Palladium allylic substitutions

Alkynes react with indium reagents such as (allyl)3ln2l3 to form dienes (allyl substituted alkenes from the alkyne). Allyltin reagents add to alkynes in a similar manner in the presence of ZrCU Alkylzinc reagents add to alkynes to give substituted alkenes in the presence of a palladium catalyst. ... 

Chiral pyridine-based ligands were, among various Ar,AT-coordinating ligands, more efficient associated to palladium for asymmetric nucleophilic allylic substitution. Asymmetric molybdenum-catalyzed alkylations, especially of non-symmetric allylic derivatives as substrates, have been very efficiently performed with bis(pyridylamide) ligands. 

Helquist et al. [129] have reported molecular mechanics calculations to predict the suitability of a number of chiral-substituted phenanthrolines and their corresponding palladium-complexes for use in asymmetric nucleophilic substitutions of allylic acetates. Good correlation was obtained with experimental results, the highest levels of asymmetric induction being predicted and obtained with a readily available 2-(2-bornyl)-phenanthroline ligand (90 in Scheme 50). Kocovsky et al. [130] prepared a series of chiral bipyridines, also derived from monoterpene (namely pinocarvone or myrtenal). They synthesized and characterized corresponding Mo complexes, which were found to be moderately enantioselective in allylic substitution (up to 22%). 

Allylic substitutions catalysed by palladium NHC complexes have been studied and the activity and selectivity of the catalysts compared to analogous Pd phosphine complexes. A simple catalytic system involves the generation of a Pd(NHC) catalyst in situ in THF, from Pdj(dba)j, imidazolium salt and Cs COj. This system showed very good activities for the substitution of the allylic acetates by the soft nucleophilic sodium dimethyl malonate (2.5 mol% Pdj(dba)3, 5 mol% IPr HCl, 0.1 equiv. C (CO ), THF, 50°C) (Scheme 2.22). Generation of the malonate nncleophile can also be carried out in situ from the dimethyhnalonate pro-nucleo-phile, in which case excess (2.1 equivalents) of Cs COj was used. The nature of the catalytic species, especially the number of IPr ligands on the metal is not clear. 

Since Pd complexes are well-known catalysts for enantioselective allylic substitution reactions, here the catalytic behaviour of palladium NPs for this reaction is examined (Scheme 1). One example involving a chiral phosphite with a carbohydrate backbone, able to coordinate firmly at the surface of NPs together with oxygen atoms capable to interact weakly with this surface, is presented. In particular. 

In 2001, Imamoto et al. reported the preparation of novel chiral S/P-bidentate ligands containing a chirogenic centre at the phosphorus atom and their stereoinduction capability in palladium-catalysed asymmetric allylic substitution reactions (Scheme 1.14)." ... 

Since carbohydrates constitute an inexpensive and highly modular chiral source for preparing chiral ligands," Claver et al. have reported the use of a series of thioether-phosphite" and thioether-phosphinite furanoside ligands" in the test palladium-catalysed allylic substitution reaction. In the first type of ligand, a systematic variation of the donor group attached to the carbon atom C5 indicated that the presence of a bulky phosphite functionality had a positive effect on the enantioselectivity. Indeed, the enantioselectivity was controlled mainly by the phosphite moiety. This was confirmed by the use of a ligand... 

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

Thus, [HRh(C0)(TPPTS)3]/H20/silica (TPPTS = sodium salt of tri(m-sulfophenyl)phopshine) catalyzes the hydroformylation of heavy and functionalized olefins,118-122 the selective hydrogenation of a,/3-unsaturated aldehydes,84 and the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic add (a precursor of naproxen).123,124 More recently, this methodology was tested for the palladium-catalyzed Trost Tsuji (allylic substitution) and Heck (olefin arylation) reactions.125-127... 

The supported aqueous phase methodology was applied to the system Pd(OAc)2/5 TPPTS, a catalytic precursor for the Trost-Tsuji reaction. The characterization of the solid by 31P MAS NMR confirms the presence of Pd°(TPPTS)3 as the main surface species. The catalytic properties of the solid were tested for the allylic substitution of E-cinnamylethylcarbonate by different nucleophiles such as ethyl acetoacetate, dimethyl malonate, morpholine, phenol, and 2-mercapto-pyridine. The absence of palladium leaching was demonstrated, and having solved the problem of water leaching from the solid to the organic phase, the SAP-Pd catalyst was successfully recycled several times without loss in its activity. It was used in a continuous flow experiment which... 

The palladium-catalyzed asymmetric allylic substitution using seven different phosphano-oxazoline ligands at various ligand-to-metal ratios was also studied.112 An aluminum block containing 27 wells was placed in a dry box in which the reactions were carried out in parallel. Analyses were performed by conventional chiral GC equipped with an autosampler. Such a setup allowed about 33 catalyst evaluations per day. Apparently, only a few dozen were carried out in the study, resulting in the identification of a catalyst showing an ee-value of 74% in the reaction of 4-acyloxy-2-pentene with malonate.112 It is not clear whether further ligand diversification would lead to catalysts more selective than the record set in this case by the Trost-catalyst (92% ee).113... 

