Aryl iodide catalyst

What follows is a description of the trials and tribulations we experienced during our development of a short synthetic route to sorbicillactone a target that Porco has described as a deceptively simple molecule. To be clear, this work led to the synthesis of racemic material. Our group does have a strong interest in developing aryl iodide catalysts for asymmetric oxidative dearomatization reactions, and we have made some progress in this area. However, this has proved to be a very challenging area of research and still requires a fair amount of development. ... 

Figure 4.1 Chiral aryl iodide catalysts for enantioselective a-oxytosylation of ketones.

Scheme 23 Stereoselective phenolic dearomatization using chiral aryl iodide catalysts 55...

New chiral aryl iodide catalysts 55 were prepared by Hamerd et al. for assessing the stereoselective phenolic dearomatization. Catalysts 55 derived from 8-iodotetralone and tartaric acid could be used to synthesize enantioenriched para-quinols (up to 60% ee) from phenols as shown in Scheme 23 [73]. 

A new chiral aryl iodide catalyst, derived from 8-iodotefralone and tartaric acid,... 

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Arylation or alkenylation of soft carbon nucleophiles such as malonate is carried out by using a copper catalyst, but it is not a smooth reaction. The reaction of malononitrile, cyanoacetate, and phenylsulfonylacetonitrile with aryl iodide is possible by using a Pd catalyst to give the coupling products. 

Tandem cyclization/3-substitution can be achieved starting with o-(trifluoro-acetamido)phenylacetylenes. Cyclization and coupling with cycloalkenyl trif-lates can be done with Pd(PPh3)4 as the catalyst[9]. The Pd presumably cycles between the (0) and (II) oxidation levels by oxidative addition with the triflate and the reductive elimination which completes the 3-alkenylation. The N-protecting group is removed by solvolysis under the reaction conditions, 3-Aryl groups can also be introduced using aryl iodides[9]. 

The 3- and4-arylfuran-2(5//)-ones 152 and 153 (Ar = Ph, 2-Me—COO—QH4, 3-CF3—C6H4, 2-Me—C6H4, 2-thienyl) were conveniently obtained by coupling of 3- and4-stannylfuranones 151 and 134 with aryl iodides using dichloro-bis(triphe-nylphosphine)Pd(II) as catalyst and toluene as the solvent [96JCS(P1)1913]. 

An intramolecular palladium(o)-catalyzed cross-coupling of an aryl iodide with a trans vinylstannane is the penultimate maneuver in the Stille-Hegedus total synthesis of (S)-zearalenone (142) (see Scheme 38).59 In the event, exposure of compound 140 to Pd(PPh3)4 catalyst on a 20% cross-linked polystyrene support in refluxing toluene brings about the desired macrocyclization, affording the 14-membered macrolide 141 in 54% yield. Acid-induced hydrolysis of the two methoxyethoxymethyl (MEM) ethers completes the total synthesis of 142. 

The Sandmeyer reaction cannot be applied to fluorides (see Secs. 8.6 and 10.4) and the cuprous catalyst is not necessary for the synthesis of aryl iodides for reasons given in Sections 8.6 and 10.6. 

The palladium-catalyzed cross-coupling of alkenylsilanols has been extensively studied with respect to the structure of both the silicon component and the acceptor halide. The preferred catalyst for coupling of aryl iodides is Pd(dba)2 and for aryl bromides it is [allylPdCl]2. The most effective promoter is tetrabutylammonium fluoride used as a 1.0M solution in THF. In general the coupling reactions occur under mild conditions (room temperature, in 10 min to 12 hr) and some are even exothermic. 

A microwave-assisted Cu-catalyzed Sonogashira-type protocol on aryl iodide substrates without the involvement of a palladium catalyst has also been published (Scheme 54) [71]. Reactions were executed using Cut and CS2CO3 in NMP at 195 °C. The application seems to be fairly limited since there are indications that only (hetero)arylacetylenes are suitable coupHng partners for this protocol. In addition, aryl bromides react more sluggishly than aryl iodides. Moreover, even on aryl iodides the reaction times required are on the order of hours. 

