The Application of HETPHOX Ligands to the Asymmetric Intermolecular Heck Reaction of 2,3-Dihydrofuran and 2,2-Disubstituted-2,3-Dihydrofurans

Abstract

A series of thiophene- and benzothiophene-oxazoline containing ligands, were applied in the intermolecular asymmetric phenylation and cyclohexenylation of 2,3-dihydrofuran 1. Phenylation proceeded in moderate to high chemical yields, with good re­gioselectivities and in up to 95% ee. Cyclohexenylations gave similarly high chemical yields and regioselectivities with the optimal result being a 96% yield of the major product in 97% ee. 2,2-Dialkyl-2,3-dihydrofurans were also tested as substrates and the phenylation and cyclohexenylation of 2,2-dimethyl-2,3-dihydrofuran proceeded in high yields and ee’s up to 91% and 89%, respectively. The phenylation and cyclohexenylation of the 2,2-diethyl analogue proceeded in excellent yields and ee’s up to 99% and 87%, respectively. For each substrate, palladium complexes formed from the t-butyl-substituted ligand 10 gave the highest yields, regioselectivities, and enantioselectivities over the broad range of reaction conditions studied. 2,2-Diisopropyl-2,3-dihydrofuran was prepared but was found to be unreactive in the intermolecular Heck reaction thus providing insight into to the steric limits for 2,3-dihydrofuran substrates.

Key words

P,N ligands - oxazoline - asymmetric catalysis - intermolecular Heck reaction - palladium

References

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End, N.; Stoessel, C.; Berens, U.; di Pietro, P.; Cozzi, P. G. submitted to Tetrahedron: Asymmetry; Special Issue on phosphorous ligands.