Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones.
ABSTRACT: Carboxylic acids have been electro-oxidatively coupled to electron-rich olefins to form lactones. Kolbe decarboxylation does not appear to be a significant competing pathway. Experimental results indicate that oxidation occurs at the olefin and that the reaction proceeds through a radical cation intermediate.
Project description:Delta-sultones, prepared by C-H insertion, can be oxidatively converted to gamma-lactones by treatment with t-BuOK/t-BuOOH. An intermediate in the synthesis of (-)-eburnamonin was prepared using this approach.
Project description:A facile substrate-encapsulated RCM-based synthesis of 7-membered lactones is reported. Coordination of the alpha,omega-dienyl ester precursor to the bulky Lewis acid (LA) aluminum tris(2,6-diphenylphenoxide) (ATPH) provides a protective extended steric pocket to the olefin moieties, thereby favoring intramolecular RCM over intermolecular ADMET oligomerization. The LA-encapsulated esters undergo ring-closure in the presence of Ru-based olefin metathesis catalysts to give previously difficult-to-access 7-membered beta,gamma- and gamma,delta-unsaturated lactones in good yields.
Project description:This paper reports a novel approach for the direct and facile synthesis of 1,2-oxyamino moieties via an intermolecular copper-catalyzed oxyamination of olefins. This strategy utilizes O-benzoylhydroxylamines as an electrophilic amine source and carboxylic acids as a nucleophilic oxygen source to achieve a modular difunctionalization of olefins. The reaction proceeded in a regioselective manner with moderate to good yields, exhibiting a broad scope of carboxylic acid, amine, and olefin substrates.
Project description:In this article we describe extensive studies of the catalytic asymmetric heterodimerization of ketenes to give ketene heterodimer ?-lactones. The optimal catalytic system was determined to be a cinchona alkaloid derivative (TMS-quinine or Me-quinidine). The desired ketene heterodimer ?-lactones were obtained in good to excellent yields (up to 90%), with excellent levels of enantioselectivity (?90% ee for 33 Z and E isomer examples), good to excellent (Z)-olefin isomer selectivity (?90:10 for 20 examples), and excellent regioselectivity (only one regioisomer formed). Full details of catalyst development studies, catalyst loading investigations, substrate scope exploration, protocol innovations (including double in situ ketene generation for 7 examples), and an application to a cinnabaramide A intermediate are described. The addition of lithium perchlorate (1-2 equiv) as an additive to the alkaloid catalyst system was found to favor formation of the E isomer of the ketene heterodimer. Ten examples were formed with moderate to excellent (E)-olefin isomer selectivity (74:25 to 97:3) and with excellent enantioselectivity (84-98% ee).
Project description:New species of lance lacewings, Spilosmylus spilopteryxsp. n. and Spilosmylus tephrodestigmasp. n., are described from the Philippines and compared with congeners. Both species are characterised by a distinctive wing pattern, which in the case of Spilosmylus spilopteryxsp. n. is relatively spectacular among lacewings. An identification key to the species of Spilosmylus Kolbe known from the Philippines is also provided.
Project description:Total syntheses of the labdane diterpene lactones marrubiin, marrulibacetal, desertine, marrulibacetal A, marrubasch F, cyllenine C, marrulanic acid, and marrulactone are described. The <i>trans</i>-decalin moiety of these molecules was constructed in a stereoselective manner by a Pauson-Khand reaction, and the resultant cyclopentenone was oxidatively cleaved for formation of the lactone ring. Elongation of the side chain at C9 was achieved by an epoxide-opening reaction with a variety of nucleophiles, and the functional group manipulations completed the syntheses of these natural products. Stereochemistries of desertine could be established by the transformations.
Project description:We report the ligand-enabled C-H activation/olefination of free carboxylic acids in the ?-position. Through an intramolecular Michael addition, ?-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the ?-position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.
Project description:Lewis pair polymerization employing N-Heterocyclic olefins (NHOs) and simple metal halides as co-catalysts has emerged as a useful tool to polymerize diverse lactones. To elucidate some of the mechanistic aspects that remain unclear to date and to better understand the impact of the metal species, computational methods have been applied. Several key aspects have been considered: (1) the formation of NHO-metal halide adducts has been evaluated for eight different NHOs and three different Lewis acids, (2) the coordination of four lactones to MgCl? was studied and (3) the deprotonation of an initiator (butanol) was investigated in the presence and absence of metal halide for one specific Lewis pair. It was found that the propensity for adduct formation can be influenced, perhaps even designed, by varying both organic and metallic components. Apart from the NHO backbone, the substituents on the exocyclic, olefinic carbon have emerged as interesting tuning site. The tendency to form adducts is ZnCl? > MgCl? > LiCl. If lactones coordinate to MgCl?, the most likely binding mode is via the carbonyl oxygen. A chelating coordination cannot be ruled out and seems to gain importance upon increasing ring-size of the lactone. For a representative NHO, it is demonstrated that in a metal-free setting an initiating alcohol cannot be deprotonated, while in the presence of MgCl? the same process is exothermic with a low barrier.
Project description:Background:The natural production of olefins (unsaturated aliphatic hydrocarbons) by certain bacterial genera represents an alternative and sustainable source of biofuels and lubricant components. The biochemical steps of olefin biosynthesis via the ole pathway encoded by oleABCD have been unraveled recently, and the occurrence of olefins has been reported for several Gram-negative and Gram-positive bacteria. However, the distribution and diversity of olefins among the Gram-positive bacteria has not been studied in detail. Results:We report the distribution of olefin synthesis gene clusters in the bacterial domain and focus on the olefin composition and the determinants of olefin production within the phylum of Actinobacteria. The olefin profiles of numerous genera of the Micrococcales order were analyzed by GC/MS. We describe for the first time olefin synthesis in representatives of the genera Pseudarthrobacter, Paenarthrobacter, Glutamicibacter, Clavibacter, Rothia, Dermacoccus, Kytococcus, Curtobacterium, and Microbacterium. By exchange of the native ole genes of Micrococcus luteus with the corresponding genes of actinobacteria producing different olefins, we demonstrate that the olefin composition can be manipulated with respect to chain length and isomer composition. Conclusions:This study provides a catalogue of the diversity of olefin structures found in the Actinobacteria. Our ole gene swapping data indicate that the olefin structures are fundamentally determined by the substrate specificity of OleA, and at the same time by the availability of a sufficient supply of suitable fatty acyl-CoA substrates from cellular fatty acid metabolism. This makes OleA of Gram-positive bacteria a promising target for structural analysis and protein engineering aiming to generate olefin chain lengths and isomer profiles which are designed to match the requirements of various industrial applications.
Project description:This Article details the development of the iron-catalyzed conversion of olefins to radicals and their subsequent use in the construction of C-C bonds. Optimization of a reductive diene cyclization led to the development of an intermolecular cross-coupling of electronically-differentiated donor and acceptor olefins. Although the substitution on the donor olefins was initially limited to alkyl and aryl groups, additional efforts culminated in the expansion of the scope of the substitution to various heteroatom-based functionalities, providing a unified olefin reactivity. A vinyl sulfone acceptor olefin was developed, which allowed for the efficient synthesis of sulfone adducts that could be used as branch points for further diversification. Moreover, this reactivity was extended into an olefin-based Minisci reaction to functionalize heterocyclic scaffolds. Finally, mechanistic studies resulted in a more thorough understanding of the reaction, giving rise to the development of a more efficient second-generation set of olefin cross-coupling conditions.