Pyridones isomiinchnones

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>. 

Mathias and Moore (30-33) described a new synthesis of isomiinchnones 55 via the thermal cyclization of A-(chloroacetyl)lactams (54) (Scheme 10.7). These isomiinchnones can be captured by NPM to give fused 2-pyridones in moderate yields. Cycloadducts from the reaction with DMAD are produced in much lower yields (<17%), and other olefinic dipolarophiles (fumarate, maleate, acrylate, and dicyanocyclobutene) are unreactive. Reaction of 7/-(chloroacetyl)benzamide (57) in the presence of NPM gave 58 in low yield. 

This strategy is a powerful route to bicyclic pyridones and their transformation products. Thus, these workers (40,41) applied this methodology to formal syntheses of the lupinine alkaloids ( )-lupinine and ( )-anagyrine (89) (Scheme 10.14). Imidosulfoxide (82) is converted to the corresponding isomiinchnone that is trapped with methyl acrylate to give 85. Oxidation, ring opening, and triflate formation... 

The dipolar cycloaddition chemistry of isomiinchnones is a powerful and concise route to polycyclic azaheterocycles, and Padwa has been the pioneer in this effort. Sheehan and Padwa (159) employed the rhodium-catalyzed isomiinchnone generation and subsequent trapping to a synthesis of 2-pyridones and the alkaloid... 

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