The development of a catalytic asymmetric method for the direct aminoallylation of aldehydes is described that is based on a chiral polyborate catalyst generated from the vaulted biaryl ligand VANOL. This method is scalable since it is chromatography free and it gives rise to unprotected homo-allylic amines with excellent asymmetric inductions over a broad range of substrates including both aryl and aliphatic aldehydes. The unique catalyst system developed for this protocol involves the synergistic interplay between a chiral Brønsted acid and a non-chiral Brønsted acid.The mode of synergetic catalysis and the origin of enantioselection observed in this reaction are investigated using a combination of experimental kinetic isotope effects (KIEs), NMR spectroscopy (11B and 13C) and theoretical calculations. The results from these mechanistic studies provide fine details of the enantioselectivity determining transition state geometry. This direct aminoallylation of aldehydes protocol was then extended to the preparation of 1,3-homo-allylic amino alcohols utilizing an unprecedented catalyst-controlled aza-Cope rearrangement and subsequently applied to the total syntheses of the Sedum alkaloids.A highly enantioselective route for the introduction of aziridines into functionalized organic molecules was developed via a tandem acylation and aziridination of TMSCHN2. The products are synthetically useful intermediates that can be readily elaborated.
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