The chiral scaffold can be modeled by a quadrant diagram of the ligand–metal complex, in which quadrants I and III (or II and IV) are equivalently hindered (Figure A6.1). These advantages have led to the development of seminal classes of chiral ligands such as bisphosphines, binapthyl derivatives, 4
The design of palladium-catalyzed dehydrogenative transformations is an important area of research for our laboratory. 1 The initial studies led to the development of an oxidative kinetic resolution of secondary alcohols using molecular oxygen as the sole stoichiometric oxidant. 2 The kinetic resolution, however, was just one example of the array of non-heteroatom transfer oxidations we were intent on developing. Oxidative heterocyclizations (Scheme 3.1.1) are another fundamental class of transformations that were of interest. These reactions involve the cyclization of a heteroatom nucleophile onto an olefin to afford a heterocycle. This process is in essence an intramolecular variant of a Wacker oxidation, where an olefin is activated by palladium(II) for subsequent nucleophilic attack. 3 Most of the systems developed for Wacker oxidations, however, are simply not amenable to asymmetric catalysis. Prompted by our studies of a palladium(II) oxidation system that clearly was amenable to enantioselective catalysis, we sought to apply this system toward oxidative heterocyclizations. 4
Palladium(II)-catalyzed nucleophilic attack onto an olefin by a heteroatom can proceed by a variety of mechanisms. One key distinction to be made among them is whether attack occurs with the metal and nucleophile on the same face (syn, internal), or on opposite faces (anti, external) of the olefin. Another subtlety is whether π-allyl palladium(II) species are involved. This section will discuss some of the evidence that has been obtained for each mechanism.
of substrate per reation, 100 µL of dichloroethane as the solvent, 5-30 mol% catalyst). Some catalysts were dosed as a well-stirred slurry in the desired reaction solvent using a single-tip pipettor with the sampling tip cut to allow free flow of the slurry, while others were added as homogeneous solutions in dichloroethane. The reaction plate was then purged and continuously back filled with oxygen using a desiccator fixed with a T valve for 3-5 minutes. The reactions were sealed and heated at 40-85 °C, depending on substrate for 16-48 hours. For each substrate, 32-40 structurally diverse catalysts were screened. The products from each screen were then analyzed against an internal standard of either biphenyl or di-tert-butyl biphenyl (10 mol%), using HPLC analysis. The product/internal standard ratio would show the conversion of the starting material to the coupling products.
the complexes showed catalytic activities to afford 100% ethylbenzene with conversions ranging from 54% to 99% within 1.5 h (Fig. S1). In order to fully account for the role of complexes 1-6 in the observed catalytic hydrogenation reactions, control experiments were conducted without the use of the palladium(II) complexes under similar reaction conditions. The low percentage conversions of 4% within 10 h (Table 1, entry 7) confirmed that complexes 1-6 were responsible for the observed higher catalytic activities. We thus further carried out detailed kinetics, selectivity and theoretical studies to establish the structure-activity relationship.
In this research work, the target molecule containing a diphenyl methanone moiety and methyl group at positions 2 and 3 respectively was synthesized. The product was obtained in good yield whereas the yield of the 2-substituted product namely [4-(1H-indol-2-yl)phenyl](phenyl) methanone which was prepared 18 by the palladium
Palladium-catalyzed carbonylation-anion capture cascade reactions: A third series of benzodiazepine-2-one analogues were prepared from 5 or 9 but employing carbon monoxide instead of allenes as relay species in the cascade processes. These reactions were accomplished with potassium carbonate (1.2 equiv) and a catalytic system comprised by palladium(II) acetate (10 mol%), and triphenylphosphine (20 mol%) in toluene at 110 º C for 26 h. First, amine 5 was employed as terminating agent in the palladium(0)-catalyzed oxidative addition-carbonylation obtaining products 11a and 11b in 89% and 81% yields, respectively (Scheme 3, eq. a). Similarly, benzodiazepine-2-ones 9a (X = H) and 9b (X = Cl) 29 were submitted to palladiumcatalyzed carbonylation anion capture reaction affording products 12a and 12b in 73% and 89% yields, respectively (Scheme 3, eq. b). Despite of being a trivial transformation introducing a benzoyl group, this procedure permit the use of more complex iodoarenes, which are much more accessible than the corresponding benzoyl chlorides. In this series a variety of reactions conditions were evaluated, such as different catalyst systems, but yields were not improved.
