One-step, efficient synthesis of combined threonine–surfactant organocatalysts for the highly enantioselective direct aldol reactions of cyclic ketones with aromatic aldehydes in the presence of water

In this work, a new class of organocatalysts have been designed and synthesized in one step by a rational combination of threonine with acyl chlorides at room temperature in trifluoroacetic acid to make a series of novel combined threonine-surfactant organocatalysts readily available on a large-scale. No protecting groups or chromatographic techniques are involved in the procedures, while certain combined threonine-surfactant organocatalysts mediate the direct aldol reactions of cyclic ketones with aromatic aldehydes to provide the aldol products in good yields with enantioselectivities of up to 99%.

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(2S,3R)-O-(n-Butyl)-l-threonine hydrochlorideC8H16ClNO4[α]D20=+16.1 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Hexanoyl)-l-threonine hydrochlorideC10H20ClNO4[α]D20=+15.0 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Octanoyl)-l-threonine hydrochlorideC12H24ClNO4[α]D20=+13.2 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Decanoyl)-l-threonine hydrochlorideC14H28ClNO4[α]D20=+13.0 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Dodecanoyl)-l-threonine hydrochlorideC16H32ClNO4[α]D20=+11.6 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Palmitoyl)-l-threonine hydrochlorideC20H40ClNO4[α]D20=+7.8 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)

(2S,3R)-O-(n-Stearoyl)-l-threonine hydrochlorideC22H44ClNO4[α]D20=+8.0 (c 1.0, MeOH)Source of chirality: (2S,3R)-threonineAbsolute configuration: (2S,3R)