After a brief survey of reaction conditions, the dicationic Wacker-type oxidation conditions were found to provide good conversions and excellent regioselectivities with allylic trifluoromethyl substituted alkenes. Under these conditions, a variety of alkenes bearing allylic trifluoromethyl groups could be oxidized in 70–91% yield. As predicted by the inductive hypothesis, each example exhibited excellent (≥ 20:1) regioselectivity for the distal oxidation product (Table 5.1). Relative to previously examined internal alkenes, the trifluromethyl substituted alkene substrates exhibited lower reactivity and thus required increased temperature (40 ºC) and catalyst loading (7.5 mol%). This is consistent with our observations regarding the influence of electronics on reaction rate (Scheme 5.1). The newly developed protocol tolerates a variety of synthetically useful alcohol protecting groups (entry 1 to 3) and amine precursors (entry 4 and 5). Even alkenes containing unprotected alcohols (entry 6) could be chemoselectively oxidized. The excellent functional group tolerance of this reaction was further demonstrated by its compatibility with nitriles (entry 7), tosylates (entry 8) and primary alkyl halides (entry 9). In all cases, selectivities of ≥ 20:1 (distal:proximal) were obtained and further establish the powerful directing
This strategy was successfully borne out with the phosphinooxazoline framework (Figure A6.4). Steric interaction between the equatorial P-aryl group and the allylic substituent controls the facial orientation of the substrate. Because of the greater π- backbonding capability of P compared to N (i.e., the trans influence), the allylic C atom trans to P is attacked preferentially and results in single-site reactivity. Increasing the
The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (–)-sparteine as chiral ligand and molecular oxygen as the sole stoichiometric oxidant. Mechanistic insights regarding the role of base and hydrogen bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting accelerated resolutions. The use of chloroform as solvent allows resolutions to be conducted at 23 °C, resulting in enhanced catalyst selectivity. Finally, the use of ambient air as the terminal oxidant for reactions in either toluene or chloroform further increases the operational simplicity and safety of the process. These developments have led to a process with a broad substrate scope 37
classical and well-established method to give excellent results in most cases. Yet significant drawbacks remain for this approach like phosphine ligands are expensive, toxic, and unrecoverable while handling. In large-scale industrial production, the phosphines might be a more serious economical burden than even palladium itself. Another reason is the poor reactivity often associated with fully ligated complexes of palladium 3 . Further 2 limitations are found in that
Zhang, Dave Ebner, Dan Caspi, Ryan McFadden, Toyoki Nishimata, and JT Mohr. Although I never worked directly with anyone at any given time on this project, I know this project would be nothing without all of their efforts. Jeff has done an excellent job in developing the oxidative kinetic resolution beyond the initial work. Raissa has done some of the most profound work on the palladium chemistry while I’ve been here. I have a great deal of respect for her skills in experimental design and execution. Haiming came in and cranked on the C-H bond functionalization chemistry. God, he runs a ton of reactions. I love that. I think his efforts have really helped to outline where the project needs to go in the future. Dave and Toyoki have both started working on non-sparteine- based systems. I’m happy to see that people are excited about taking the chemistry in this direction, despite how difficult it may be, and I wish them the best. I really admire their willingness to work on projects that can be challenging, but could eventually lead to some thrilling outcomes. I think that although there’s still a bunch to be done, the project has come a long way in a pretty short amount of time. I have tried to point out their specific contributions in the text of the thesis, but I wanted to thank them collectively here as well.
company is going to conduct testing on the compound, they cannot afford to waste 96% of their original materials. Thus, it is important for academic groups to discover as many different types of reactions and ways to disconnect natural products as possible. It is also important to have a modular synthesis, so that analog compounds can be made and tested. In many cases, the best pharmaceutical agents are modified versions of natural products. Natural products offer the great advantage of having already been compatible with at least one living system, the one from which they were isolated. If that creature was able to survive with this compound inside it, it is more likely that a human will be able to tolerate the compound than for a molecule that has been 100% designed. Some important drugs that are natural products or derivatives include the antibiotics penicillin and vancomycin, contraceptives (+)-norgestrel and 17α-ethynylestradiol, the anti- inflammatory agent indomethacin, and the ovarian, breast, and small lung cancer drug paclitaxel (taxol).
Enzymatic catalysis 1 is the paradigm for the synthesis of complex polycycles from simple olefinic precursors in vivo. Steroids, 2 fragrances, 3 and ladder polyether toxins 4 are all examples of the complexity achieved through evolution of specific cyclization enzymes 5 that can guide a polyunsaturated molecule into a preferred cyclization geometry, achieving complete regioselectivity and stereoselectivity. As shown in Scheme 1-1, the conversion of squalene 1 to cholesterol 5 occurs by enzymatic oxidation of a terminal trisubstituted olefin to form 2,3-oxidosqualene 2, which is enzymatically opened via a “chair-boat-chair” conformer 1 to form cationic 3 after a stereoselective cascade reaction. Enzyme-assisted methyl and hydride migration occur to produce lanosterol 4, which serves as the basic [6-6- 6-5] tetracyclic steroid architecture.
