Enantioselective Decarboxylative Animation: Synthesis of Axially Chiral Allenyl Amines

摘要

Naturally occurring biomolecules that display chirality are enantiomerically enriched and different enantiomers show different biological activities. Thus, the development of new enantioselective approaches for chiral compounds are still of great interest. Allenes are now an important class of compounds and versatile intermediates in organic synthesis. Thus, efficient methodologies for synthesizing allenes is of current interest for organic chemists. The synthesis of axially chiral allenes are particularly important because of their efficient chirality transfer and their existence as core structures in natural products and pharmaceuticals. Typically, the synthesis of axially chiral allenes relies on the resolution of racemic allenic precursors and the chirality transfer of chiral propargyl alcohols or propargyl amine derivatives. However, most of these procedures require stoichiometric amounts of enantiomerically enriched chiral compounds, and are thus inefficient. Recently, asymmetric catalysis for the synthesis of chiral allenes has attracted much attention. Trost et al. and Imada et al. have independently reported the asymmetric synthesis of allenyl amines with 76-91 % ee by using intermolecular reactions. Interestingly, in two reported examples, 95 or 97 % of ee has been realized (Scheme 1, top). Herein, we disclose a different protocol for the construction of axially chiral allenyl amines, bearing an extra hydroxy group or C=C bond, by the decarboxylative amination' of allenyl N-tosylcarbamates; the products are obtained in 91-99% ee (Scheme 1, bottom).