A N o v e l R o u t e t o 1 , 2 , 4 -t r i s u b s t i t u t e d P y r r o l e s Abstract: 2-(Acylmethylene)propanediol diacetates, which cyclize readily under acidic conditions to give furans (76-84%) react with primary amines under palladium catalysis to give 1,2,4-trisubstituted pyrroles in moderate to good yields (39-53%). When glycine methyl ester is used as the amine, substituted methyl pyrrol-1-ylacetates (31-82%) are obtained.Probably the best known access to furans and pyrroles is by the Paal-Knorr synthesis. 1 1,4-Dicarbonyl compounds are cyclized under acid catalysis and with dehydration to give furans; in the presence of primary amines or ammonium salts, the corresponding pyrroles are formed. By a similar mechanism, but under much milder conditions, furans are also formed under acid catalysis from a,b-unsaturated g-hydroxyketones of type 1 (Scheme 1). 2 Starting from readily available dihydroxyacetone diacetate 3, 3 we have extended a known access 4 to functionally substituted furans 6 and developed an analogous, yet palladiumcatalyzed reaction leading to pyrroles. Scheme 1 Furans from a,b-unsaturated g-hydroxyketonesIn this extension of the furan synthesis, a,b-unsaturated gacetoxyketones 5a-c which were obtained by HornerWadsworth-Emmons olefination of 1,3-diacetoxy-2-propanone (3) with b-ketophosphonates 4a-c in 62-83% yield, were used as precursors (Scheme 2, Table 1). 5 Upon treatment of the 3,3-bis(acetoxymethyl)-substituted enones 5 with hydrochloric acid in methanol at 50°C for 30-60 minutes, the corresponding 2-substituted 4-hydroxymethylfurans 6a-c were formed in 76-84% yield. 5 This reaction involves the hydrolysis of the two acetoxy moieties to give the bisallylic alcohol which, under the acidic conditions, forms the furan. Formation of the 4-fluorophenyl-substituted furan 6c proceeded much faster than the formation of the methyl-and ethyl-substituted furans 6a,b.In a first attempt to further extend the scope of this reaction to the synthesis of pyrroles, the simple addition of primary amines and ammonium salts to precursors 5a-c was tested under acidic and basic conditions. But no trace of a pyrrole could be detected in any case. Since pyrroles can only be formed after nucleophilic substitution of at least one of the allylic acetoxy groups in 5 by an amine, and this kind of substitution is generally catalyzed by palladium(0), 6,7 compounds 5a,c were treated with two equivalents of benzylamine and 5 mol% of tetrakis(triphenylphosphine)palladium in refluxing tetrahydrofuran to give the desired pyrroles 7a,c as orange oils in 53 and 39% yield, respectively (Scheme 3, Table 2). 5

