Transition-Metal-Catalyzed Substitution Reactions

Nucleophilic substitution of aromatic halides lacking activating substituents is generally difficult. It has been known for a long time that the nucleophilic substitution of aromatic halides is often catalysed by the presence of copper salts.128 129 130 Synthetic procedures based on this observation are used to prepare aryl nitriles by reaction of aryl bromides with Cu(I)CN. The reaction is usually carried out at elevated temperature in DMF or a similar solvent. 

A general mechanistic description of the copper-promoted nucleophilic substitution pictures an oxidative addition of the aryl halide at Cu(I) followed by collapse of the arylcopper intermediate with a ligand transfer (reductive elimination).131 

Many other kinds of nucleophiles can be arylated by copper-catalyzed substitution.132 Among the reactive nucleophiles are carboxylate ions,133 alkoxide ions,134 amines,135 

It has been found that palladium-phosphine combinations are even more effective catalysts for these nucleophilic substitution reactions. For example, conversion of aryl iodides to nitriles can be done under much milder conditions. 

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Aryl- and heteroaryl halides can undergo thermal or transition metal catalyzed substitution reactions with amines. These reactions proceed on insoluble supports under conditions similar to those used in solution. Not only halides, but also thiolates [76], nitro groups [76], sulfinates [77,78], and alcoholates [79] can serve as leaving groups for aromatic nucleophilic substitution. 

The transition-metal-catalyzed substitution reaction of allylic alcohol derivatives with sulfur reagents not only provides the solution to problematic regiochemical outcome, but also offers an opportunity to engineer the stereochemical outcome of reactions. In general, the... 

The Sonogashira reaction is a transition metal-catalyzed coupling reaction which is widely used for the preparation of alkyl-, aryl- and diaryl-substituted acetylenes (Table 4.7) [120]. This reaction is a key step in natural product synthesis and is also applied in optical and electronic applications. Sonogashira reactions involve the use of an organic solvent with a stoichiometric portion of a base for capturing the... 

Organic halides play a fundamental role in organic chemistry. These compounds are important precursors for carbocations, carbanions, radicals, and carbenes and thus serve as an important platform for organic functional group transformations. Many classical reactions involve the reactions of organic halides. Examples of these reactions include the nucleophilic substitution reactions, elimination reactions, Grignard-type reactions, various transition-metal catalyzed coupling reactions, carbene-related cyclopropanations reactions, and radical cyclization reactions. All these reactions can be carried out in aqueous media. 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

Metal-catalyzed substitution reactions involving propargylic derivatives have not been studied in much detail until recently [311, 312]. In this context, the ability shown by transition-metal allenylidenes to undergo nucleophilic additions at the Cy atom of the cumulenic chain has allowed the development of efficient catalytic processes for the direct substitution of the hydroxyl group in propargylic alcohols [313]. These transformations represent an appealing alternative to the well-known and extensively investigated Nicholas reaction, in which stoichiometric amounts of [Co2(CO)g] are employed [314-317]. 

With respect to the large number of unsaturated diazo and diazocarbonyl compounds that have recently been used for intramolecular transition metal catalyzed cyclopropanation reactions (6-8), it is remarkable that 1,3-dipolar cycloadditions with retention of the azo moiety have only been occasionally observed. This finding is probably due to the fact that these [3+2]-cycloaddition reactions require thermal activation while the catalytic reactions are carried out at ambient temperature. A7-AUyl carboxamides appear to be rather amenable to intramolecular cycloaddition. Compounds 254—256 (Scheme 8.61) cyclize intra-molecularly even at room temperature. The faster reaction of 254c (310) and diethoxyphosphoryl-substituted diazoamides 255 (311) as compared with diazoacetamides 254a (312) (xy2 25 h at 22 °C) and 254b (310), points to a LUMO (dipole) — HOMO(dipolarophile) controlled process. The A -pyrazolines expected... 

Ionic liquids serve as very useful reaction media, which can facilitate easy separation of product(s) and a catalyst after the reaction. These substitutes of organic solvents as reaction media have already been successfully applied to a variety of transition metal-catalyzed organic reactions such as Heck reaction, Suzuki cross-coupling, hydroformyla-tion, and alkoxycarbonylation. ... 

In the last years transition metal-silyl complexes have received special attention for several reasons [1, 2], On the one hand, they are assumed to be important intermediates in catalytic processes [2] (transition metal-catalyzed hydrosilylation reaction, dehydrogenative coupling of silanes to polysilanes, etc.), on the other metal-substituted silanes show special properties, which can be tuned systematically by judicious choice of the metal and its ligands [3] Furthermore, silylenes (silanediyls) are stabilized by unsaturated transition metal fragments leading to metal-silicon double-bonds [4]. In the light of a possible application in MOCVD processes some of these complexes are of interest as potential single-source precursors for the manufacture of thin silicide films [5]. 

