title: New Chemistry of Imidazolinium ylides
Creators: name: Lory, Pedro M. J.
Publisher: name: The Open University
Year: 2001

description: Previous work in this group has shown 4,5-dihydroimidazolium ylides, formed by N- alkylation of 4,5-dihydroimidazoles, to undergo 1,3-dipolar cycloadditions with a range of dipolarophiles in a highly regio- and stereoselective fashion. <br> We have investigated two further aspects of this chemistry: (1) the synthesis of 4,5-dihydroimidazoles substituted with a heteroatom at C-2 and the subsequent N-alkylation of those templates followed by deprotonation to potentially access novel azomethine ylides; and (2) an intramolecular variant of the 1,3-dipolar cycloaddition, synthesising for this purpose a series of bromomethyl(co-l)-oxoalkenoates as dipolarophiles and subsequently reacting these with some 4,5-dihydroimidazole templates. <br><br> The synthesis of 4,5-dihydroimidazoles substituted with a heteroatom at C-2 was developed from 1-enzyltetrahydroimidazol-2-thione <b>131</b>. Methylation of this with either iodomethane or methyl trifluoromethanesulfonate provided a key methylthioimidazolium iodide intermediate <b>135</b> from which 2-alkanethio- (<b>136</b>), 2-alkoxy (<b>137</b>) and 2-dialkylamino- (<b>138</b>) 4,5-dihydroimidazoles could be prepared by deprotonation, reaction with an alkoxide or reaction with a dialkylamine, respectively. N-Alkylation of the heterocycles was found to be unsuccessful. An alternative strategy, involving the synthesis of l-benzyl-3-methoxycarbonylmethyltetrahydroimidazol-2-one <b>143a</b> and -2-thione <b>143b</b>, was developed. The oxygen-containing compound <b>143a</b> was transformed into its corresponding <i>0</i>-substituted salts by treatment with triethyloxonium tetrafluoroborate, trimethylsilyl trifluoromethanesulfonate or trifluoromethanesulfonic anhydride. The sulfur analogue <b>143b</b> was <i>S</i>-methylated using methyl trifluoromethanesulfonate. However, neither of the salts was found to undergo a 1,3-dipolar cycloaddition reaction upon treatment with DBU followed by methyl acrylate. <br><br> <i>Intramolecular</i> 1,3-dipolar cycloaddition reactions of a variety of ɑ-bromoketones with 1- benzyl4,5-dihydroimidazoles proved successful. Thus, reaction of 1-benzyl-4,5- dihydroimidazole <b>29</b> with methyl <i>E</i>-8-bromo-7-oxooct-2-enoate <b>196a</b> followed by treatment with DBU afforded the tricyclic pyrroloquinoxaline adducts methyl 1-benzyl-2,3,7,8,9,9a-hexahydro-1<i>H</i>-pyrrolo[1,2,3-<i>de</i>]quinoxaline-6-carboxylate <b>217</b>. This arises from the primary cycloadduct undergoing a cascade involving an eliminative ring-opening, recyclisation, loss of water and prototropic shift cascade. Seven other examples of this reaction, involving 2- and 4-phenyl-4,5-dihydroimidazoles, and ethyl and <i>tert</i>butyl <i>E</i>-8-bromo-7-oxooct-2-enoate, as well as with 2- and 3-methyl substituted octenoates (<i>i.e</i> trisubstituted double bonds). In these cases no cycloaddition reaction involving the double bond occurs. In one instance, the reaction of (<i>R</i>)-4-phenyl-4,5-dihydroimidazole <b>112</b> with <i>tert</i>-butyl <i>E</i>-8-bromo-7-oxooct-2-enoate <b>278</b>, we were able to isolate the primary cycloadduct, <i>tert</i>-butyl (3<i>R</i>,4a<i>R</i>,8a<i>S</i>,9<i>S</i>,9a<i>R</i>)-1-benzyl-5-oxo-3-phenyldecahydro-1<i>H</i>-imidazo[1,2-ɑ] indole-9-carboxylate <b>283</b>. It would appear that the combination of sterically demanding phenyl and tert-butyl groups precludes eliminative ring-opening.