Experimented scheme

A well-known example of non-prototropic tautomerism is that of azolides (acylotropy). The acyl group migrates between the different heteroatoms and the most stable isomer (annular or functional) is obtained after equilibration. In indazoles both isomers are formed, but 2-acyl derivatives readily isomerize to the 1-substituted isomer. The first order kinetics of this isomerization have been studied by NMR spectroscopy (74TL4421). The same publication described an experiment (Scheme 8) that demonstrated the intermolecular character of the process, which has been called a dissociation-recombination process. 

To pursue the development of environmentally benign synthesis routes for ionic liquids, the alkylation step (Menschutkin reaction) was investigated by the authors in detail. The preparation of the ionic liquid 1-hexyl-3-methyhmidazohum chloride ([CeMlMJCl) was taken as a representative experiment (Scheme 7.2). The process parameters temperature (T = 70-100°C), solvent (ethanol, xylene, cyclohexane, n-heptane, solvent free), concentration of the N-base (c = 1.6-6.7 M), molar ratio n n = 1 0.5-1 4) and reaction time (f = 10-144 h) were investigated. In addition, the N-base was altered in order to proof the transferability of the reaction parameters. 

The oxidation state of the metal is of the utmost importance since no conversion is observed with complexes in a different oxidation state. CatalyticaUy active species are electron-rich d or d complexes. A general catalytic cycle has been proposed on the basis of deuterium-labeling experiments (Scheme 4-14) [280]. It is beUeved to occur for aU the catalysts used. 

Further evidence consistent with the polar radical pair mechanism was provided by a crossover experiment (Scheme 6.26). A 1 1 mixture of labeled 8Z /8 and unlabeled 8Z/8E was heated in xylene at 125 °C for 2h and at 135 °C for 4h to afford hydroxypyrimidinones 3 and 3. Analysis of the products by high resolution mass spectrometry showed no crossover between the labeled and unlabeled fragments. This result reinforces the computational results discussed previously wherein PRP recombines to give product within the solvent cage (Scheme 6.24). 

The homoallylation is applicable to multigram-scale experiments (Scheme 15) [36]. In the presence of 3mol% of Ni(acac)2, a mixture of 25 mmol of benzaldehyde, 50 mmol of Et3B, and 50 mmol of isoprene provides anti-3-methyl-l-phenyl-4-pentenol in 92% yield (4.1 g) with excellent 1,3-anti stereoselectivity. The product is purified by means of a single Kugelrohr distillation of the reaction mixture after an appropriate aqueous workup. 

The acrylato-bridged dicobalt(III) complex 97 (241) was selected in an orienting experiment (Scheme 9). Indeed, bromination of the kinetically inert complex proceeded smoothly and produced complex 98 as the sole product, as established by IR... 

The structures of the radical anions were confirmed by the following experiment (Scheme 9). The reduction of the ladder polysilanes was monitored by UY-visible-NIR spectroscopy. When the absorption of the ladder polysilanes was completely replaced by the absorption of the radical anions, the sealed tube was opened. The radical anions were immediately oxidized, and the starting ladder polysilanes were recovered in high isolated yields. It is reasonable to conclude that the radical anions of the ladder polysilanes retain the ladder structure, and the Si-Si bond cleavage or skeletal rearrangement does not occur. 

The formation of an allenyl ketone as the sole product can be achieved by using an excess (2 equiv.) of propargyl bromide (entries 3—6, Table 5.9). Use of an increased amount (3 equiv.) of the acylzirconocene chloride in the reaction with propargyl bromide and/or tosylate yields a significant amount of a 1,4-dicarbonyl compound derived from Michael-type addition of the acylzirconocene chloride to the initially formed allenyl ketone (entry 2, Table 5.9). The Michael-type addition of acylzirconocene chlorides to allenyl ketones under Cu(I)-catalyzed conditions has been confirmed by an independent experiment (Scheme 5.31). 

Sibi and Chen demonstrated for the first time that relative and absolute stereocenters of both a and fJ> carbons can be controlled in the intermolecular addition trapping experiments (Scheme 55) [149]. Magnesium and copper Lewis acids performed better than zinc. The use of 30 mol % of chiral Lewis acid gave higher selectivities than the stoichiometric amounts for both magnesium and copper. Interestingly, copper triflate gave better selectivities with... 

If an aqueous solution saturated with oxygen is sonicated hydrogen peroxide formation occurs. This is due to hydroxyl ( OH) and hydroperoxyl ( OOH) radical recombination outside the cavitation bubble (Scheme 4.1). These radicals result from HjO and O2 homolytic cleavage inside the bubble and have been observed by spin trapping experiments (Scheme 4.1) [19]. 

DCB radical anions. Stabilities of the intermediates were estimated by calculated heats of formation. Employing these, the theoretical results were in good agreement with the experiment (Scheme 15) [21]. 

Tetraneopentyl zirconium reacts in the same way as tetraneopentyl titanium to give, on a silica (soo), a tris(neopentyl) monografted species [32]. Treatment under H2 of this surface species yields silica-supported zirconium hydrides [33], which have been characterized as a mixture of mono- (65-70%) and bis- (35-30%) hydrides based on double quanta NMR experiments (Scheme 2.11) [34]. Interestingly, the double quantum experiment allows us to prove not only the presence of the two hydrides and the monohydride of zirconium by the presence or the absence of the double quanta correlation but also to detect the through space magnetic interaction between the zirconium monohydride and the silicon di-hydride, proving thus the spatial arrangement on the surface. This confirms the mechanism by which these hydrides have been formed on the surface. 

