A highly enantioselective asymmetric catalytic synthesis of alkynyl aziridines can be achieved from alkynyl imines with diazo compounds mediated by a chiral boroxinate (BOROX) catalyst generated from VANOL or VAPOL ligand. In contrast to the aziridination reaction (AZ reaction) with aryl and alkyl substituted imines, alkynyl imines react to give cis-substituted aziridines with both diazo esters and diazo acetamides. Unexpectedly, the two diazo compounds afford different enantiomers of the cis-aziridine from the same enantiomer of the catalyst. The (S)-BOROX catalyst promotes the reaction of ethyl diazoacetate such that reaction occurs with the Si-face of the imine and the Si-face of the diazo compound. However, in the case of a diazo acetamide, the (S)-BOROX catalyst switches the facial selectivity for reaction of both substrates from Si-face to Re-face. A diverse family of chiral boroxinate Brønsted acids is generated from a library of thirty-one VANOL derivatives that are substituted in the 7,7'-positions. A direct and convergent synthetic access to the ligand library is made viable by a cycloaddition/electrocylization cascade from various p-substituted phenyl acetic acids. The family of ligands is used to screen the catalytic asymmetric AZ reaction of two different benzhydryl imines, one from an aryl aldehyde and the other from an aliphatic aldehyde. Remarkably, the highest asymmetric induction for each substrate was recorded with the same ligand, 7,7'-di-t-butylVANOL. This ligand was in turn screened with a set of 10 different benzhydryl imines to find that this ligand gives an average of 97% ee over all ten imines whereas the corresponding unsubstituted ligand VANOL gives an average of 87% ee and the VAPOL ligand gives an average of 86% ee. Three sets of VANOL ligands: 1) naphthalene skeleton modified; 2) C3-aryl group modified; 3) C1-symmetric VANOL derivatives were synthesized and evaluated in the AZ reaction. Those modifications lead to complicated outcomes. Generally, 7,7'-substituents are beneficial to the AZ reaction, whereas 4,4'- or 8,8'-substituents are detrimental to the AZ reaction. Modification of the C3-aryl effects the enantioselectivity to some extent. Four VAPOL derivatives were prepared and evaluated in the AZ reaction. In addition to the AZ reaction, those VANOL and VAPOL derivatives were evaluated in the reduction of 2-quinolines and VAPOL was found to be the optimal ligand. A novel DMAP-squaramide catalyst was prepared from BINAM and evaluated in the Michael addition of a nitroalkane to a nitroalkene.
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