Suzuki couphng

Scheme 25). The introduction of greater diversity at C-2 and C-4 can be achieved by intercepting the tetrahydropyridinone intermediate in a multi-step sequence involving C-2 ammonolysis, microwave-assisted N-acylation, acid-catalyzed cyclization (to introduce diversity at C-2), treatment with POCI3, and either microwave-assisted nucleophiUc substitution or Suzuki couphng (to introduce diversity at C-4) [89]. 

The biaiyl phenol (X) was the penultimate intermediate in the synthesis of this final drag substance. Thus after the Suzuki coupling reaction is performed to give the phenol, the levels of Pd have to be lowered to < 10 ppm. In the pharma industry this can be a significant problem. Additionally there is always batch to batch variability observed when catalysts like Pd2(dba)3 have been used in Suzuki couphng reactions. 

In contrast to solid-phase Suzuki couphng, very low amounts of the Pd-catalyst (0.2 mol%) were sufficient and high conversions (87-99%) to biaryls (65) were obtained to yield relatively pure products (>90%, GC/MS, NMR) after ultrafiltration. In some cases most of the polymer supported boronic compound precipitated during the reaction and therefore no further purification was required. Nonetheless, quantitative removal of catalyst traces was not yet possible with either work-up protocol. 

Suzuki couphng, the palladium-catalyzed cross-coupling of aryl or vinyl hahdes with organoboronates, is employed widely in organic synthesis. The reaction is most often carried out in an organic solvent (benzene) in the presence of a base [228]. Because of the reasonable stabihty of boronic acids and esters towards hydrolysis, Suzuki couphng can also be carried out in aqueous media. An extensive study of the reaction has shown that similar results are obtained in aqueous and non-aqueous systems [229]. 

The use of Suzuki couphng for the synthesis of polyphenylene polymers was introduced by Rehahn, Schlueter and Wegner [Eq. (9)] [230]. Poly(p-2,5-di-n-hexylphe-nylene) was prepared in a biphasic mixture of benzene and water as a reaction medium, using sodium carbonate as a water-soluble base. This AB-type polymerizahon afforded polymers containing, e.g., an average of about 28 phenylene units. 

For the Suzuki couphng of 5-bromopyrimidine and protected p-boronophenylalanine 52 to assemble 53, Pd(dppf)Cl2 was found to be an effective catalyst [43], whereas using 2-bromopyrimidine as the substrate gave the corresponding adduct in only 20% yield. 

The complexes were employed as catalysts in Suzuki couphngs and were removed from the product by filtration. No fluorous solvents were used [32]. 

The StiUe couphng is the reaction of a trialkylaryl stannane or a trialkyl vinyl stannane (50) with an aromatic iodide, bromide, or triflate. Its mechanism differs from that of the Suzuki couphng by the fact that OH , RO, CO , or F is not required for the progression of the catalytic cycle (Scheme 9). 

Pergament, 1., and Srebnik, M., Control of hydroboration of 1-alkynylphosphonates, followed by Suzuki couphng provides regio- and stereospecific synthesis of di-substituted 1-alkenylphosphonalcs, Tetrahedron Lett.. 42. 8059, 2001. 

Diiodo-l-phenysulfonylindole can be converted by sequential, in situ, magnesium-iodine exchanges into various 3-substituted indol-2-ylboronates, which participate in Suzuki couphngs. ... 

The modified 2 1 Ni-COD complex in which the metal also binds to an imidazolidene unit shows superior selectivity in the Suzuki couphng of polyfluoioatenes. For example, reaction of perfluorotoluene occurs at the p-position of the trifluoromethyl group. ... 

Coupling reactions. Using complexes in which Pd is coordinated with polymer-supported azolecarhene ligands Suzuki couphng between ArB(OH)2 and Ar N2Bp4 or haloarenes has heen studied. ... 

With a cationic 2,2 -bipyridyl ligand the Suzuki couphng in water proceeds very efficiently (TOP up to 81,000 per hr, TON up to 395,000). ... 

Using the standard Suzuki couphng condition utilizing tetrakis (triphenylphosphine) palladium... 

For example, Yu et al. showed that polystyrene-bound peptides could be hydrolyzed in 7 min in a domestic MW oven, a process normally taking 24 h. Furthermore, traditional soHd-phase peptide couplings were achieved in 4 min in 99-100% conversion with no detected racemization. A broad range of solid-phase reactions was found to undergo substantial rate acceleration, including Claisen and Knoeve-nagel condensations, nucleophilic substitutions, sucdnimide and hydantoin formation, and Suzuki coupHngs. 

The protected diol side-chain of 170 is introduced by asymmetric dihydroxy-lation and directs diastereoselectivity in the formation of 172 by hthiation. The most acidic position of 170, between the two methoxy groups, is first protected by silylation. Suzuki couphng of 173 with the boronic acid 174 gives the kinetic product 175 - the more severe hindrance to bond rotation in this compound... 

The synthesis of Spiro-DPSP 115 starts with 2,7-dibromospirobifluorene (9), which is iodinated in the 2 and 7 position by the procedure of Merku-shev [35]. After Suzuki couphng [72] of 120 with biphenylboronic acid, the target compound is formed by Hartwig-Buchwald coupling [103] of 121 with diphenylamine (Fig. 43). 

Syntheses of bioinspired trisporphyrin scaffoldings from stepwise Suzuki couphng strategies 13MG13. 

An important observation regarding Suzuki couplings of aryl chlorides was reported in 1997 by Shen, who established that palladium complexes that include a bulky, electron-rich trialkylphosphine, such as tricyclohexylphosphine (PCys), catalyze Suzuki couphngs of activated aryl chlorides at 100°C (Equation 2.14) [25]. 

Fluorenyldialkylphosphines represent another interesting class of trialkyl-phosphines that can be used for Suzuki couphngs of aryl chlorides. Sulfonylation of the aromatic moiety of the fluorenyl group results in a water-soluble ligand that can be used for couplings in aqueous solvent (Equation 2.20) [35-37]. 

S. GuUlerez and G. Bidan. New convenient synthesis of highly regioregular poly(3-octylthiophene) based on the Suzuki couphng reaction. Synth. Met. 93(2), 123-126 (1998). 

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