Studies on Syntheses of 1-Azaspirocycles, 2,6-Disubstituted 3-Piperidinols and cls-Decahydroquinolines
type: CreativeWork
description: Pyrrolidines and piperidines bearing a nitrogen-substituted quaternary stereocenter are commonly encountered structural motifs in many naturally occurring alkaloids, and therefore development of methods for their synthesis are important. The Rh(II)-catalyzed intramolecular tertiary C-H insertion reaction of 5-(-diazoacetoxy)piperidin-2-ones and 3-(-diazoacetoxy)pyrrolidines carrying C6 and C2 alkyl substituents, respectively, was investigated for the formation of bicyclic lactones bearing a nitrogen-substituted quaternary stereocenter. Both Rh(II)-carboxylate and Rh(II)-carboxamidate catalysts with varying electronic and steric properties were examined; however, these reactions usually resulted in the formation of complex mixture of products and the desired tertiary CH insertion products were not formed. The steric interactions encountered by the Rh(II)-carbenoid with the tertiary CH insertion site might have impeded the desired CH insertion reaction pathway. Alkylidenecarbene generation-1,5-CH insertion reaction of 5-(3-oxobutyl)pyrrolidin-2-ones and 6-(3-oxobutyl)piperidin-2-ones was next investigated for the formation of 7-methyl-2-azaspiro[4,4]non-6-ene-3-ones and 2-methyl-6-azaspiro[4,5]dec-1-ene-7-ones, respectively. The precursors 5-(3-oxobutyl)pyrrolidin-2-ones and 6-(3-oxobutyl)piperidin-2-ones required for this study were obtained from Wacker oxidation of 5-(but-2-enyl)pyrrolidin-2-ones and 6-(but-2-enyl)piperidin-2-ones, respectively with excellent regioselectivity (11:1). Further studies on Wacker oxidation have suggested that the lactam ring has a strong influence on the observed regioselectivity. Optimization studies for alkylidenecarbene generation-CH insertion reaction indicated that the efficiency of the CH insertion reaction is sensitive to the reaction temperature and the amount of lithio(trimethylsilyl)diazomethane employed. Under the optimized reaction conditions, 7-methyl-2-azaspiro[4,4]non-6-ene-3-ones and 2-methyl-6-azaspiro[4,5]dec-…
abstract: Pyrrolidines and piperidines bearing a nitrogen-substituted quaternary stereocenter are commonly encountered structural motifs in many naturally occurring alkaloids, and therefore development of methods for their synthesis are important. The Rh(II)-catalyzed intramolecular tertiary C-H insertion reaction of 5-(-diazoacetoxy)piperidin-2-ones and 3-(-diazoacetoxy)pyrrolidines carrying C6 and C2 alkyl substituents, respectively, was investigated for the formation of bicyclic lactones bearing a nitrogen-substituted quaternary stereocenter. Both Rh(II)-carboxylate and Rh(II)-carboxamidate catalysts with varying electronic and steric properties were examined; however, these reactions usually resulted in the formation of complex mixture of products and the desired tertiary CH insertion products were not formed. The steric interactions encountered by the Rh(II)-carbenoid with the tertiary CH insertion site might have impeded the desired CH insertion reaction pathway. Alkylidenecarbene generation-1,5-CH insertion reaction of 5-(3-oxobutyl)pyrrolidin-2-ones and 6-(3-oxobutyl)piperidin-2-ones was next investigated for the formation of 7-methyl-2-azaspiro[4,4]non-6-ene-3-ones and 2-methyl-6-azaspiro[4,5]dec-1-ene-7-ones, respectively. The precursors 5-(3-oxobutyl)pyrrolidin-2-ones and 6-(3-oxobutyl)piperidin-2-ones required for this study were obtained from Wacker oxidation of 5-(but-2-enyl)pyrrolidin-2-ones and 6-(but-2-enyl)piperidin-2-ones, respectively with excellent regioselectivity (11:1). Further studies on Wacker oxidation have suggested that the lactam ring has a strong influence on the observed regioselectivity. Optimization studies for alkylidenecarbene generation-CH insertion reaction indicated that the efficiency of the CH insertion reaction is sensitive to the reaction temperature and the amount of lithio(trimethylsilyl)diazomethane employed. Under the optimized reaction conditions, 7-methyl-2-azaspiro[4,4]non-6-ene-3-ones and 2-methyl-6-azaspiro[4,5]dec-…
author: Annadi, Krishna Reddy
language: en
date published: 2015-07
date modified: 2026-07-24T04:03:41Z
provider: University of Regina
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Faculty of Graduate Studies and Research, University of Regina

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10294/6578

PropertyValue
property ID: DOI
value: 10.82465/4636