Substitution, electrophilic complexes

Air sensitive (ij4-l//-azepine)tricarbonyliron(0) (28) on treatment with tropylium tetrafluoro-borate undergoes electrophilic substitution to yield the 3-substituted iron complex 29.118... 

Kinetic studies are of little value in attempting to determine the extent of complex formation in the reaction path of electrophilic substitution. The reasons for this have been adequately presented elsewhere29 and the conclusions are that, unless the formation of the complex is rate-determining, the kinetic form is independent of complex formation. Further, the influence of complex formation on reaction rates only comes from the factors which lead in the first place to complex formation, and substituent effects are inadequate for showing the extent of complex formation though when they indicate similar effects on substitution and complex formation they provide evidence that the latter is a pathway of the former. 

The zirconium TMM complexes also react with organic electrophiles, including unactivated ones, according to Scheme 99 under formation of the corresponding substituted allyl complexes. ... 

The reaction of (cyclobutadiene)metal complexes with X2 results in the oxidative decomplexation to generate either dihalocyclobutenes or tetrahalocyclobutanes. In comparison, substitution of (cyclobutadiene)MLn complexes 223 [MLn = Fe(CO)3, CoCp, and RhCp] with a variety of carbon electrophiles has been observed (equation 34)15. Electrophilic acylation of 1-substituted (cyclobutadiene)Fe(CO)3 complexes gives a mixture of regioisomers predominating in the 1,3-disubstituted product and this has been utilized for the preparation of a cyclobutadiene cyclophane complex 272 (equation 35)246. For (cyclobutadiene)CoCp complexes, in which all of the ring carbons are substituted, electrophilic acylation occurs at the cyclopentadienyl ligand. 

Terminal alkynes readily react with coordinatively unsaturated transition metal complexes to yield vinylidene complexes. If the vinylidene complex is sufficiently electrophilic, nucleophiles such as amides, alcohols or water can add to the a-carbon atom to yield heteroatom-substituted carbene complexes (Figure 2.10) [129 -135]. If the nucleophile is bound to the alkyne, intramolecular addition to the intermediate vinylidene will lead to the formation of heterocyclic carbene complexes [136-141]. Vinylidene complexes can further undergo [2 -i- 2] cycloadditions with imines, forming azetidin-2-ylidene complexes [142,143]. Cycloaddition to azines leads to the formation of pyrazolidin-3-ylidene complexes [143] (Table 2.7). 

Fig. 2.11. Conversion of alkynyl complexes into heteroatom-substituted carbene complexes (E+ electrophile).

A further general route to heteroatom-substituted carbene complexes is based on the a-abstraction of nucleophiles from alkyl complexes (electrophilic abstraction Figure 2.13). 

Fig. 2.20. Reaction of heteroatom-substituted carbene complexes with nucleophilic and electrophilic tin derivatives.

Heteroatom-substituted carbene complexes are less electrophilic than the corresponding methylene, dialkylcarbene, or diarylcarbene complexes. For this reason cyclopropanation of electron-rich alkenes with the former does not proceed as readily as with the latter. Usually high reaction temperatures are necessary, with radical scavengers being used to supress side-reactions (Table 2.16). Also acceptor-substituted alkenes can be cyclopropanated by Fischer-type carbene complexes, but with this type of substrate also heating is generally required. 

Several reaction sequences have been reported in which Fischer-type carbene complexes are converted in situ into non-heteroatom-substituted carbene complexes, which then cyclopropanate simple olefins [306,307] (Figure 2.22). This can, for instance, be achieved by treating the carbene complexes with dihydropyridines, forming (isolable) pyridinium ylides. These decompose thermally to yield pyridine and highly electrophilic, non-heteroatom-substituted carbene complexes (Figure 2.22) [46]. 

Closely related to the ring-closing metathesis of enynes (Section 3.2.5.6), catalyzed by non-heteroatom-substituted carbene complexes, is the reaction of stoichiometric amounts of Fischer-type carbene complexes with enynes [266,308 -315] (for catalytic reactions, see [316]). In this reaction [2 + 2] cycloaddition of the carbene complex and the alkyne followed by [2 -t- 2] cycloreversion leads to the intermediate formation of a non-heteroatom-substituted, electrophilic carbene complex. This intermediate, unlike the corresponding nucleophilic carbene... 

Non-heteroatom-substituted carbene complexes can also be generated by treatment of electrophilic transition metal complexes with ylides (e.g. diazoalkanes, phosphorus ylides, nucleophilic carbene complexes, etc. Section 3.1.3). Alkyl complexes with a leaving group in the a-position are formed as intermediates. These alkyl complexes can undergo spontaneous release of the leaving group to yield a carbene complex (Figure 3.2). 

