Intramolecular processes

Two independent isomerization processes are exhibited by organo-zirconium-aluminium compounds (1) according to n.m.r. spectroscopic studies. The first 

Equilibration of the non-equivalent rj-CsHs and benzyl a-protons in the n.m.r. spectrum of the carbene complex [Ta(CH2Ph)(CHPh)(7 -C6H5)2] is attributed to the onset of rotation of the carbene ligand with a free-energy value of 19.3 0.1 kcal 

In one of the first examples of gold-catalyzed hydroamination, Utimoto reported the gold(III)-catalyzed intramolecular hydroamination of 5-alkynyl amines to form 

Utimoto has also shown that simple gold(III) salts catalyze the intramolecular hydroamination of alkynes with arylamines [4]. For example, treatment of 2-(3,3-dimethyl-l.butynyl)aniline with a catalytic amount of sodium tetrachloroaurate in refluxing TH F for 30 min led to isolation of 2-f-butylindole in 90% yield (Eq. (11.3)). Marinelli has modified and expanded the scope of Utimoto s procedure through employment of ethanol, ethanol/water [5], or ionic liquids 6] solvents. As an example of this modified protocol, treatment of 2-alkynylaniline 2 with a catalytic amount of NaAuCU dihydrate in ethanol at room temperature for 6h led to isolation of 2-(4-chlorophenyl)indole 3 in 92% yield (Eq. (11.4)). A similar hydroamination protocol employing AUCI3 as a catalyst has been recently reported by Majumdar [7]. 

Arcadi has reported the gold(111)-catalyzed hydroamination of alkynes with en-aminones [8]. For example, treatment of 4 with a catalytic amount of NaAuCh dihydrate in ethanol at 60°C for 2h led to cychzation and subsequent isolation of 

5-tetrasubstituted pyrrole S in 75% yield (Eq. (11.5)). Alternatively, treatment of a 1 1.5 mixture of 2-(3-propynyl)-2,4-pentanedione and benzylamine with a catalytic amount of NaAuQ4 dihydrate led to isolation of 4 in quantitative yield via sequential condensation/hydroamination (Eq. (11.5)). Dyker has reported the gold(III) ata-lyzed intramolecular reaction of o-secondary benzyl amines with alkynes to form isoindoles and dihydroisoquinolines [9]. 

Carbamates are also effective nucleophiles for the gold(I) atalyzed intramolecular hydroamination of alkynes [12]. For example, treatment of O-propargylic carbamate 10 with a catalytic 1 1 mixture of (PPh3)AuCl and AgOTf in dichloromethane at room temperature led to isolation of 2,5-dihydroisoxazole 11 in 88% yield (Eq. (11.8)). The transformation was effective for alkyl-, alkenyl- and aryl-substituted internal alkynes and terminal alkynes and for N-Boc, Cbz, and Ts derivatives. A similar 

Owing to their high versatility, selectivity and compatibihty with densely functionalized substrates, radical cyclizations are now frequently introduced in retrosynthetic strategies and have aheady led to the total synthesis of various and relevant natural products [3]. Two recent contributions fully illustrate this. Thus, Muratake and Natsume used a 5-exo-trig cyclization of a vinyl radical to provide a congested methylenebicyclo [2.2.2] octane as a key step in the total synthesis of ( )-nominine [4], and Reddy et al. exploited a sim- 

As discussed in the last chapter, the Doi-Edwards theory describes how the stress initiated by a step deformation relaxes by the reptational process after the equilibration time Teq of the segmental redistribution along the primitive chain. As will be shown below, the reptational process plays the most important role in the terminal region of the relaxation modulus. 

The G t) curve in Fig. 9.1 shows two distinct relaxation processes separated by a plateau. The first one has been called the transition process (denoted by HA t) below) while the second is called the terminal process (denoted by nc t) below). As shown in Figs. 4.6 and 4.9, the plateau widens, and the two relaxation processes separate further apart as the molecular weight increases. For a nonlinear relaxation modulus G(A,t) as 

As described above, we can clearly observe three distinct relaxation processes. It is obvious that to fully describe the relaxation modulus, G t) or G t, A), we need to consider other processes in addition to the reptational process. These additional processes may suggest the answer for the deviation of the observed scaling, t] oc M , from the prediction of the pure reptational chain model, p oc M . 

