Co-catalyzed reductive cyclization of azido and cyano substituted α,β-unsaturated esters with NaBH4: enantioselective synthesis of (R)-baclofen and (R)-rolipram ☆

Abstract Sodium borohydride in combination with a catalytic amount of CoCl 2 has been found to be an excellent catalytic system in reductive cyclizations of suitably substituted azido and cyano groups of α,β-unsaturated esters to afford γ and δ-lactams in high yields. The process has been demonstrated for the enantioselective synthesis of ( R )-baclofen, ( R )-rolipram, and ( R )-4-fluorophenylpiperidinone, a key intermediate for (−)-paroxetine.