Norbornene Heck reaction

To date, only double Heck reactions have been described, but triple Heck reactions are also possible [39]. Reaction of the alkynyl aryl iodide 6/1-55 with norbor-nene in the presence of Pd(OAc)2, triphenylphosphane and triethylamine as base led to the cyclopropanated norbornene derivate 6/1-59 as a single diastereomer in 40% yield (Scheme 6/1.13). It can be assumed that the alkenyl Pd-species 6/1-56 is first formed stereoselectively, and this undergoes a Heck reaction with norbornene... 

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>... 

The Heck reaction yields the final product through a p-hydride elimination whereas hydroarylation or hydrovinylation generates the final product via a reductive elimination. Nonetheless, both reactions share a common first step, that is, addition of an aryl or a vinyl palladium species to an alkene, and thus are briefly discussed here. Norbornene 595 is the most studied alkene to evaluate an the... 

Scheme8.22. Cyclopalladation during Pd-mediated homocoupling of aryl iodides [156] and Heck reaction with norbornene [157]. Ar = 2-(tBu)C6H4.

Likewise, Lautens and coworkers have demonstrated the strength of the concept of sequential alkylation-alkenylation by application to the synthesis of fused aromatic rings. Hence, in the presence of 10% of Pd acetate, 20% of tri-2-furylphosphane, two equivalents of norbornene, and two equivalents of cesium carbonate, bromoenoates and related derivatives, ortho-substituted aryl iodides react in boiling acetonitrile in the sense of a Pd-catalyzed ortho-alkylation-intramolecular Heck reaction to furnish fused aromatic carbocy-cles 47-53 in moderate to excellent yields (Scheme 17) [74]. 

Asymmetric hydroarylation/hydrovinylation, although not strictly a Heck reaction as the P-hydride ehmination step is replaced by reductive ehmination, nevertheless shares a common mechanistic pathway with regard to the enantiose-lective step and so will be discussed briefly. In 1991 Brunner et al. first reported hydrophenylations of norbornene and norbornadiene using aryl iodides, al-... 

In 2010, Buchmeiser [56] developed a similar system that capitalized on the thermally reversible carboxylation [11] of NHCs (Scheme 31.13, inset). By employing the NHC-CO2 adduct (which essentially is a protected NHC), the reaction conditions did not have to be stringently air- and moisture-free to prevent NHC decomposition. Synthesis of the norbornene-functionalized monomer 37 allowed the molybdenum-catalyzed ROMP with l,4,4a,5,8,8a-hexahydro-l,4,5,8-exo-ewdo-dimethanonaphthalene (a ditopic norbornene) to produce crossHnked polymer 38 with pendant CO2-masked NHCs (Scheme 31.13). Upon heating in the presence of Rh, Ir, or Pd species, the NHC-metal-functionalized polymers 39 were formed and found to contain >20mol% metal, as determined with inductively coupled plasma optical emission spectrometry (ICP-OES). The C02-masked NHC material was found to catalyze the carboxylation of carbonyl compounds and the trimerization of isocyanates upon thermal deprotection (i.e., decarboxylation). Moreover, the NHC-metal-crosslinked materials were found to catalyze Heck reactions, transfer hydrogenations, and also the polymerization of phenylacetylene (M = 8.4 kDa, PDI = 2.45, as determined with GPC in DMF against PS standards). This modular system provides an array of options for catalysis from simple modifications of polymer-supported, C02-masked NHCs. 

Cyclization reactions of (7,77 -enylpalladium complexes are intramolecular insertions of the coordinated double bond into the Pd-C(organic synthesis (intramolecular Heck reactions) and, when polyene substrates are used, sequential insertions in undetected <7,77 -enyls lead to polycyclic compounds in a synthetically very efficient process. Examples of this reaction starting from isolated, well characterized a,if-onyh of palladium are, however, scarce. Equation (62) shows the formation of a tricyclic derivative by cyclization of a a,if-enyl derived from < ti-5-vinyl-2-norbornene promoted by CuCl2. ... 

The complex catalytic cycle commences with oxidative palladium insertion on the aryl iodide bond. The following carbopalladation with norbornene creates a bulky intermediate that is not prone to p-hydride elimination and allows C-H activation of the ortho position of the aryl moiety. Subsequent oxidative addition of the alkyl iodide allows cross-coupling and elimination of the norbornene by retro-carbopalladation. The remaining intermediate 146 then undergoes aMizoroki-Heck reaction with the acrylate, which completes the catalytic process and furnishes the desired cinnamate 148 derivative. 