Other 2-substituted cyclopropylideneacetates of type 3-X also entered this cycloaddition (Scheme 15) [19]. The endolexo selectivity is low but usually still higher than that of simple acrylic acid esters. The relative Diels-Alder reactivities of dienophiles 1-Me and 3-X as determined by competition experiments (Scheme 15) suggest a mechanism involving either diradicals or zwitterions as intermediates [19]. Surprisingly, the 2-fluoro derivative 3-F is less reactive than the parent compound 3-H. The 2-chloro and 2-bromo derivatives 1-Me and 3-Br have similar reactivities and cycloadd to furan (57) about 16 times faster than methyl acrylate. 

Hayashi proved the validity of this catalytic cycle by the observation of aU three intermediates and their respective transformations using NMR experiments (Scheme 3.5) [16]. Transmetallation of a phenyl group from boron to rhodium takes place by addi-hon of phenylboronic acid 2 m to hydroxo-rhodium complex 16 in the presence of tri-phenylphosphine to generate the phenylrhodium complex 17. The reaction of 17 with 2-cyclohexenone la gives oxa- j-allylrhodium 18, which is converted immediately into hydroxo-rhodium complex 16 upon addition of water, liberating the phenylation product 3 am. In this NMR study, triphenylphosphine was used to stabilize the phenylrho-dium(I) complex. In the absence of triphenylphosphine, the characterization of the phenyl-rhodium species was unsuccessful. 

Similar 0—4 generations silica-supported Pd-PAMAM dendrimers with various spacer lengths were used by Alper et al. as recyclable catalysts for the hydroesterification reaction of alkenes (55) and the oxidation of terminal alkenes to methyl ketones (56). The hydroesterification experiments (Scheme 16) showed that (PPh3)2Pd-PPh2-PAMAM-Si02 complexes were highly active catalysts for styrene derivatives and linear long-chain alkenes (numbers of turnovers up to 1200). 

All reactions marked with an asterisk were observed in MIKES experiments. Scheme 1... 

Four supported amines, one primary, one secondary, and two arylamines, were reacted with guanylating agents in solution and on a solid phase in a set of comparative experiments (Scheme 19).41 The supported primary and secondary amines 15 and 16 gave high yields of product (>85%) when... 

When the metalation of 2-fluoropyridine (8) was carried out at lower temperatures (-60°C), aside from the product of addition 13, evidence for the DoM product 12 was obtained by a TMSC1 quench experiment (Scheme 4). Complete chemospecificity was achieved only with the more selective LDA base at -75°C. [81JOC4494,81JOM(215)139]. Whereas the soft character of n-BuLi favors nucleophilic reactivity, the hard LDA leads to preferential protophilic attack. The stronger kinetic basicity... 

Competition between fluoro and N-pivaloyl DMGs was demonstrated in the metalation of 227 as evidenced by dimethyl disulfide quench experiments (Scheme 67) (83JOC3401). While exclusive ortho-to-Af-pivaloyl deprotonation was shown to occur using f-BuLi/Et20/-78°C conditions, almost equal metalation to the two DMGs was observed under n-BuLi/ THF/0°C. 

Under n-BuLi (3 equiv./Et2O/0°C) conditions, 2-N-pivaloylaminoquin-oline (232) undergoes smooth 3-lithiation as demonstrated by iodine 233 and D20 quench experiments (Scheme 69) (86S670). On the other hand, using the n-BuLi/TMEDA complex resulted in equal metalation and addition, as evidenced by the formation of 233 and 234 in almost equal amounts. 

In l,2,3-triazolo[5,l-a]isoquinoline (520), the N-3 atom appears to direct metalation to the peri C-4 position, as seen from the products 521 derived from electrophile quench experiments (Scheme 158) [85JCS(P1)1897]. With TMSC1, besides 60% of 521 (E=TMS), 23% of 1,5-disubstituted... 

The DMPV technique can be viewed as a variant of DDPV (see Scheme 4.3), where the initial conditions are not recovered during the experiment (Scheme 7.2). Thus, the pulse length (rp) is much shorter than the period between pulses (tj), ti/t p = 50 — 100. 

The synthetic utility of ion exchange resins in combinatorial chemistry has been demonstrated by the use of a basic polymeric base PTBD (l,5,7-triazabicydo[4.4.0]dec-5-ene) 26 in a series of O- and N-alkylation experiments (Scheme 7) [15]. For example, deprotonation of the phenol 27 with this polymeric base PTBD 26 gave the ionic polymeric species 28 which contained the more nucleophilic phenolate. Addition of the 2-bromo aryl ketone 29 gave the aryl ether 30 in reasonable yield and in high purity (Scheme 7). The basic polymeric scavenger PTBD 26 removed all the unwanted HBr produced within the reaction mixture (in the form of 31) and advantageously eliminated the need for an aqueous extractive work-up procedure. 

Nuclear Overhauser effect (NOE) experiments have been used to determine the stereochemical relationship between the groups on adjacent carbon atoms of the ring <1997JOC5953, 20020L1299, 2005SL1559>. For example, m-azetidinc 16 and /ra/M-azetidine 17 have been characterized using NOE experiments (Scheme 3) <2005SL1559>. 

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