Side reactions palladium synthesis

Finally, Buchwald and co-workers developed a high-yield, general method for the palladium-catalyzed formation of 1,4-benzodioxane. Bulky, electron-rich o-biphenylphosphines of type 214 together with Pd(OAc)2 have proved to be the most general catalytic system to avoid the /3-hydride elimination side reaction <2000JA12907>. This strategy was extended to the synthesis of enantiomerically pure 2-substituted-l,4-benzodioxanes 213 from 212 (Equation 37) <2001JA12202>. 

The previous extension of solvent mixtures involved solvent interfaces. This organic-water interfacial technique has been successfully extended to the synthesis of phenylacetic and phenylenediacetic acids based on the use of surface-active palla-dium-(4-dimethylaminophenyl)diphenylphosphine complex in conjunction with dode-cyl sodium sulfate to effect the carbonylation of benzyl chloride and dichloro-p-xylene in a toluene-aqueous sodium hydroxide mixture. The product yields at 60°C and 1 atm are essentially quantitative based on the substrate conversions, although carbon monoxide also undergoes a slow hydrolysis reaction along with the carbonylation reactions. The side reaction produces formic acid and is catalyzed by aqueous base but not by palladium. The phosphine ligand is stable to the carbonylation reactions and the palladium can be recovered quantitatively as a compact emulsion between the organic and aqueous phases after the reaction, but the catalytic activity of the recovered palladium is about a third of its initial activity due to product inhibition (Zhong et al., 1996). 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

C-H borylation is a widely used methodology for the synthesis of organoboronates [63-65]. Most of the applications have been presented for the synthesis of aryl-boronates. However, functionalization of alkenes has also attracted much interest [66, 67]. In most applications, iridium catalysis was used. However, in case of alkenes, borohydride forms as a side product of the C-H borylation, which undergoes hydroboration with alkenes. This side reaction can be avoided using palladium catalysis under oxidative conditions. In a practically useful implementation of this reaction, pincer-complex catalysis (Ig) was appHed (Figure 4.17) [51]. The reaction can be carried out under mild reaction conditions at room temperature using the neat aUcene 34 as solvent. In this reaction, hypervalent iodine 36, the TFA analog of 29, was employed. In the absence of 36, borylation reaction did not occur. 

In contrast to the on-chain phosphorescent palladium centers, which are accidentally incorporated into the polymer backbone by a transmetallation-type side reaction during the synthesis, the formation of keto-type defects in PF derivates is found to be an oxidative degradation process taking place already during synthesis as a consequence of the chemical structure of the monomer units. 

The most common preparative method to prepare the aryl allyl ether is the Williamson s ether synthesis [la,b]. Typically, aryl allyl ethers can be obtained from phenol derivatives and allylic halide under basic conditions (KjCOj) in refluxing acetone. This method is convenient for the preparation of simple allyl aryl ethers. However, some side reactions such as a competitive C-allylation (Sn2 type reaction) often accompany the formation of undesired byproducts. Mitsunobu reaction of phenol derivatives with allylic alcohols instead of allylic halides can be used under mild conditions [13]. In particular, when the allyl halide is unstable, this procedure is effective instead of the Williamson s ether synthesis. This method is also useful for the preparation of chiral allyl aryl ether from chiral allylic alcohol with inversion at the chiral center. Palladium catalyzed O-allylation of phenols is also applicable, but sometimes a lack of site-selectivity with unsymmetrical allylic carbonate [14] may be a problematic issue. 

Allylpalladium halides are formed very readily, for example from alkenes and palladium salts. The reaction is assisted by a base such as sodium acetate, which removes hydrogen chloride. Yields are improved if copper(II) acetate is added to reoxidize any palladium metal which may be formed in side reactions (cf. p. 380). Allylpalladium reagents have found considerable application in organic synthesis, both in stoichiometric and catalytic reactions (p. 261). 

Carbonylation of cinnamyl acetate in the presence of NEt3, acetic anhydride, and catalytic amounts of a palladium phosphine complex such as Cl2Pd(PPh3)2 gives 1-naphthyl acetate in good yield (Scheme 2) Esterification of 1-naphthol, the initial product, by acetic anhydride is essential to avoid side reactions leading to a complex mixture. Cinnamyl bromide reacts similarly, but the yield is lower probably because formation of the quaternary ammonium salt from the bromide and NEts competes with the carbonylation. This reaction is applicable to the synthesis of various substituted 1-naphthyl acetates. In the reaction of cinnamyl acetates with a meta-substituent, two possible regioisomeric products are obtained, where the para-cyclization predominates. 

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