Abstract: Phosphines having a high degree of instability in their syntheses, it is necessary to find conditions for obtaining stable products in order to propose new stable and active compounds. It is this concern that responds to the theoretical study of stability and selectivity. This theoretical study of chemical reactivity was carried out using the Density Functional Theory (DFT) method, at the B3LYP/6-31G (p) calculation level. The use of the Frontier Molecular Orbital (FMO) theory, with the Single Orbital Molecular Orbital (SOMO) cation model, made it possible to study the stability of some isomers formed during the addition of free phosphines to the carbon-carbon triple bond. The analysis of these reactivity quantities allowed us to conclude that the presence of halogens on acetylene influences the stability of the stereoisomers during their formation. This stability increases as the electronegativity of the halogen decreases. The large number of π conjugation favors the formation of Cis isomers and the lack or small amount of π conjugation orients the formation of Trans isomers. The nature of the aryl substituent and the number of low electronegativity halogen on the phosphine are capable of promoting the production of stable products.
The findings of the Papers 2-4 are indispensible in the future design of improved hindered amine light stabilisers, optimised for targeted protection of the specific materials against the radical damage. Firstly, efficiency of a given HALS depends on how easily it can initially be converted into the active species, nitroxide radical. We have shown that different activation mechanisms are realised depending on the N- substitution in the initial HALS molecule, as well as the structure and service conditions of the protected material. Furthermore, once generated, the nitroxide radical enters one of the catalytic cycles of its regeneration depending strongly on the chemical structure of the substrate and the operation temperature. With this respect, discoveries of the Chapter 2 provide the crucial information on which are the main damaging species to be deactivated by HALSs. On this basis, HALSs can be customised to match the protected material and the conditions of its exploitation. However, even when optimised carefully, efficiency of the stabiliser can be greatly diminished due to its physical loss via volatilisation. Our results reveal how the initial HALSs are converted into the volatile low molecular weight compounds, and thus afford developing new antioxidants, resistant against these undesired side-reactions.
synthetic disciplines. In other words, there will always be a need for new catalysts in niche, but important applications, many of which are only starting to be explored. One example of a new application is Z-selective olefin metathesis, and new, selective olefin metathesis catalysts based on Mo, W, and Ru have only recently been reported. The development of these catalysts has finally enabled the preparation of Z-olefins using metathesis. Despite this progress, significant improvements in both catalytic activity and selectivity are necessary for these catalysts to become industrially relevant. Moreover, mechanistic studies focused on catalyst stability and the origin of Z-selectivity will be essential to developing improved catalysts, just as they were in the development of previous generations of metathesis catalysts. New catalysts for use in polymer synthesis and materials science will also be required. The importance of metathesis in these areas has been demonstrated by its inclusion as the basis for self-healing materials, 18 as a method for the facile
Nowadays frontier molecular orbitals analysis is well known to explain the reactivity of compounds  by using different computational methods. The HOMO/ LUMO band gap has direct correlation with the reactiv- ity, e.g. if the band is less the compound will be kineti- cally less stable (more reactive) and vice versa . The FMOs analysis of all derivatives (3a–3p) was carried out by using B3LYP/6-31G(d,p) basis set. As observed from the HOMO/LUMO, the trend of dispersion of isoden- sity was almost similar in all compounds. Therefore, as a model here we have given the HOMO/LUMO surfaces of compound 3a only (Fig. 1) (the rest are provided in Additional file 1: Figure S1). The corresponding HOMO and LUMO energies along with band gap are narrated in Table 2.
Photoemission spectroscopy was used to investigate the initial oxidation of the Ce/Ta(110) interface at room temperature. The oxidation of Ta(110) is dramatically enhanced by a thin Ce overlayer. A Ta suboxide TaOχ (0.5≤χ≤1) is formed first in the interface, followed by the rapid formation of Ta2O5 upon further oxygen exposure. A weak interface reaction exists in Ce/Ta(110), but is excluded as the main cause of the catalytic oxidation. An earlier suggestion is reconfirmed that the Ce layer converts O2 to oxygen ions and thus promotes the oxidation of the substrate.
Although the kinetics of oxidation of hydrazides by variety of oxidants has been studied, but their reactions with ammonium metavanadate in presence of micellar catalysts seem to have received much little attention. On the basis of literature survey and in the light of above discussion, it is clear that enough information regarding the mechanism of oxidation of aliphatic acid hydrazides is not known. Hence the study of kinetics of oxidation of aliphatic acid hydrazides by Vanadium (V) has been undertaken. The common oxidising agents used for organic substrates are K 2 Cr 2 O 7 and KMnO 4 etc. which are strong oxidising agents.