Additional methods for preparing non-heteroatom-substituted carbene complexes include nucleophilic or electrophilic additions to carbyne complexes (Section 3.1.4), electrophilic additions to alkenyl or alkynyl complexes (Section 3.1.5), and the isomerization of alkyne or cyclopropene complexes (Section 3.1.6). 

Electrophilic transition metal complexes can react with organic ylides to yield alkylidene complexes. A possible mechanism would be the initial formation of alkyl complexes, which are converted into the final carbene complexes by electrophilic a-abstraction (Figure 3.18). This process is particularly important for the generation of acceptor-substituted carbene complexes (Section 4.1). 

Non-heteroatom-substituted carbene complexes are in principle accessible either by electrophilic or by nucleophilic addition to alkynyl or alkenyl complexes (Figure 3.26). 

Of these potential approaches addition of electrophiles only has attained some relevance in the preparation of non-heteroatom-substituted carbene complexes. 

Carbene C-H (and Si-H, [695]) insertion is characteristic of electrophilic carbene complexes. In particular the insertion reactions of acceptor-substituted carbene complexes (Section 4.2) have become a valuable tool for organic synthesis. 

Electrophilic carbene complexes generated from diazoalkanes and rhodium or copper salts can undergo 0-H insertion reactions and S-alkylations. These highly electrophilic carbene complexes can, moreover, also undergo intramolecular rearrangements. These reactions are characteristic of acceptor-substituted carbene complexes and will be treated in Section 4.2. 

The most important synthetic access to acceptor-substituted carbene complexes is the reaction of ylides with electrophilic, coordinatively unsaturated transition metal complexes (Figure 4.1 see also Section 3.1.3). 

The different synthetic applications of acceptor-substituted carbene complexes will be discussed in the following sections. The reactions have been ordered according to their mechanism. Because electrophilic carbene complexes can undergo several different types of reaction, elaborate substrates might be transformed with little chemoselectivity. For instance, the phenylalanine-derived diazoamide shown in Figure 4.5 undergoes simultaneous intramolecular C-H insertion into both benzylic positions, intramolecular cyclopropanation of one phenyl group, and hydride abstraction when treated with rhodium(II) acetate. 

Synthetic Applications of Acceptor-Substituted Carbene Complexes 191 Table 4.9. Intermolecular C-H insertion reactions of electrophilic carbene complexes. 

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

Acceptor-substituted carbene complexes are electrophilic intermediates which react readily with lone pairs, giving the corresponding ylides. These can be valuable intermediates, capable of undergoing a broad range of synthetically useful transformations. This subject has been treated in several reviews [38,995,1077-1079,1086]. 

If chiral catalysts are used to generate the intermediate oxonium ylides, non-racemic C-O bond insertion products can be obtained [1265,1266]. Reactions of electrophilic carbene complexes with ethers can also lead to the formation of radical-derived products [1135,1259], an observation consistent with a homolysis-recombination mechanism for 1,2-alkyl shifts. Carbene C-H insertion and hydride abstraction can efficiently compete with oxonium ylide formation. Unlike free car-benes [1267,1268] acceptor-substituted carbene complexes react intermolecularly with aliphatic ethers, mainly yielding products resulting from C-H insertion into the oxygen-bound methylene groups [1071,1093]. 

Electrophilic carbene complexes can also react with organic halides to yield halonium ylides. Reaction of acceptor-substituted carbene complexes with allyl... 

As already commented in the introduction of this chapter, regardless of its substitution pattern, the main trends of allenylidene reactivity are governed by the electron deficient character of the C and Cy carbon atoms of the cumulenic chain, the Cp being a nucleophilic center [9-15]. Thus, as occurs with their allcarbon substituted counterparts, electrophilic additions on 7i-donor-substituted allenylidene complexes are expected to take place selectively at Cp, while nucleophiles can add to both C and Cy atoms. However, the extensive 71-conjugation present in these molecules results in a reduced reactivity of the cumulenic chain and, in some cases, in marked differences in the regioselectivity of the nucleophilic additions when compared to the all-carbon substituted allenylidenes. In the following subsections updated reactivity studies on 7i-donor-substituted allenylidene complexes are presented by Periodic Group. 

Electrophilic aromatic substitution of 3-methoxy-4-methylaniline (655) using the 2-methoxy-substituted iron complex salt 665, followed by oxidative cyclization with concomitant aromatization of the resulting iron complex salt 666, affords 2,7-dimethoxy-3-methylcarbazole (667). Oxidation of the carbazole 667 with DDQ... 