A wide variety of organoalkynyl derivatives of cotarnine hydrochloride, a cyclic iminium salt with rich biological activity, were prepared from the direct alkynylation of cotarnine hydrochloride using silver(l) alkynyls.180 Substituted enynes were prepared from the coupling reactions of silver alkynyls with the palladium allyl intermediates, which was... 

Palladium(0)-catalyzed coupling reactions - i. e. the Heck and Sonogashira reactions, the carbonylative coupling reactions, the Suzuki and Stille cross-coupling reactions, and allylic substitutions (Fig. 11.1) - have enabled the formation of many kinds of carbon-carbon attachments that were previously very difficult to make. These reactions are usually robust and occur in the presence of a wide variety of functional groups. The reactions are, furthermore, autocatalytic (i.e. the substrate regenerates the required oxidation state of the palladium) and a vast number of different ligands can be used to fine-tune the reactivity and selectivity of the reactions. 

Palladium-catalyzed allylic substitution reactions are popular in the chemical community and the number of applications of the reaction, perhaps in particular for asymmetric procedures, continues to grow [53]. The efficiency of asymmetric chemistry is best described in terms of the enantiomeric excess (ee) of the reaction, and it... 

Another example is the palladium catalyzed allylic substitution of 3-phenyl-2-propenyl-carbonic acid methyl ester to yield iV-(3-phenyl-2-propenyl)morpho-line reported by Reetz, Kragl and co-workers. This reaction was performed in the presence of phosphino-terminated amine dendrimers [17, 18] loaded with Pd11 cations as shown in Scheme 10. For this particular dendrimer with a molecular weight of 10 212 g/mol, a retention of 0.999 per residence time [35] was estimated in a membrane reactor with a SELRO MPF-50 membrane. It must be noted that a very high retention is a prerequisite for a continuous operating system, since a small leaching of the dendrimer leads to an exponential decrease in the amount... 

Ceric ammonium nitrate promoted oxidative addition of silyl enol ethers to 1,3-butadiene affords 1 1 mixtures of 4-(/J-oxoalkyl)-substituted 3-nitroxy-l-butene and l-nitroxy-2-butene27. Palladium(0)-catalyzed alkylation of the nitroxy isomeric mixture takes place through a common ij3 palladium complex which undergoes nucleophilic attack almost exclusively at the less substituted allylic carbon. Thus, oxidative addition of the silyl enol ether of 1-indanone to 1,3-butadiene followed by palladium-catalyzed substitution with sodium dimethyl malonate afforded 42% of a 19 1 mixture of methyl ( )-2-(methoxycarbonyl)-6-(l-oxo-2-indanyl)-4-hexenoate (5) and methyl 2-(methoxycarbonyl)-4-(l-oxo-2-indanyl)-3-vinylbutanoate (6), respectively (equation 12). 

Depending on the substrate and the other reaction parameters, very high re-gioselectivities towards either a or y substitution can be obtained. In certain cases, the regioselectivity can easily be switched between the two modes by changing the reaction conditions [11]. Compared to, for example, palladium(0)-catalyzed allylic substitution reactions, the possibility of switching between Sn2 and Sn2 selectivity... 

Iridium-catalyzed allylic substitution was first investigated after many years of development of allylic substitution reactions catalyzed by a variety of complexes of other metals, particularly those containing palladium. While iridium-catalyzed... 

After the initial demonstration of stoichiometric nucleophilic attack on 7i-allyl ligands, catalytic allylic substitution reactions were pursued. In 1970, groups from Union Carbide [3, 4], Shell Oil [5], and Toray Industries [6] published or patented examples of catalytic allylic substitution. All three groups reported allylic amination with palladium catalysts. The Toray Industries report also demonstrated the exchange of aryl ether and ester leaving groups, and the patent from Shell Oil includes catalysts based on rhodium and platinum. 

The first iridium catalysts for allylic substitution were published in 1997. Takeuchi showed that the combination of [fr(COD)Cl]2 and triphenylphosphite catalyzes the addition of malonate nucleophiles to the substituted terminus of t -allyliridium intermediates that are generated from allylic acetates. This selectivity for attack at the more substituted terminus gives rise to the branched allylic alkylation products (Fig. 4), rather than the linear products that had been formed by palladium-catalyzed allylic substitution reactions at that time [7]. The initial scope of iridium-catalyzed allylic substitution was also restricted to stabilized enolate nucleophiles, but it was quickly expanded to a wide range of other nucleophiles. 

Hartwig and coworkers reported an approach to address this limitation involving tandem catalytic reactions. In this tandem process, sequential palladium-catalyzed isomerization of the branched isomer to the linear isomer, followed by iridium-catalyzed allylic substitution leads to the branched product with high enantiomeric excess [105]. More specifically, treatment of branched allylic esters with catalytic amounts of the combination of Pd(dba)2 and PPhs led to rapid isomerization of the branched allylic ester to the linear isomer, and the linear isomer underwent allylic substitution after addition of the iridium catalyst and nucleophile (Scheme 31). 

Scheme 2.8 Palladium-catalyzed allylic substitution an example of pseudodilute conditions.

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