Oxidative addition of allylic substrates

The Tsuji-Trost reaction is the palladium-catalyzed allylation of nucleophiles [110-113]. In an application to the formation of an A-glycosidic bond, the reaction of 2,3-unsaturated hexopyranoside 97 and imidazole afforded A-glycopyranoside 99 regiospecifically at the anomeric center with retention of configuration [114], Therefore, the oxidative addition of allylic substrate 97 to Pd(0) forms the rc-allyl complex 98 with inversion of configuration, then nucleophilic attack by imidazole proceeds with a second inversion of configuration to give 99. 

Oxidative addition of allylic substrates to palladium(O) is also a well-established reaction for generating 7i-allyl palladium species (Scheme 8.36). A wide range of allylic substrates have been used as precursors of these intermediates, and nucleophilic attack generally occurs at the less hindered terminus of the 7i-allylpalladium species [84]. 

The first oxidative addition of allylic substrates to the isolable coordinatively unsaturated complex (C5Me5)Ru(> -amidinate) has been observed, and this leads to a... 

One of the most important reactions in the synthesis of 77 -allylic palladium complexes is the oxidative addition of allylic substrates, such as allylic halides, carboxylates, carbonates, ammonium or phosphonium salts, to Pd(0) complexes. Besides its preparative value, this reaction is the origin of 77 -allyl palladium intermediates in most Pd-catalyzed transformations of allylic substrates, and the nature of the Pd allyl often determines the outcome of the reaction. 

The reaction mechanism (Scheme 6.25) involves formation of a cationic 7t-allylpalladium complex by the oxidative addition of the substrate onto the catalyst. In case of a dimethylallyloxycarbonyl protecting group this step is disfavoured compared to Alloc and therefore the removal of dimethylallyl groups is slower or requires more catalyst. Accordingly, in homogeneous CH3CN/H2O solutions deprotection of (allyl)phenylacetate proceeded instantaneously with 2 mol % [Pd(OAc)2]/TPPTS while it took 85 min to remove the dimethylallyl group (cinnamyl is an intermediate case with 20 min required for complete deprotection). The reactivity differences are... 

In order to permit complete conversion to one product enantiomer under the influence of a chiral catalyst, substrates for palladium-catalyzed allylic substitution either have to possess a meso structure (equation 1) or else give rise to complexes with 7t-allyl ligands as depicted in equations 2 and 3. Whereas oxidative addition of the substrate to the palladium(O) species constitutes the enantioselective step for meso compounds (equation 1), nucleophilic attack determines the absolute configuration of the product for reactive intermediates with a meso tt-allyl ligand (equation 2) or a zr-allyl unit that undergoes rapid epimerization by the n-a-n mechanism10-59 relative to substitution (equation 3). 

If the interconversion of the Jt-allyl intermediates 34 and 35 is much slower than nucleophihc attack, the product distribution depends on the nature of the substrate. In this case the two enantiomeric chiral substrates 30 and ent-30 are converted to the corresponding product enantiomers 36 and ent-36 with overall retention of configuration. Starting from a racemic mixture of 36 and ent-36, the two product enantiomers 36 and ent-36 are formed in a 1 1 ratio and, therefore, a chiral catalyst cannot induce enantioselectivity (except for kinetic resolution). However, the analogous reaction of the hnear, achiral substrate 31 can be rendered enantioselective if a chiral catalyst is used that adds preferentially to one of the enantiotopic faces of 31 to give either complex 34 or 35. In this case, the enantioselectivity is determined in the oxidative addition of the substrate to the catalyst while nucleophilic addition to the 7i-allyl intermediate is irrelevant for the enantiomeric excess of the overall reaction. The relative rates of k-O-k isomerization and the other processes shown in Scheme 15 strongly depend on... 

Heck carbonylation involving the oxidative addition of aryl halides is not applicable to aliphatic halides, since alkyl halides react directly with nucleophiles. Tsuji developed a process of carbonylating allyl carbonates to form carboxylic esters by palladium-catalyzed carbonylation that is applicable to aliphatic substrates [60]. The process probably involves (a) the oxidative addition of allyl carbonates to Pd(0) species to form r/ -allyl palladium species, (b) CO insertion into the allyl-Pd bond to give acylpalladium species, (c) decarboxylation of the carbonate ligand to give alkoxide, and (d) liberation of butenoate esters by combination with the alkoxides as shown in Scheme 1.21. 

Stereochemistry of oxidative addition of allylic acetate to a Pd(0) complex was unequivocally confirmed by using optically active substrate (Scheme 3.22) [42], The oxidative addition resulted in the formation of enantiomerically pure r/ -allylpalladium(II) complex showing inversion of configuration. Further treatment of the isolated r) -allylpalladium(II) complex with sodium dimethyl malonate led to the alkylation with inversion of configuration. Consistently, the catalytic reaction gave net retention product. This is a direct evidence for the stereochemistry of oxidative addition and alkylation. 