The last method for the preparation of 2-quinolones described in this chapter relies on a intramolecular Heck cyclization starting from heteroaryl-amides (Table 2) [57]. These are synthesized either from commercially available pyrrole- and thiophene-2-carboxylic acids (a, Table 2) or thiophene-and furan-3-carboxylic acids (b, Table 2) in three steps. The Heck cyclization is conventionally performed with W,Ar-dimethylacetamide (DMA) as solvent, KOAc as base and Pd(PPh3)4 as catalyst for 24 h at 120 °C resulting in the coupled products in 56-89% yields. As discussed in Sect. 3.4, transition metal-catalyzed reactions often benefit from microwave irradiation [58-61], and so is the case also for this intramolecular reaction. In fact, derivatives with an aryl iodide were successfully coupled by conventional methods, whereas the heteroarylbromides 18 and 19, shown in Table 2, could only be coupled in satisfying yields by using MAOS (Table 2). 

Another successful approach to catalyst immobilisation involves attachment of the carbene precursor to a peptide on solid support. Treatment with base generates the corresponding carbenes that undergo in situ complexation to Pd(ll) centres (Scheme 6.33). Again, the main drawback of this approach was the low reactivity of the catalytic system that only allowed the coupling of aryl iodides and bromides [116], The reasons for this outcome are in need of further studies. 

Xia and co-workers synthesised a number of Pd-NHC complexes (33, 34, 36) for carbonylative Suzuki reactions (Fig. 9.6) [41], Various aryl iodides were carbonylatively coupled (P = 1 atm) with either phenylboronic acid or sodium tetraphenylborate. All the complexes were highly active, but 33 provided the best results with >76% selectivity for ketone in all the reactions. Xia followed this work with the double carbonylation of various aryl iodides with several secondary amines using the catalysts [CuX(Mes)] (37-X) and [Cu(IPr)X] (38-X) (X = I, Br, Cl) (3 MPa, 100°C, 10 h) (Scheme 9.7) [42],... 

However, given that other, supposedly stable and leach-resistant catalysts that we had previously studied seemed to operate solely by a leaching mechanism, with no supported Pd apparently active for the reaction (vide supra) and that other authors had found precatalysts of this type to operate by solely a leaching mechaiusm in Heck conversions of aryl iodides (19), we decided to investigate this system further using the solid poison testing method. 

Suzuki coupling reactions with aryl halides. Two as-prepared BaCei cPd c03. ( materials (x = 0.05 and 0.10) were successfully utihzed in several Suzuki coupling reactions. Both aryl iodides and aryl bromides react smoothly with 4-phenylboronic acid, eq 1, to yield the corresponding biatyls in high yields (> 95%). For both 4-bromoanisole and 4-iodoanisole, the biatyl yields reached nearly 100% in 3 min with BaCeo 95Pdoo503 5 as the catalyst, corresponding to an effective TON of ca. 2,000 and an effective TOF of nearly 50,000 h. Resnlts are smmnarized in Table 27.1. 

In Section 8.2.3.2, we discussed arylation of enolates and enolate equivalents using palladium catalysts. Related palladium-phosphine combinations are very effective catalysts for aromatic nucleophilic substitution reactions. For example, conversion of aryl iodides to nitriles can be done under mild conditions with Pd(PPh3)4 as a catalyst. 

A palladium catalyst with a less electron-rich ligand, 2,2-dipyridyl-methylamine-based palladium complexes (4.2), is effective for coupling of aryl iodides or bromides with terminal alkynes in the presence of pyrrolidine and tetrabutylammonium acetate (TBAB) at 100°C in water.37 However, the reactions were shown to be faster in NMP solvent than in water under the reaction conditions. Palladium-phosphinous acid (POPd) was also reported as an effective catalyst for the Sonogashira cross-coupling reaction of aryl alkynes with aryl iodides, bromides, or chlorides in water (Eq. 4.18).38... 

Besides palladium catalysts, nickel was also found to be an effective catalyst for the Sonogashira reaction in aqueous media. Recently, Beletskaya et al. reported a Ni(PPh3)2Cl2/CuI-catalyzed Sonogashira coupling reaction of terminal acetylenes with aryl iodides in aqueous dioxane in high yields (Eq. 4.19).39... 

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