Efficient synthesis of chiral Δ2-1,3,4-thiadiazolines from α-pinene and verbenone

The synthesis of chiral cyclobutane 1,3,4-thiadiazoline derivatives starting from (−)-α-pinene and (−)-verbenone was studied. The diastereoisomeric excesses of the products obtained depended strongly upon the starting chiral ketone. The stereochemical assignments of the synthesized compounds were performed by NMR spectroscopy, X-ray analysis, and theoretical calculations.

Figure optionsDownload as PowerPoint slide

[(1R,3S)-3-Methoxycarbonyl-2,2-dimethylcyclobut-1-yl]methyl thiosemicarbazoneC11H19N3O2SEe = 90%[α]D23=−45.0 (c 1.1, acetone)Source of chirality: (−)-(S)-verbenoneAbsolute configuration: (1R,3S)

[(1R,3S)-3-Hydroxymethyl-2,2-dimethylcyclobut-1-yl]methyl thiosemicarbazoneC10H19N3OSEe = 90%[α]D23=−19.0 (c 0.4, acetone)Source of chirality: (−)-(S)-verbenoneAbsolute configuration: (1R,3S)

(3S)-3-Methoxycarbonyl-2,2-dimethylcyclobutanone thiosemicarbazoneC9H15N3O2SEe = 90%[α]D23=−16.0 (c 0.9, acetone)Source of chirality: (−)-(S)-verbenoneAbsolute configuration: (3S)

(2S,4R)-(1,1-Dimethyl-2-methoxycarbonyl-6-N-acetyl-8-acetyl)spiro[3,4]-5-tia-7,8-diazaocta-6-enoC13H19N3O4SEe = 90%[α]D23=+4.5 (c 0.7, acetone)Source of chirality: (−)-(S)-verbenoneAbsolute configuration: (2S,4R)

(1R,3S)-3-Butyldiphenylsilyloxymethyl-2,2-dimethyl-cyclobutylmethylketoneC25H34O2SiEe = 90%[α]D23=−46.0 (c 0.5, chloroform)Source of chirality: (−)-(S)-verbenoneAbsolute configuration: (1R,3S)

[(1R,3R)-3-Methylacetate-2,2-dimethylcyclobut-1-yl]methyl thiosemicarbazoneC12H21N3O2SEe = 90%[α]D23=−33.8 (c 0.3, acetone)Source of chirality: (−)-(S)-verbenoneAbsolute configuration: (1R,3R)