Diazotization DIELS-ALDER REACTION

Diazo transfer reactions p-Toluenesulfonyl azide, 226 Diazotization Sodium nitrite, 170, 282 Dicarboxylation (see Addition reactions to carbon-carbon multiple bonds) Diels-Alder reaction (For a list of dienes and dienophiles see Type of Compound Index)... 

In Chapter 23 we met the remarkable intermediate benzyne and mentioned that convincing evidence for its existence was the trapping by a Diels-Alder reaction. An ideal method for generating benzyne for this purpose is the diazotization of anthranilic acid (2-aminobenzoic acid). 

A neat intramolecular trap for benzyne works in this way. A standard benzyne-generating reaction—the diazotization of an ortho-amino benzoic acid (Chapter 23) gives a zwitterion that loses nitrogen and CO2 to release the benzyne. A furan tethered to the next ortho position traps the benzyne in an intramolecular Diels-Alder reaction. The yield is impressive and the trap is very efficient. 

Best and Wege59have reported the first total synthesis of Mansonone F and this is described in Scheme 10. Phenol (111)60 was made to react with 2-chloroacetyl-5-methylfuran (112) in dimethylsulfoxide and sodium methoxide to yield (113). Ketalization of (113) followed by catalytic reduction and basic hydrolysis afforded anthranilic acid (114). Diazotization followed by pyrolysis with propene oxide in 1,2-dichloroethane probably yielded aryne (115), which undergoes intramolecular Diels-Alder reaction producing the adduct (116). Deoxygenation and then acid hydrolysis afforded the product (117). This was subjected to Grignard reaction. The resulting tertiary alcohol on nitration yielded the nitro compound (118) which was subjected to reduction and oxidation respectively to obtain (119). It yielded Mansonone F (120) on dehydration. 

Sol 7. (d) Diazotization of anthranilic acid gives a diazonium salt, which on treatment with a mild base undergoes elimination of CO2 and N2 to give benzyne intermediate (I). It immediately undergoes Diels—Alder reaction to... 

Simple pyrroles do not react as 4n components in Diels-Alder cycloadditions exposure of pyrrole to benzyne, for example, leads only to 2-phenylpyrrole, in low yield. However A-substitution, particularly with an electron-withdrawing group, does allow such reactions to occur, for example adducts with arynes are obtained using l-trimethylsilylpyrrole. Whereas pyrrole itself reacts with dimethyl acetylenedicar-boxylate only by a-substimtion, even at 15 kbar, ° A-acetyl- and A-alkoxycarbonyl-pyrroles give cycload-ducts, addition being much accelerated by high pressure or by aluminium chloride catalysis. The most popular A-substituted pyrrole in this context has been A-Boc-pyrrole, with benzyne (from diazotization of anthranilic acid) for example, a 60% yield of the cycloadduct is obtained. ... 

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