title: Systematic Investigation into the Matsuda-Heck Reaction of α-Methylene Lactones: How Conformational Constraints Direct the β-H-Elimination Step.
abstract: α-Methylene-γ-butyrolactone and α-methylene-δ-valerolactone undergo Pd-catalyzed Matsuda-Heck couplings with arene diazonium salts to α-benzyl butenolides or pentenolides, respectively, or to α-benzylidene lactones. The observed regioselectivity is strongly ring size dependent, with six-membered rings giving exclusively α-benzyl pentenolides, whereas the five-membered α-methylene lactone reacts to mixtures of regioisomers with a high proportion of (E)-α-benzylidene-γ-butyrolactones. DFT calculations suggest that the reasons for these differences are not thermodynamic but kinetic in nature. The relative energies of the conformers of the Pd σ-complexes resulting from insertion into the Pd-aryl bond were correlated with the dihedral angles between Pd and endo-β-H. This correlation revealed that in the case of the six-membered lactone an energetically favorable conformer adopts a nearly synperiplanar Pd/endo-β-H arrangement, whereas for the analogous Pd σ-complex of the five-membered lactone the smallest Pd/endo-β-H dihedral angle is observed for a conformer with a comparatively high potential energy. The optimized conditions for Matsuda-Heck arylations of exo-methylene lactones were eventually applied to the synthesis of the natural product anemarcoumarin A.
authors.affiliation: Universitaet Potsdam , Institut fuer Chemie, Karl-Liebknecht-Straße 24-25, D-14476 Potsdam-Golm, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: Universitaet Potsdam , Institut fuer Chemie, Karl-Liebknecht-Straße 24-25, D-14476 Potsdam-Golm, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Wolf
authors.affiliation: Universitaet Potsdam , Institut fuer Chemie, Karl-Liebknecht-Straße 24-25, D-14476 Potsdam-Golm, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ehlert