Part 1, see [la].
' ) ')
For a recent review on the application of this reaction to the synthesis of natural products, see [2]. The formation of an acetophenone and an unidentified product from the reaction of cinnamaldehyde and 4-hydroxycoumarin has also been reported [7]. HELVETICA CHIMICA ACTA ~ VOl. 73 (1990) Scheme 1. Reaction of Farnesal(2) and Cifral(3) with CHydroxycoumarin O H + -I;"? 2 R=(CH,),C=CHCH, 3 R=H.(ZE/Z)-mlxture 1 R = (CH,),C=CHCH, tautOmeilzatlon, double-bond shift, and isomerization I 4 R=H,A"' 5 R = H , A E 9 modes are summarized in Scheme 2. Their inconsistency prompted us to carry out a systematic investigation on the reaction of 4-hydroxycoumarin and enals. The aim was to assess its utility for the synthesis of 2H-pyrano[3,2-c]coumarins (= 2H,SH-pyrano[3,2-c]-[ I]benzopyran-5-ones). These, besides being in some cases natural products [ IOl4), had previously been obtained only in multistep syntheses [ 111 [ 121 and were needed in gram amounts for structure-activity-relationship studies.
Results and Discussion. -Owing to the thermal unstability and low boiling point of some enals, all reactions were carried out at room temperature. Reaction conditions were optimized using farnesal(2); the best results were obtained in MeOH or EtOH as solvent and in the presence of catalytic amounts of ethylenediammonium diacetate . Under these conditions, the reaction was complete in < 3 h, and the yield was 88%. The use of organic bases (pyridine, Et,N, (i-Pr),NH) as solvent resulted in much lower yields and longer reaction times ( > 60 h), as did substitution of acetone for MeOH or EtOH, probably on account of the poorer solubility of 4-hydroxycoumarin. The latter is a relatively strong acid (pK, ca. 4) [14], and its alcoholic solutions are red to methylorange 4, The review [10a] updates the book [lob].