Synthesis of C3-substituted enantiopure 2-(p-tolylsulfinyl)-furans: the sulfoxide group as a chiral inductor for furan dienes as precursors of a wide variety of chiral intermediates

(−)-(1R,2S,5R)-Menthyl (SS)-p-toluenesulfinate and its enantiomer are a common source for a chiral sulfoxide group in organic synthesis, by means of nucleophilic substitution. The replacement of the menthyloxy group, with complete inversion of configuration at the sulfur center of the chiral sulfoxide, allows the inclusion of this organic function into numerous substrates, with defined stereochemistry and high enantiomeric purity. Nine C3-substituted, enantiomerically pure, 2-sulfinylfurans were prepared by this synthetic methodology with moderate to high yields. These enantiopure C3-substituted 2-sulfinylfurans can be used as chiral dienes for [4+3] cycloaddition reactions and in other chemical transformations, in which π-facial selectivity should be induced in order to obtain enantioselective reactions.

Figure optionsDownload as PowerPoint slide

(S)-3-Bromo-2-(p-tolylsulfinyl)furanC11H9BrO2SAbsolute configuration: (S)Source of chirality: commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate[α]D21=-71.04 (c 1.5, CHCl3)

(S)-[2-(p-Tolylsulfinyl)-3-furyl]methanolC12H12O3SAbsolute configuration: (S)Source of chirality: commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate[α]D21=+12.1 (c 0.66, CHCl3)

(S)-N-Ethyl-N-[(2-(p-tolylsulfinyl)furan-3-yl)methyl]ethanamineC16H21NO2SAbsolute configuration: (S)Source of chirality: commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate[α]D21=-20.9 (c 1.0, CHCl3)

(S)-2-(p-Tolylsulfinyl)-3-furoic acidC12H10O4SAbsolute configuration: (S)Source of chirality: commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate[α]D21=+27.4 (c 0.5, CHCl3)

Methyl (S)-2-(p-tolylsulfinyl)-3-furoateC13H12O4SAbsolute configuration: (S)Source of chirality: commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate[α]D21=-86.7 (c 0.66, CHCl3)

Ethyl (S)-2-(p-tolylsulfinyl)-3-furoateC14H14O4SAbsolute configuration: (S)Source of chirality: commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate[α]D25=-159.1 (c 0.11, CHCl3)

(1S,2R,5S)-Myrtanyl (S)-2-(p-tolylsulfinyl)-3-furoateC22H26O4SAbsolute configuration at the sulfur atom: (S)Source of chirality:(a) commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate(b) commercially available (−)-(1S,2R,5S)-myrtanol[α]D25=-158.8 (c 0.072, CHCl3)

(S)-N,N-Diethyl-2-(p-tolylsulfinyl)-3-furamideC16H19NO3SAbsolute configuration at the sulfur atom: (S)Source of chirality: commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate[α]D25=-82.3 (c 0.13, CHCl3)

(SS,S)-N-(1-Phenylethyl)-2-(p-tolylsulfinyl)-3-furamideC20H19NO3SAbsolute configuration at the sulfur atom: (S)Source of chirality:(a) commercially available (−)-(1R,2S,5R)-menthyl (SS)-p-toluenesulfinate(b) commercially available (−)-(S)-1-methylbenzylamine[α]D25=+77.5 (c 0.18, CHCl3)