Total synthesis of (R)-(−)-actisonitrile via O-alkylation of optically active 4-hydroxymethyloxazolidin-2-one derivative

The enantioselective synthesis of (R)-(−)-actisonitrile 1 has been achieved via O-alkylation of (4R,αS)-4-hydroxymethyl-3-(α-methylbenzyl)oxazolidin-2-one (αS)-4 with 1-iodohexadecane in the presence of CsOH in DMF. Under these reaction conditions, the O-alkylation was much faster than the intramolecular acyl transfer of (αS)-4.

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Diethyl (S)-(α-methylbenzyl)aminomalonateC15H21NO4[α]D27=-58.0 (c 1.0, CHCl3)Source of chirality: (S)-(α-methylbenzyl)amineAbsolute configuration: (S)

(S)-2-(α-Methylbenzyl)amino-1,3-propanediolC11H17NO2[α]D27=-58.0 (c 1.0, CHCl3)Source of chirality: (S)-(α-methylbenzyl)amineAbsolute configuration: (S)

(4R,αS)-4-Hydroxymethyl-3-(α-methylbenzyl)oxazolidin-2-oneC12H15NO3[α]D24=-99.1 (c 1.0, CHCl3)Source of chirality: (S)-(α-methylbenzyl)amineAbsolute configuration: (4R,αS)

(4R,αS)-4-(Hexadecyloxymethyl)-3-(α-methylbenzyl)oxazolidin-2-oneC28H47NO3[α]D25=-49.2] (c 0.6, CHCl3).Source of chirality: (S)-(α-methylbenzyl)amineAbsolute configuration: (4R,αS)

(4R,αR)-4-(Hexadecyloxymethyl)-3-(α-methylbenzyl)oxazolidin-2-oneC28H47NO3[α]D28=-10.3 (c 0.43, MeOH)Source of chirality: (R)-(α-methylbenzyl)amineAbsolute configuration: (4R,αR)

(R)-4-(Hexadecyloxymethyl)oxazolidin-2-oneC20H39NO3[α]D30=+24.7 (c 1.0, CHCl3)Source of chirality: (S)-(α-methylbenzyl)amineAbsolute configuration: (R)

(S)-2-Amino-3-(hexadecyloxy)propan-1-olC19H41NO2[α]D29=-3.2 (c 1.0, MeOH)Source of chirality: (S)-(α-methylbenzyl)amineAbsolute configuration: (S)

(S)-N-(1-(Hexadecyloxy)-3-hydroxypropan-2-yl)formamideC20H41NO3[α]D26=-13.4 (c 0.62, CHCl3)Source of chirality: (S)-(α-methylbenzyl)amineAbsolute configuration: (S)

(R)-2-Formamido-3-(hexadecyloxy)propyl acetateC22H43NO4[α]D30=-4.1 (c 0.65, CHCl3)Source of chirality: (R)-(α-methylbenzyl)amineAbsolute configuration: (S)

(R)-3-(Hexadecyloxy)-2-isocyanopropyl acetate, (R)-(−)-actisonitrileC22H41NO3[α]D31=-15.1 (c 0.3, CHCl3)Source of chirality: (R)-(α-methylbenzyl)amineAbsolute configuration: (R)

(2R,αR)-3-(Hexadecyloxy)-2-[3-(α-methylbenzyl)ureido]propyl acetateC30H52N2O4[α]D34=-42.6 (c 0.10, CHCl3)Source of chirality: (R)-(α-methylbenzyl)amine (for two chiral centers)Absolute configuration: (2R,αR)

(2R,αS)-3-(Hexadecyloxy)-2-(3-α-methylbenzyl)ureidopropyl acetateC30H52N2O4[α]D33=+5.1 (c 0.06, CHCl3)Source of chirality: (R)- and (S)-(α-methylbenzyl)amines (for two chiral centers)Absolute configuration: (2R,αS)