Development of new asymmetric allylic alkylations with Morita- Baylis-Hillman fluorides and difluoroalkenes

Abstract

Asymmetric catalysis has been one of the main topics in organic chemistry in the last 50 years. Traditionally, asymmetric allylic alkylation reactions (AAA) were based on transitionmetal-catalysed reactions. Recently, the organocatalytic AAA has been developed where small organic molecules, such as chiral tertiary amines and phosphines, are used as catalysts instead of transition metals. The objective of the TFG has been the development of a new asymmetric allylic alkylation reaction (AAA) using Morita-Baylis-Hillman (MBH) fluorides and nucleophiles activated by the fluoride anion (difluoroalkenes). The leaving group of the MBH adduct activates the nucleophile, and it is incorporated in the final product as a trifluoromethyl group, this is the distinguishing aspect of the reaction. The products are interesting because of its trifluoromethyl group, a singular group in organic chemistry which is commonly used in pharmaceutical industry. The reactivity has been tested using chiral tertiary amines as catalyst, such as β-isocupreidine, a compound derived from quinine, to synthesise the corresponding enantioenriched products. The characterisation of the products has been performed by spectroscopic and chromatographic methods such as NMR and chiral HPLC, respectively