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Zur Untersuchung der Solvolysereaktionen der 2-Cycloalkin-lylmcthyl-4-nitrobenzolsulfonatc 9a, b wurden zunachst dic 2-Cycloalkin-I-ylmethanole 17a, b synthetisiert. Nachdem es gelungen war durch Oxidation der cyclischen Allene 12a, b mit Pb(OAc)4 die Propargylacetate 13a, b und daraus die entsprechenden Propargylbromide 161, b im praparativen MaBstab zu gewinnen, wurden diese mit Zink und Formaldehyd in die Alkohole 17a, b iibergefiihrt. Die Solvolysen von 9a, b in Losungsmitteln unterschiedlicher lonisierungsstarke verlaufen ausschlieBlich unter Beteiligung der Dreifachbindung. 2-Cyclononin-1 -ylmethyl-4-nitrobenzolsulfonat (9a) reagiert zum Cyclopropylidenmethyl-Kation 21 a. das anschlieBend zu dem sekundaren, ringerweiterten cyclischen Homopropargyl-Kation 22a und zum 2,3-iiberbriickten Cyclobutenyl-Kation 25a umlagert, aus denen die Substitutionsprodukte 23a und 26a bzw. 24a und 28a erhalten werden. Bei der Solvolyse von 2-Cyclodecin-1 -ylmethyl-4-nitrobenzolsulfonat (9b) wurdc iiber das cyclische Homopropargyl-Kation 22b ausschlieBlich der entsprechende Homopropargylalkohol 23 b erhalten.Homopropargylverbindungen 1 mit guten Abgangsgruppen X solvolysieren in geeigneten Losungsmitteln (z. B. Trifluorethanol, Trifluoressigsaure) unter Beteiligung der Dreifachbindung (kA-ProzeD). Als reaktive Zwischenstufen bilden sich dabei die Vinylkationen 2 und 3, die mit Wasser entweder direkt oder nach Hydrolyse der entsprechenden Enolether bzw. Ester 4 und 5 zu den Cyclopropylketonen 6 und den Cyclobutanonen 7 reagieren','' (Schema 1). The 2-cycloalkyn-1-ylmethanols 17a, b were synthesized to study the solvolysis behavior of their 4-nitrobenzenesulfonic esters 9a and 9b. After having been succeeded in preparing the propargyl acetates 13a,b by oxidation of the cyclic allenes 12a,b with Pb(OAc), and subsequently the propargyl bromides 16a, b in preparative scale, the latter were converted to the alcohols 17a, b with zinc and formaldehyde. The solvolyses of 9a. b in solvents of varying ionizing power proceed exclusively with participation of the triple bond. 2-Cyclononyn-1-ylmethyl 4-nitrobenzenesulfonate ( 9 4 reacts to give the cyclopropylidenemethyl cation 21 a, which rearranges subsequently to the secondary, ring enlarged cyclic homopropargyl cation 22a and to the 2,3-bridged cyclobutenyl cation 251, from which the substitution products 238 and 26a as well as 24a and 28a are obtained. The corresponding homopropargyl alcohol 23b was obtained exclusively from the solvolysis of 2-cyclodecyn-1-ylmethyl 4-nitrobenzenesulfonate (9 b) via the cyclic homopropargyl cation 22b.Abgangsgruppen X [Tosylate,, Trifluormethansulfonate (Triflate)] in den Hintergrund gedrangt werden kann.Von den bei der Homopropargylumlagerung auftretenden Vinylkationen 2 und 3 ist nach ab initio-Berechnungen das unsubstituierte Cyclobutenyl-Kation 3 (R = H) etwa 8 kcal/mol stabiler als das isomere Cyclopropylidenmethyl-Kation 2 (R = H)3). Die Untersuchung der entsprechenden Ionen in der Gasphase durch Stol3-aktivierungsmassenspektroskopie liefert eine ...

RuCl(H)(CO)(PPh 3 ) 3 ](2) was found to catalyze, in the presence of H 2 C=CHSiMe 3 (3), the trimerisation of aldehydes RCHO [R=Et (4a), i-Bu (4b)] yielding 1,3,5-trioxanes (5) and the aldol condensation yielding a,b-unsaturated aldehydes (6). When (4a) was used as a reactant, from these reaction mixtures, the ruthenium complex [RuCl 2 (CO)(PPh 3 ) 2 (EtCH@CMeACHO-jO)] (7) having the aldol condensation product as the ligand crystallized. In the analogous reaction with (4b), the complex [RuCl 2 (CO)(PPh 3 ) 2 (i-BuCHO-jO)] (8) with the aldehyde as ligand was obtained. The constitution of these complexes was established by single-crystal X-ray diffraction measurements. The ruthenium centers are octahedrally coordinated having the aldehyde and the carbonyl ligand in mutually trans positions (coordination index: OC-6-12). The aldehydes are monodentately coordinated via the carbonyl oxygen atom (jO). The coordination induced elongations of the C@O double bonds [1.242(4) Å (7), 1.234(4) Å (8)] indicate an activation of the aldehydes. Furthermore, the RuACO bond lengths [1.842(4) Å (7), 1.823(4) Å (8)] exhibit a relatively low trans influence of the aldehyde ligands. The formation of the complexes (7) and (8) give an indication that the Lewis acidity of the ruthenium center is of importance for aldehyde activation in the catalytic process.

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