An Isomünchnone-Based Method for the Synthesis of Highly Substituted 2(1H)-Pyridones

Abstract

1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p-acetamidobenzenesulfonyl azide and triethylamine. Treatment of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomünchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1H)-pyridone ring system. The 3-hydroxy-2(1H)-pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (±)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (−)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomünchnone intermediate. The starting material for this process was prepared from l-pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh2(OAc)4 in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.

Design and Parallel Solid-Phase Synthesis of Ring-Fused 2-Pyridinones That Target Pilus Biogenesis in Pathogenic Bacteria

“…Some of the more recent reports include intramolecular Dieckmannlike condensations, 21 Michael additions, [22][23][24] as well as cycloaddition [25][26][27][28] and cyclization procedures. 29,30 However, practical procedures for the synthesis of 2-pyridinones on solid support appeared as late as 1999.…”

Use of nitrogen and oxygen dipole ylides for alkaloid synthesis

“…71 The synthesis of 144 began with formation of the known cycloadduct 139a (R 1 = H; R 2 = CO 2 Me) by cycloaddition of the isomünchnone dipole derived from diazo sulfone 138 with methyl acrylate (Scheme 27). [67][68][69][70] This multistep sequence proceeded smoothly and in high yield when catalyzed by rhodium(II) acetate. Hot aqueous hydrobromic acid then effected decarbomethoxylation of 139a to give 139b in 82% yield.…”

“…As depicted in Scheme 26, structural manipulation of the pyridinone ring and subsequent functional group interconversions provides access to several indolizidine alkaloids. [67][68][69][70] The C 6 hydroxyl substituent, protected as triflate 134, allows for an assortment of cross coupling-possibilities. The Padwa group demonstrated the versatility of the method through the synthesis of the angiotensin converting enzyme inhibitor (-)-A58365A 135, (±)-ipalbidine 136, -carbolinone 137 and a variety of other novel indolizidine-based compounds.…”

A Modular Approach to Oxoindolizino Quinolines: Efficient Synthesis of Mappicine Ketone (Nothapodytine B)

“…[9,10] The synthesis of 1 a began with the formation of the known adduct 4 a by cycloaddition of the carbonyl ylide derived from 3 with methyl acrylate (Scheme 2). [11] This multistep sequence proceeded smoothly and in high yield when catalyzed by rhodium(ii) acetate. Hot aqueous hydrobromic acid then effected decarbomethoxylation of 4 a to give 4 b in 82 % yield.…”

“…Hot aqueous hydrobromic acid then effected decarbomethoxylation of 4 a to give 4 b in 82 % yield. [11] Etherification of 4 b with commercially available (E)-1-bromo-2-pentene and cesium carbonate in dimethylformamide produced the expected substitution product, which cleanly underwent Claisen rearrangement [6a] in refluxing chlorobenzene to afford the desired derivative 5 in 74 % overall yield. This transformation is a rare example of a Claisen rearrangement in a hydroxypyridone system.…”