhydropyrano[3,4-c]pyrrol-4-one and 1-benzyl-3-(2-bromoethyl)-4-ethoxycarbonylpyrrolidinium bromide is described. Modification of the method, by incorporation of a chiral substituted benzyl group on the nitrogen atom, has led to the first reported process for the preparation of these esters in enantiomerically pure form. The absolute configuration of the bicyclic esters was deduced by X-ray crystallography of an intermediate, 2-[(S)-1-phenylethyl]perhydropyrano[3,4-c]pyrrole-4-one.

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 13 followed by deprotection of the pyrrolidine nitrogen leads to cyclisation yielding the (4R)-1- azabicyclo[2.2.1 ] heptane derivatives 14 and 15.