NEW, CONCISE ROUTE TO INDOLES BEARING OXYGEN OR SULFUR SUBSTITUENT ATTHE 4-POSITION - SYNTHESIS OF (PLUS-OR-MINUS)-PINDOLOL AND (S)-(-)-PINDOLOL AND (PLUS-OR-MINUS)-CHUANGXINMYCIN

A new method for the synthesis of 4-alkoxy- and 4-[alkyl (or aryl)thio ]indoles has been developed by using the indolone 3 as a common interm ediate. The indolone 3 was prepared from N-(phenylsulfonyl)pyrrole (7) and the alpha-chlorosulfide 8 in four steps. Heating of a mixture of 3 and an appropriate alcohol in the presence of p-toluenesulfonic acid and cupric chloride afforded the 4-alkoxyindoles 11a-d. The method wa s applied to the synthesis of(+/-)-pindolol (19) and (S)-(-)-pindolol (20). Thiols also reacted with 3 in the presence of boron trifluoride to give 4-[aryl (or alkyl)thio]indoles 12, 21a, b, and 22a-b. The (ind ol-4-ylthio)acetate 22c was employed as a key intermediate for a conci se total synthesis of(+/-)-chuangxinmycin (27).