3-Carbonyl-2-pyrones, cycloaddition reactions

High pressure was used to effect [4+2] cycloaddition of 5-raethoxy-carbonyl-2-pyrone with irida-2(7),5-diene 46 as the key step in a synthesis of ( )-shizuka-acoradienol. In this case, thermal conditions alone were unsuccessful in promoting the cycloaddition, and in fact, upon heating at ambient pressure, the cycloadduct undergoes retro-Diels-Alder reaction to give starting materials. 

Carbon-heteroatom double bonds can also participate in this reaction. These include both carbonyl compounds (Scheme 11.37) and imines (Scheme 11.38). Addition to aldehydes is co-catalysed by tin(II) or indium(III) salts. Under these conditions, tetrahydrofiirans are obtained. The presence or absence of the co-catalyst can also switch the reaction from one mode to another (Scheme 11.39). An indium cocatalysed cycloaddition to a 7-pyrone aldehyde 11.117 was used in a synthesis of aureothin 11.122 and A-acetylaureothamine 11.123 (Scheme 11.40). Cross-metathesis of the exo-cyc ic alkene 11.118 allowed a subsequent Suzuki coupling with a gem-dibromide 11.120 that showed the expected selectivity (Section 2.1.4.2). This reaction required the use of thallium ethoxide as the Lewis base to suppress the formation of side products. A Negishi coupling completed the synthesis of aureothin 11.122. Reduction and acylation of the nitro group yielded A-acetylaureothamine 11.123. The latter compound is active digainst Helicobacter pylori, a bacterium behind stomach ulcers. 

As important hetero Diels-Alder reactions catalyzed by aluminum Lewis acid, two kind of reactions, namely, [4 + 2] cycloaddition of Danishefski s diene with carbonyls and [4 + 2] cycloaddition of nitroalkenes with electronic rich alkenes, have been well known. The former reaction provides highly functionalized pyrones. As the first example of pyrone synthesis through catalytic asymmetric hetero Diels-Alder reaction with chiral aluminum complexes, in 1987, Quimpere and Jankowski reported the reaction of oxomalonate with 1-methyl-1,3-butadiene using Koga s catalyst (48). However, the asymmetric induction and chemical yield were quite poor (Scheme 6.147) [175]. 

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