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Stereoelectronically controlled cyclization reactions on the way to peri ‐fused tetrahydropyrazolo[1,5‐ a ]pyridines as aza analogs of ergoline partial structures
Author(s) -
Gmeiner Peter,
Sommer Josef
Publication year - 1991
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.1991199101157
Subject(s) - chemistry , ring (chemistry) , enol , alkylation , annulation , ketone , yield (engineering) , ether , enol ether , medicinal chemistry , stereochemistry , closure (psychology) , condensation , organic chemistry , catalysis , materials science , metallurgy , market economy , economics , physics , thermodynamics
The synthesis of the 3‐substitued tetrahydropyrazolopyridin‐4‐ylalkyl iodides 7a, 7b, 8a and 8b as well as their behavior towards anionic cyclization conditions have been investigated. An (enol endo )‐ exo ‐tet‐type ring closure only proceeds when a seven‐membered ring is annulated ( 9b, 10b ). Otherwise, treatment of the β‐keto ester 7a with NaH results in O‐alkylation to yield the stereoelectronically favored ( Z )‐enol ether 13a , which can be isomerized to the thermodynamically more stable ( E ) isomer 13b . Various attemps to achieve ring closure of the methyl ketone 8a failed; instead, β‐elimination is observed. Annulation of a six‐membered carbocycle is acchieved when the triester 17 is treated by a Dieckmann condensation to give the tricyclic products 18 and 19 .