Diastereoselective reduction of ketimines derived from (R)-3,4-dihydroxybutan-2-one: an alternative route to key intermediates for the synthesis of anticancer agent ES-285

A simple and convenient procedure for the diastereoselective reduction of imines derived from (R)-3,4-dihydroxybutan-2-one is described. The use of sodium borohydride as a reducing agent in the reactions with pre-synthesised imines gave aminodiol derivatives with the appropriate stereochemistry for use as intermediates in the synthesis of anticancer agent ES-285. The aminodiols were isolated in ca. 62% yield.

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(R)-3,4-Bis(benzyloxy)butan-2-oneC18H20O3[α]D25=+32.2 (c 0.91, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (R)

(S)-N-Benzyl-1-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanamineC14H21O2[α]D25=+37.1 (c 1.00, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,1′S)

(2S,3S)-N-Benzyl-3,4-bis(benzyloxy)butan-2-amineC25H29NO2[α]D25=-3.5 (c 0.70, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S,3S)