Catellani and Lautens have independently reported unique palladium/ norbornene-catalyzed reactions of aryl halides, which mechanistically involve a reversible alkene insertion/p-carbon elimination process [11]. For example, iodobenzene reacted with 1-iodobutane and methyl acrylate to form the multiply-alkylated benzene 29 (Scheme 7.9) [12]. The following mechanism is proposed oxidative addition of phenyl iodide onto palladium generates phenylpalladium(ll) iodide. A double bond of norbornene inserts into the C-Pd bond to form an alkylpalladium species, which cleaves a C-H bond nearby to form the palladacycle 25. -Butyl iodide then reacts with 25 to form the Pd(IV) intermediate 26, which undergoes reductive elimination. Repetition of the cyclometalation/alkylation process leads to the formation of 27. Then, P-carbon elimination affords the arylpalladium species 28 together with norbornene. Subsequently, a Heck-type reaction takes place with methyl acrylate, giving rise to 29. 

The Pd(PhCN)2Cl2-catalyzed addition reaction of 1-alkenylstannane reagents with two molecules of norbornene afforded polycyclic products via the oxidative addition of the tin reagent with Pd(0), double insertion, and an intramolecular Heck reaction (eq 34). ... 

Aryl cyanides add to norbornene and norbornadiene under nickel catalysis to give (2/U,35 )-3-aryl-2-cyanobicyclo[2.2.11heptanes and (2/U,3.S )-3-aryl-2-cyanobicy-clo[2.2.1]hept-5-enes in good yields with a broad substrate scope. On the other hand, the reaction of an aryl cyanide with triethoxy(vinyl)silane gives a Heck-type arylation product, suggesting the arylnickelation pathway in the catalytic cycle.68... 

As indicated in the previous example, carbopalladation does not necessarily culminate in /i-hydride elimination as the expected outcome of reactions under Heck conditions. In those cases where the initial carbopalladation can be reversed at a later stage in the sequence fascinating options for catalytic processes may evolve. In particular, Catellani (for an overview see [67]) has established that norbornene, a strained olefin, which is reversibly introduced and eliminated, might efficiently serve as a relay to open new pathways for Pd-mediated processes. Indeed, most of the processes were explored and conducted both in a stoichiometric and in a catalytic fashion. 

The carbopalladation of a double bond in a Cj-bridge of a bicyclic alkene leads to an intermediate, which does not contain a syn-oriented P-hydrogen and thus cannot undergo a syn-P-hydride eHmination to recreate a double bond. Such carbopalladation intermediates of, for example, norbornene with arylpalladium hahdes therefore find other modes of reaction (Section 8.3.7). In the presence of formic acid or potassium formate as a hydride source, norbornene (65), norbornene derivatives, and heteroanalogs such as 247 and 248, as well as bicyclooctene[2.2.2]octene (251), under typical Heck conditions undergo hydroarylation and hydroalkenyla-tion reactions (Scheme 8.52) [374]. A number of hydroarylation products of type... 

The first step of the catalytic cycle proposed for this complex reaction consists of the oxidative addition of the aryl iodide reactant to palladium(O) (Scheme 19.11). Subsequent reversible insertion of norbornene into the Pd-Ar bond gives rise to complex 9, which undergoes base-mediated intramolecular C-H activation to give palladacycle 10. Oxidative addition of the primary alkyl iodide furnishes palladium(IV) complex 11, which, after reductive elimination and deinsertion of norbornene, generates a paUadium(II) species (12) able to undergo cross-coupling reactions such as the Mizorold-Heck coupling, as illustrated in Scheme 19.10. 

The carbonylative cyclization of 2-iodophenols with norbornadiene or norbornene was also carried out. In 1989, Catellani s group studied the annulation of 2-iodophenol with norbornadiene to coumarin (Scheme 3.11a). ° In this method, the elimination of cyclopentadiene via retro-Diels-Alder reaction was involved in the formation of the terminal product. Fiaud and co-workers reported the palladium-catalyzed carbonylative cyclization of 2-iodophenol with norbornene in 1997 (Scheme 3.11b). They reported that the selectivity for the production of the two regioisomers can be controlled. Catellani and co-workers studied the intramolecular cyclization of ort/zo-iodophenyl 3-butenoate to 4-methylcoumarin with a palladium catalyst. 85% of 4-methylcoumarin was produced in the presence of benzonitrile and carbon monoxide, which is compulsory (Scheme 3.12a). Silva, Costa and their co-workers reported a tandem process for the synthesis of coumarins from 2-iodophenols and enoates with the assistance of a palladium catalyst (Scheme 3.12b). The general scope of this Heck-lactonization involves E- and Z-enoates as substrates. It was shown that this reaction is sensitive to steric hindrance around the double bound in... 

In contrast, Gu and coworkers achieved the synthesis of rhazinal by using an intermoiecuiar C-H arylation of pyrroles at the C3 position and subsequent Heck alkylation (Scheme 16.12b) [26]. When iodopyrrole 60 was reacted with aryl iodide 61 in the presence of catalytic PdCl2, PPh3, and excess amounts of norbornene (6 equiv.), a Catellani-type reaction occurred to give intermediate 62. This intermediate then underwent reductive elimination and norbornene release... 

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