Palladium-catalysed reaction types

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

The Heck reaction has now been reviewed448,449. Evidence for the formation of zerova-lent palladium from (AcO Pd and Ph3P via a redox process has been provided450. This explains the origin of Pd(0) required for certain palladium-catalysed reactions in cases where Pd(II) is added to the reaction as the primary form of the Pd-catalyst. Thallium has been found to accelerate the Heck-type cyclization-carbonylation451. 

The rate of the palladium-catalysed Heck-type phenylation of allylic alcohols has been found to be markedly enhanced by addition of tertiary amines454. Regioselectivity can be increased, in some cases, by adding E NCl or employing a Wilkinson Rh catalyst (rather than pd)455 456. Another Heck-type reaction involves addition of arenediazonium tetraflu-oroborates to a-silylstyrenes to give (Z )-PhCH=CHAr. A BF4 -mediated vyw-elimination of silicon and palladium has been suggested to account for the stereochemistry457. 

A standard Heck reaction, as shown in the example below, involves the palladium-catalysed reaction of a halide with an alkene, most commonly an electron-deficient aUcene such as an acrylate, but other types can also be used. Heck-type cyclisation onto olefins is a useful reaction for ring synthesis. 

This chapter describes in general terms the types of reactivity found in the typical six-and five-membered aromatic heterocycles. In addition to discussions of classical substitution chemistry, considerable space is devoted to radical substitution, metallation and palladium-catalysed reactions, since these areas have become very important in heterocyclic manipulations. In order to gain a proper appreciation of their importance in the heterocyclic context we provide an introduction to these topics, since they are only poorly covered in general organic text-books. Emphasis on the typical chemistry of individual heterocyclic systems is to be found in the summary/revision chapters (4, 7, 10, 12, 16, and 20) and a more detailed examination, of typical heterocyclic reactivity, and many more examples for particular heterocyclic systems are to be found in the chapters - Pyridines reactions and synthesis etc. For the advanced student, it is recommended that this present chapter should be read in its entirety before moving on to the later chapters, and that the introductory summary/revision chapters, like Typical reactivity of pyridines, quinolines and isoquinolines should be read before the more detailed discussions. 

This reaction type also has been used to prepare C-inethyl 5-pyrimidine-carboxylic acids l94H(38)1375l. Pyrimidinylzinc halides obtained upon oxidative addition of active zinc to 2- or 4-iodopyrimidines have been shown to be transformed into aiylated pyrimidines by palladium-catalysed reaction [93T(49)9713]. Covalent hydration at the 2- and 4-position of monomethyl- and dimethyl-S-pyrimidinecaiboxylic acids has been investigated [94H(38)137S]. 

In contrast to traditional Heck-type additions, palladium-catalysed reaction of aromatic iodides with an alkene pendant (32) has been reported to afford cyclic iodide (33). The use of a palladium catalyst with bulky phosphine ligands proved to be crucial to attain this outcome. ... 

The TlPS-protected 2-deoxyribonolactone was used in the synthesis of the 3- and 4-pyridyl nucleoside phosphoramidites [20a, b]. These nucleosides were used in oligonucleotide base pairing experiments and had as complementary base the 2 -deoxyribosyl-l-(4-(2",6",2"-bypyridyl))pyrimidinone phosphoramidite [20c].Other new C-nucleoside phosphoramidites include the pyrido[l,2-a][l,3,5]triazin-4-one derivatives [21a-c] which were obtained via Heck-type palladium-catalysed reaction between 2-alkyl-9-iodo-pyr-ido[l,2-a][l,3,5]triazin-4-one and a silyl protected furanoglycal. ... 

Palladium-catalysed Heck-type reaction of ort/io-functionalized aryl iodides (75) with bicyclic hydrazines (76) has been designed as a facile route towards heteroannulated cyclopentenes (77)7 ... 

Palladium catalysed Hiyama-type cross-coupling reactions of benzylic phosphates (74) with the aryl-silane (75) afforded corresponding di-arylmethanes (76) (Scheme 21). The reaction tolerated either electron-donating or electron-withdrawing functional groups providing products (76) in high to excellent yields. ... 

An unusual Sn -type substitution has been noted in the palladium-catalysed reaction of benzyhc c bonates, such as (90), 3-methyl-9,10-dihydrophenanthrenes... 

Indoles with carbocyclic halogen or triflate substituents are potential starting materials for vinylation, arylation and acylation via palladium-catalysed pro-cesses[l]. Indolylstannanes. indolylzinc halides and indolylboronic acids are also potential reactants. The principal type of substitution which is excluded from such coupling reactions is alkylation, since saturated alkyl groups tend to give elimination products in Pd-catalysed processes. 

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... 

In 1999, Ikeda et al. reported a new type of sulfur-oxazoline ligands with an axis-fixed or -unfixed biphenyl backbone prepared in good yields by coupling reactions of methoxybenzene derivatives substituted with a chiral oxazoline and a sulfur-containing Grignard reagent. These ligands were subsequently evaluated for the test palladium-catalysed asymmetric allylic alkylation... 

These workers have developed another new type of chiral S/N ligands, namely aziridine sulfides, which were easily synthesised in a straightforward synthetic route from inexpensive and readily available (i )-cysteine. The efficiency of this sterically and electronically varied set of ligands was then examined as chiral catalysts in the palladium-catalysed test reaction. The alkylated product was obtained in excellent yields and stereoselectivities of up to 99% ee, as shown in Scheme 1.44. 

Almost no attention has been paid to diphosphine sulfides employed as chiral ligands for palladium-catalysed nucleophilic substitution reactions. In this context, enantiomerically pure diphosphine sulfides derived from 2,2 -biphosphole, which combined axial chirality and phosphorus chiralities, were synthesised, in 2008, by Gouygou et al. through a four-step synthetic sequence. Among various palladium catalytic systems derived from this type of ligands and evaluated for the test reaction, that depicted in Scheme 1.62... 

An expeditious route to the cyclic sulfamide HIV-1 protease inhibitors of type 145 and 146 (tetrahydro-l,2,7-thiadiazepine 1,1-dioxide derivatives) from 141 and 142 hinges on palladium-catalysed amidation reactions. These reactions of 144 and 143 were microwave promoted and provided, after removal of the cyclic ketal protecting group, moderate to good yields of (145, 57%) and (146, 66%) for example with R = NHCOCH2-2-naphthyl <06T4671>. 

As indicated under section 2.2. the overall result is the same as that of an insertion reaction, the difference being that insertion gives rise to a yw-addition and nucleophilic attack to an anri-addition. Sometimes the two reaction types are called inner sphere and outer sphere attack. There is ample proof for the anti fashion the organic fragment can be freed from the complex by treatment with protic acids and the organic product can be analysed [19], Appropriately substituted alkenes will show the syn or anti fashion of the addition. The addition reaction of this type is the key-step in the Wacker-type processes catalysed by palladium. 

Not only acetylene derivatives do undergo palladium catalysed intarmolecular carbon-nitrogen bond formation with amines. The similar reaction of olefins in a Wacker-type process also leads to ring closure. (0-Aminopentenes bearing a suitable leaving group in the 4-position were converted to pyrroles in a cyclization-isomerisation-elimination sequence (3.65.),82... 

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