Coumarin 7-hydroxy-, ring synthesis

Coumarin is usually prepared by heating salicylaldehyde with acetic anhydride and sodium acetate (i.e., the Perkin cinnamic acid synthesis, p. 23 6), whereby the 0" hydroxy-cinnamic acid (I) undergoes cyclisation to coumarin. Coumarins having substituents in the benzene ring can often be similarly prepared. 

Additional examples of this fascinating chemistry are listed in Table 1 [9, 10]. For Entries 1-3, the initially formed m-chlorobenzoate product is methanolized to the methyl ether (not shown). Entry 3 represents an attractive synthesis of pyrrolo[3,2-d]pyrimidines [11]. Water is the nucleophile in Entry 4, not m-chlorobenzoate, in a sequence that provides pyrrolo[3,2-c]coumarins [12]. Entry 5 describes the preparation of pyrrolo[3,2-c] [1] benzothi-opyran-4-ones, which is a new ring system and where water has captured the intermediate 3-methylene-2-hydroxy indoline [13]. Entry 6 features the synthesis of pyrrolo[3,2-c]pyrones [14]. Entry 7 describes a similar rearrangement of A-alkyl-A-allenylmethylanihnes with magnesium monoperoxyphthalate (MMPP) to afford 2-vinylindoles [15], This reaction presumably follows the one described earlier, although none of the presumed intermediates could be isolated. 

Finally, in the context of a recent total synthesis of smyrindiol 69 starting from 2,4-dihydroxybenzaldehyde, the pyrone ring was generated by reduction of the ethyl (2-hydroxyphenyl)-propiolate 67 with the Lindlar catalyst (Scheme 29) [122]. The resulting orf/zo-hydroxy-(Z)-cinnamate ring-closed immediately to the corresponding coumarin 68. 

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