Isomiinchnones cycloaddition reactions

Padwa and co-workers employed a rhodium-catalyzed [3+2] cycloaddition reaction to generate a number of 3-hydroxy-2-pyridones, including the tricyclic 146, obtained using fV-phenylmaleimide 145 as the dipolarophile. The rhodium-catalyzed cyclization of 143 generates an isomiinchnone intermediate 144, which undergoes the cycloaddition (Scheme 11) <1997JOC438>. 

The reader was given a taste of the power of isomiinchnone dipolar cycloaddition chemistry in Section 10.2.1. As discussed by Potts (1) and Gingrich and Baum (10), the isomiinchnone ring system—a masked carbonyl dipole—is exceptionally reactive as a 1,3-dipole in 1,3-dipolar cycloaddition reactions. In the intervening years since these two excellent reviews the major research efforts in isomiinchnone chemistry have entailed synthetic applications to specific targets such as alkaloids and other natural and unnatural products. 

Gowravaram and Gallop (169) adapted the rhodium-catalyzed generation of isomiinchnones from diazo imides to the solid-phase synthesis of furans, following a 1,3-dipolar cycloaddition reaction with alkynes. A variety of furans were prepared in this fashion. With unsymmetrical electron-deficient alkynes (e.g., methyl... 

Padwa et al. (187,188) concisely summarized his domino cycloaddition/ A -acyliminium ion cyclization cascade process, which involves sequentially the generation of an isomiinchnone 1,3-dipole, intramolecular 1,3-dipolar cycloaddition reaction, 77-acyliminium ion formation, and, hnally, Mannich cyclization. Kappe and co-workers (189) utilized Padwa s cyclization-cycloaddition cascade methodology to construct several rigid compounds that mimic the putative receptor-bound conformation of dihydropyridine-type calcium channel modulators. 

Ibata was the first to show that the masked carbonyl ylide embedded within the isomiinchnone framework would readily undergo 1,3-dipolar cycloaddition with various dipolarophiles [34], The isolable isomiinchnone 4 was observed to react with dimethyl fumarate to produce cycloadduct 7 which possesses the 7-oxa-2-azabicyclo[2.2.1]heptane skeleton. When the reaction of 1 was carried out using catalytic amounts of Cu(acac)2 in the presence of various dipolarophiles, smooth dipolar cycloaddition was observed to occur giving mixtures of endo and exo isomers. In most cases, the exo isomers were favored. All of Ibata s isomiinchnone cycloadditions contain aromatic substituent groups, presumably selected to facilitate dipole formation. The synthetic utility of the cycloaddition reaction is diminished, however, because of the low reactivity of the aromatic substituents toward further manipulation. 

Prompted by our earlier work dealing with the internal dipolar cycloaddition reaction of mesoionic oxazolium ylides of type 74, we subsequently studied the rhodium(II) catalyzed reactions of the related a-diazo ketoamide system 154 <97JOC2001 04OL3241 05JOC2206>. Attack of the amido oxygen at the rhodium carbenoid produces a push-pull carbonyl ylide dipole (i.e., 155) that is isomeric with the isomiinchnone class of mesoionic betaines. 

A traceless linker strategy for the synthesis of functionalised furans based on mesoionic isomiinchnones generated on solid support, was developed by Gallop et alP- The key step of this protocol takes advantage of an efficient [3+2] cycloaddition reaction with electron deficient acetylenes, followed by a thermally promoted cycloreversion reaction. 3- 7 As shown in Scheme... 

Kappe and co-workers have extended their intermolecular isomiinch-none cycloaddition reaction (see Scheme 26) to an intramolecular version to obtain the conformationally rigid polyheterocycles 206, which mimic the putative receptor-bound conformation of dihydropyrimidine-type calcium channel modulators [159]. The key step in the synthesis involves the regio- and diastereoselective intramolecular 1,3-dipolar cycloaddition reaction of a dihydropyrimidine-fused isomiinchnone dipole. The diazoimides... 

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