Chiral amine organocatalysts for the syn-aldol reaction involving substituted benzaldehydes and hydroxyacetone

A new series of cyclohexanediamine organocatalysts that contain the primary amine functionality has been designed, synthesized and tested as catalysts for the asymmetric aldol reaction involving hydroxyacetone and a variety of substituted benzaldehydes. High enantioselectivites and diasteroselectivites were obtained using catalyst 1a for these reactions. A key step in this reaction for the formation of the syn-product is the formation of a stable intramolecular hydrogen bonded Z-enamine isomer, which in addition to the steric bulk of the catalyst, serve to dictate the course of the stereochemical outcome of the reaction.

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C18H29N3O3S[α]D20=+30.2 (c 0.51, CH2Cl2)

C18H27N3O2[α]D20=-24.7 (c 0.2, MeOH)

C19H29N3O2[α]D20=-24.4 (c 0.21, CH2Cl2)

C19H30N3O2[α]D20=-25.6 (c 0.2, MeOH)

C22H27N3O2[α]D20=+2.5 (c 0.95, MeOH)

C19H25F6N3O3S[α]D20=+8.3 (c 0.12, MeOH)

C20H25F6N3O2[α]D20=+48.6 (c 0.21, MeOH)