Phenylboronic acid derivatives

A/,A/ -3,5-Bis(trifluoromethyl)phenylboronic Acid Derivative, 594 A/-[Phenyl(pentacarbonylchromium- or-tungsten)]carbenyl, 595 A/-Copper or A/-Zinc Chelate, 595 18-Crown-6 Derivative, 596... 

As compounds exhibiting enhancing effects on CL reactions, a variety of phenols, e.g., firefly luciferin and 6-hydroxybenzothiazole derivatives [12,13], 4-iodophe-nol [14], 4-(4-hydroxyphenyl)thiazole [15], 2-(4,-hydroxy-3 -methoxy-benzyli-dene)-4-cyclopentene-l,3-dione (KIH-201) [16], and 2-(4-hydroxyphenyl)-4,5-diphenylimidazole (HDI) and 2-(4-hydroxyphenyl)-4,5-di(2-pyridyl)imidazole (HPI)[17] (Fig. 6A), and phenylboronic acid derivatives, e.g., 4-phenylylboronic acid [18], 4-iodophenylboronic acid [19], and4-[4,5-di(2-pyridyl)-l //-imidazol-2-yl]phenylboronic acid (DPPA) [20] (Fig. 6B), in the luminol/hydrogen peroxide/peroxidase system are well known. Rhodamine B and quinine are used as sensitizers in the CL-emitting reaction between cerium (IV) and thiol compounds. This CL reaction was successfully applied to the sensitive determination of various thiol drugs [21-32],... 

DiCesare N, Adhikari DP, Heynekamp JJ, Heagy MD, Lakowicz JR. Spectroscopic and photophysical characterization of fluorescent chemosensors for monosaccharides based on /V-phenylboronic acid derivatives of 1,8-naphthalimide. Journal of Fluorescence 2002, 12, 147-154. 

Heagy MD. IV-Phenylboronic acid derivatives of arenecarboximides as saccharide prohes with virtual spacer design. In Geddes CD, Lakowicz JR (Eds), Topics in Fluorescence Spectroscopy, Vol. 11. Springer, New York, 2006, pp. 1-20. 

Pentanediol [(R,/ )-28] has been used for the formation of chiral acetals and as a precursor for chiral alkenes (Sections D.1.5.1. and 1.6.1.5.). The original procedure for the resolution of the phenylboronic acid derivative with brucine39 was impractical, but recently a kinetic resolution by lipase-catalyzed esterification and hydrolysis has been developed40. In addition, a good method for catalytic reduction of 1,3-diketones with Raney nickel modified with sodium bromide and tartaric acid (for a procedure, see Section D.2,3.1.) allowed the production for commercial purposes41. Similarly, sterically more hindered and less water-soluble 2,6-dimethyl-3,5-heptanediol (29) has been introduced for the same purpose. It is obtained in the same way from the diketone and separated from the meio-compound by simple recrystallization42. 

Boronic acids bearing strong electron-poor aromatic groups (such as pyridinyl) were reported to lack reactivity in the Petasis-Akritopoulou reaction, using standard conditions (dichloromethane, room temperature) [54]. Boronic esters were also studied [57] and the authors reported that the mechanism of formation of the boronate species was different from that with phenylboronic acid derivatives. Piettre and coworkers considered the use of hexafluoro-iso-propyl alcohol (HFIP), which is an alcohol with higher ionizing power, as the solvent in the Petasis-Akritopoulou reaction with boronic esters (Scheme 6.43). Compared to the use of methanol as solvent and microwave-assisted irradiation (MW), the yields were much higher (a maximum of 99% yield was obtained ) [58]. 

Heagy and Lakowicz have been investigating N-phenylboronic acid derivatives of 1,8-naphthalimide (37a,b, Figure 12.9) - with these systems the fluorescence is substantially quenched (ca. 5-fold) on saccharide binding [95, 96]. The fluorescence... 

