Conformational lock in a Brønsted acid–Lewis base organocatalyst for the aza-Morita–Baylis–Hillman reaction

(S)-3-(N-Isopropyl-N-3-pyridinylaminomethyl)BINOL has been established as an efficient asymmetric bifunctional organocatalyst for the aza-MBH reaction. The acid–base functionalities cooperate in substrate activation and fixing of the organocatalyst conformation to promote the reaction with high enantiocontrol.

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(R)-4-Methyl-N-(2-methylene-1-naphthalen-1-yl-3-oxobutyl)benzenesulfonamideC22H21NO3SEe = 70% by HPLC on Daicel Chiralpak AD-H column[α]D20=+18.3 (c 0.6, CHCl3)Source of chirality: enantioselective additionAbsolute configuration: (R)

(R)-N-[1-(2-Chlorophenyl)-2-methylene-3-oxobutyl]-4-methylbenzenesulfonamideC18H18ClNO3SEe = 62% by HPLC on Daicel Chiralpak AD-H column[α]D20=+13.0 (c 0.6, CHCl3)Source of chirality: enantioselective additionAbsolute configuration: (R)

(R)-N-[2-Benzoyl-1-(4-nitrophenyl)allyl]-4-methyl-benzenesulfonamideC23H20N2O5SEe = 58% by HPLC on Daicel Chiralpak OD-H column[α]D20=-3.3 (c 0.6, CHCl3)Source of chirality: enantioselective additionAbsolute configuration: (R)

(R)-N-[1-(4-Cyanophenyl)-2-methylene-3-oxobutyl]-4-methylbenzenesulfonamideC19H18N2O3SEe = 91% by HPLC on Daicel Chiralpak AD-H column[α]D20=+20 (c 0.6, CHCl3)Source of chirality: enantioselective additionAbsolute configuration: (R)