Diels−Alder Reactions of N-Acyl-2-alkyl(aryl)-5-vinyl-2,3-dihydro-4-pyridones

Abstract

Readily available N-acyl-5-vinyl-2,3-dihydro-4-pyridones undergo Diels-Alder cyclization with various dienophiles to afford novel octahydroquinolines containing synthetically useful functionality. With dihydropyridone 5 and cis-disubstituted dienophiles, the resulting cycloadducts were obtained as single diastereomers in good to excellent yield. The corresponding reaction of 5 with methyl acrylate, acrylonitrile, and phenyl vinyl sulfone showed modest preference for the endo adducts. The effect of the dihydropyridone C-2 and C-4 substituents on the degree of diastereofacial control was examined. By using this methodology, the core decahydroquinoline skeleton of gephyrotoxin was prepared in a stereocontrolled fashion. Interesting reactivity was observed with certain dienophiles leading to ring-opening of the initially formed cycloadducts. This tandem reaction provides a route to uniquely substituted beta-aminoketones, alcohols, and unnatural amino acids.

Practical, Scalable, High-Throughput Approaches to η3-Pyranyl and η3-Pyridinyl Organometallic Enantiomeric Scaffolds Using the Achmatowicz Reaction

“…Methyl groups were chosen to generically represent other substituents. Entries 1−3 highlight the ease with which 2-and 4-methyl-substituted pyranyl (18,19) and 4-methyl-substituted pyridinyl (20) complexes may be synthesized starting from appropriately-substituted furans. The synthetic protocol to prepare the methyl-substituted pyranyl scaffolds 18 and 19 shown in Table 1 is analogous to that used to prepare the unsubstituted parent oxopyranyl complex: (1) Achmatowicz oxidative rearrangement of the appropriate methyl-substituted furfuryl alcohol, (2) acetylation of the intermediate hydroxypyranone, and (3) one-pot transformation into the substituted oxopyranyl scaffold with Mo(DMF) 3 (CO) 3 and KTp.…”

“…Although not explored in this current study, the use of commercially available chiral, nonracemic alcohols to prepare and resolve diastereomeric substituted 6-alkoxypranones is expected to provide the desired substituted TpMo(CO) 2 (oxopyranyl) scaffolds (18,19) in high enantiopurity as observed in the asymmetric preparation of the parent, unsubstituted pyranyl scaffolds. Similarly, the use of chiral, nonracemic urethane protecting groups derived from appropriate commercially-available chiral, nonracemic alcohols is expected to allow straightforward resolution of diastereomeric substituted oxopyridinyl complexes (like 20) after metalation.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…The intermolecular Stille reaction continued to be extensively used in organic synthesis [33]. Synthetic targets include, the heterocyclic core of GE 2270 [34], peridinin [35], pyrones isolated from placobranchus ocellatus [36], terpenepolyketide natural products [37], dihydroxerulic and xerulinic acid [38], bipinnatin J [39], elipticine [40], (+)-7-deoxytrans-dihydronarciclasine [41], gambierol [42], taiwaniaquinol [43], (−)-scabronine G [44], garsubellin A [45], piericidin A1 and B1 [46], lucilactaene [47], fostriecin [48], lupine alkaloids [49], ␤-C-glycosides [50], (+)-crocacin D [51], lobatamide analogs [52], epoxyquinoid compounds [53,54], (+)-SCH 351448 [55], 3-methyl-2,5-dihydro-1-benzoxepin carboxylic acids [56], (+)-ochromycinone and (+)-rubiginone B 2 [57], EI-1941-1 and EI-1941-2 [58], mycothiazole [59], 6 -epiperidinin [60], aureothin and N-acylaureothamine [61], cyercene A and placidenes [62], herbindole B [63], (+)-tubelactomicin A [64], saudin [65], peroxyacarnoates A and D [66], aureothin, N-acetylaureothamine, aureonitrile [67], elysiapyrones [68], altromycin B [69], (+)-phorboxazole A and analogues [70,71], (−)-SNF4435 C and (+)-SNF4435 D [72],...…”

Copper‐Catalyzed β‐Iodovinylation of Carbamates: Expedient Access to Highly Functionalized Vinyl‐Carbamates

“…As mentioned previously, β‐iodovinyl‐carbamates are key intermediates in many organic transformations. For example, β‐iodovinyl‐carbamates have been used in various metal‐catalyzed C–C bond forming reactions such as Suzuki,–, Sonogashira,, Heck, Stille, and Nozaki–Hiyama–Kishi . To the best of our knowledge, they are no reports of their use in C‐heteroatom bond forming reactions.…”