Intermolecular palladium -mediated

Based on Watanabe s intermolecular hydroacylation of olefins with aldehydes,348 Kondo and Misudo developed the first ruthenium-catalyzed hydroacylation of 1,3-dienes with aldehydes (Scheme 71). Usually, palladium-mediated hydroacylations of 1,3-dienes with aldehydes give tetrahydropyran and/or open-chain homoallylic alcohol derivatives.350 However, in the present ruthenium-catalyzed transformations, the corresponding /3,7-unsaturated... 

Palladium chemistry of heterocycles has its idiosyncrasies stemming from their different structural properties from the corresponding carbocyclic aryl compounds. Even activated chloroheterocycles are sufficiently reactive to undergo Pd-catalyzed reactions. As a consequence of a and y activation of heteroaryl halides, Pd-catalyzed chemistry may take place regioselectively at the activated positions, a phenomenon rarely seen in carbocyclic aryl halides. In addition, another salient peculiarity in palladium chemistry of heterocycles is the so-called heteroaryl Heck reaction . For instance, while intermolecular palladium-catalyzed arylations of carbocyclic arenes are rare, palladium-catalyzed arylations of azoles and many other heterocycles readily take place. Therefore, the principal aim of this book is to highlight important palladium-mediated reactions of heterocycles with emphasis on the unique characteristics of individual heterocycles. 

De Meijere and co-workers have extended the scope of this process by applying this palladium-mediated multicomponent reaction to the bicyclopropylidene 72 as the alkene partner (Scheme 8.33). In this case, the intermolecular trapping of 7r-allyl palladium intermediate 73 with a soft carbonucleophile or with primary or secondary amines affords only products 74 having a methylenecyclopropane end group [78],... 

Palladium-mediated intramolecular aminations onto an allylic alcohol <1998TL5971> or allene <1998TL5421> are reported for the synthesis of piperidines. An intermolecular version of the allene-based reactions has been reported in the synthesis of spiropiperidines (Equation 167) <1998JOC2154>. 

A series of l-benzazepin-5-ones were furnished via a rhodium-catalyzed intermolecular hydroacylation of an allyl amine onto an aryl aldehyde (14AGE3688) while a one-step synthesis of a number of tetrahydro-3-benzazepines was achieved through the palladium-mediated reaction of phenylethylamines with allenes (14JOC9578). 

A simple method for the direct catalytic allylic alkylation of aldehydes and cyclic ketones has been developed.26 The direct catalytic highly chemo- and regio-selective intermolecular a-allyhc alkylation reaction has been mediated by an unprecedented combination of palladium and enamine catalysis which furnishes a-allylic alkylated aldehydes and cyclic ketones in high yield. 

Metal-mediated approaches to the synthesis of imidazoles have been reported. PaUadium(ll)-catalyzed intermolecular 1,2-diamination of conjugated dienes with ureas led to 4-alk enyl-2-imidazolones in good yields rmder mild conditions <05JA7308>. Palladium-catalyzed cyclization of O-pentafluorobenzoylamidoximes 74 furnished l-benzyl-2-substituted-4-methylimidazoles 75 <050L609>. Direct copper(I)-chloride mediated reaction of nitriles 76 with a-amino acetals 77 followed by acidic reaction led to a variety of 2-substituted imidazoles 78 <05TL8369>. 

Since the intermolecular oxidative coupling of benzene to biphenyl using stoichiometric amounts of PdCl2 was first described by van Helden and Verberg in 1965 [41], the intramolecular oxidative coupling of two arenes mediated by a palladium catalyst to synthesize cyclic compounds has also attracted great attention. 

Ruthenium-mediated regioselective intermolecular homo- and heterodimerization of substituted propiolates leads to 2H-pyran-2-one-5-carboxylates and 2H-pyran-2-one-6-carboxylates (140L652). 6-Aryl-2J-f-pyran-2-ones arise from a palladium-catalyzed oxidative aimulation of internal alkynes with acrylic acid with excellent regioselectivity and in high yields (140L2146). A one-pot isothiourea-promoted cascade reaction of (phenylthio) acetic acids with a,P-unsaturated trifluoromethyl arylke-tones provides 4-aryl-6-trifluoromethyl-2f/-pyran-2-ones (Scheme 42) (140L964). 

In contrast with the initial report employing boronic esters that follow a Pd(II)/ (0) pathway [52], the current methodology is proposed to occur via a Pd(II)/ (IV) mechanism. No reaction was observed in the presence of a Pd(0) source or in the absence of the silver salt. A plausible catalytic cycle involves an initial C-H activation step of palladium complex A to provide palladacycle B, followed by oxidative addition of the aryl iodide to give a highly reactive Pd(IV) complex C, which undergoes rapid reductive elimination to provide the desired product and a Pd(II) complex D (Scheme 30). The last step is loss of iodide, mediated by the silver salt. The use of the weakly coordinating -NHTf group by the Yu lab has allowed for the development of the first intermolecular and enantioselective C(sp )-H activation via a Pd(n)/(IV) catalytic cycle. 

In a recent variant on this process reported by Michael [16], a palladium(ll)-mediated intramolecular aminopalladation is followed by an oxidation of the palladium(ll) intermediate by the FN(S02Ph)2 oxidant to give a palladium(lV) complex. The palladium(lV) complex then mediates an intermolecular electrophilic aromatic substitution followed by C-C bond formation via reductive elimination (Scheme 9). 

Diunsubstituted coumarins are available from the palladium(II)-catalyzed intermolecular annulation reaction of phenols with methyl acrylate (13AGE12669) and from an organocatalytic cascade reaction of salicylalde-hydes with malonic acid half-thioesters mediated by a combination of ben-zylamine and triethylamine (Scheme 60) (13EJ04499). 

The ability of palladium to mediate decarboxylations of certain heteroaromatic carboxylates was demonstrated by Steglich et al. for intramolecular couplings, as well as by Forgione and Bilodeau for intermolecular couplings (Scheme 16) [56-58]. However, the scope of this reaction indeed seems to be more limited than its bimetallic counterpart. It so far includes mainly five-ring heteroarenes with carboxylate groups in the 2-position. AUcynylcarboxylic acids have also been decarboxylatively coupled with palladium alone [59]. 

Complete intermolecular [2 + 2 + 2] cycloaddition involving arynes is mediated by the palladium(O) complexes. This strategy is the most convenient, although the product yields and ee values are low to moderate. 

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