Alkyl complexes selected reactions

Finally, the most complex synthetic reaction clearly catalysed by RNA molecules generated by in vitro selection is the formation of the C-N bond of a nucleoside (Scheme 7), from 4-thiouracil and most of the natural substrate for the natural (uracil phos-phoribotransferase) reaction.1461. (Thiouracil was used because it is easily tagged by alkylation on sulfur.) The catalytic RNAs produced by 11 rounds of selection required Mg++ cations and had kcat as high as 0.13 min-1,with kcaJKM at least 107 times greater than the (undetectable) uncatalyzed reaction. Once again these systems are convincing, rather efficient enzyme mimics. 

Figure 2 shows the generally accepted dissociative mechanism for rhodium hydroformylation as proposed by Wilkinson [2], a modification of Heck and Breslow s reaction mechanism for the cobalt-catalyzed reaction [3]. With this mechanism, the selectivity for the linear or branched product is determined in the alkene-insertion step, provided that this is irreversible. Therefore, the alkene complex can lead either to linear or to branched Rh-alkyl complexes, which, in the subsequent catalytic steps, generate linear and branched aldehydes, respectively. 

Electron-rich carbyne complexes can react at the carbyne carbon atom with electrophiles to yield carbene complexes. Numerous examples of such reactions, mostly protonations, have been reported [519]. Depending on the nucleophilicity of the carbyne complex, such reactions will occur more or less readily. The protonation of weakly nucleophilic carbyne complexes requires the use of strong acids, such as triflic [533], tetrafluoroboric [534] or hydrochloric acid [535,536]. More electron-rich carbyne complexes can, however, even react with phenols [537,538], water [393,539], amines [418,540,541], alkyl halides, or intramolecularly with arenes (cyclometallation, [542]) to yield the corresponding carbene complexes. A selection of illustrative examples is shown in Figure 3.25. 

In 2002, Grubbs and co-workers reported the first CM reactions of allyl phosphines.In an initial reaction, subjecting allyl diphenylphosphine to catalyst 5 (5 mol%) failed to produce any of the desired cross-product. However, by protecting the phosphine as its borane complex, CM reactions could be achieved in good yield with high E-selectivity (Equation (5)). Notably, catalyst 5 failed to dimerize borane-protected vinyl diphenylphosphine. This result was attributed to substrate trapping of the catalyst as an unreactive Fischer carbene, a situation analogous to that observed in the CM reactions of alkyl vinyl ethers. 

Isomer formation can occur at the alkene insertion step This is probably reversible and the rates of the CO insertion for the alkyl complexes formed will therefore also affect the ultimate product distribution. Higher temperatures favour the formation of the branched isomer.509 Often, the alcohol is used as solvent for these reactions. The addition of another solvent of lesser polarity has been shown to reverse the usual selectivity, giving the branched product as the major isomer. Again, complex (102) was used as catalyst.510... 

Similarly to the hydroformylation, under certain reaction conditions the formation of the intermediate palladium-alkyl complex can be practically irreversible as shown by the different prevailing chirality of the 2-methylbutanoic acid ester obtained from 1-butene and (Z)-2-butene, as well as from ( )- and (Z)-2-butene. Therefore, re-gioselection and enantioface selection must occur, as in hydroformylation, during or before the formation of the postulated palladium-alkyl intermediate (see Scheme IV). 

The stereochemistry of the addition has been recognized on the basis of structural features and chemical behavior of the complexes 9, produced in selected reactions of j with 1-ethoxy-1-oxo-2-phospholene 8. Neutralization of these complexes gave exclusively cis-3-substituted phospholane oxides J 0 while alkylation resulted in stereoselective formation of cis-3, cis- -disubstituted phospholane oxides JJ. The progress of the latter reaction was strongly dependent on the size of the alkyl groups involved. 

The study of pyridine-piperidine reactions under high pressure conditions has given much information concerning the kinetics of HDN, but these results are however complicated by alkyl transfer (disproportionation) reactions, and thus the possibility of using such reactions as an easy test for determination of mechanism and as a catalyst probe is partly excluded. The study of polycyclic amines (quinoline, etc.) for the same purpose is limited by the complexity and the number of different possible routes, but is a very interesting test reaction for an overall study of catalytic activity or selectivity toward HDN in industrial conditions. Because no disproportionation occurs and the numbers of products and routes are reasonable, the studies of pyridine-piperidine and alkylpyridine-alkylpiperidine HDN under normal H2 pressure and low amine pressure (< lOTorr) are very powerful test reactions both for mechanism determination and catalyst study, although these conditions are far removed from those of industrial practice. 