amounts of catalyst and 6 did not alter the catalyst efficiency or the product distribution; however, a 3- to 5-fold increase in the radical trap concentration strongly inhibited the reaction and affected the product distribution towards the formation of byproduct 5 (Table 1, entries 1-5). At this point, a further increase in the radical trap concentration led to complete reaction inhibition (Table 1, entries 6-8). A similar trend was observed in the presence of the other radical traps that caused strong to complete inhibition of the oxidation reaction (Table 1, entries 9-17). Interestingly, no substrate-trap adducts were observed when the reaction was conducted in the presence of these radical trapping agents. Moreover, the alcohol product 11 was not formed in the presence of any radical trapping reagent and the alkyl bromide byproduct 12, which can be easily identified in Gif type oxidations performed in the presence of radical trap 7, was not detected either. 6 These observations in combination with the lack of alcohol product formation suggest that the mechanism of the Fe(OTf) 2 L1
The present research work has undertaken the study of the bi-activation of some coupling reactions by phase transfer catalysis (PTC) coupled with ultrasounds. The effect of phase transfer catalysis associated with ultra- sound waves on the reactivity of certain organic reactions such as Suzuki and Hiyama was therefore also ex- amined. The obtained results have demonstrated that Suzuki reactions are significantly favored in the presence of ultrasound in an aqueous environment. The use of Aliquat-336 plays an important role in the reduction of Pd(II) as well as in the stabilisation and solubilisation of Pd(0).
We initially focused on the Pd-catalyzed coupling reac- tion of phenyl boronic acid with phenyl iodide in the presence of diol-functionalized IL, 1. The previous studies  observed that the choice of solvent was very important for the reaction. Water represents one of the most economically and environmentally viable options. However, catalysts gave low activities when the reaction was carried out in neat water due to the low solubility of phenyl iodide in water. Therefore, 1:1 CH 3 CN/H 2 O was
A mechanism which involves intramolecular attack of the ketone oxygen atom on the activated triple bond of ketone 7, followed by a turn-over limiting [4+2] cycloaddition step was proposed by the author (Scheme 3). This general mechanism was later corroborated by theoretical calculation, although the [4+2] cycloaddition was found to be stepwise in nature, first via a Huisgen-type [3+2] cycloaddition (B3LYP/LANL2DZ). 3b Importantly, both Au(III) and Au(I) catalytic pathways were
In chapter seven, written by Kevin H. Shaughnessy (The University of Alabama, USA), cross-coupling reactions in aqueous media is the topic. Water being a cheap, non-toxic, non-fl ammable, renewable solvent makes it a sensible solvent choice. However, with organic compounds, problems of solubility along with often water labile reaction systems mean that the use of aqueous media is frequently avoided. The author discusses the resurgence of aqueous based organic chemistry, aspects of Pd that lend it to aqueous reaction systems and developments in water soluble ligands. The actual need for solubility is also discussed with effi cient organic reactions being performed ‘on water’, that is, where solubility in the solvent is not required to achieve chemical transformations. A range of examples are given: fi rstly in aqueous media, then in biphasic systems of water and organic solvent mixtures. An example of a water-only mediated Suzuki reaction was performed by Basu et al. (8). A ligand free coupling of tropolone with an aryl trihydroxyborate allowed Pd(OAc) 2 and tetrabutylammonium bromide
These are non toxic and homogeneous catalyst reported by several workers. [9-10] Scant attention has been paid on catalytic role of ruthenium(III) chloride with potassium bromated as oxidant. [11-12] Ir(III) chloride is seen to be a good catalyst in recent years. It has been investigated very little as a homogeneous catalyst with N-bromosuccinimide.  Iridium(III) chloride has also been used as catalyst in N-bromoacetamide oxidation  of some organic compounds. Kinetics of Ir(III) catalysis have also been reported  . Oxidant chosen for the present work is potassium bromated (KBrO 3 ) which has been reported to be a powerful oxidant with redox
The reaction between Vanadium (V) and Butyric and Isobutyric acid hydrazide is carried out in a mixture of perchloric acid and sodium perchlorate. The reaction proceeds through formation of complex with reactant, which decomposes in subsequent steps to give product. The various thermodynamic parameters were determined by studying the reaction at five different temperatures ranging from 30 to 50 0 C. Oxidation of hydrazides by Vanadium (V) proceeds through complex formation between hydrazide and the oxidant. Free radical formation can be confirmed by effect of acrylonitrile. The activation parameters were also determined and the mechanism is predicted.
