Oxidative addition coupling

Examples of oxidative addition coupled with some other transformations were mentioned in previous sections. Here we discuss other reactions of oxidative addition, which are rather complicated and do not lead to the formation of organyl hydrides. 

Oxidative ADDITIONS COUPLED with insertions 3.3.1. Carbonylation insertion of CO in the Ph-H bond... 

Oxidative addition coupled with insertion 3.3.1. Oxidative addition + CO insertion... 

Success of the reactions depends considerably on the substrates and reaction Conditions. Rate enhancement in the coupling reaction was observed under high pressure (10 kbar)[l 1[. The oxidative addition of aryl halides to Pd(0) is a highly disfavored step when powerful electron donors such as OH and NHt reside on aromatic rings. Iodides react smoothly even in the absence of a... 

Three-component coupling with vinylstannane. norbornene (80). and bro-mobenzene affords the product 91 via oxidative addition, insertion, transme-tallation, and reductive elimination[85]. Asymmetric multipoint control in the formation of 94 and 95 in a ratio of 10 1 was achieved by diastereo-differ-entiative assembly of norbornene (80), the (5 )-(Z)-3-siloxyvinyl iodide 92 and the alkyne 93, showing that the control of four chiralities in 94 is possible by use of the single chirality of the iodide 92. The double bond in 92 should be Z no selectivity was observed with E form[86]. 

The most interesting and difficult cross-coupling is alkyl-alkyl coupling, because oxidative addition of alkyl halides having /i-hydrogen is slow. In addition, easy elimination of /d-hydrogen is expected after the oxidative addition. 

The a-bromo-7-lactone 901 undergoes smooth coupling with the acetonyltin reagent 902 to afford the o-acetonyl-7-butyrolactone 903[763j. The o-chloro ether 904, which has no possibility of //-elimination after oxidative addition, reacts with vinylstannane to give the allyl ether 905, The o -bromo ether 906 is also used for the intramolecular alkyne insertion and transmetallation with allylstannane to give 907[764],... 

Tandem cyclization/3-substitution can be achieved starting with o-(trifluoro-acetamido)phenylacetylenes. Cyclization and coupling with cycloalkenyl trif-lates can be done with Pd(PPh3)4 as the catalyst[9]. The Pd presumably cycles between the (0) and (II) oxidation levels by oxidative addition with the triflate and the reductive elimination which completes the 3-alkenylation. The N-protecting group is removed by solvolysis under the reaction conditions, 3-Aryl groups can also be introduced using aryl iodides[9]. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

There are also palladium-catalysed procedures for allylation. Ethyl 3-bromo-l-(4-methylphenylsulfonyl)indole-2-carboxylate is allylated at C3 upon reaction with allyl acetate and hexabutylditin[27], Ihe reaction presumably Involves a ir-allyl-Pd intermediate formed from the allyl acetate, oxidative addition, transmetallation and cross coupling. 

The Stille coupling of an aryl triflate normally calls for the addition of at least one equivalent of LiCl. Presumably, the transmetallation is facilitated by replacing triflate with CP at the palladium intermediate generated from oxidative addition. As Stille demonstrated in 1988, 4-quinolinyl triflate 100 was coupled with phenylstannane 101 in the presence of Pd(Ph3P)4 and LiCl in refluxing 1,4-dioxane to furnish biaryl 102, which was used as an intermediate for the first total synthesis of antibiotic amphimedine (88JA4051). 

The boronic acid 2 is first converted to an activated species 8 containing a tetravalent boron center by reaction with a base. Halides or triflates (OTf = trilluoromethanesulfonate) are used as coupling partners R-X for the boronic acids. In many cases the rate-limiting step is the oxidative addition. With respect to the leaving group X, the rate decreases in the order ... 

The ease of formation of the carbene depends on the nucleophilicity of the anion associated with the imidazolium. For example, when Pd(OAc)2 is heated in the presence of [BMIM][Br], the formation of a mixture of Pd imidazolylidene complexes occurs. Palladium complexes have been shown to be active and stable catalysts for Heck and other C-C coupling reactions [34]. The highest activity and stability of palladium is observed in the ionic liquid [BMIM][Brj. Carbene complexes can be formed not only by deprotonation of the imidazolium cation but also by direct oxidative addition to metal(O) (Scheme 5.3-3). These heterocyclic carbene ligands can be functionalized with polar groups in order to increase their affinity for ionic liquids. While their donor properties can be compared to those of donor phosphines, they have the advantage over phosphines of being stable toward oxidation. 

The postulated steps that constitute the Suzuki coupling process are shown in Scheme 25. After oxidative addition of the organic halide to the palladium(o) catalyst, it is presumed that a metathetical displacement of the halide substituent in the palladium(ii) complex A by ethoxide ion (or hydroxide ion) takes place to give an alkoxo-palladium(ff) complex B. The latter complex then reacts with the alkenylborane, generating the diorganopalladium complex C. Finally, reductive elimination of C furnishes the cross-coupling product (D) and regenerates the palladium(o) catalyst. 

In the direct coupling reaction (Scheme 30), it is presumed that a coordinatively unsaturated 14-electron palladium(o) complex such as bis(triphenylphosphine)palladium(o) serves as the catalytically active species. An oxidative addition of the organic electrophile, RX, to the palladium catalyst generates a 16-electron palladium(n) complex A, which then participates in a transmetalation with the organotin reagent (see A—>B). After facile trans- cis isomerization (see B— C), a reductive elimination releases the primary organic product D and regenerates the catalytically active palladium ) complex. 

The use of this phosphine facilitates assignment of configuration as virtual coupling is observed when the phosphines are trans (section 2.9.5).) Syntheses follow established routes using methyllithium as an alkylating agent the platinum(iV) complexes can be made by direct alkylation of platinum(IV) compounds or by oxidative addition to platinum(II) species. 

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

The general mechanism of coupling reactions of aryl-alkenyl halides with organometallic reagents and nucleophiles is shown in Fig. 9.4. It contains (a) oxidative addition of aryl-alkenyl halides to zero-valent transition metal catalysts such as Pd(0), (b) transmetallation of organometallic reagents to transition metal complexes, and (c) reductive elimination of coupled product with the regeneration of the zero-valent transition metal catalyst. 

The general catalytic cycle for the coupling of aryl-alkenyl halides with alkenes is shown in Fig. 9.6. The first step in this catalytic cycle is the oxidative addition of aryl-alkenyl halides to Pd(0). The activity of the aryl-alkenyl halides still follows the order RI > ROTf > RBr > RC1. The olefin coordinates to the Pd(II) species. The coordinated olefin inserts into Pd—R bond in a syn fashion, p-Hydrogen elimination can occur only after an internal rotation around the former double bond, as it requires at least one /I-hydrogen to be oriented syn perpendicular with respect to the halopalladium residue. The subsequent syn elimination yields an alkene and a hydridopalladium halide. This process is, however, reversible, and therefore, the thermodynamically more stable (E)-alkene is generally obtained. Reductive elimination of HX from the hydridopalladium halide in the presence of a base regenerates the catalytically active Pd(0), which can reenter the catalytic cycle. The oxidative addition has frequently assumed to be the rate-determining step. 

One other point to note in regard to this study (141) is that any evidence of oxidative addition, particularly with the chloro-olefins, was absent. The similarity of the spectra, coupled with the nonobservation of any bands in the visible region, as well as the observation of vc-c in the region commonly associated with 7r-complexation of an olefin (141, 142), all argue in favor of normal ir-coordination, rather than oxidative insertion of the metal atom into, for example, a C-Cl bond. Oxidative, addition reactions of metal atoms will be discussed subsequently. 

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