Mechanistic control experiments

Another piece of mechanistic evidence was reported by Snapper et al. [14], who describe a ruthenium catalyst caught in action . During studies on ring opening metathesis, these authors were able to isolate and characterize carbene 5 in which a tethered alkene group has replaced one of the phosphines originally present in Id. Control experiments have shown that compound 5 by itself is catalytically active, thus making sure that it is a true intermediate of a dissociative pathway rather than a dead-end product of a metathetic process. 

A similar isomerization of an allenyl ketone, catalyzed by a Cr(CO)sL complex, is most probably the mechanistic key step of the palladium-catalyzed conversion of chromium carbene complexes and propargyl bromide to furans. In control experiments different aryl and alkyl allenyl ketones 96 isomerized to the furans 99 in the presence of 10 mol% of Cr(CO)5(NEt3) in good yields (Scheme 15.31) [70],... 

Several lines of inquiry have been explored to address key mechanistic issues in the rhodium-catalyzed C-H insertion of carbamates and sulfamates (Scheme 17.32) [99]. A pathway involving initial condensation between substrate 96 and PhI(OAc)2 to form iminoiodinane 97 was envisioned in the original design of this chemistry. Coordination of 97 to an axial site on the rhodium dimer would promote nitrene formation and the ensuing C-H insertion event Surprisingly, control experiments with PhI(OAc)2 and sulfamate 96 (or analogous carbamates) give no indication for a reaction between these two components. 

Ironoxetane intermediates are also supported by experiments with reconstituted P450LM2 and ( )-l-D, -propene 108 which unexpectedly afforded a mixture of 98% methyloxirane 109 and 2% trarcs-2-Di-l-methyloxirane 110 [76], This remarkable stereospecific H/D-exchange at the active site was confirmed in a control experiment by incubation of unlabelled propene in D20 (80% D) which gave a mixture consisting of 80% 110 and 20% 109. In agreement with these results is a mechanistic hypothesis (Fig. 17) involving the oxetane... 

Although it has been established that the HOMO (diazoalkane)-LUMO (alkene) controlled concerted cycloaddition occurs without intervention of any intermediate for the reactions of simple diazoalkanes with alkenes, Huisgen once proposed a mechanistic alternative 4 namely an initial hypothetical nitrene-type 1,1-cycloaddition reaction of phenyldiazomethane to styrene followed by a vinylcyclopropane-cy-clopentene-type 1,3-sigmatropic rearrangement Control experiments, however, excluded this hypothesis for the bimolecular 1,3-dipolar cycloaddition reaction of diazomethane (Scheme 60).204... 

This observation is not related to traces of base or acid from the silver salts used since control experiments mled out this possibility. It was known from the literature that the 5-exo-dig versus 6-endo-dig cyclization mode could depend on the nature of the carbonyl group,56 57 of the alkyne substituent,58 59 and of the nature60 61 and oxidation state62 of the metallic source used. Also, work from Yamamoto25 demonstrated the importance of both a- and Jt-Lewis acidity properties of silver(I) complexes. Therefore, depending on the silver salt used, two mechanistic pathways were proposed (pathways A and B, Scheme 5.15). 

Other pertinent mechanistic evidence is provided as well. The authors report no observation of any intermediates. A control experiment showed that the iminium ion derived by C-protonation of 27 (Ar = Ph, L = H) and/or its conjugate base imine would,... 

While mechanistic simulators, based on the population balance and other methods, are being developed, it is appropriate to test the abilities of conventional simulators to match data from laboratory mobility control experiments. The chapter by Claridge, Lescure, and Wang describes mobility control experiments (which use atmospheric pressure emulsions scaled to match miscible-C02 field conditions) and attempts to match the data with a widely used field simulator that does not contain specific mechanisms for surfactant-based mobility control. Chapter 21, by French, also describes experiments on emulsion flow, including experiments at elevated temperatures. 

As stated above, czs-stilbene is a frequently used substrate for the study of olefin epoxidation mechanisms [100] because of mechanistic information associated with the ratio of the cis- and frazzs-isomers in the stilbene oxide product. Catalytic f-BuOOH epoxidation of czs-stilbene was performed, with our Mn (Me2EBC)Cl2 catalyst, under and product analysis shows that czs-stilbene oxide contains 25 0.3% incorporation of from atmospheric 02 versus 1.7 0.3% in a control experiment using ordinary air, whereas frzzzzs-stilbene oxide contains 55.1 1% incorporation of O from O2 versus 2.6 1% incorporation in a control experiment. Similar incorporation ratios are expected for the cis- and frzzzzs-stilbene oxides if all epoxidation products result from only one reaction pathway and a single reactive intermediate. However, the incorporation of in czs-stilbene oxide (25 0.3%) is definitely different from that in frzzzzs-stilbene oxide (55.1 1%). This result leads to the conclusion that, at least two distinct reactive intermediates occur in these epoxidation reactions. This is also consistent with the results described above for norbomylene epoxidation. 

The product yields at different temperatures are shown in Table 12. The formation of 3-cyanopjurole is probably mechanistically insignificant, for control experiments show that 2- and 3-cyanopyrrole interconvert at elevated temperatures 33). If 2-cyanopyrrole is the primary product of ring contraction, it will be chemically activated by > 54 kcal/mol due to the exothermicity of the reaction. This will suffice to interchange it with 3-cyanop5UTole. 

Despite the biological and mechanistic obscurity, heat stabilization of cells and subcellular fractions is of profound operational significance. The association of molecules and/or processes with insoluble subcellular fractions must be regarded with considerable skepticism if based solely on results of cell fractionation experiments. What are apparently trivial variables of tissue (cell) manipulation either in vivo or in vitro can alter dramatically molecular behavior. Such alterations are easily misinterpreted if relevant variables are not identified. Appropriate control experiments must be performed. 

Several non-noble metal-catalyzed iV-alkylation reactions have also been reported in recent years. In 2010, Ramon, Yus and co-workers reported Cu(OAc)2-catalyzed A-alkylation of poor nucleophilic amine derivatives and alcohols (Eq. 30) [125]. Control experiments indicated that a base was indispensable in the reaction to force the alcohol dehydrogenation step, which was later confirmed by DFT calculations reported by Liu, Huang and co-workers [63]. In 2011, Ramon and co-workers reported the results of their own mechanistic studies and proposed two possible catalytic cycles [126]. The main aldehyde-free cycle, depicted with plain arrows, requires the presence of a base. The minor cycle, depicted in dashed arrows, may proceed when an aldehyde exists in the reaction media (Scheme 23). In the same year, Li and co-workers also disclosed a CuCl-catalyzed A-alkylation of heteroarylamines [127]. 

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