Chromium(III)-catalyzed asymmetric pericyclic reactions: Discovery and mechanism

A new chromium(III)-catalyzed hetero-ene reaction is developed between 2-methoxypropene and benzaldehyde derivatives, generating beta-hydroxyenol ethers in high yields and enantioselectivities. These products are readily converted to the corresponding beta-hydroxyketones and beta-hydroxyesters. This ene reaction is extended to employ 2-trimethylsilyloxypropene as ene component. No silyl transfer product is observed. Subtle changes made to the tridentate Schiff base chiral ligand architecture facilitate the use of aliphatic aldehydes as enophiles. The resultant beta-hydroxytrimethylsilyl enol ethers are protected and employed as nucleophiles in subsequent boron trifluoride-promoted aldol reactions. Further changes to the catalyst electronics enable the development of hetero-ene reactions between electron-deficient aryl aldehydes and cyclic trimethylsilyl enol ethers that proceed in high enantioselectivities and high anti diastereoselectivities.; Extensive mechanistic studies performed on these hetero-ene reactions and a Cr(III)-catalyzed hetero-Diels-Alder reaction are highlighted. The reactions display similar kinetics, but different behavior in non-linear effects studies. The likely reason for this discrepancy is determined by independent crystallizations of the catalysts used in these transformations. They adopt distinct dimeric structures that are shown to have different signature signals by circular dichroism (CD) spectroscopy. This CD assay allows for the identification of structures adopted by newly synthesized catalysts.