TY  - JOUR
A1  - Schmidt, Bernd
A1  - Wolf, Felix
A1  - Ehlert, Christopher
T1  - Systematic Investigation into the Matsuda-Heck Reaction of alpha-Methylene Lactones: How Conformational Constraints Direct the beta-H-Elimination Step
T2  - The journal of organic chemistry
N2  - alpha-Methylene-gamma-butyrolactone and alpha-methylene-gamma-valerolactone undergo Pd-catalyzed Matsuda-Heck couplings with arene diazonium salts to alpha-benzyl butenolides or pentenolides, respectively, or to alpha-benzylidene lactones. The observed regioselectivity is strongly ring size dependent, with six-membered rings giving exclusively alpha-benzyl pentenolides, whereas the five-membered alpha-methylene lactone reacts to mixtures of regioisomers with a high proportion of (E)-alpha-benzylidene-gamma-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 sigma-complexes resulting from insertion into the Pd-aryl bond were correlated with the dihedral angles between Pd and endo-beta-H. This correlation revealed that in the case of the six-membered lactone an energetically favorable conformer adopts a nearly synperiplanar Pd/endo-beta-H arrangement, whereas for the analogous Pd sigma-complex of the five-membered lactone the smallest Pd/endo-beta-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.
Y1  - 2016
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/44740
SN  - 0022-3263
VL  - 81
SP  - 11235
EP  - 11249
PB  - American Chemical Society
CY  - Washington
ER  -