yield (Table 1, entry 1). To improve the yield of 3a addition of external oxidant was envisaged to regenerate the active Pd-catalyst, because substrates are oxidatively coupled by Pd-catalyst whereby two protons are removed and palladium also reduced to Pd(0). Thus, the addition of 1 equivalent of CuI improved the yield of 3a to 48% (Table 1, entry 2). Decreasing the equivalent of CuI to 5 mol % and use of molecular oxygen as co-oxidant at 1 atm, led to the formation of 3a in 72% yield (Table 1, entry 3). Interestingly, increase in the yield (92%) of 3a was observed when molecular oxygen was used as sole oxidant, without CuI (Table 1, entry 4). Next, importance of palladium and base in the present reaction was examined. Reaction in the absence of Pd(OAc) 2 did not afford the product 3a, only 1a was recovered (Table 1, entry 5). On the other hand, decrease in the yield (52%) was observed with removal of K 3 PO 4 (Table 1, entry 6). This reveals that both Pd(OAc) 2 and K 3 PO 4 are important and the reaction indeed catalyzed by palladium.
In this communication we report our studies of two different gold-catalyzedreactions using solution EXAFS at the L3-edge (11.919 keV) in combination with more traditional analytical tools, i.e. NMR and mass spectrometry. The two selected reactions are an enantioselective intramolecular hydroalkoxylation of allenes, catalyzed by a gold-phosphine complex containing a chiral phosphate counterion reported by Toste 12 and a benzannulation of 2-carbonylphenylalkynes reported by
Enzymes are very effective and biodegradable catalysts, and act under mild conditions such as room temperature, atmospheric pressure, and around pH 7. Consequently, the applications of enzymes to the organic synthesis have extensively been studied from the standpoint of the development of sustainable synthetic processes (Truesdell, 2005). Enzymes exhibit the high activity and specificity not only in conventional aqueous solutions but also in non-aqueous reaction media (Klibanov, 2001; Noritomi et al., 2007a). Enzymes in non-aqueous media have especially been applied to numerous synthetic processes because of the following benefits, although the enzyme has the low activity in organic solvents compared with that in water: (i) the solubilities of non-polar reactants and products are improved; (ii) the thermostability of enzymes is highly improved; (iii) the stereoselectivity of enzymes is markedly altered; (iv) the thermodynamic equilibria of many processes such the formation of peptide bond by protease are favorable; (v) the immobilization of enzymes is not necessary, and enzymes are easily recycled by recovering them with the filtration or the centrifugation, since enzymes are insoluble in organic solvents; (vi) the product is easily recovered with the evaporation when using the volatile organic solvent as the reaction medium; (vii) the contamination due to the growth of microorganisms is inhibited by organic solvents. Furthermore, it has been found that the activity and selectivity of enzymes can be manipulated by the choice of solvents or enzyme preparation, although they were changed only by protein engineering or enzyme screening prior to the advent of nonaqueous enzymology (Koskinen & Klibanov, 1996; Noritomi et al., 1996; Wescott et al., 1996).
The applicability of the E-parameters of tritylium ions is more limited, however, since the sensitivity of bulky reagents towards variation of the steric requirements of the reaction partner will be large. Because our approach, like Ritchie’s, does not explicitly treat steric effects, we have recommended that reactions of bulky reagents should not be treated with eq. 2.2. 5,8 The satisfactory agreement between calculated (eq. 2.2) and experimental rate constants indicates, however, that reactivities of tritylium ions toward n-nucleophiles can generally be reproduced by eq. 2.2, in accord with Ritchie’s previous work.
Palladium-catalyzed bond forming reactions are nowadays one of the most common tools synthetic chemists employ, in industry as well as in academia.  Enormous resources have been directed into the development of efficient methodologies to perform this class of transformations in an environmentally and economically advantageous manner. In the last two decades, the design of electron-rich, bulky ligands, has addressed many challenges in this field, allowing the coupling of highly unactivated coupling partners under mild conditions and using low catalyst loadings.  The -arylation of ketones, simultaneously disclosed by Buchwald and Hartwig,  is potentially one of the most powerful and atom-economical C-C bond formation as it uses simple and widely available substrates and generates a minimum amount of side-products; the general reaction mechanism is depicted in Figure 1. 
In conclusion, a variety of 1,4-benzodiazepine-2-one derivatives can be accessed through a simple one-pot molecularly diverse multicomponent cascade protocol proceeding via palladium(0)- catalyzed allenylation anion capture and cascade palladium-catalyzed carbonylation anion capture reactions. In these processes C(sp 2 )-C(sp 2 ) + C(sp 3 )-N(sp 3 ) new bonds and C(sp 2 )-C(sp 2 ) + C(sp 2 )-N(sp 3 ) new bonds are generated, respectively. In addition, with a double relay system, C(sp 2 )- C(sp 3 ) + C(sp 3 )-C(sp 2 ) + C(sp 2 )-N(sp 3 ) new bonds are easily formed using the appropriate starter. With this methodology a range of allenes and aryl halides can be employed in good to excellent yields tolerating many functional groups. The molecular complexity of each component can be increased in order to build sophisticated architectures or even natural core products.