The chloroindolenine – imino ether – oxindole sequence. A reexamination

Abstract

The chloroindolenines of deserpidine and reserpine, and the isomeric chloroindolenines derived from yohimbine – characterized for the first time – have been treated with methanol and methoxide ion under a variety of conditions. In the traditional medium of methanolic hydroxide, chlorodeserpidine partially undergoes rearrangement to imino ether, whereas chlororeserpine suffers only substitution of chloride by methoxide; only the α-isomer of the two yohimbine chlorides undergoes rearrangement to a methyl imino ether, the β-isomer being degraded to an intractable mixture. In refluxing neat methanol, the α-chloride of yohimbine rearranges readily and cleanly to imino ether at a rate comparable to that of chlorodeserpidine rearrangement, but vastly greater than that of the β-chloride. However, under silver oxide catalysis all the chloroindolenines rearrange at closely similar rates. The rearrangement of chloroindolenine to methyl imino ether is stereospecific, α-chloride leading to α-spiro imino ether and β-chloride to β-spiro imino ether. The results are rationalized on the basis of stereoelectronic considerations applied to a process of addition of methanol to the imine bond, followed by elimination of hydrogen chloride from the methanol adduct.