Initial mechanistic studies

In 1978, Sugasawa et al., at Shionogi Pharmaceutical Co. reported ortho-selective Friedel-Craft acylation with free anilines with nitrile derivatives [4]. Sugasawa reported that the reaction requires two different Lewis acids (BC13 and A1C13) and does not proceed when N,N-dialkyl anilines are used. He proposed that boron bridging between nitriles and anilines led to exclusive ortho-acylation but a conclusive mechanism was not elucidated. The report did not offer any reason why two different Lewis acids were required and why the reaction did not progress with N,N-dialkyl anilines. Therefore, we initiated mechanistic studies. 

The Pd[(-)-sparteine]Cl2 complex catalyses the formation of dialkyl acetals ArC (OMe)2Me from styrene derivatives ArCH=CH2 with Markovnikov regioselectivity. Initial mechanistic studies indicate that the reaction proceeds through an enol ether intermediate and a Pd hydride.73... 

These initial mechanistic studies with bis(phosphine) catalysts were able to distinguish between overall associative and dissociative possibilities [86]. As shown in pathway (a) of Fig. 4.30, an associative mechanism involves coordination of an olefin directly to the 16-electron pre-catalyst, to form an 18-electron olefin complex that then undergoes [2 -I- 2] cycloaddition. In contrast, pathways (b) and... 

In the initial mechanistic studies of the Ir-catalyzed hydrogenation of imines catalytic cycles involving imine coordination to the metallic center have been considered. - However, in the recent computational study of Hopmann and Bayer it has been shown that in the case of asymmetric hydrogenation with [lr(PHOX)(cod)]+BArF" 9 various catalytic cycles containing coordinated imine are characterized with unreasonably high activation barriers (35-50 kcal/mol). On the other hand, a catalyhc cycle resembling that outlined in 2006 by Oro et al. (Figure 1.30) - has been found kinetically feasible. 

Because of its advanced clinical status, efforts are ongoing to study in detail the chemical and biological properties of MGd. Initial mechanistic studies revealed a clearance pathway that was largely hepatic [3] and provided support for a very novel mechanism of action [10,11]. This latter mechanism, manifest... 

Furan and its derivatives have been subjects of interest for several years, given their roles in several combustion processes, and this interest has expanded significantly in the past decade as attention to biomass-derived fuels has increased. This section wiU summarize mechanistic studies of the pyrolytic and oxidative chemistry of furan and its substituted derivatives (Figure 10). Studies of the combustion pathways of furan and its methyl-substituted derivatives are particularly intertwined together, these studies provide a comprehensive case of foUowing initial mechanistic studies through the development of a fuU chemical kinetic mechanism. 

The time-dependent Schrddinger equation governs the evolution of a quantum mechanical system from an initial wavepacket. In the case of a semiclassical simulation, this wavepacket must be translated into a set of initial positions and momenta for the pseudoparticles. What the initial wavepacket is depends on the process being studied. This may either be a physically defined situation, such as a molecular beam experiment in which the paiticles are defined in particular quantum states moving relative to one another, or a theoretically defined situation suitable for a mechanistic study of the type what would happen if. .. 

In a mechanistic study, the aim is not to quantitatively reproduce an experiment. As a result it is not necessary to use the methods outlined above. The question here is what drives a reaction in a particular direction, or what would happen if the molecule is driven in different ways. The initial conditions are then at the disposal of the investigator to be chosen in a way to answer the relevant question, using a suitable spread of positions and energies. 

Reaction between butadiene and CO2 has been extensively studied (171) since the reaction was first demonstrated (167—170). This reaction has been shown to be catalyzed by Pd (172,173), Ni (174), Ru (175), Pt (178), and Rh (172,173) catalysts. Products include gamma (5) and delta lactones (6), acids (7,8), and esters (9). Mechanistic studies have shown that butadiene initially forms a dimer (Pd, Ru, Ni) or trimer (Rh) intermediate followed by CO2 insertion (171). The fate of these intermediates depends on the metal, the ligands, and the reaction conditions. 

The mechanism of the Hurd-Mori reaction has been discussed extensively in the review by Stanetty. The mechanism of the reaction was initially postulated by Hurd-Mori based on the isolation of intermediate 10. This intermediate was shown to transform into the desired thiadiazole upon heating in ethanol, either with or without acid. The reaction was thought to proceed via the four-membered intermediate 11, which would release the volatile ethylformate as a by-product. In 1995, Kobori and co-workers were able to isolate and determine crystallographically a very similar intermediate structure to 10 in their mechanistic studies of the reaction. ... 

Pickel DL, Politakos N, Avgeropoulos A, Messman JM (2009) A mechanistic study of alpha-(amino acid)-N-carboxyanhydride polymerization comparing initiation and termination events in high-vacuum and traditional polymerization techniques. Macromolecules 42 7781-7788... 

As a rule, short nucleation times are the prerequisite for monodisperse particle formation. A recent mechanistic study showed that when Pt(acac)2 is reduced by alkylalu-minium, virtually all the Pt cluster nuclei appear at the same time and have the same size [86]. The nucleation process quickly consumes enough of the metal atoms formed initially to decrease their concentration below the critical threshold. No new metal cluster nuclei are created in the subsequent diffusion-controlled growth stage. 

In contrast to the borylation of alkane C-H bonds, the coupling of aryl halides with amines was based on a literature precedent from another group published about a decade before our initial studies. Kosugi, Kameyama and Migita published the coupling of aryl halides with tin amides." Mechanistic studies we conducted on this process led us to the perhaps obvious realization that the reaction" could be conducted with amines and a silylamide base instead of tin amides (equation 4)." Surveys of bases with similar p a values led Janis Louie to conduct reactions with alkoxide bases. Similar studies were conducted at nearly the same time by Steve Buchwald and coworkers."... 

There is a discussion of some of the sources of radicals for mechanistic studies in Section 11.1.4 of Part A. Some of the reactions discussed there, particularly the use of azo compounds and peroxides as initiators, are also important in synthetic chemistry. One of the most useful sources of free radicals in preparative chemistry is the reaction of halides with stannyl radicals. Stannanes undergo hydrogen abstraction reactions and the stannyl radical can then abstract halogen from the alkyl group. For example, net addition of an alkyl group to a reactive double bond can follow halogen abstraction by a stannyl radical. 

FIGURE 6.42 Oxidation of 3-oxa-chromanol 58 in the presence of 1 equivalent of water mechanistic study hy means of selectively deuterated starting material. The initially formed ortho-quinone dimethide 63 rearranges into styrene derivative 64, which then reacts with water to provide acetophenone 61. 

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

This reaction has been the subject of a great deal of theoretical and mechanistic study, largely because of the commercial importance of the polymers to which it can give rise. Like the other radical reactions we have discussed, it can be said to involve three stages—(a) initiation, (i>) propagation, and (c) termination ... 

Since group 3 metallocene alkyls are isoelectronic with the cationic alkyls of group 4 catalysts they may be used as olefin polymerization initiators without the need for cocatalysts. The neutral metal center typically results in much lower activities, and detailed mechanistic studies on the insertion process have therefore proved possible.216-220 Among the first group 3 catalysts reported to show moderate activities (42 gmmol-1 h-1bar-1) was the yttrocene complex (77).221... 

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