Heck aryl iodides with olefins

Scheme 6.36 Heck reaction of aryl iodides with olefins using 52 in water.

Over 35 years ago, Richard F. Heck found that olefins can insert into the metal-carbon bond of arylpalladium species generated from organomercury compounds [1], The carbopalladation of olefins, stoichiometric at first, was made catalytic by Tsutomu Mizoroki, who coupled aryl iodides with ethylene under high pressure, in the presence of palladium chloride and sodium carbonate to neutralize the hydroiodic acid formed (Scheme 1) [2], Shortly thereafter, Heck disclosed a more general and practical procedure for this transformation, using palladium acetate as the catalyst and tri-w-butyl amine as the base [3], After investigations on stoichiometric reactions by Fitton et al. [4], it was also Heck who introduced palladium phosphine complexes as catalysts, enabling the decisive extension of the ole-fination reaction to inexpensive aryl bromides [5],... 

Substitution of aryl and vinylic halides. Dieck and Heck have reported a reaction of aryl and vinylic bromides and iodides with olefins catalyzed by palladium acetate and 2 eq. of triphenylphosphine that is related to the reaction mentioned above. New olefins are formed by replacement of the vinylic hydrogen of the original olefin by the Ar or R group of the halide. 

Selective or/Ao-alkylation and -aiylation of aryl iodides can be achieved by the cooperative catalytic action of palladium and noibomene. The first reported case was the or/Ao-dialkylation of aryl iodides, followed by Heck reaction. Here an aiyl iodide with free o-positions reacts with an aliphatic iodide and a terminal olefin in the presence of palladium/noibomene as catalyst and a base, to give a 2,6-substituted virtylarene. Analogously, an aryl iodide with one substituted o-position leads to a virtylarene containing two different ortho groups. ... 

In 1975, three different protocols were available in the literature, each describing the synthesis of internal alkynes. Cassar described palladium- or nickel-mediated reactions between aryl or vinyl halides and alkynes complexes with phosphine as ligands in the presence of NaOMe [1]. As a second protocol, Heck pubhshed a variation of the Mizoroki-Heck couplings, in which the olefins were replaced by alkynes and coupled with (hetero)aryl, as weU as alkenyl bromides or iodides at 100 °C in the presence of a basic amine [2]. More than a decade earUer, Stephens and Castro had described the details of a palladium-free coupling of aryl iodides with cuprous acetylides in refluxing pyridine [3]. 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

The most widely used version of the Heck reaction is the coupling of aryl bromides or iodides with activated olefins such as styrene or acrylic acid derivatives, using conditions first described by Spencer [18], The catalysts are generated in situ by combining Pd(OAc)2 with two to four equivalents of triphenyl- or tri-o-tolyl-phosphine. Triethylamine, K2C03, NaHC03, or NaOAc are often used as the base. 

An orf/io-directed lithiation allows the conversion of 25 to aryl iodide 40. Reductive ether formation of aldehyde 40 with crotyl alcohol yields compound 41. Intramolecular Heck reaction of 41 affords a mixture of the olefins 42 and 43. The undesired alkene 42 can be isomer-ized quantitatively to the desired enol ether 43 with Wilkinson s catalyst. Sharpless dihydroxylation ee 94 %) of the enol ether 43 provides lactol 44, which is oxidized directly to lactone 45. Finally, the pyridone-O-methyl ester is cleaved under acid conditions (45 — 7). 

Xiao et al. [213] recently reported that the intermolecular Heck arylation with several electron-rich olefins can be effected with both aryl bromides and iodides in a highly regioselective manner by the use of ionic liquids. Regioselectivity towards the branched cr-olefin was up to 99/1 and there was no need for additional halide scavenger. In this case the ionic liquid seems to serves not only as a quite polar solvent but also as halide scavenger. 

The Mizoroki-Heck reaction, a palladium-catalyzed coupling of olefins with aryl or vinyl halides/triflates, is a powerful method for carbon-carbon bond formation. " " High efficiency is usually obtained only by starting from expensive aryl iodide (or bromide) or by using a fairly large amount of catalyst. Improvement of the catalytic activity as well as recovery and recycling of the catalyst is needed. 

However, clear evidence of the IL effect was found for the regioselective arylation of olefins. It is generally accepted that the Heck reaction may proceed via two pathways, a neutral pathway leading to the preferential formation of linear olefins and an ionic counterpart more likely to give rise to branched olefins. Thus, Pd(OAc)2 and l,3-bis(diphenylphosphino)propane (DPPP) immobilized in [G4GiIm]BF4 promote the exclusive a-arylation of several classes of electron-rich olefins with a wide range of aryl iodides and bromides in the absence of halide scavengers (Scheme 3). ... 

The first palladium-catalyzed carbonylations of aryl halides were published in 1974 and 1975 (Equation 17.59). ° Heck first reported the synthesis of benzoates by the reaction of an aryl iodide, carbon monoxide, and an alcohol in the presence of a tertiary amine and catalytic amoimts of the combination of palladium acetate and triphenylphosphine. Concurrently, he reported the synthesis of benzamides from an aryl iodide, carbon monoxide, a primary amine, and a tertiary amine as base catalyzed by the same type of palladium complex. The related reactions of vinyl halides were also reported, and these reactions occurred with retention of the olefin geometry. ... 

Palladium-catalysed Heck addition of Ar-I to terminal olefins RCH=CH2 has been reported to proceed under ligand-free conditions, with just (AcO)2Pd and AcOAg in AcOH at 110°C, and shown to afford double arylation products RCH=CAr2. Both electron-poor and electron-rich aryl iodides react efficiently. ... 

Ternary Pd-catalyzed coupling reactions of bicyclic olefins (most often norbor-nadiene is used) with aryl and vinyl halides and various nucleophiles have been investigated intensively over the past few years [44]. A new approach in this field is to combine Heck and Suzuki reactions using a mixture of phenyliodide, phenyl-boronic acid and the norbornadiene dicarboxylate. Optimizing the conditions led to 84% of the desired biphenylnorbornene dicarboxylate [45]. Substituted phenyl-iodides and phenylboronic acids can also be used, though the variation at the norbornadiene moiety is highly limited. 

Palladium-catalyzed arylation of olefins and the analogous alkenylation (Heck reaction) are the useful synthetic methods for carbon-carbon bond formation.60 Although these reactions have been known for over 20 years, it was only in 1989 that the asymmetric Heck reaction was pioneered in independent work by Sato et al.60d and Carpenter et al.61 These scientists demonstrated that intramolecular cyclization of an alkenyl iodide or triflate yielded chiral cyclic compounds with approximately 45% ee. The first example of the intermolecular asymmetric Heck reaction was reported by Ozawa et al.60c Under appropriate conditions, the major product was obtained in over 96% ee for a variety of aryl triflates.62... 

The palladacycle 29 is either prone to reductive elimination, furnishing the minor by-product 26, or to an oxidative addition of an alkyl iodide, giving rise to an octahedral Pd(IV) species 30. Reductive elimination places the alkyl substituent in the ortho position and another CH activation furnishes the palladacycle 31. Again, an octahedral Pd(IV) intermediate 32 is obtained after an oxidative addition of an alkyl iodide. As before, reductive elimination occurs and gives an alkyl-Pd intermediate 33 that sets the stage for a jd-elimination and expulsion of norbornene. Now, the resulting ortho, ortho double alkylated aryl Pd intermediate 34 reacts with the terminal olefin and finally concludes the sequence with a Heck vinylation to give the final product 27. 

---