Christopher F. Palmer

PREPARATION OF (S)-2-QUINOLYLALANINE BY ASYMMETRIC HYDROGENATION

Abstract The synthesis of ( S )-2-quinolylalanine through asymmetric hydrogenation with ( S,S )-Et-DuPHOS-Rh is described. The reaction has been extended to other 2-pyridylalanie derivatives.

Synthesis of carbocyclic clitocine

Abstract Cyclopentadiene has been converted into carbocyclic clitocine (2) in eleven steps.

Conversion of (–)-4-hydroxy-2-oxabicyclo[3.3.0]oct-7-en-3-one into the anti-HIV agent carbovir

The lactone (±)-1 was resolved using Pseudomonas fluorescens lipase and vinyl acetate; the ester (–)-3 obtained by this process was subsequently converted into the anti-HIV agent carbovir (–)-9.

Unexpected stereoselectivity in the cis dihydroxylation of some 2-cyclopentene-1-carboxamides

While 4-substituted-2-cyclopentene-1-carboxylate esters gave no facial selectivity in the cis dihydroxylation of the olefin function with osmium tetroxide/N-methylmorpholine-N-oxide, the corresponding carboxamides unexpectedly gave high diastereoselectivity for the isomer useful for carbocyclic ribofuranosyl nucleosides.

Synthesis of monohydroxylated 2-azabicyclo[2.2.1]heptan-3-ones

Oxymercuration/demercuration of 2-benzyl-2-azabicyclo[2.2.1]hept-5-en-3-one (1) and biohydroxylation of the corresponding saturated lactam (−)-( 8 ) are compared as methods for the preparation of monohydroxylated 2-azabicyclo[2.2.1]heptan-3-ones.

CHEMOENZYMATIC SYNTHESIS OF A NOVEL LIGAND FOR RHODIUM-CATALYSED ASYMMETRIC HYDROGENATION

The hydrogenation of alkenes 7a–g using a chiral rhodium catalyst 6 (based on a bicyclo[3.2.0]heptane framework) takes place to give the phenylalanine derivatives 8a–g with remarkably high stereoselectivity (59–92% ee).

An unprecedented entry to 5,6-dihydroxy-2-azabicyclo[2.2.1]heptan-3-one

A catecholborane mediated reaction of the lactam epoxide unexpectedly gave the cis-diol a useful intermediate for adenosine agonists. The origin of this reaction is postulated to arise from the formation of a boronic anhydride which is transferred to the electron deficient C-6 via transannular attack by the amide nitrogen.

Rearrangement of 2-azabicyclo[2.2.1]hept-5-en-3-ones: synthesis of cis-3-aminocyclopentane carboxylic acid derivatives

The γ-lactam 4 was converted into the bromo ester 6 and the latter compound was transformed in five steps into the diester 10. Similarly the lactam 4 was converted into the hydroxy amide 17via the intermediacy of the dihalogeno compound 11. Compounds 10 and 17 are potential precursors of deoxycarbocyclic nucleosides. Unexpectedly, the lactam 4 furnished the addition product 25 on reaction with benzeneselenenyl bromide and a tentative rationale for the preferred reaction pathway is proposed.

Electrophilic substitution of a 2-azabicyclo[2.2.1]hept-5-en-3-one as a potential route to 3-deoxycarbocyclic nucleosides

The γ-lactam 9 reacted with bromine in the presence of acetic acid or fluoride ion to give the 6,7-substituted 2-azanorbornan-3-ones 10 or 15 respectively. The latter compounds were converted into the cyclopentylamine derivatives 14 and 16 which represent potentially useful precursors for carbocyclic 3-deoxyribonucleosides.

Conversion of one enantiomer of the carbocyclic nucleoside synthon 2-azabicyclo[2.2.1]hept-5-en-3-one into the other

The lactam synthon 2-azabicyclo[2.2.1]hept-5-en-3-one was converted into its enantiomer by a 5-step sequence incorporating a skeletal rearrangement mediated by anchimeric assistance of the nitrogen atom; the route proceeded via a tosylate intermediate prone to racemization.