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

Abstract

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.

Structure Guided Design of VANOL-Imidodiphosphorimidate Catalysts for the Catalytic Enantioselective Bromospiroketalization Reaction

“…The synthesis of a library of substituted VAPOL derivatives is likely to require a lengthier synthesis that will need to be individually crafted for each position on VAPOL which contrasts with the synthesis of the VANOL derivatives. 45,47,50 Optimization of Catalyst Structure. Two important factors led us to evaluate VANOL imidodiphosphorimidates as potential catalysts.…”

“…The effect of the aryl substituent is most probably related to steric interactions that lead to a more well-defined catalytic pocket, as will be demonstrated in the VANOL family of analogues ( vide infra ). The synthesi s of a library of substituted VAPOL derivatives is likely to require a lengthier synthesis that will need to be individually crafted for each position on VAPOL which contrasts with the synthesis of the VANOL derivatives. ,, …”

“…As depicted in Figure , the “major groove” of the vaulted systems resides in the center of the molecule. We anticipated that the activation of the halenium source via proton delivery from the triflimide occurs in this region, and thus surmised a larger binding cavity might allow for a more structured arrangement of the reaction components. − ,− VAPOL imidodiphosphorimidate (2a) 2 -D was prepared from VAPOL and (triflyl)­phosphorimidoyl trichloride following reported procedures for BINOL catalysts and was evaluated as the catalyst for the bromospiroketalization of 4a . The desired product 5a was obtained in good yield but low er (Figure ).…”

Probing Catalyst Function – Electronic Modulation of Chiral Polyborate Anionic Catalysts

“…The effect of electronic modulation in the VANOL ligand was also probed on the aziridination of imine 22a with ethyl diazoacetate 11 with the boroxinate catalyst generated from the series of 5,5-disubstituted VANOL ligands shown in Table . The 5,5′-disubstituted VANOL ligands 3a to 3f were chosen since substituents in the 5- and 5′-positions would be in conjugation with the phenol groups of the VANOL ligands and hence with the boroxinate core of the VANOL boroxinated catalysts of the type 4 generated therefrom (Scheme ). In addition, substituents in the 5- and 5′-positions would be expected to exert the least steric influence upon the reactions occurring in the active site of the VANOL boroxinate catalysts.…”