Phosphine ligands aryl halide formation

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]. 

The Pd-catalyzed intermolecular C—O bond formation has also been achieved [105-108]. Novel electron-rich bulky phosphine ligands utilized by Buchwald et al. greatly facilitated the Pd-catalyzed diaryl ether formation [109], When 2-(di-tert-butylphosphino)biphenyl (95) was used as the ligand, the reaction of triflate 93 and phenol 94 elaborated diaryl ether 96 in the presence of Pd(OAc)2 and K3PO4. The methodology also worked for electron-poor, neutral and electron-rich aryl halides. 

The Pd-catalyzed carbonylation of aryl halides (cf Section 2.1.2) occurs with high turnover numbers and reaction rates in SCCO2 as the solvent using standard precursor complexes and commercially available phosphine or phosphite ligands [30]. The generally better performance of the phosphite-based catalysts was attributed to their better solubility in the reaction mixture, but the formation of Pd carbonyl complexes was also mentioned as a possibility. The [Ni(cod)2]/dppb system (dppb = l,4-bis(diphenylphosphino)butane) was investigated in an early study as a catalyst for the synthesis of pyrones from alkynes and CO2 under conditions beyond the critical data of carbon dioxide [31]. Replacing dppb with PMcs results in a system with better solubility and catalytic performance, albeit catalyst deactivation remains a problem [3 c, 15]. 

As an example, a new palladium based method has been developed for the alkylation of tyrosine residues [34], In this reaction, allylic carbonates, esters, and carbamates are activated by palladium(O) complexes in aqueous solution, resulting in the formation of electrophilic zr -allyl complexes (such as 16), Fig. 10.3-8(a). These species react at pH 8-10 with the phenolate anions of tyrosine residues, resulting in the formation of aryl ether 17 and regeneration of the Pd(0) catalyst. The reaction requires no organic cosolvent, is catalytic in palladium, and requires P(m-QjH4S03 )3 as a water-soluble phosphine ligand. In contrast to alkyl or allylic halides, the inert character of the allyloxycarbonyl compounds used in this reaction ensures that nonspecific... 

One of the most important transformations catalysed by palladium is the Heck reaction. Oxidative addition of palladium(O) into an unsaturated halide (or tri-flate), followed by reaction with an alkene, leads to overall substitution of a vinylic (or allylic) hydrogen atom with the unsaturated group. For example, formation of cinnamic acid derivatives from aromatic halides and acrylic acid or acrylate esters is possible (1.209). Unsaturated iodides react faster than the corresponding bromides and do not require a phosphine ligand. With an aryl bromide, the ligand tri-o-tolylphosphine is effective (1.210). The addition of a metal halide or tetra-alkylammonium halide can promote the Heck reaction. Acceleration of the coupling can also be achieved in the presence of silver(I) or thallium(I) salts, or by using electron-rich phosphines such as tri-tert-butylphosphine. ... 

For insoluble development in Heck-type reactions is P-C and N-C bond formation, which results from coupling of aryl halides with phosphorous compounds [38] and amines [39]. The first application in aqueous medium was achieved by coupling of a dialkyl phosphite with an aromatic iodide to give an arylphosphonate in 99% yield. In 1996, Stelzer and co-workers presented a P-C cross-coupling reaction between primary and secondary phosphines and functional aryl iodides to water-soluble phosphines [Eq. (9)], which are potentially applicable as ligands in aqueous-phase catalysis [40]. 

Cross-coupling reactions leading to the formation of C-X (X = heteroatom) bonds catalyzed by Pd(dba)2 have been reported. Aniline derivatives have been prepared via reaction of amine nucleophiles with aryl halides in the presence of Pd(dba)2 and phosphines, especially P( Bu)3. Likewise, diaryl and aryl alkyl ethers are produced from aryl halides (Cl, Br, I) and sodium aryloxides and alkoxides under similar conditions. Conditions effective for the coupling of aryl chlorides with amines, boronic acids, and ketone enolates using an easily prepared phosphine chloride as a ligand have recently been uncovered (eq 22). The preparation of aryl siloxanes and allyl boronates via Pd(dba)2-catalyzed C-Si and C-B coupling have been reported as well. 

The success of the new method is due to selection of bases which are stable under the reaction conditions and also the use of bulky phosphine ligands. Later, reductive elimination was fovmd to be crucial in the C—N bond formation, which is accelerated by bulky ligands. As bases, MN(TMS)2 (M = Li, Na, K) and r-BuONa give good results. Alkoxides such as MeONa, EtONa, and n-BuONa seem to be unsuitable, because oxidation of alcohols and reduction of aryl halides occur via facile jS-H elimination of the palladium alkoxide 5. 

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