One of the most common methods employed for the generation of allylpalladium complexes involves oxidative addition of allylic electrophiles to Pd . This transformation has been explored by several groups, and has been the topic of recent reviews [69]. A representative example of this process was demonstrated in a recent total synthesis of (+ )-Biotin [70]. The key step in the synthesis was an intramolecular amination of 89, which provided bicydic urea derivative 90 in 77% yield (Eq. (1.40)). In contrast to the Pd"-catalyzed reactions of allylic acetates bearing pendant amines described above (Eq. (1.10)), which proceed via alkene aminopalladation, Pd -catalyzed reactions of these substrates occur via initial oxidative addition of the allylic acetate to provide an intermediate Jt-allylpalladium complex (e.g., 91). This intermediate is then captured by the pendant nudeophile (e.g., 91 to 90) in a formal reductive elimination process to generate the product and regenerate the Pd catalyst. Both the oxidative addition and the reductive elimination steps occur with inversion... 

Oxidative addition of allylic compounds to Ni(0) precursors is a reliable route to Ni-allyl complexes, with allyl halides being the most commonly used substrates for this purpose. For example, addition of BrGH2G(R)=GH2 (R = Me or H) to Ni(cod)2, followed by reaction with NaBPh4 and dippe, has given the cationic species [Ni(77 -GH2G(R)=GH2)(dippe)]BPh4. Other substrates such as allylic nitriles can also be versatile precursors for the formation of interesting allyl species. Thus, the reaction of Ni(cod)2 with 2-methyl-3-butenenitrile has been reported to proceed by the oxidative activation of the allyl-GN bond to form an allyl intermediate, which has been trapped as the cyano complex 69 in the presence of l,4-bis(diphenylphosphino)butane (dppb), as shown in Scheme 20. The closely related complex of dippe, 71, has been prepared by the reaction of the cationic species 70 " with various sources of cyanide ion. ... 

The unusual retention of stereochemistry upon oxidative addition of allylic acetates has been accomplished using allylic substrates bearing a coordinating group such as -PPh2. This group binds to Pd and fixes the orientation of the reactive allylic fragment and the reaction outcome (Equation (39)). ... 

The mechanism of oxidative addition of allylic carboxylates and allylic carbonates in the presence of phosphine ligands has been studied by conductivity measurements, and the nature of the starting Pd(0) and final cationic Pd(ll) species has been established. These studies confirm the coordination of the double bond to Pd(0) prior to oxidative addition and the reversibility of the process for both substrates. The reverse reaction is a nucleophilic attack of free X in solution (X = carboxylate, carbonate) to the cationic > -allylic Pd(ii) complex. 

The intermolecular Heck reaction of halopyridines provides an alternative route to functionalized pyridines, circumventing the functional group compatibility problems encountered in other methods. 3-Bromopyridine has often been used as a substrate for the Heck reaction [124-126]. For example, ketone 155 was obtained from the Heck reaction of 3-bromo-2-methoxy-5-chloropyridine (153) with allylic alcohol 154 [125]. The mechanism for such a synthetically useful coupling warrants additional comments oxidative addition of 3-bromopyridine 153 to Pd(0) proceeds as usual to give the palladium intermediate 156. Subsequent insertion of allylic alcohol 154 to 156 gives intermediate 157. Reductive elimination of 157 gives enol 158, which then isomerizes to afford ketone 155 as the ultimate product This tactic is frequently used in the synthesis of ketones from allylic alcohols. 

The addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

A. 1.1. Covalently Functionalized Dendrimers Applied in a CFMR The palladium-catalyzed allylic substitution reaction has been investigated extensively in the preceding decades and provides an important tool for the formation of carbon—carbon and carbon—heteroatom bonds 14). The product is formed after attack of a nucleophile to an (f/ -allyl)Pd(II) species, formed by oxidative addition of the unsaturated substrate to palladium(0) (Scheme 1). To date several nucleophiles have been used, mostly resulting in the formation of carbon—carbon and... 

The most widely used preparative method of allylindium(m) or propargylindium(lll) compounds is the oxidative addition of metallic indium or indium(l) halides to allylic or propargyl substrates.4 26 27 Allylic bromides and iodides serve as good allylic sources without any other activation. In the case of allylic chlorides, a proper additive such as lithium iodide is required to promote the oxidative addition. Allylic indium compounds prepared by oxidative addition of metallic indium are considered to exist as the sesquihalide structure (allyl jImXj), which has been... 

Oxidative addition of HCN onto 9.54 with the elimination of COD leads to the formation of 9.56. Oxidative addition by HCN and coordination by the substrate onto 9.55 and 9.56, respectively, lead to the formation of 9.57. Insertion of the alkene functionality into the Ni-H bond leads to the formation of the p3-allyl intermediate 9.58. Substrate addition or oxidative addition of... 

Transformations involving chiral catalysts most efficiently lead to optically active products. The degree of enantioselectivity rather than the efficiency of the catalytic cycle has up to now been in the center of interest. Compared to hydrogenations, catalytic oxidations or C-C bond formations are much more complex processes and still under development. In the case of catalytic additions of dialkyl zinc compounds[l], allylstan-nanes [2], allyl silanes [3], and silyl enolethers [4] to aldehydes, the degree of asymmetric induction is less of a problem than the turnover number and substrate tolerance. Chiral Lewis acids for the enantioselective Mukaiyama reaction have been known for some time [4a - 4c], and recently the binaphthol-titanium complexes 1 [2c - 2e, 2jl and 2 [2b, 2i] have been found to catalyze the addition of allyl stannanes to aldehydes quite efficiently. It has been reported recently that a more active catalyst results upon addition of Me SiSfi-Pr) [2k] or Et2BS( -Pr) [21, 2m] to bi-naphthol-Ti(IV) preparations. 

---