Catalytic Enantioselective Povarov Reactions of Ferrocenecarbaldehyde-Derived Imines - Bronsted Acid Catalysis at Parts-Per-Million Level Loading

Despite the broad interest in ferrocene containing compounds, ferrocenyl substrates have been employed in catalytic asymmetric settings only sporadically. Herein, catalytic asymmetric Povarov reactions with ferrocenecarbaldehyde-derived N-aryl imines are presented. This study demonstrates that the stereoelectronic properties of ferrocenyl imines do not preclude their engagement in enantioselective phosphoric acid catalysis: cycloadducts derived from benzyl N-vinylcarbamate were obtained in good yields and nearly enantiopure form using 0.1mol% of a standard Bronsted acid catalyst. Furthermore, it is shown that specific optimisation with some substrates allowed to lower the catalyst loading up to 10-20 parts-per-million, an unprecedented value for phosphoric acid catalysts. Such low loading protocol could be applied to a preparative scale reaction, and to imines derived from arylaldehydes.