Acid-catalysed cyclisation of o-sulphonamido ketene dithioacetal S-oxides: a novel synthesis of the indole ring system

Abstract

Treatment of o-sulphonamido aryl ketene dithioacetal S-oxides with hydrochloric acid in the presence of hydrogen sulphide gives 2methylthioindoles.We have previously described in preliminary form a novel approach to indoles involving acid-catalysed cyclisation of ketene dithioacetal S-oxides 1 (Scheme l), to give in approximately equal amounts the products 2 and 3. We now present full details of this work, together with a modification which allows 1 to be converted into compound 2 alone.

2-(Tosylamino)benzyltrimethylammonium Halides as Precursors of 2-Substituted Indoles

“…The crude residue purified by crystallization fiom 9 isopropyl alcohol gave 2 (5.9 g, 88%), mp146-148°C (Lit., 148-150°C). The sulfonium phase was dried (Na2SOq) and evaporated to dryness.…”

Miscellaneous Indole Ring Syntheses

“…Echavarren described a novel oxidative rearrangement to give indoles that was induced by 1,4-benzoquinone (equation 3) [8]. The acid-catalyzed cyclization of o-sulfonamido aryl ketene dithioacetal S-oxides in the presence of H 2 S led to indoles, as reported by Hewson and colleagues (equation 4) [9]. The function of H 2 S is to preclude formation of 3-chloroindoles.…”

A Microwave-Assisted Alternative Synthesis of 8-Amino-2-methyl-3,4-dihydroisoquinoli­n-1-one

“…The use of toxic reagents such as allyltributyltin, CrO 3 / H 2 SO 4 and (PhO) 2 P(O)N 3 , along with the particularly low-yielding permanganate oxidation step 3 (a) and an overall yield of 12% made the first route (Scheme 1) unattractive.…”

“…3 or DMSO-d 6 as solvent. Chemical shifts are expressed in ppm downfield from TMS, which was used as an internal standard.…”