The bromination of tris(acetylacetonato)chromium(III) was first reported by Reihlen.781 There have been many studies of electrophilic substitution at complexes of both acetylaceton-ate and its derivatives this work has been extensively reviewed.782,783 Some typical reactions are outlined below (equation 42). In this section, we shall briefly mention some more recent work the interested reader is recommended to study the extensive, although somewhat dated, review by Collman,782 and Mehrotra s book.783... 

There are several pathways by which one ligand may replace another in a square planar complex, including nucleophilic substitution, electrophilic substitution, and oxidative addition followed by reductive elimination. The first two of these are probably familiar from courses in organic chemistry. Oxidative addition and reductive elimination reactions will be covered in detail in Chapter 15. All three of these classes have been effectively illustrated by Cross for reactions of PtMeCItPMe-Ph),.-... 

Attempts have been made to investigate the electrophilic substitution reactivity of coordinated aniline relative to the free ligand. For CrCl3 (an)3, little rate enhancement was observed for bromina-tion reactions, but extensive complex decomposition accompanied the substitution.895 Complexes such as m-CoCl(en)2(an)2+ have abnormally high base hydrolysis rates when compared with their alkylamine analogues.15... 

The addition of carbon nucleophiles to complex (27), followed by demetallation, is equivalent to the y-alkylation of cyclohexenone. This overall transformation can also be accomplished directly via addition of electrophiles to dienolsilanes, but it becomes nontrivial for cases where the cyclohexenone C-4 position is already substituted.37 On the other hand, 1 -substituted cyclohexadienyliron complexes, such as (30), react very cleanly with certain carbon nucleophiles, at the substituted dienyl terminus. This provides useful methodology for the construction of 4,4-disubstituted cyclohexenones, and has been employed in a variety of natural product syntheses. 

Even now, there are two further limiting cases, for if k equilibrium constant for complex formation. Experimentally it will be a matter of extreme difficulty to distinguish either of these possibilities from mechanism SE2(open) or SE2 (cyclic), since all of these mechanisms require the reaction to follow second-order kinetics. Indeed, Reutov4 appears to include a situation such as (7), if the complex is present but in very low concentration, under the mechanistic title of SE2. This is also the nomenclature used by Traylor and co-workers11, but Abraham and Hill5 refer to such a situation as SEC (substitution, electrophilic, via co-ordination). 

Substitution, electrophilic, in which the substrate and electrophile react via a complex present only in low concentration 1.4 Se2, SEC SE2(co-ord)... 

First, the preparation of the substituted benzene 172 is explained. In the reaction of substituted benzene complex 175 with carbanions, the meta orientation to give 176 is observed even in the presence of ortho- and para-orienting electron-donating groups, such as methoxy and amino groups [45], Using this property, the nucleophilic substitution reaction, complementary to ordinary electrophilic substitution reaction, is... 

Wide synthetic possibilities for modification of coordinated ligands are opened up by the classic reactions of electrophilic and nucleophilic substitution in complexes of aliphatic, aromatic, and heterocyclic compounds [314,359,418 422]. For example, the transformations (3.196) were known long ago [419] ... 

Electrophilic additions with activated alkynes also occur readily with ri2-pyrrole complexes.12bl3b In methanol solution, the pyrrole (20) and 1-methylpyrrole (21) complexes undergo conjugate addition cleanly at C-3 with 3-butyn-2-one to give the p-enone-substituted pyrrole complexes 56 and 58 in high yield (Figure 13). In contrast to what is observed... 

In the presence of Lewis acids, N-substituted aniline complexes of [Os] also add electrophiles at C4, again at the arene face opposite to that involved in metal coordination. This reaction has been shown to be general for a broader range of Michael acceptors than may be utilized with anisole complexes of [Os]. The N-ethyl aniline complex, for example, adds Michael acceptors and acetals in yields ranging from 53-95 % (Table 13, entries 1-6) [27]. The N,N-dimethyl aniline complex (entries 7-9) also adds Michael acceptors to C4 in moderate to high yields (Table 13) and adds to the <5-carbon of an a,/ ,y,<5-un saturated ester (entry 3). 

Phenol complexes of [Os] display pronounced reactivity toward Michael acceptors under very mild conditions. The reactivity is due, in part, to the acidity of the hydroxyl proton, which can be easily removed to generate an extended enolate. Reactions of [Os]-phenol complexes are therefore typically catalyzed using amine bases rather than Lewis acids. The regio-chemistry of addition to C4-substituted phenol complexes is dependent upon the reaction conditions. Reactions that proceed under kinetic control typically lead to addition of the electrophile at C4. In reactions that are under thermodynamic control, the electrophile is added at C2. These C2-selective reactions have, in some cases, allowed the isolation of o-quinone methide complexes. As with other [Os] systems, electrophilic additions to phenol complexes occur anti to the face involved in metal coordination. 

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