Isomunchnone

A novel type of heterocyclisation reaction involving the dipolar cycloaddition of jV,A-dialkylamino substituted thioisomunchnones and azodicarboxylates giving 1,2,4-triazine derivatives has been reported. The cycloadduct 26 is initially formed from the isomunchnone 24 and the azodicarboxylate 25, it then undergoes a selective fragmentation to give the 1,2,4-triazine 27 <99TL8675>. 

Isomunchnones play a large part in the synthetic efforts Padwa and co-workers (91-94,96,98,110,111). The Lycopodium alkaloids are a large family of natural products and have inspired numerous synthetic routes to approach these compounds. Interest in this class of alkaloids stems from the myriad of biological properties they exhibit. Padwa utilized the carbonyl ylide methodology in tandem with a cationic 71-cyclization to complete a formal synthesis of ( ) lycopodine (Scheme 4.55) (96,112). 

The isomunchnone dipole approach has been successfully applied to the synthesis of alkaloids ( )-lycopodine. As outlined in Scheme 9, 5-methylcyclohexenone 73 was converted to a-diazo imide 74 in seven steps. The diazo decomposition of 74 with Rh2(pfb)4 in CH2CI2 at 25 °C gives expected tandem ylide cycloaddition products 76 and... 

Kappe et al. (103,104) approached dihydropyrimidines, a potent group of calcium channel modulators, through the use of an isomunchnone-type cyclization. Kappe prepared the cyclization precursor 195 in the course of a three component Biginelli condensation process (Scheme 4.49). 

The 3 + 2-cycloaddition of ring-fused isomunchnones with various dipolarophiles produces predominantly die exo-dipolar adduct exo selectivity could be enhanced by the inclusion of substituents on any position of the fused five-membered ring.112 Dihydropyrimidine-fused isothiomunchnones and isomunchnones (80) undergo intramolecular 1,3-dipolar cycloadditions to form cycloadducts (81) with high regio-and stereo-selectivity (Scheme 28).113 The tandem 1,3-dipolar cycloadditions of 1,3-... 

The first example of a bimolecular 1,3-dipolar cycloaddition between an isomtinchnone and an electron-rich dipolarophile was reported by our group several years ago [27]. The reaction of diethyl ketene acetal and isomtinchnone 9 gave cycloadduct 29 in high yield. Again, only one regioisomer was obtained and the regiochemistry encountered is consistent with cycloaddition involving the HOMO of diethyl ketene acetal and the LUMO of isomunchnone 12 (n = 1). 

Wudl, Padwa, and co-workers found that the Rh(II)-catalyzed 1,3-dipolar cycloaddition of several isomunchnone precursors with C6o readily affords the [3 + 2] cycloadducts, such as ( )-213 (Scheme 1.17).364 On thermolysis, the adducts cleanly regenerated the mesoionic heterocycles, for which they may be used as a repository (Scheme 1.17). When a chiral, racemic isomunchnone precursor was used as starting material, the diastereoisomeric adducts with C60 were formed in unequal amounts which, in the absence of significant steric effects, points toward subtle electronic interactions between the reaction partners.364... 

Scheme 1.17. Rhodium-catalyzed addition of an isomunchnone precursor to C(,q. The adduct readily undergoes thermal cycloreversion under liberation of the mesoionic heterocycle, as shown by its trapping with A-phenylmaleinimide.

The results obtained clearly demonstrated that the initially formed rhodium carbenoid prefers to cyclize onto the adjacent imide carbonyl group to form an isomunchnone rather than undergo C-H insertion. The explanation proposed to rationalize this result is that the preferred rhodium carbenoid conformer 79 is the one which avoids unfavorable dipole repulsion between the two carbonyl groups of the imide (i.e. 80). The conformational... 

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