A Lewis Acid-Controlled Enantiodivergent Epoxidation of Aldehydes.

Two epoxidation catalysts, one of which consists of two VANOL ligands and an aluminum and the other that consists of two VANOL ligands and a boron, were compared. Both catalysts are highly effective in the catalytic asymmetric epoxidation of a variety of aromatic and aliphatic aldehydes with diazoacetamides, giving high yields and excellent asymmetric inductions. The aluminum catalyst is effective at 0 °C and the boron catalyst at -40 °C. Although both the aluminum and boron catalysts of (R)-VANOL give very high asymmetric inductions (up to 99% ee), they give opposite enantiomers of the epoxide. The mechanism, rate- and enantioselectivity-determining step, and origin of enantiodivergence are evaluated using density functional theory calculations.

Probing Catalyst Function - Electronic Modulation of Chiral Polyborate Anionic Catalysts.

Boroxinate complexes of VAPOL and VANOL are a chiral anionic platform that can serve as a versatile staging arena for asymmetric catalysis. The structural underpinning of the platform is a chiral polyborate core that covalently links together alcohols (or phenols) and vaulted biaryl ligands. The polyborate platform is assembled in situ by the substrate of the reaction, and thus a multiplex of chiral catalysts can be rapidly assembled from various alcohols (or phenols) and bis-phenol ligands for screening of catalyst activity. In the present study, variations in the steric and electronic properties of the phenol/alcohol component of the boroxinate catalyst are probed to reveal their effects on the asymmetric induction in the catalytic asymmetric aziridination reaction. A Hammett study is consistent with a mechanism in which the two substrates are hydrogen-bonded to the boroxinate core in the enantiogenic step. The results of the Hammett study are supported by a computational study in which it is found that the H-O distance of the protonated imine hydrogen bonded to the anionic boroxinate core decreases with an increase in the electron releasing ability of the phenol unit incorporated into the boroxinate. The results are not consistent with a mechanism in which the boroxinate catalyst functions as a Lewis acid and activates the imine by a Lewis acid/Lewis base interaction.

Resolution of Vaulted Biaryl Ligands via Borate Esters of Quinine and Quinidine.

Given the sudden and unexplained rise in the cost of (+)- and (-)-sparteine, an alternative method for the resolution of vaulted biaryls has been developed. This method involves the reaction of a racemic vaulted biaryl ligand with one equivalent of BH3·SMe2 and one equivalent of either quinine or quinidine. A precipitate then forms from the resulting mixture of diastereomeric borates as a result of differential solubilities. Hydrolysis of the precipitate then liberates the (S)-ligand in the case of quinine and the (R)-ligand in the case of quinidine, both with >99% ee. This method has been applied to 16 different vaulted biaryl ligands, including 10 whose preparation is described here for the first time. In addition, proof of principle has been demonstrated for the dynamic thermodynamic resolution of the vaulted biaryl ligands with this method in combination with a nonchiral copper(II) complex that can racemize the ligand.

Catalytic Asymmetric Epoxidation of Aldehydes with Two VANOL-Derived Chiral Borate Catalysts.

A highly diastereo- and enantioselective method for the epoxidation of aldehydes with α-diazoacetamides has been developed with two different borate ester catalysts of VANOL. Both catalytic systems are general for aromatic, aliphatic, and acetylenic aldehydes, giving high yields and inductions for nearly all cases. One borate ester catalyst has two molecules of VANOL and the other only one VANOL. Catalysts generated from BINOL and VAPOL are ineffective catalysts. An application is shown for access to the side-chain of taxol.