Novel organocatalytic activation of unmodified Morita-Baylis-Hillman alcohols for the synthesis of bicyclic α-alkylidene-ketones.

The organocatalytic activation of Morita-Baylis-Hillman alcohols via H-bonding-iminium-ion formation is demonstrated for the first time. This activation strategy enables the Morita-Baylis-Hillman alcohols to undergo a formal SN2' reaction. In combination with the well-established enamine reactivity, this creates a new reactivity pattern. The application of this new activation mode for the synthesis of bicyclic α-alkylidene-ketones is demonstrated. The developed reaction sequence proceeds efficiently affording nature-inspired target products with four contiguous stereogenic centers in a highly stereoselective manner.