Formal total synthesis of (–)- and (+)-balanol: two complementary enantiodivergent routes from vinyloxiranes and vinylaziridines ☆

Abstract Formal total syntheses of both enantiomers of balanol have been achieved by the preparation of the protected hexahydroazepine core 2 . Two complementary routes have been investigated. The first relied on the regioselective opening of 1,2-epoxycyclohex-3-ene with a chiral-auxiliary version of the Burgess reagent to provide a diastereomeric pair of cis-fused cyclic sulfamidates. The sulfamidates were transformed to trans -amino benzoates with ammonium benzoate and, after separation, converted to (−)- 2 and (+)- 2 by oxidative cleavage and reductive amination. The second approach utilized vinylaziridines derived from 1-bromo-2,3-dihydroxycyclohexa-4,6-diene obtained by the whole-cell fermentation of bromobenzene with Escherichia coli JM109(pDTG601). Stereoselective opening of the aziridines generated the requisite trans -amino alcohol derivatives, which after saturation of the vinyl bromide moieties were converted to (−)- 2 and (+)- 2 by oxidative cleavage of the cis -diol and reductive amination. Experimental and spectral data are provided for all new compounds.