Functionalization of olefins and asymmetric halo aldol reaction

Abstract

The development of new asymmetric synthetic methodologies is both challenging and crucial for modern organic synthesis. The amino functionalization of olefins, especially the α,β-unsatuarated carbonyl system, gives very important building blocks for organic and pharmaceutical synthesis. The asymmetric halo aldol reaction can greatly extend the scope of the classic aldol reaction, and can serve as a powerful tool for asymmetric carbon-carbon bond formations.

This dissertation presents a versatile system for the electrophilic amino functionalization of the α,β-unsatuarated carbonyl compounds. By changing reaction conditions, the reaction can result in four different and important products: vicinal chloroamines, N-protected aziridines, diamines and α,β-dehydroamino acid derivatives. All of these transformations showed good chemical yields and excellent regio- and stereoselectivities. It is very easy to perform these reactions economically in large scale.

Several new asymmetric halo aldol reactions have been achieved in this dissertation. For the chiral auxiliary-controlled asymmetric halo aldol reaction, menthyl and Evans oxazolidinone were used as the chiral auxiliaries and Et2AlI/MgI2 were used as the Lewis Acid catalysts. The reagent-controlled protocol take advantage of the combination of chiral Salen and Et2AlI as the chiral reagent. Finally, an efficient asymmetric catalytic halo aldol reaction was established, in which a catalytic amount of chiral aluminum complex was used as the catalyst. All of these approaches resulted in good chemical yields and moderate to good diastereomeric and enantiomeric excesses.