Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes via an Organocatalytic Nitroalkane-Michael/Henry Domino Reaction

An organocatalytic nitroalkane-Michael/Henry reaction sequence to functionalized 1,2,3,4-tetrahydronaphthalen-1-ols is described. Starting from 2-(nitromethyl)benzaldehyde and nitroalkenes a bifunctional quinine-based squaramide organocatalyst is used to afford the title compounds in moderate to very good yields (2584%), high diastereomeric ratios (dr>95:5) after crystallization and good to excellent enantioselectivities of 6399% ee. Starting from -nitro aldehydes and ketones secondary and tertiary cyclohexanols bearing four stereogenic centers can also be prepared with this Michael/Henry domino reaction.