The parent system 4 has also been jnepared employing a double reductive ring closure of a dinitrodiphenylbenzene derivative (Scheme 25). The required starting material, 195, was prepared using a palladium-catalyzed coupling of 1,4-dibromo-2,5-dinittobenzene with phenylboronic acid and after reaction with tri-ethylphosphite in hot tert-butylbenzene, 4 could be isolated in a moderate yield (92JHC1237). 

For the synthesis of a suitable arylboron compound, usually an aryl halide is converted to an aryllithium or aryl Grignard derivative, and then reacted with a trialkoxyborane to yield an arylboronic ester, e.g. the phenylboronic acid diisopropyl ester 13 from bromobenzene 11 ... 

Some other enantioselective approaches have been attempted, still with moderate enantioselectivities, by making use of in situ systems containing a chiral NHC precursor. Luo and co-workers reported on the use of the bidentate chiral imidazo-lium salt 16, derived from L-proUne, in combination with [RhCia-COCcod)], leading to an enantiometic excess of around 20% [30]. The use of chiral imidazolium salt 17 in combination with [RhCl(CH2=CHj)j]j by Aoyama afforded slightly better ee (Fig. 7.3) [31 ]. So far, Bohn and co-workers have obtained the best enantioselectivities (up to 38% ee) for the catalytic addition of phenylboronic acid to aromatic aldehydes by using planar chiral imidazolium salts 18, derived from paracyclophane, in combination with [Rh(OAc)2]2 [32]. 

Recently, Suzuki-type reactions in air and water have also been studied, first by Li and co-workers.117 They found that the Suzuki reaction proceeded smoothly in water under an atmosphere of air with either Pd(OAc)2 or Pd/C as catalyst (Eq. 6.36). Interestingly, the presence of phosphine ligands prevented the reaction. Subsequently, Suzuki-type reactions in air and water have been investigated under a variety of systems. These include the use of oxime-derived palladacycles118 and tuned catalysts (TunaCat).119 A preformed oxime-carbapalladacycle complex covalently anchored onto mercaptopropyl-modified silica is highly active (>99%) for the Suzuki reaction of p-chloroacetophenone and phenylboronic acid in water no leaching occurs and the same catalyst sample can be reused eight times without decreased activity.120... 

Indolyltriflates have been used in Suzuki couplings by Mdrour [138, 139]. Thus, the readily available l-(phenylsulfonyl)indol-2-yl triflate (131) smoothly couples with arylboronic acids in 65-91% yield. Similarly, Pd-catalyzed cross-coupling of phenylboronic acid with l-benzyl-2-carbomethoxyindol-3-yl triflate affords the 3-phenyl derivative (62% yield) [139]. 

An interesting asymmetric transformation is the asymmetric conjugate addition to a-acetamidoacryhc ester 30 giving phenylalanine derivative 31, which has been reported by Reetz (Scheme 3.10) [10]. The addition of phenylboronic acid 2m in the presence of a rhodium complex of l,T-binaphthol-based diphosphinite ligand 32 gave a quantitative yield of 31 with up to 11% enantiomeric excess. In this asymmetric reaction the stereochemical outcome is determined at the hydrolysis step of an oxa-7r-aUylrhodium intermediate, not at the insertion step (compare Scheme 3.7). 

Surprisingly, when the same authors started from a 6,8-dichloropurine derivative, the course of the reaction depended on the reagent. Phenylboronic acid showed a marked preference for the 6-position again, while the iron catalyzed coupling of methylmagnesium chloride proceeded selectively in the 8-position (8.3.), The rationale behind the observed selectivity is still unclear.8... 

Polystyrene-derived phenylboronic acids have been used for the attachment of diols (carbohydrates) as boronic esters [667]. Cleavage was effected by treatment with acetone/water or THF/water. This high lability towards water and alcohols severely limits the range of reactions that can be performed without premature cleavage of this linker. Arylboronic acids esterified with resin-bound diols can be oxidatively cleaved to yield phenols (Entry 8, Table 3.36). Alcohols have also been prepared by nucleophilic allylation of aldehydes with polystyrene-bound, enantiomerically enriched allyl-silanes [668], as well as by Pummerer reaction followed by reduction of resin-bound sulfoxides [669]. 

