Hetero‐ Diels ‐ Alder cycloadditions of α,β‐unsaturated acyl cyanides. Part 2 . Reactions with N , N ‐dimethyluracils, a new route to 5‐substituted uracil derivatives

The [4 + 2] cycloadditions of 2‐oxobut‐3‐enenitrile ( 1a ), 2‐oxopent‐3‐enenitrile ( 1b ), and ethyl 4‐cyano‐4‐oxobut‐2‐enoate ( 1c ) with 1,3‐dimethyluracil ( 2 ), 1,3, 6‐trimethyluracil ( 9 ), or 1,3,5‐trimethyluracil ( 16 ) were investigated. The reactions of 1a with 2 or with 9 lead to bicyclic adducts 3 and 10 , respectively. These hexahydro‐ cis ‐pyranopyrimidines undergo ring opening under acidic conditions, restoring in 4 and 11 , respectively, an uracil system comprising 2‐hydroxybut‐2‐enenitrile as a side chain at C(5). The surprisingly stable enols tautomerize slowly to the corresponding acyl cyanides 6a and 13a , respectively. Reacting 1b or 1c with 2 and with 9 does not afford cycloadducts; instead the uracil derivatives 6b, c and 13b, c , respectively, show up, carrying at C(5) α‐oxobutanenitrile side chains. Cleavage of the acyl cyanide functions in 6a–c and 13a–c with nucleophilic agents produces various acids, esters, or amides, i.e. derivatives 8a–c and 15–c , respectively. The methyl esters 8a (X MeO, R H) and 15a (X MeO, R H) are also formed directly from the adducts 3 and 10 , respectively, with acid or base catalysis in presence of MeOH. The cycloadducts 17a and 17c , resulting from the reaction of 1a and 1c with 16 , respectively, have a Me group at the ring junction C(4a) and are stable. The structure of 17c proves that this hetero‐ Diels‐Alder addition of inverse electron demand follows the endo ‐mode.