Doi has proposed a theory, which will be discussed in detail in Chapter 12, describing A) as the relaxation of tension on the primitive chain. The theory predicts that the t, A) process is not observable in the linear region, which has been found to be in agreement with experiment. However, corresponding to the dynamics of A), there is a process 

Considering the transition of the stress level given by Eq. (8.37) to that given by Eq. (8.32), Lin has proposed that a minor process exists 

Rather less success has attended continuing efforts to label the mechanism of cis-trans isomerization in [MCl2(PR3)2] and related complexes. The best that can be said in view of current data is that a unique mechanism seems unlikely. 

Finally we should add that, as in previous years, we have remained flexible in choosing subject headings. Apart from main headings by group, these reflect the trends in the period under review rather than conforming to a predetermined pattern. 

At 211 K the N n.m.r. spectrum of the N-enriched titanocene dinitrogen adduct of stoicheiometry [NaTi(Me5C5)2] consists of two doublets and a sharp singlet. The results indicate that below 228 K the complex exists as an equilibrium of two forms (1) and (2), (1) giving rise to the two doublets and having VC N- N) = 7 2 Hz. 

The variable-temperature behaviour of the and C n.m.r. spectra supports this interpretation and also serves to dismiss the presence below 228 K of alternative disproportion products. Eight-co-ordination can engender three structural forms (Dad, and Ca ), interconversion between which is readily feasible. Attempts to 

Publication of studies in this area has continued to increase so that some selectivity of the contents in the main text of this chapter has been necessary and other relevant papers are added in a bibliography. The use of n.m.r. spectroscopy in kinetic studies is now well established and there are three useful reviews of this technique in organometallic chemistry. -  

Three reviews in ref. 11 pertinent to the contents of this Report are concerned with fluxional and non-rigid 7r-complexes (J. W. Faller), o ji rearrangements (M.Tsutsui and A. Courtney), and rearrangements in polynuclear complexes (J. Evans). 

The naphthalene complex [TaCl( j -CioH8)(dmpe)2] [dmpe= l,2-bis(dimethyl-phosphino)ethane] has an approximately pentagonal-bipyramidal structure. Variable-temperature and n.m.r. spectra are consistent with the 

The exchange of hydride ligand with ethylenic protons in the complex [NbH-(C2H4)a(dmpe)2l is not observed on the n.m.r. time-scale at 95 and hence the dynamic insertion-deinsertion process is considerably slower than in the isoelec-tronic cation [MoH(C2H4)2(dmpe)2].  

With the advent and perfection of increasingly sophisticated n.m.r. techniques, the number of reports and amount of information on fluxional molecules has increased substantially. This is nowhere more evident than in the field of n.m.r. spectroscopy. 

The variable-temperature behaviour of the n.m.r. spectrum of [Ti (C8H8)2] is thought to result from a fluxional process involving a redox conversion (1) (2) having = 71.9 0.9kJmol-. [HfCCsHs) contains two 

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Bunsen. Discussion on Intramolecular processes Ber. Bunsenges. Phys. Chem. 92 209 50 Bunsen. Discussion on Unimolecular reactions Ber. Bunsenges. Phys. Chem. 101 304-635 Faraday Discuss. Chem. Soc. 1983 Intramolecular kinetics. No 75... 

Molecular spectroscopy offers a fiindamental approach to intramolecular processes [18, 94]. The spectral analysis in temis of detailed quantum mechanical models in principle provides the complete infomiation about the wave-packet dynamics on a level of detail not easily accessible by time-resolved teclmiques. 

Tautomerism has been discussed in Section 4.04.1.5.2. It concerns prototropic tautomerism and the decreasing order of stability is (hydrazone) >A (azo)> A (enehydrazine). The isomerization A -> A occurs via a A -pyrazoline (65BSF769). Pyrazolidones and amino-A -pyrazolines exist as such. The only example of non-prototropic tautomerism deals with the isomerization (403) —> (404) (74CJC3474). This intramolecular process is another example (Section 4.04.1.5) of the thermodynamic analogy between prototropy and metallotropy. 

Photolytic epimerizations of this type would represent a potentially useful method of direct inversion of chiral centers. However, competition by numerous other intramolecular processes vide infra) frequently renders its more general utilization less practical. 

An intramolecular reaction requires the presence of two suitably positioned functional groups, the substrate function and the reagent function, in the same molecule. The demonstration of an intramolecular process is obvious when the product is cyclic, as in this lactonization ... 

The mechanisms available to intramolecular reactions are the same as those of intermolecular reactions. The same problems of kinetic equivalence of rate terms may arise, and Table 6-3 shows some kinetically equivalent mechanisms for intramolecular reactions of the acyl function. The efficiency of intramolecular reactivity may be difficult to assess. One technique, described above as a method for the detection of an intramolecular reaction, is to make a comparison with an analog incapable of the intramolecular process. Thus p-nitrophenyl 5-nitrosalicylate, 17, hydrolyzes about 2500 times faster than p-nitrophenyl 2-methoxy-5-nitrobenzoate, 18. 

