Transition metal catalyzed processes

From a synthetic point of view, direct alkylation of lithium and magnesium organometallic compounds has largely been supplanted by transition-metal-catalyzed processes. We will discuss these reactions in Chapter 8 of Part B. 

Most of the synthetic applications of organomercury compounds are in transition metal-catalyzed processes in which the organic substituent is transferred from mercury to the transition metal in the course of the reaction. Examples of this type of reaction... 

Domino transition metal-catalyzed processes can also start with a cross-coupling reaction most often, Suzuki, Stille and Sonogashira reactions are used in this context They can be combined with another Pd-catalyzed transformation, and a number of examples have also been reported where a pericydic reaction, usually a Diels-Alder reaction, follows. An interesting combination is also a Pd-catalyzed borina-tion followed by a Suzuki reaction. 

Late transition metal-catalyzed processes also proved to be very useful tools for formation of the C-O bond of the 1,3-oxazine ring from the corresponding alkynes. In the presence of 1-5 mol% of a cationic gold(l) complex, A -BOC-protected alkynylamines 450 were converted to 6-alkylidene-l,3-oxazin-2-ones 451 under very mild conditions (Equation 49) <2006JOC5023>. 

Of the steps listed in Table 1. some are encountered more frequently, while others are less common. Transition metal catalyzed processes usually begin with oxidative addition or coordination-addition as an Entry, which is commonly followed by transmetalation or insertion in the Attachment phase. The final Detachment step is either reductive elimination, or p-hydride elimination, depending on the nature of the intermediate. 

In a series of late transition metal catalyzed processes the first step in the catalytic cycle is the coordination of the reagent to the metal atom, which is in a positive oxidation state, followed by its covalent attachment through the concomitant breaking of an unsaturated carbon-carbon bond or a carbon-hydrogen bond. These processes usually require a highly electrophilic metal centre and are frequently carried out in an intramolecular fashion. The carbometalation processes that follow a similar course, but take place only at a later stage in the catalytic cycle, will be discussed later. 

Probably the most common detachment step in late transition metal catalyzed processes is reductive elimination. In this transformation two groups, that are both attached to the same metal centre, will be released and form a covalent bond, with the concomitant formation of a metal whose formal oxidation state, coordination number and electron count are decreased by two. Figure 1-9 presents a general order of the ease of reductive elimination for the most common complexes. 

Although most transition metal catalyzed processes are built up of similar steps, they are usually divided into categories (sometimes name reactions) by the synthetic chemists. This classification is usually made on the basis of their synthetic utility rather than on mechanistic considerations. This chapter gives an overview of the most commonly used reactions, briefly outlining their mechanism as well as the scope and limitation of substrates in these processes. 

Since the use of ammonia is not practical in transition metal catalyzed processes, the identification of its synthetic equivalents is of major importance. Benzophenone imine was found to couple with 3-bromopyridine readily under the above mentioned conditions (7.72.), The masking benzophenone was removed in transamination with hydroxylamine, which gave the desired 3-aminopyridine in 81% overall yield.92 Allylamine was also successfully employed as ammonia equivalent93... 

The role of carbenes and metal carbene complexes in transition metal-catalyzed processes is suspected of being quite extensive (61). For example, the role of carbenes in the olefin metathesis reaction as described in the previous section is probably important (55, 60). It is quite possible that the o-v rearrangement is important in these reactions also, but this has not been investigated in detail. 

A reasonable expectation for a transition metal catalyzed process would be the ability to control the micro structure of the product and in this case the polysilane, EI(RSiEI )VE 1, that is produced. An unusual selectivity seemed to be apparent in the condensation of PhSiH3 by bis(indenyl)- and bis(tetrahydroindenyl)zirconium dimethyl catalysts and was originally attributed to stereoregulation in the polymerization but was later proposed to be due to an unusual selectivity in the production of cyclics.36,79 In an earlier report17 of the condensation of PhSiH3 with rac- E BI)ZrCl2/2"BuLi... 

Another important factor to deduce the involvement of radicals in a transition metal-catalyzed process is the integrity of stereocenters. In oxidative addition or Sr 2-type processes the stereochemical information - retention or inversion, respectively - is preserved for optically active substrates like sec-butyl bromide (Sect. 2.2), while racemic products are observed when radical intermediates are generated. On the other hand, stereochemical convergence is observed for strongly biased diastereomeric substrates, such as exo- and endo-norbomyl substrates 25 (Fig 9) The reactions occur almost exclusively at the exo-face of the norbomyl... 

Radical intermediates and transition metal-catalyzed reactions are in principle ideally suited to be linked together. A prerequisite to perform successful radical reactions is that the concentration of radicals has to be kept low to promote the desired reaction and to avoid competing homocoupling and disproportionation, which occur often diffusion-controlled. Including radical intermediates in the regime of a transition metal catalyzed process is thus ideal to keep their concentrations low, since their maximum concentration cannot exceed that of the metal catalyst. On the other hand, radicals are much more reactive than closed-shell organotransition metal intermediates. Thus, the involvement of radicals in transition metal catalysis often leads to a strong acceleration of the reactions compared to a process where only closed-shell intermediates are involved [101]. 

Transition metal-catalyzed radical based processes often occur under mild conditions and are quite fast. The fine-tuning of the electronic properties of the metal complex catalysts to maximize the facility of radical generation and to modulate the lifetime of the radicals for follow-up reactions is still in its infancy and has not been studied systematically. This is, however, important to allow the design of radical processes at the slower end of the reactivity scale, as the current methodology is mostly limited to very fast radical processes in the framework of transition metal catalysis. The kinetics of almost all processes described in this review is not known. Only detailed investigations in this field will allow the rational design of radical-based transition metal-catalyzed processes. 

Me3SiCN is a convenient, reactive cyanide donor in transition metal-catalyzed processes. The Pd-catalyzed reaction of aryl iodides with Me3SiCN is useful for the synthesis of aryl cyanides.257 Me3SiCN works also as an effective co-catalyst for the Pd-catalyzed cyanation of aryl iodides with KCN.258 Allylic acetates, carbonates, and the related compounds undergo the Pd-catalyzed cyanation with Me3SiCN.259-261 The tandem cyclization-cyanation reaction of 2-bromo-l,6-heptadienes with Me3SiCN proceeds under catalysis by an Ni complex (Equation (68)).262... 

Just as in aryl halides, the halogen can be replaced by hydrogen and by a metal, or be involved in transition metal-catalyzed processes (covered in Section 3.2.3.11.2). Three of the mechanisms of such nucleophilic substitutions are familiar from benzene chemistry via arynes, SrnI processes, and Pd(0)-catalyzed sequences. However, of the two further mechanisms of nucleophilic replacement, the ANRORC (Addition of Micleophile, Ring Opening, Ring Closure) is unique to heterocycles, and Sae reactions occur only with strongly activated benzenoid systems. 

These organometallic nucleophiles show most of the typical reactions with carbon electrophiles associated with benzenoid Grignard reagents and aryllithiums They also allow the introduction of other metals, and nonmetals, on to the ring, such as mercury, boron, phosphorus, tin, and arsenic (Scheme 104) (see also Section 3.2.3.10.2.5), some of which are of great use as partners in transition metal-catalyzed processes. 

Among the non-enzymatic, catalytic-asymmetric reactions, homogeneous transition metal catalyzed processes play a predominant role... 

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