Isocoumarin ring synthesis

Pyridopyrimidines and pyrimidines fused with five- or six-membered heterocycles can be prepared via the ring closure of intermediate ethynylpyrimidines, which are themselves obtained by the Pd-catalyzed cross-coupling of halopyrimidines with alkynic compounds (Scheme 34). ° ""° o-Alkynylanilines such as (51), which are made by Pd-catalyzed coupling reactions of alkynes with o-haloaniline precursors, are easily cyclized to the indoles in the presence of base (Scheme 35). " " Similar meth( s can be employed in the synthesis of isocoumarins," thienopyridines," furopy-ridines" and the marine alkaloid asptamine." ... 

The isocoumarin and the dihydroisocoumarin ring systems occur widely in nature Their synthesis by lithiation method is according to type C and involves ortho metalation of N-methyl arylcarboxamides. The organometallic compounds on treatment with electrophilic reagents such as an epoxide or allylbromide followed by hydrolysis and cyclisation furnish the dihydroisocoumarins. Bromination at benzylic position followed by dehydrobromination then gives the isocoumarins themselves. 

Belgaonkar, V.H., and R.N. Usgaonkar Isocoumarins Part XIX. Synthesis of 8-Hydroy-3-methylisocoumarin and ( )-Mellein from w-Dinitrobenzene and a Convenient Synthesis of 3-Methoxyhomophthalic Acid. Indian J. Chem. 17B, 430 (1979). Bellinger, G.C.A., W.E. Campbell, R.G.F. Giles, and J.D. Tobias Formation of Some 3-Aryl-3,4-dihydroisocoumarins by Thermal Ring Closure of Stilbene-2-carboxylic Acids. J. Chem. Soc. Perkin Trans. 1 1982, 2819. 

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