2,3,4,9-Tetrahydrothiopyrano[2,3-b]indoles: synthesis via an intramolecular indole Grignard reaction and conformational study by 1H and 13C NMR spectroscopy

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Abstract
Cycloalkylation reactions of 2-alkylthioindoles, (2; X = OSO2R, halogens, or epoxy) to 2,3,4,9-tetrahydrothiopyrano[2,3-b]indoles (3)via the corresponding metallated indole intermediates have been studied. Compound (2) could be cyclized to (3) in good yield and regioselectivity on treatment with a Mg or Zn reagent, whereas Li, Na, and K reagents afforded (3) and/or its regioisomer. The leaving group (X) and the solvent were shown to be crucial for reactivity. The reaction of (2; X = OSO2R as leaving group) and a Grignard reagent in non-polar solvents effectively afforded (3). The cyclization was demonstrated to proceed via an SN2 process. Analyses of the 1H and 13C NMR spectra of (3) revealed that the thiopyrano ring entity of (3) was anchored in a half-chair conformation which ensured that any C-4 substituent introduced was in the pseudoaxial position. Assignments for the 1H and 13C signals of (3) are also reported.