complexes. Structures C, D, and E have lower R indices, perhaps as a consequence of the bidentate coordination of the phenylpyridine substrate, which can be redox non-innocent. Species TS-E’-F’ and F’, associated with the oxidative addition step, can be considered to have ruthenium(IV) character but the low R index (close to 50%) suggests an almost equivalent contribution of ruthenium(II). Contrary to what is sometimes believed, the value of the partial charge on ruthenium is completely unrelated to its formal oxidation state and character.
Publication 2 details successful total syntheses of uleine alkaloids 7-10 by using palladium-catalyzed Ullmann cross-coupling and Raney cobalt mediated reductive cyclization reactions as key steps. The syntheses commenced (as shown in Scheme 4) from commercially available 4-ethylcyclohexanone (11), which was converted into iodide 12 in six steps. Compound 12 was subjected to a palladium-catalyzed Ullmann cross-coupling reaction with o-iodonitrobenzene generating product 13. Treatment of this last compound with 200 wt % of freshly prepared Raney cobalt 1 in the presence of hydrogen and p-
Nanotubes (MWCNT), and Single Wall Carbon Nano- tubes (SWCNT) were purchased from Aldrich. Oxidized graphite (OG) was prepared by oxidation for 10 h with aqueous nitric and sulfuric acids . The reactions of benzylic oxidation were performed by passing air at the rate of 1 mL/min through 37 mg of a catalyst, suspended in 5 mL of p-xylene, and 0.3 mL of cyclohexene under reflux for 24 h. After addition of 10 ml of hexane, the catalyst was removed by filtration. The filtrate was con- centrated in vacuum and the residue was analyzed by non-overlapping 1 H NMR signals, characteristic for the
Abstract: A continuous-flow, visible-light-promoted method has been developed to overcome the limitations of iron- catalyzed Kumada–Corriu cross-coupling reactions. A variety of strongly electron rich aryl chlorides, previously hardly reactive, could be efficiently coupled with aliphatic Grignard reagents at room temperature in high yields and within a few minutes residence time, considerably enhancing the applic- ability of this iron-catalyzed reaction. The robustness of this protocol was demonstrated on a multigram scale, thus provid- ing the potential for future pharmaceutical application.
The successful development of a novel substrate class for palladium-catalyzed allylic alkylation, namely dihydropyrido[1,2-a]indolones (DHPIs), has enabled divergent syntheses of multiple monoterpene indole alkaloids. By setting the C20 quaternary stereocenter present within these alkaloids at an early stage in the synthesis, the remaining stereocenters can be forged with exquisite levels of control. Critical to the success of this work was the identification of highly tunable and predictable cyclizations between an indole and a C2-tethered iminium moiety. Regiodivergent cyclizations were used to complete the first catalytic enantioselective total synthesis of (–)-goniomitine, along with efficient formal syntheses of (+)-aspidospermidine and (–)-quebrachamine. Stereodivergent cyclization strategies were then employed in total syntheses of (+)- limaspermidine and (+)-kopsihainanine A. Synthetic efforts toward the highly caged Kopsia alkaloids (–)-kopsinine, (–)-kopsinilam, and (–)-kopsifoline G are also discussed.