Comforth has reviewed literature reports and independently studied the special cases of reaction of 1 with salicylaldehyde and with 2-acetoxybenzaldehyde. Coumarins (10) are afforded in the condensation of 1 with salicylaldehyde or its imine, whereas when 2-acetoxybenzaldehyde is used, acetoxy oxazolone 12 is the major product. The initial aldol condensation product between the oxazolone and 2-acetoxybenzaldehyde is the 4-(a-hydroxybenzyl)oxazolone 11, in which base-catalyzed intramolecular transacetylation is envisioned. The product 9 (R = Ac) can either be acetylated on the phenolic hydroxy group, before or after loss of acetic acid, to yield the oxazolone 12, or it can rearrange, by a second intramolecular process catalyzed by base and acid, to the hydrocoumarin, which loses acetic acid to yield 10. When salicylaldehyde is the starting material, aldol intermediate 9 (R = H) can rearrange directly to a hydrocoumarin. Comforth also accessed pure 4-(2 -hydroxyphenylmethylene)-2-phenyloxazol-5(4//)-one (13) through hydrolysis of 12 with 88% sulfuric acid. 

If the grafting is carried out in air, the active sites on the polymeric backbone is attacked by atmospheric oxygen leading to the formation of macroperoxy radical, which might abstract the hydrogen atom from the backbone polymer by an inter- or intramolecular process to give hydroperoxide groups as shown. 

The metathesis of acyclic alkadienes and higher polyenes may involve both inter- and intramolecular processes. An example of an intermolecular reaction is the conversion of 1,5-hexadiene into 1,5,9-decatriene and ethene ... 

Deeatriene may, of course, react further to 1,5,9,13-tetradeca-tetraene, 1,5,9,13,17-octadecapentaene, etc. (18). Even the conjugated system 1,3-butadiene participates in metathesis reactions (14). An example of an intramolecular process is the reaction of 1,7-octadiene, which gives cyclohexene and ethene (13, 15) ... 

The intramolecular process does not give rise to a new polymer chain and is considered in Section 4.4.3. It will not be considered further in this section. 

Margerum et al (Ref 9) photolyzed solns of aromatic nitrocompds in 95% ale using an unfiltered 400 watt mercury lamp. No compd was found to be phototropic which did not have a nitrogroup ortho to a benzyl hydrogen. They hypothesized that an intramolecular process involving an H-atom transfer was operative ... 

Among the halogens, fluorine does not undergo rearrangement, and what evidence there is suggests that the rearrangement of chlorine is an intramolecular process (1,2 shift) whereas that of bromine appears to take place by both inter-and intramolecular routes. Less is known about iodine migration. 

A careful distinction must be drawn between transition states and intermediates. As noted in Chapter 4, an intermediate occupies a potential energy minimum along the reaction coordinate. Additional activation, whether by an intramolecular process (distortion, rearrangement, dissociation) or by a bimolecular reaction with another component, is needed to enable the intermediate to react further it may then return to the starting materials or advance to product. One can divert an intermediate from its normal course by the addition of another reagent. This substance, referred to as a trap or scavenger, can be added prior to the start of the reaction or (if the lifetime allows) once the first-formed intermediate has built up. Such experiments are the trapping experiments referred to in Chapters 4 and 5. 

Other examples of [2C+2S+1C0] cycloaddition reactions have been described by Herndon et al. by the use of chromium cyclopropyl(methoxy)carbenes. These complexes react with alkynes releasing ethene and forming cyclopenta-dienone derivatives, which evolve to cyclopentenone derivatives in the presence of chromium(O) and water [122] (Scheme 76). This reaction has been extended to intramolecular processes and also to the synthesis of some natural products [123]. These authors have also described another process involving a formal [2C+2S+1C0] cycloaddition reaction. Thus, the reaction of methyl and cyclo-propylcarbene complexes with phenylacetylene derivatives does not afford the expected benzannulated products, and several regioisomers of cyclopentenone derivatives are the only products isolated [124] (Scheme 76). 

In vanadium-dependent haloperoxidases, the metal center is coordinated to the imidazole system of a histidine residue, which is similarly responsible for creating hypochlorite or hypobromite as electrophilic halogenating species [274]. Remarkably, a representative of this enzyme class is capable of performing stereoselective incorporation of halides, as has been reported for the conversion of nerolidol to various snyderols. The overall reaction commences through a bromonium intermediate, which cyclizes in an intramolecular process the resulting carbocation can ultimately be trapped upon elimination to three snyderols (Scheme 9.37) [275]. 

