A short synthesis of (+)-harzialactone A and (R)-(+)-4-hexanolide via proline-catalyzed sequential α-aminooxylation and Horner–Wadsworth–Emmons olefination of aldehydes

An efficient and short enantioselective synthesis of the antitumor marine metabolite, (+)-harzialactone A 1 and pheromone, (R)-(+)-4-hexanolide 2 using l-proline-catalyzed sequential α-aminooxylation and Horner–Wadsworth–Emmons olefination of the respective aldehydes is described.

Figure optionsDownload as PowerPoint slide

(R)-Ethyl 4-anilinoxy-5-phenylpent-2-enoateC19H21NO3[α]D25=+47 (c 1, CHCl3)Source of chirality: α-aminooxylationAbsolute configuration: (R)

(S)-Ethyl 4-hydroxy-5-phenylpentanoateC13H18O3[α]D25=+14.54 (c 1, CHCl3)Source of chirality: α-aminooxylationAbsolute configuration: (S)

(S)-5-Benzyl-dihydrofuran-2(3H)-oneC11H12O2Ee = 97% (HPLC)[α]D25=+24.7 (c 1, CHCl3)Source of chirality: α-aminooxylationAbsolute configuration: (S)

(R)-Ethyl 4-anilinoxyhex-2-enoateC14H19NO3[α]D25=+88 (c 2, CHCl3)Source of chirality: α-aminooxylationAbsolute configuration: (R)

(R)-Ethyl 4-hydroxyhexanoateC8H16O3[α]D25=+27 (c 2, CHCl3)Source of chirality: α-aminooxylationAbsolute configuration: (R)