Allylamines palladium complexes

The arylation reaction of primary and secondary amines has been investigated using nickel or palladium complexes as catalysts, and bromo- or chloroarenes as arylating agents. Among the complexes tested, the more efficient catalyst is the bis (bipyridyl) nickel (II) bromide, bipy2NiBr2, which affords for example high yields in the arylation of allylamine with /n-bromotrifluoromethylbenzene. The reduction of the haloarene, sometimes observed with the nickel complexes, becomes predominant with palladium catalysts whatever the complex used. 

An iV-phenyl-allylamine has been arylated terminally using phosphine-free conditions and a heteroaryl iodide in the synthesis of an H+/K+-ATPase inhibitor (Figure 3.31) [91]. This class of inhibitors has attracted the interest of many medicinal chemistry groups due to the large sales of the blockbuster Losec/Prilosec (Omeprazole). In the cited case, the allylic amine moiety was added at a late stage of the synthesis and the primary amine was protected by Boc to prevent formation of 7r-allyl palladium complexes. The deprotection was then performed with trifluoroacetic acid. 

In the last few years, several groups have developed enantioselective domino reactions catalysed by combinations of organocatalysts with palladium complexes. As an example, Murkheqee and List have reported a domino synthesis of p-all earbon quaternary amines on the basis of a highly enantioseleetive a-allqrlation of a-branched aldehydes, involving an achiral palladium catalyst and a chiral phosphoric acid. Under the catalysis of phosphoric acid, a secondary allylamine reacted with an a-branehed aldehyde to form an enammonium phosphate salt, which upon reaction with palladium catalyst afforded a cationic 7t-allyl palladium complex (Scheme 7.2). This intermediate resulted in the formation of an a-allylated iminium ion, whieh eould be reduced to the corresponding final chiral amine in high yield and exeellent enantioselectivity of 97% ee. The synthetic utility of this transformation was also demonstrated hy a formal synthesis of (+)-cuparene. 

The most frequently used metallic catalysts for acyldiazo- and (alkoxycarbonyl)dia-zomethanes are complexes or salts of rhodium, palladium and copper. Alkenylboronic esters A-silylated allylamines and acetylenes are successfully cyclopropanat-ed with diazocarbonyl compounds under catalysis of one of those metal derivatives. Newly developed metallic catalysts for diazoacetic esters include polymer-bound, quantitatively recoverable Rh(II) carboxylate salts ", Cu(II) supported on NATION ion exchange poly-mer ruthenacarborane clusters, Rh2(NHCOCH3)4 which produces cyclopropanes with substantially enhanced trans (anti) selectivity as shown below and (rj -CsHs)... 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

Deprotection of A-allyloxycarbonylamines can sometimes lead to the formation of small amounts of 7V-allylamines, as the liberated amine can compete with NHEt2 for the jt-allylpalladium complex. However, the increase of diethylamine concentration and larger amounts of palladium catalyst help to eliminate this problem [70]. Another useful method of deprotection applied to 0-allyl derivatives of carbohydrates and natural polyols... 

A new route from alkyl halides to the corresponding amines (as acyl derivatives) involves reaction with A-acyl allylamines (Scheme 34), and subsequent deallylation with Pd salts used catalytically. Palladium species also intervene in the conversion of optically active benzyl halides, with inversion at the original C-halogen bond, to acyl Pd complexes ie.g. 71 ->72) which may be further transformed to carboxylic esters as shown. Alkyl halides give unpredictable results in this sequence. A related conversion can be carried out under phase... 

Allylamines can be synthesized in good yield by treatment of n-allyl palladium chloride complexes with amines (Akermark and Zetterberg, 1975). Highest yields and fastest reactions occurred when a coordinating ligand such as tri-n-butylphosphine was present. In the example given, the reaction is stereospecific ( -olefin), but in some instances small quantities of the Z-isomer were isolated, as well as an isomeric allylamine. 

The hydration of C-C multiple bonds is a reaction with prevalent industrial interest due to the usefulness of the products as chemical intermediates. The wool-Pd complex is an economical and highly active catalyst for hydration of olefins. It is very stable and can be reused several times without any remarkable change in the catalytic activity [73, 74]. In particular, to convert alkenes to the corresponding alcohols in excellent enantioselectivity, a new biopolymer-metal complex constituted of wool-supported palladium-iron or palladium-cobalt was prepared and used, such as allylamine to amino-2-propanoI, acrylonitrile to lactonitrile and unsaturated acids to a-hydroxycarboxylic acids [75-77]. The same catalytic system was also used for hydration of substituted styrenes to produce chiral benzyl alcohols. The simple and cleaner procedure, mild reaction conditions, high stability and recovery rate of catalyst made these catalytic systems an attractive and useful alternative to the existing methods (Scheme 37). 

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