A synthetic approach toward the synthesis of indolizines via 1,3-dipolar cycloaddition reactions of cycloammonium ylide

Abstract

Dehydrohalogenatlon of N-(2-aroylmethyl)9-plcollnlum and -4-picollnlum bromlde, prepared by the quanternlzation of corresponding bromlde salt with triethylamine, afforded a hlghly reactive cyclolmmonlum yllde. Its 1,3-dipolar cycloaddition reactions with varlous dipolarophlles have been lnvestlgated. These reactions ultlmately result in the formation of novel heterocycllc compounds. The structural assignment of the products were made on the basis of elemental analyses and spectroscopic data. I ntroductlonThe chemistry of cycloimmonium ylide has engaged the attention of chemists because of their importance as useful intermediates in the synthesis of novel heterocyclics. Despite the wide applicability of cycloimmonium ylide ( 7 -7 7 ) in synthetic studies, no information is available concerning the 1,3-dipolar cycloaddition reactions of methyl-substituted pyridinium ylide.I n the course of our investigations on the preparative utility of cycloimmonium ylide, we wish to report the syntheses and physical and spectral properties of indolizines having biological activities. Results and DiscussionTreatment of w-bromo ketones with picolines in anhydrous benzene at reflux temperature lead to the quarternization of picolines giving N-(2-aroylmethyl)picolinium bromides (Scheme I), in excellent yield. The bromide salts when treated with triethylamine in dry benzene immediately generated a dark red coloration due to the formation of corresponding ylide, which on subsequent reaction with various dipolarophiles (acetylenic esters) gave five-membered heterocyclic derivatives (5a-d, 7a-d).( 4 a 4 , 6a-d 1The reaction of picolinium ylides with the acetylenic triple bond of acetylenic ester such as dimethyl acetylenedicarboxylate and diethyl acetylenedicarboxylate appears to proceed by the nucleophilic attack of the carbanion similar to the first step of Michael type of addition. The stabilization of this zwitterion presumably takes place by internal nucleophilic attack of the carbanion on the a-position of the picoline ring

The Chemistry of α-Haloketones and Their Utility in Heterocyclic Synthesis

“…The reaction of α-haloketones with N -heterocyclic compounds shown in Scheme 19 is completely different and leads to quarternization in most cases [ 141 , 142 ]. This reaction has been used in the Chichibabin quaternization followed by cycloaddition of the obtained ylides with alkenes or alkynes to give the corresponding fused pyrrole derivat-ives starting from pyridines [ 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ], pyridazines [ 152 ], pyrimid-ines [ 153 , 154 ], pyrazines [ 155 , 156 , 157 ], imidazoles [ 158 , 159 , 160 , 161 ], thia-zoles [ 162 , 163 ], and triazoles [ 164 , 165 , 166 , 167 , 168 ]. This general synthetic route to pyrroles a-fused to a heterocyclic ring may be represented by the preparation of 68 starting from 66 ( Scheme 19 ).…”

The Chemistry of α‐Haloketones and Their Utility in Heterocyclic Synthesis

“…The reaction of α-haloketones with N-heterocyclic compounds shown in Scheme 19 is completely different and leads to quarternization in most cases [141,142]. This reaction has been used in the Chichibabin quaternization followed by cycloaddition of the obtained ylides with alkenes or alkynes to give the corresponding fused pyrrole derivatives starting from pyridines [143][144][145][146][147][148][149][150][151], pyridazines [152], pyrimidines [153,154], pyrazines [155][156][157], imidazoles [158][159][160][161], thiazoles [162,163], and triazoles [164][165][166][167][168]. This general synthetic route to pyrroles a-fused to a heterocyclic ring may be represented by the preparation of 68 starting from 66 (Scheme 19).…”