Alkoxycarbonyl-Substituted 3-Trifloxypropene Iminium Salts and Iminium-Substituted Δ^2,3-Butenolides: Synthesis and Reactivity toward Nucleophiles

Abstract

Triflic anhydride reacts regioselectively with the ethoxycarbonyl-substituted enaminones 6a-h to give the novel 3-trifloxypropene iminium salts 7a-d or iminium-substituted D 2,3 -butenolides 8a-d and 9a-d in good yields. Hydride reduction of the iminium salts 7a,b affords new 2-dialkylamino-4-trifloxy-but-3-enoates 13a,b, while mild hydrolysis generates 2-oxo-4-trifloxybutenoates 14a,b. Butenolides 8b,d, and 9c react with methyl hydrazine to afford 4-dialkylamino-pyridazin-3(2H)-ones 12a-c.Triflic anhydride (Tf 2 O) reacts readily with enaminones 1 to yield 3-trifloxypropene iminium triflates 2 which are useful substrates in nucleophilic vinylic substitution reactions 1,2 as well as intra-and intermolecular S E (Ar) reactions. 3,4 They are also readily transformed into a wide range of propyne iminium triflates 3 by b-elimination of triflic acid (HOTf) (Scheme 1). 4-6 The NR 2 R 3 moiety in 2 and 3 can be a dialkylamino, morpholino, pyrrolidino or piperidino group (with R 1 = Me, Ph). Also, the iminium function can be incorporated in a ring system, e.g. R 1 -R 2 = (CH 2 ) n (n = 3-5) and R 3 = Me, homoallyl or benzyl. 1,6,7 In order to extend the applications of conjugated iminium salts 2 and 3, we wanted to introduce additional functionalization into propene iminium salts 2. To this end, we turned our attention to alkoxycarbonyl-substituted enaminoketones 4. We wondered whether the geminal capto-dative substitution of the enone moiety in 4 would have an effect on the reactivity and regioselectivity of sulfonylation with triflic anhydride and whether the presence of an ester group in the ambident propene iminium moiety of salts 2 (R 1 = COOR) would affect the regioselectivity of a nucleophilic attack.Here, we describe the O-sulfonylation of 2-amino-4-oxobutenoates 4 with Tf 2 O and some reactions of the resulting products with nucleophiles.The required enaminoketones 6 were prepared by analogy to a published procedure 8 that was slightly modified (see Experimental Part): addition of the alkynyl lithium reagent derived from ethyl propiolate to an aromatic aldehyde followed by oxidation of the thus formed alcohol with MnO 2 (Scheme 2) yielded the acetylenic ketones 5.Conjugate addition of secondary amines to alkynylketones 5a, 9 b,c yielded regio-and stereoselectively ethyl 2-amino-4-oxo-butenoates 6a-h. 10 The 1 H NMR spectra (400 MHz) of compounds 6a,c,g showed remarkably broadened signals for the pyrrolidine ring, indicating a partial double bond character for the N-C2 and C3-C4 bond due to p-delocalization in the enaminoketone. A NOESY experiment for 6f suggested the E(2,3),Z(3,4) stereochemistry (Scheme 2).When Tf 2 O was added to cooled solutions of the 2-amino-4-oxobutenoic acid esters 6a-d in CH 2 Cl 2 , the yellow solutions turned reddish and the moisture-sensitive salts 7a-d were formed in good yield. They could be precipitated completely from the reaction solution by the addition of Et 2 O or pentane (Scheme 3). The constitution of the novel alkoxycarbonyl-substituted 3-trifloxypropene iminium salts 7 wa...