Alkyl bromides ligand effects

The favourable effect of steric demand was also confirmed by the experiments of Fu while studying the coupling of primary alkyl bromides. Good yields were achieved using lAd HCl, under mild conditions and in the presence of Cul [127]. The results can be further improved using bulkier ligands such as lAd (bisdiamantyl-substituted NHCs) [128] (Scheme 6.42). 

This has led to the discovery of electron-deficient styrenes, such as those shown in Figure 2. As detailed later, these ligands have been shown to be effective for the Ni-catalyzed alkylation of organozincs with primary alkyl iodides and bromides91. More recently, Fu88k has reported that a catalyst consisting of Ni(COD)2 and s-Bu-Pybox (3) is satisfactory even for the reaction of primary alkylzincs with secondary alkyl bromides... 

An interesting recent development is the demonstration that the reactivity of a stannyl radical can be controlled by amines that act intra- or inter-molecularly as ligands for the tin. Thus the stannyl radicals that are derived from dibutyl-2(2-pyridylethyl)tin hydride and butylbis-2(2-pyridylethyl)tin hydride show a reduced reactivity towards alkyl bromides and chlorides, and the presence of bipyridyl effectively suppresses the reduction of C12H25CI by Bu3SnH.56... 

In the initial study, which focused on palladium-catalyzed cross-couplings of primary alkyl bromides with vinylstannanes, use of P(t-Bu)2Me provided the best yields (solvent=THF) [27]. PCy3 was slightly less effective, whereas a variety of other ligands, including JV-heterocyclic carbenes, were essentially ineffective. The choice of activator (Me4NF) and the presence of molecular sieves were important for the success of these reactions. Some examples of Pd/P(t-Bu)2Me-catalyzed Stille couplings of alkyl bromides with vinylstannanes are provided in entries 1-3 of Table 6. 

Lee and Fu reported that coupling of phenyltrimethoxysilane (7) with alkyl bromides is possible under selected conditions. 1-Phenyldodecane was obtained in 81 % yield by the reaction of 7 with n-dodecyl bromide at room temperature. P(t-Bu)2Me as an effective ligand and BU4NF (2.4 equiv.) as an activator were used [86]. 

Arylations of primary alkyl bromides with aryl and heteroarylstannane reagents have also been achieved using palladium catalysts. Fu reported that aryltributyl-stannanes could be used for the arylation of certain functionalized alkyl bromides and iodides (Equation 5.13). An electron-rich phosphine ligand PCy(l-pyrrolidi-nyl)2 showed a pronounced accelerating effect in this cross-coupling reaction. Notably, not only aryl-substituted stannanes but also a pyridinylstannane, was shown to participate in the functionalization reaction [15]. 

Table 1 Effect of the Ligand on the Stille Coupling of an Alkyl Bromide...

For the Pd-catalyzed cross-coupling involving organic bromides and chlorides, especially alkyl bromides and chlorides, the use of bulky alkyl-containing phosphines, " 7V-heterocyclic carbenes (NHCs), and others have been shown to be effective ligands. In contrast, those Pd catalysts containing PPhs and other conventional aryl phosphines are generally ineffective for these cases. 

The beneficial effect of added phosphine on the chemo- and stereoselectivity of the Sn2 substitution of propargyl oxiranes is demonstrated in the reaction of substrate 27 with lithium dimethylcyanocuprate in diethyl ether (Scheme 2.9). In the absence of the phosphine ligand, reduction of the substrate prevailed and attempts to shift the product ratio in favor of 29 by addition of methyl iodide (which should alkylate the presumable intermediate 24 [8k]) had almost no effect. In contrast, the desired substitution product 29 was formed with good chemo- and anti-stereoselectivity when tri-n-butylphosphine was present in the reaction mixture [25, 31]. Interestingly, this effect is strongly solvent dependent, since a complex product mixture was formed when THF was used instead of diethyl ether. With sulfur-containing copper sources such as copper bromide-dimethyl sulfide complex or copper 2-thiophenecarboxylate, however, addition of the phosphine caused the opposite effect, i.e. exclusive formation of the reduced allene 28. Hence the course and outcome of the SN2 substitution show a rather complex dependence on the reaction partners and conditions, which needs to be further elucidated. 

Ohtomi et al. (1976) have studied the catalytic effect of polypode ligands, such as [ 116] on the reactions of alkyl halides under liquid-liquid phase-transfer conditions (Table 34). Primary alkyl iodides are seen to be more reactive than the corresponding bromides. In contrast, the reactivity towards CN- declines in the order RBr > RI > RC1. It is interesting to note that this order differs from that observed in solid-liquid two-phase systems catalysed by crown ethers (Cook et al., 1974). 

The syntheses of iron isonitrile complexes and the reactions of these complexes are reviewed. Nucleophilic reagents polymerize iron isonitrile complexes, displace the isonitrile ligand from the complex, or are alkylated by the complexes. Nitration, sulfonation, alkylation, and bromina-tion of the aromatic rings in a benzyl isonitrile complex are very rapid and the substituent is introduced mainly in the para position. The cyano group in cyanopentakis(benzyl isonitrile)-iron(ll) bromide exhibits a weak "trans" effect-With formaldehyde in sulfuric acid, benzyl isonitrile complexes yield polymeric compositions. One such composition contains an ethane linkage, suggesting dimerization of the transitory benzyl radicals. Measurements of the conductivities of benzyl isonitrile iron complexes indicate a wide range of A f (1.26 e.v.) and o-o (1023 ohm-1 cm.—1) but no definite relationship between the reactivities of these complexes and their conductivities. 

In some systems it is necessary to add a large amount of salts to obtain polymers with low polydispersities. This happens when salts participate in ligand/anion exchange (special salt effect) and when they enhance ionization of covalent compounds through the increase of ionic strength. The special salt effect may either reduce or enhance ionization. Strong rate increases observed in the polymerization of isobutyl vinyl ether initiated by an alkyl iodide in the presence of tetrabutylammonium perchlorate or triflate can be explained by the special salt effect [109]. The reduction in polymerization rate of cyclohexyl vinyl ether initiated by its HI adduct in the presence of ammonium bromide and chloride can be also ascribed to the special salt effect [33]. The breadth of MWD depends on the relative rate of conversion of ion pairs to covalent species and is affected by the structure of the counterions. 

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