Preparation of 3a-Substituted Pyrrolo[2,3-6]indoles

Utilizing the unique features of 1-hydroxy- and 1-methoxyindoles, three kinds of useful routes for preparing 3a-alkoxy-1,2,3,3a,8,8a-hexahydro-pyrrolo[2,3-fr]indoles have been developed [30].

The first route is the treatment of 1-hydroxy-Nb-methoxycarbonyl-tryptamine (52) in refluxing Ac2O giving rise to 3a-acetoxy-8-acetyl-1-methoxycarbonyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-fr]indole (92, 72%, Scheme 12), whose structure is proved by X-ray single-crystal analysis [30]. The key step is a [3,3] sigmatropic rearrangement of the 1-acetoxy group of 93 to the 3-position providing the imine (94).

Mild hydrolysis of 92 produces 8-acetyl-3a-hydroxy-1-methoxycarbonyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-fr]indole (95a, 96%). Various 3a-alkoxy derivatives, for example 95b (95%), can be prepared by the alkylation of the 3a-hydroxy group with alkyl halides and NaH.

A second route involving either chlorination or bromination and subsequent substitution with water has been developed [30]. The reaction of 1-methoxy-Nb-methoxycarbonyltryptamine (35) with NCS (1-moleq.) in MeOH affords 3a-chloro-1,2,3,3a,8,8a-hexahydro-8-methoxy-1-methoxycar-

I2, morpholine in'an appropriate alcohol

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