The exact mechanism has still not been completely worked out. Opinions have been expressed that it is completely intermolecular, completely intramolecular, and partially inter- and intramolecular. " One way to decide between inter- and intramolecular processes is to run the reaction of the phenolic ester in the presence of another aromatic compound, say, toluene. If some of the toluene is acylated, the reaction must be, at least in part, interraolecular. If the toluene is not acylated, the presumption is that the reaction is intramolecular, though this is not certain, for it may be that the toluene is not attacked because it is less active than the other. A number of such experiments (called crossover experiments) have been carried out sometimes crossover products have been found and sometimes not. As in 11-14, an initial complex (40) is formed between the substrate and the catalyst, so that a catalyst/substrate molar ratio of at least 1 1 is required. 

A sigmatropic rearrangement is defined as migration, in an uncatalyzed intramolecular process, of a a bond, adjacent to one or more n systems, to a new position in a molecule, with the n systems becoming reorganized in the process. Examples... 

Table 27 Light-induced intramolecular processes for phosphazene copolymers...

The stability of a trivial assembly is simply determined by the thermodynamic properties of the discrete intermolecular binding interactions involved. Cooperative assembly processes involve an intramolecular cyclization, and this leads to an enhanced thermodynamic stability compared with the trivial analogs. The increase in stability is quantified by the parameter EM, the effective molarity of the intramolecular process, as first introduced in the study of intramolecular covalent cyclization reactions (6,7). EM is defined as the ratio of the binding constant of the intramolecular interaction to the binding constant of the corresponding intermolecular interaction (Scheme 2). The former can be determined by measuring the stability of the self-assembled structure, and the latter value is determined using simple monofunctional reference compounds. 

These results demonstrate that the hole transfer rate decreases with the increase of the distance between Py and Ptz (Scheme 7, path b). When Ptz and Py were separately conjugated to different ODNs, both Py + and Ptz + were observed at 100 /zs after the electron pulse during pulse radiolysis of the mixture of 0.2 mM each of Py- and Ptz-conjugated ODNs in other words no interstrand hole transfer occurred. Therefore, the observed results are accounted for by intramolecular processes. 

The various intramolecular processes initiated by light absorption are illustrated schematically in Figure 1.1. Such a schematic representation of the energy levels and photophysical processes which can occur in the excited... 

The metalloalkyne complex Ru ( )-CH=CH(CH2)4C CH Cl(CO)(P,Pr3)2 exhibits behavior similar to that of cyclohexylacetylene (Scheme 10).40 Thus, it reacts with OsHCl(CO)(P Pr3)2 to give the hydride-vinylidene derivative (P Pr3)2 (CO)ClRu ( )-CH=CH(CH2)4CH=C OsHCl(CO)(P,Pr3)2, which evolves in toluene into the heterodinuclear-pi-bisalkenyl complex (P Pr3)2(CO)ClRu (is)-CH=CH(CH2)4CH=CH-( ) OsCl(CO)(P,Pr3)2. Kinetic measurements between 303 and 343 K yield first-order rate constants, which afford activation parameters ofAH = 22.1 1.5, kcal-mol-1 andAS = -6.1 2.3 cal-K 1-mol 1. The slightly negative value of the activation entropy suggests that the insertion of the vinylidene ligand into the Os—H bond is an intramolecular process, which occurs by a concerted mechanism with a geometrically highly oriented transition state. 

Heating of a racemic mixture of2-820 in xylene at 140 °C led to the diastereomeri-cally pure cycloadduct 2-822 via 2-821 in two intramolecular processes in a yield of 90% (Scheme 2.183). Clearly, enantiopure isoxazolidines can also be obtained starting from enantiopure epoxides [412a]. 

The rearrangement of 24 to 19 is an intramolecular process with 1st order kinetics. The rearrangement does not occur by reductive elimination of TMS from 24 and by readdition of free TMS to the [(dtbpm)Pt(O)] fragment in a subsequent C-Si activation step. This possibility can be excluded rigorously by performing the 24 to 19 transformation in fully deuterated Si(CD3)4 or in hexamethydisi-loxane as solvents 24 only yields undeuterated 19 in d -TMS and does not lead to 21 in hexamethyl-disiloxane (which would have to be seen as a dissociative mechanism, as [(dtbpm)Pt(O)] had been previously shown to activate hexamethydisiloxane under the same reaction conditions). 

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