Enantioselective 6-endo-trig Wacker-type cyclization of 2-geranylphenols: application to a facile synthesis of (−)-cordiachromene

An enantioselective intramolecular oxidative cyclization of 2-geranylphenols catalyzed by a Pd(II)-spiro bis(isoxazoline) complex is reported. The reaction proceeds in a 6-endo-trig manner to give chromene derivatives in reasonable yields and with moderate enantioselectivities. This transformation can be applied to a protecting-group-free total synthesis of naturally occurring cordiachromene.

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(R)-6-Hydroxy-2-methyl-2-(4-methylpent-3-enyl)-2H-benzopyran (cordiachromene)C16H20O2Ee = >54%[α]D25=-58.1 (c 0.04, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)