Allylic substitution reaction palladium-catalyzed

The most important class of allylic substitutions are palladium-catalyzed reactions with so-called soft nucleophiles such as stabilized carbanions or amines, and with few exceptions, the enantioselective transformations discussed in this chapter belong to this category. The mechanism of these reactions has been firmly established and a detailed picture of the catalytic cycle can be drawn [1, 2,3,4,5,6,13,14,15]. The course of allylic substitutions catalyzed by metals other than palladium is less clear and information about the intermediates involved is scarce. 

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... 

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... 

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. 

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... 

Amino acids can be accessed by a palladium-catalyzed allylic substitution reaction (Scheme 22.19).145 Some ligand screening is necessary to obtain high selectivity in a specific case. Indeed, a wide range of ligands has been proposed for this and analogous reactions.145 143... 

The various allylic substitution reactions are illustrated in a synthesis of Tipranavir (11), an HIV protease inhibitor. A palladium-catalyzed opening of a vinyl epoxide set the quaternary stereogenic center (Scheme 22.23). A molybdenum-catalyzed allylic nuclophilic displacement was used to access the benzylioc stereogenic center (Scheme 22.24).153... 

Certain aspects of the Heck and Suzuki reactions and one example of a palladium-catalyzed allylic substitution reaction have also lent themselves to ESI-MS analysis via inherently charged intermediates. 

Multinuclear metal complexes that may act as active catalysts or off-cycle species can also be easily identified and studied via ESl-MS. For example, analysis of a simple Pd-catalyzed allylic substitution reaction lead to the discovery of two reversibly formed binuclear bridged palladium complexes (Fig. 6) that act as a reservoir for the active mononuclear catalyst [21], The observation of dimers when using ESl-MS is common and it is crucial to confirm that they truly exist in solution and are not just formed during the ESI process, in this case the detection was supported by P and H NMR studies of stoichiometric reaction mixtures and in situ XAFS experiments [49]. 

Fig. 6. Two binuclear palladium-bridged allylic complexes discovered by ES1(+)-MS analysis. They are proposed to serve as reservoirs for the active catalyst in a palladium-catalyzed allylic substitution reaction 2f. ...

Sesay, S. J. Williams, J. M. J. Palladium-Catalyzed Enantioselective Allylic Substitution Reactions, Adv Asym. Synth., Vol. 3, Hassner, A., Ed., JAI Press, Stamford, CT, 1998. 

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

Reactions with Sulfur Nucleophiles. The use of sulfur nucleophiles in palladium-catalyzed allylic substitution reactions is less well documented than that of carbon, nitrogen and oxygen nucleophiles. The asymmetric synthesis of allylic sulfones utilizing a catalytic phase transfer system has been used to produce (35)-(phenylsulfonyl)cyclohex-l-ene on a 45 g scale (eq 10). In many cases, it has been reported that allylic carbonates are more reactive than allylic acetates in asymmetric allylic substitution... 

Optically active ferrocenylbisphosphines, (/J)-N,iV-dimethyl-l-[(5)-1, 2-bis(diphenylphosphino)ferrocenyIJethylamine [(/J)-(5)-BPPFA] and its derivatives, are efficient chiral bisphos-phine ligands for rhodium-catalyzed asymmetric hydrogenation, palladium-catalyzed asymmetric allylic substitution reactions, and gold-catalyzed asymmetric aldol-type reactions of a-isocyano carboxylates. ... 

Two types of palladium-catalyzed asymmetric reaction have been reported. One is the allylation of nucleophiles in which a new chiral carbon center is created in the nucleophile and the other is the allylic substitution reaction in which it is created in the allylic substrate (Scheme 2-24). Chiral ferrocenylbisphosphines designed and modified on the side chain have been successfully used for both of the two types of asymmetric reaction [5 c, d]. 

The Trost-Tsuji Reaction Palladium-Catalyzed Allylic Substitution ... 

Kellogg, R. M. Enantioconvergent synthesis by sequential asymmetric Horner-Wadsworth-Emmons and palladium-catalyzed allylic substitution reactions. Chemtracts 2002, 15, 69-73. 

Negishi, E.-i. Palladium-catalyzed cross-coupling involving 3-hetero-substituted compounds. Palladium-catalyzed a-substitution reactions of enolates and related derivatives other than the Tsuji-Trost allylation reaction. Handbook of Organopalladium Chemistry for Organic Synthesis 2002, 1, 693-719. 

The tetratertiary phosphine (110) has been successfully used in palladium-catalyzed allylic substitution reactions,226 while dinuclear palladium complexes of (105) catalyze the electrochemical reduction of C02 to CO in acidic DMF solutions.236... 

Phosphino)amines and their complexes have been shown to be efficient catalysts for the palladium-catalyzed Suzuki coupling reaction of chloroarenes,449 rhodium-catalyzed hydroformy-lations458 and asymmetric hydrogenations,463,466 allylic substitution reactions,47, 472 conversion of isocyanates to isocyanurates,478 and as ethylene polymerization catalysts.479... 

An S—P-type chiral phosphinooxathiane was developed as an effective ligand for palladium-catalyzed allylic substitution reactions [131]. A polymer-supported chiral phosphinooxathiane 208 was also prepared and applied to asymmetric alkylations and aminations of acetate 201 [132]. Enanhoselechvihes of up to 99% ee were obtained in asymmetric Pd-catalyzed allylic amination of acetate 201 using the polymeric catalyst prepared from a PS-diethylsilyl support (Scheme 3.68). 

Due to the insolubility of anions in BTF (see Sect. 3.8), a palladium catalyzed allylic substitution reaction using the malonate anion [67] could not be tried. However, an intramolecular version using tosylcarbamate as nucleophile (11.4)... 

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