The same group also showed that mono(cyclopentadienyl) mixed hydride/ aryloxide dimer complexes of several lanthanide elements (Y, Dy, Lu) could be synthesized easily by the acid-base reaction between the mixed hydride/alkyl complexes and an aryl alcohol [144]. These complexes reacted with C02 to generate mixed formate/carboxylate derivatives, which were moderately active initiators for the copolymerization of C02 and cyclohexene oxide, without requiring a co-catalyst. The lutetium derivative 21 was the most active (at 110°C, TOF = 9.4 h ), yet despite a good selectivity (99% carbonate linkages), the molecular weight distribution remained broad (6.15) (Table 6). 

Several related examples of transition metal-catalyzed addition of C-H bonds in ketones to olefins have been reported (Table 2) [11-14]. The alkylation of diterpenoid 6 with olefins giving 7 proceeds with the aid of Ru(H)2(CO)(PPh3)3 (A) or Ru(CO)2(PPh3)3 (B) as catalyst [11], Ruthenium complex C, Ru(H)2(H2)(CO) (PCy3)2, has catalytic activity in the reaction of benzophenone with ethylene at room temperature [12]. The alkylation of phenyl 3-pyridyl ketone 8 proceeds with A as catalyst [13], Alkylation occurs selectively at the pyridine ring. Application of this C-H/olefin coupling to polymer chemistry using ce,co-dienes such as 1,1,3,3-tetramethyl-l,3-divinyldisiloxane 11 has been reported [14]. 

Based on these results, conditions for alkyl-Sonogashira coupling reactions were developed. Primary alkyl halides reacted with terminal alkynes catalyzed by 5 mol% of complex 24a and Cul in the presence of substoichiometric amounts of Nal for bromides or Bu4NI for alkyl chlorides (entry 29) [73]. The latter serves to catalyze the in situ generation of more reactive alkyl iodides under the reaction conditions. The internal alkyne products were isolated in 57-89% yield. The Sonogashira coupling can also be combined to the Kumada reaction described above. a,o)-Chloroalkyl bromides underwent the Kumada coupling first selectively... 

The main methodologies developed until now for enantioselective oxidation of sulfides are effective only in the oxidation of alkyl aryl sulfoxides. Dialkyl sulfoxides on the other hand are generally oxidized with only poor selectivity. In an attempt to solve this problem, Schenk s group69 recently reported a stereoselective oxidation of metal-coordinated thioethers with DMD. The prochiral thioether is first coordinated to a chiral ruthenium complex by reaction with the chloride complexes [CpRu[(S,S)-chiraphos]Cl], 36. Diastereoselective oxygen transfer from DMD produces the corresponding sulfoxides in high yield and selectivity. The chiral sulfoxides 37 are liberated from the complexes by treatment with sodium iodide. Several o.p. aryl methyl sulfoxides have been obtained by this method in moderate to high ee (Scheme 12). 

The regioselectivity of the reductive cleavage of alkyl vinyl ethers with Cp /Sm(TI11 ) , that is, competition (Scheme 318) between (i) sp2 C-O fission () leading to vinyl species and alkoxides and (ii) sp3 C-O fission to enolates and alkyl complexes has been studied. Interestingly, it was found that the selectivity depends on the substituent R3. The path (i) was observed for R3 = Me (R1 =Ph, R2 = H), while (ii) was found for R3 = benzyl. The reactions were detected by H NMR spectroscopy. Hydrolysis, deuterolysis, and electrophilic trapping of the intermediates were used to prove the kind of bond cleavage.1110... 

Other efforts have been focused on a conceptually new, directed aldol condensation [54]. Mixed aldol condensations between two different carbonyl compounds with several possible sites for enolization are extremely difficult and there is a variety of undesired pathways involving proton transfer and over-alkylation. The aldol reaction of an a,/ -unsaturated carbonyl compound with an aldehyde was investigated in the presence of ATPH. The reaction first involves fhe demand for control of reactivity and selectivity of the a, -unsaturated carbonyl compound, which upon deprotonation leads to the corresponding extended dienolate of ATPH. A second carbonyl compound aldehyde which serves as an electrophile is activated electronically (but sterically deactivated) by complexation with ATPH. This activation would enable rapid in-situ capture of fhe extended dienolate. ATPH was the reagent of choice, because it could effectively make a strong coordination bond upon encapsulating a number of a, -unsaturated carbonyl compounds. 

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