The use of aryl tosylates as electrophiles is attractive, since they can be synthesized from readily available phenols with less expensive reagents than those required for the preparation of the corresponding triflates. More importantly, tosylates are more stable towards hydrolysis than are triflates. However, this greater stability renders tosylates less reactive in transition metal-catalyzed coupling reactions. As a result, protocols for traditional cross-coupling reactions of these electrophiles were only recently developed [1], In contrast, catalytic direct arylations with aryl tosylates were not reported previously. However, a ruthenium complex derived from heteroatom substituted secondary phosphine oxide (HASPO) preligand 72 [81] allowed for direct arylations with both electron-deficient, as well... 

Functionalizations via Silyl Hydride Functionalization and Hydrosilation A new general functionalization method based on the combination of living anionic polymerization and hydrosilation chemistry has been developed as illustrated in Scheme 7.26 [281]. First, a living polymeric organolithium compound is quantitatively terminated with chlorodimethylsilane to prepare the corresponding co-silyl hydride-functionalized polymer. The resulting co-silyl hydride-functionalized polymer can then react with a variety of readily available substituted alkenes to obtain the desired chain-end functionalized polymers via efficient regioselective transition-metal-catalyzed hydrosilation reactions [282-284]. 

The concept of C2-symmetric ligands has widely been recognized as an ideal design of asymmetric ligands, which include DIOP, chiraphos, and BINAP. These ligands have been applied to a variety of transition metal-catalyzed asymmetric reactions and have been fairly successful. However, this situation is not always applied to rr-allylpalla-dium-mediated asymmetric allylic substitutions. In the reaction, which has been the most frequently examined asymmetric reaction catalyzed by 7r-allylpalladium complexes, two factors need to be controlled for the sake of high stereoselectivity. One is... 

Typically the desired isocyanide substitution products are obtained in good yield from such reactions. However, a major drawback of this strategy entails the prior preparation and purification of the labile precursor complexes. The transition metal catalyzed substitution of the metal hexacarbonyls [M(CO)e] (M = Cr, Mo, W) by isocyanides has, by way of contrast, proved to be a direct and rapid synthetic route that reliably gives the products [M(C0)6, (CNR)J (n = 1-3) in high yield. We describe here general procedures that illustrate the methods involved and that highlight the synthetic utility of these reactions. 

For reviews on the Fujiwara-Moritani reaction, see (a) Fujiwara, Y. (2002) Palladium-promoted alkene-arene coupling via C—H activation, in Handbook of Organopalladium Chemistry in Organic Synthesis, Vol. 2 (eds E.-i. Negishi and A. de Meijere), John Wiley Sons, Inc., New York, pp. 2863-71 (b) Jia, C., Kitamura, T. and Fujiwara, Y. (2001) Catalytic functionalization of arenes and alkanes via C—H bond activation. Acc. Chem. Res., 34, 633-9 (c) Fujiwara, Y. and Jia, C. (2001) New developments in transition metal-catalyzed synthetic reactions viaC—H bond activation. PureAppl. Chem., 73,319-24 (d) Moritani, I. and Fujiwara, Y. (1973) Aromatic substitution of olefins by palladium salts. Synthesis, 524-33. 

The following conclusions can be drawn after analysis of the Csp -S and Csp Se bond formation in the transition-metal-catalyzed substitution and addition reactions involving RZZR and RZH species ... 

Yamamoto was first to report that orfho-alkynylanilines, which are fully substituted at the N-site, could undergo a transition metal-catalyzed cycloisomerization reaction to give indoles via a formal 1,3-migration of a suitable migrating group from the... 

Recently, transition metal-catalyzed hydroamination reaction of alkynes with hydrazines was used to generate aryl hydrazones, highly reactive and versatile intermediates in a subsequent metal-catalyzed Fischer indole synthesis. Thus, Odom first reported a 3 + 2 synthesis of 1,7-fused, di-, and tri-substituted indoles 285 featuring the Ti(IV)-catalyzed hydroamination of various alkynes 283 with... 

Functionalization of Azaferrocene Catalysts. Chiral azaferrocenes are highly useful in enantioselective acylation as nucleophilic catalysts, and in transition metal-catalyzed asymmetric reactions as chiral ligands. Enantioselective lithiation of an azaferrocene moiety followed by functionalization with (TMS0)2 resulted in a lateral hydroxyl-substituted product with excellent optical purity, but in poor yield (eq 7). The low yield was attributed to the poor reactivity of (TMSO)2 toward the labile azaferrocene substrate. 

Transition Metal-catalyzed Cross-addition of TIPS-acetylene to Alkynes. Transition metal-catalyzed coupling reaction of a bulky silyl-substituted terminal alkyne through the addition of the C-H bond to carbon-carbon triple bonds can lead... 

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