Heck reaction palladium -catalysed

Heck-, Suzuki- and Stille-type Couplings - The Heck reaction, palladium-catalysed coupling of aryl or vinyl halides with alkenes or alkynes, is an extremely useful synthetic method. Only recently have Heck reactions been performed in aqueous media, probably due to the perception that water must be carefully... 

Effect of ligands on palladinm-catalysed phenylative cyclisation reaction and competitive Mizoroki-Heck reaction Palladium-catalysed intramolecular ary-lative cyclisation reactions of A/-Allylacetamide 46 with bromobenzene afforded... 

The asymmetric Heck reaction is catalysed by enantiomerically pure palladium catalysts formed with chelatingbiphosphines, especially BINAP, and this has proved an effective method for the synthesis of sterically constrained carbon centres, including quaternary centres. This chapter concludes with a brief discussion of enantioselective alkylmetallations using Grignard and organoaluminium species, which have proved useful in the diastereo- and enantioselective synthesis of polyene systems. 

Scheme 9.17 The Heck reaction is catalysed over palladium zeolites.

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. ... 

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. 

Another methodology that is widely used for C-C bond formation is the Heck coupling (Heck, 1985 T.suji, 1995). The Heck reaction involves the palladium-catalysed arylation of olefinic double bonds (Eqn. (12)) and provides an alternative to Friedel-Crafts reactions for attaching carbon fragments to aromatic rings. 

Polyethylene glycol) (PEG) was used as a soluble polymeric support in the efficient preparation of the 2-benzazepine 58 via a phosphine-free palladium-catalysed Heck reaction from 57 <06T10456>. 

A tandem palladium-catalysed ort/io-alkylation/intramolecular Heck reaction coupling sequence was used effectively to access in fair yields the tetrahydro 1-benzoxepines 67 from the iodoaryl precursor 66 and the appropriate alkyl bromide. The norbornene plays a relay role in the proposed reaction cycle <06JOC4937>... 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

Palladium-catalysed Heck reactions have been carried out in a mixture of acetonitrile and D-100 as shown in Scheme 10.3. Using a fluorinated phosphine allowed simple recycling of the catalyst by decantation [4],... 

Palladium-catalysed C-C bond formation under Heck reaction conditions, which normally requires anhydrous conditions and the presence of copper(I) salts, is aided by the addition of quaternary ammonium salts. It has been shown that it is frequently possible to dispense with the copper catalyst and use standard two-phase reactions conditions [e.g. 18, 19]. Tetra-/i-butylammonium salts catalyse the palladium-catalysed reaction of iodoarenes with alkynes to yield the arylethynes in high yield [20, 21], whereas the reaction with 3-methylbut-1 -yn-3-ol (Scheme 6.30) provides a route to diarylethynes [22]. Diarylethynes are also formed from the reaction of an iodoarene with trimethylsilylethyne [23], Iodoalkynes react with a,p-unsaturated ketones and esters to produce the conjugated yne-eneones [19],... 

Several important industrial applications of the Heck reactions are known. The world s largest producer of Naproxen is Albemarle and they make Naproxen using two homogeneously catalysed steps, a Heck reaction and a palladium catalysed hydroxycarbonylation. The last step is carried out using palladium without chiral ligand and the enantiomers obtained are separated, see Figure 13.18. 

The palladium catalysed sequential alkylation-alkenylation of 5-iodoquinoline leads to the formation of the quinolooxepin ring system (5.20.), The process, closely related to the Catellani reaction,19 runs through an ort/zo-alkylation - Heck reaction sequence. The preparation of a series of benzoxepines has also been achieved in this manner, starting from such iodobenzene derivatives, where one of the or/7 o-positions was blocked by substitution.20... 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichloro-9/T-fluoren-9-yIidene (15) may lead to the formation of fullerene fragments.89 The amiulation reaction, under palladium catalysis, between iodoanflines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck aiylation of cyclic enamides.93... 

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. 

Most recently, the test has been applied to examination of the mechanism of a heterogeneous Heck reaction, promoted by Pd on alumina [25]. In the presence of the solid catalyst, 4-iodobenzamide coupled efficiently with butyl acrylate yielding the cinnamate, and it was suspected that the catalytic agent was a soluble form of palladium released from and then recaptured by the alumina support. To test this, the amide was attached to a commercially available resin with suitable functionality, and the supported amide (15 in Scheme 9.10) was allowed to react with the acrylate and Pd on alumina. The same product, identified after release from the polymer by TFA treatment, was formed, and further experiments were able to narrow down the form of the soluble catalysing palladium species. 

The palladium-catalysed addition of aryl, vinyl, or substituted vinyl groups to organic halides or triflates, the Heck reaction, is one of the most synthetically useful palladium-catalysed reactions. The method is very efficient, and carries out a transformation that is difficult by more traditional techniques. The mechanism involves the oxidative addition of the halide, insertion of the olefin, and elimination of the product by a p-hydride elimination process. A base then regenerates the palladi-um(0) catalyst. The whole process is a catalytic cycle. 

Scheme6.10 Proposed general mechanism for some palladium catalysed cross-coupling reactions other than the Heck reaction...

A second source of amino functionalised imidazolium salts is the quest for functionalised ionic liquids [146,147]. Wan et al. used a piperidine functionaUsed imidazolium salt as a base in a palladium catalysed Heck reaction in an ionic liquid medium. The system was designed such that the phosphane Ugand, the base and the solvent were all imidazolium based ionic Uquids [148] (see Figure 3.51). Given the fact that imidazolium based ionic liquids can act as carbene precursors for coordination to transition metals [149] that coordinate better than phosphane Ugands (with cationic substituents in the present case), it is far from certain which is acmally the ligand in that carefully designed system. 

When the alkyl halide method is used to introduce a hydroxy functional group it can as easily provide two hydroxy functionahties in the same wingtip group. An example comes from Cai et al. who reacted A-methylimidazole with 3-chloro-2-hydroxypropanol to form the corresponding imidazolium salt (see Figure 4.13) that was then used in the palladium catalysed Heck reaction between phenyl iodide and ethyl acrylate [51]. 

As with all solvent alternatives discussed in this book, palladium catalysed C-C bond-forming reactions in RTILs have been studied at length. Because of the low volatility of ionic liquids and their rapid dielectric heating upon microwave irradiation, reaction times for Heck couplings have been significantly reduced by combining the two technologies. ... 

Alkenyl, Alkynyl, Aryl and Heteroaryl Acids. Treatment of readily accessible (E)- and (Z)-alkyl and aryl substituted vinyl boronates (196) with triethyl phosphite in the presence of lead diacetate results in their stereospecific transformation into (E)- and (Z)-vinylphosphonates (197) (Scheme 53). ° Palladium acetate catalysed Mizoroki-Heck reaction of arylboronic acids (198) with diethyl vinylphosphonates (199) is an effective synthetic approach to... 

CL Alkene-alkene coupling. The palladium(O) catalysed arylation or alkenylation of alkenes is known as the Heck reaction (equation l2l) and has found extensive applications in synthesis (Table 23). Several variations of the Heck reaction have also been reported. 

---