The Influence of Ligand Side Chain on the Enantioselectivity of Lewis Acid Catalyzed Diels-Alder Reactions.

Abstract

The enantioselective Lewis acid-catalyzed Diels-Alder reaction of 3-(2-propenoyl)-1,3-oxazolidin-2-one 8 with cyclopentadiene was examined using a series of chiral mox ligands 2-6, deferring in the side chain at 2-position of the chiral oxazoline and in the nature of the substituent at the chiral center (4-position) of the oxazoline ring, and a combination of N-[(1R)-2-chloro-1-phenylethyl]-2-[(4R)-4-phenyl-4,5-dihydrooxazol-2-yl]butyramide 2-MgI 2 -I 2 was the most efficient catalyst.

Copper-Catalyzed Diels−Alder Reactions

“…When structural modifications were made to the bis(oxazoline), disappointing results were observed. Indeed, the use of mono-oxazoline ligands possessing a lateral chain that incorporated a nitrogen atom capable of coordination to the copper center provided low enantioselectivity. , Poor enantioselectivities were also observed when the two oxazolidinyl moieties of the bis(oxazoline) were not able to bind the same copper center because of the spacer used …”

“…Indeed, the use of mono-oxazoline ligands possessing a lateral chain that incorporated a nitrogen atom capable of coordination to the copper center provided low enantioselectivity. 92,118 Poor enantioselectivities were also observed when the two oxazolidinyl moieties of the bis(oxazoline) were not able to bind the same copper center because of the spacer used. 119 Tris(oxazoline) ligands were also designed and applied in the copper-catalyzed Diels-Alder reaction, but they do not compete with the excellent enantioselectivities given by the related bis(oxazoline) ligands.…”