Simple and inexpensive threonine-based organocatalysts for the highly diastereo- and enantioselective direct large-scale syn-aldol and anti-Mannich reactions of α-hydroxyacetone

Simple and inexpensive threonine-based organocatalysts that promote syn-aldol reactions and three-component asymmetric anti-Mannich reactions of α-hydroxyacetone achieving a respectable level of enantioselectivities are reported. The syn-aldol products could be obtained with up to a 99:1 syn/anti ratio and >99% ee while the anti-Mannich products could be obtained with up to a 96:4 anti/syn ratio and >99% ee. Catalyst 1c can be used efficiently on a large-scale with the enantioselectivities of the syn-aldol and anti-Mannich reactions being maintained at the same level, which offers a great possibility for application in industry.

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(2S,3R)-O-(n-Butyryl)-l-threonineC8H15NO4[α]D20=+16.1 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Hexanoyl)-l-threonineC10H19NO4[α]D20=+15.0 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Octanoyl)-l-threonineC12H23NO4[α]D20=+13.2 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Decanoyl)-l-threonineC14H27NO4[α]D20=+13.0 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n- Dodecanoyl)-l-threonineC16H31NO4[α]D20=+11.6 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(Benzoyloxy)-l-threonineC11H13NO4[α]D20=-12.8 (c 1.02, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(Cyclohexylcarbonyl)-l-threonineC11H19NO4[α]D20=+15.7 (c 1.1, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(1-Adamantylcarbonyl)-l-threonineC15H23NO4[α]D20=+5.4 (c 1.2, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)