The first work in this field was probably that of Piletsky et al. [84] that described a competitive FILA for the analysis of triazine using the fluorescent derivative 5-[(4,6-dichlorotriazin-2-yl)amino]fluorescein. The fluorescence of the supernatant after incubation was proportional to the triazine concentration and the assay was selective to triazine over atrazine and simazine. The same fluorescent triazine derivative was applied to competitive assays using atrazine-imprinted films [70]. To this end an oxidative polymerization was performed in the presence of the template, the monomer(s) 3-thiopheneboronic acid (TBA) or mixtures of 3-amino-phenylboronic acid (APBA) and TBA (10 1) in ethanol-water (1 1 v/v) where the template is more soluble. The polymers were grafted onto the surface of polystyrene microplates. The poly-TBA polymers yielded a detection limit of 8 pM atrazine whereas for the poly-TBA-APBA plates it was lowered to 0.7 pM after 5 h of incubation. However, a 10-20% decrease in the polymer affinity was observed after 2 months. 

Lastly, the condensation of phosphine 56 with phenylboronic acid afforded the salicylic acid-derived compound 57 (Scheme 35).65 Following the same strategy, Gudat et al. recently prepared derivative 59 combining a phosphine group and a benzo 1,3,2-dioxaborol moiety (Scheme 35). 66 Compounds 57 and 59, both obtained in quantitative yields, were characterized by multinuclear NMR spectroscopy, mass spectrometry, and elemental analysis. 

In addition to these two series of reactions based on the substitution of hydrogen, a third set of data may be derived from reactions which involve the replacement of groups other than hydrogen.1 Kuivila, Benkeser, and Eaborn and their associates employed this approach to study the effects of many substituents. For example, Kuivila and Hendrickson (1952) examined the bromodeboronation of substituted phenylboronic acids. 

One of the clearest pieces of evidence for the reversibility of some covalent interactions came from the work of Gunther Wulff at the University of Dusseldorf, Germany [172], He used imprinted polymers of o-aminomethyl phenylboronic acids as chromatographic stationary phases for the separation of saccharides. Older studies [173] also point to the reversible nature of the boronic acid-saccharide interaction. The pioneering studies of fluorescent transduction of this phenomenon by Czarnik and Yoon [174] (Ohio State University), Aoyama et al. [175] (Kyushu University, Japan), and Shinkai et al. [176] (Kyushu University, Japan) have been reviewed previously [9], Our concern in this review is particularly with the systems that clearly involve PET. Czarnik and Yoon s 93 [177] which interacts with catechol derivatives to produce 94 also belongs here. It... 

Synthesis and Cytostatic Activity of Substituted 6-Phenylpurine Bases and Nucleosides Application of the Suzuki—Miyaura Cross-Coupling Reactions of 6-Chloropurine Derivatives with Phenylboronic Acids... 

The Suzuki—Miyaura reaction of protected 6-chloropurine and 2-amino-6-chloropurine bases and nucleosides with substituted phenylboronic acids led to the corresponding protected 6-(substituted phenyl)purine derivatives 6—9. Their deprotection yielded a series of substituted 6-phenylpurine bases and nucleosides 10—13. Significant cytostatic activity (IC50 0.25—20 /tmol/ L) in CCRF-CEM, HeLa, and L1210 cell lines was found for several 6-(4-X-substituted phenyl-purine ribonucleosides 12 (X = H, F, Cl, and OR), while the 6-phenylpurine and 2-amino-6-phenylpurine bases 10 and 11, as well as 2-amino-6-phenylpurine ribosides 13, were entirely inactive against these cell lines. 

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