SYNTHESIS arylboronate esters

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 ... 

SYNTHESIS OF ORTHO SUBSTITUTED ARYLBORONIC ESTERS BY IN SITU TRAPPING OF UNSTABLE LITHIO INTERMEDIATES 2-(5,5-DIMETHYL-l,3,2-DIOXABORINAN-2-YL)BENZOIC ACID ETHYL ESTER... 

The direct preparation of arylboronic esters from aryl halides or triflates now allows a one-pot, two-step procedure for the synthesis of unsymmetrical biaryls (Scheme 1-41) [147]. The synthesis of biaryls is readily carried out in the same flask when the first coupling of the triflate with diboron 82 is followed by the next reaction with another triflate. The synthesis of naturally occurring biflavanoids and the couphng of N-(phenylfluorenyl)amino carbonyl compounds to polymeric supports are reported [154]. 

For the domino transition metal-catalyzed synthesis of macrocycles, conditions must be found for two distinct cross-coupling reactions, of which one is inter- and the other intramolecular. For this purpose, Zhu s group [115] has developed a process of a Miyura arylboronic ester formation followed by an intramolecular Suzuki reaction to give model compounds of the biphenomycin structure 6/1-232 containing an endo-aryl-aryl bond. 

The first synthesis of arylboronic esters 209-215 via the coupling of bis(pinacolato)diborane(4) with easily prepared aryldiazonium tetra-fluoroborate salts was reported. The palladium-catalyzed borylation reaction proceeds efficiently under mild reaction conditions in the absence of a base to afford various functionalized arylboronic esters in moderate to high yields (Scheme 34).121... 

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

Arylboronic esters (Figure 5.48) can be oxidized with H202 in acetic acid to give aryl borates, which can then be hydrolyzed to provide phenols. The mechanism for this oxidation is similar to that for the OOH oxidation of trialkylboranes and is discussed in Section 14.4.3. In combination with the frequently simple synthesis of arylboronic esters one can thus achieve the overall conversions Ar—H —> Ar—OH or Ar—Br —> Ar-OH in two or three steps. 

A nonaqueous workup procedure has been reproted for the preparation of arylboronic esters [ArBCOR a)]-" Uncontrollable polymerization or oxidation of much of the boronic acid occurred during the final stages of the isolation procedure, but could be avoided by in situ conversion to the dibutyl ester by adding the crude product to 1-butanol. The samarium(lll)-catalyzed hydroboration of olefins with catecholborane is a good synthesis of boronate esters." ... 

The total synthesis of the proteasome inhibitor cyclic peptide TMC-95A was accomplished by. S.J. Danishefsky and co-workers. The biaryl linkage in the natural product was constructed by a Suzuki cross-coupling between an aryl iodide and an arylboronic ester derived from L-tyrosine. The required arylboronic pinacolate substrate was prepared using the Miyaura boration. The aryl iodide was exposed to b/s(pinacolato)diboron in the presence of a palladium catalyst and potassium acetate in DMSO. The coupling proceeded in high yield and no symmetrical biaryl by-product was observed. 

The efficient synthesis of a potent topoisomerase I poison terbenzimidazole was developed in the laboratory of P.J. Smith. The desired aryl-aryl bonds were created via iterative Suzuki-cross couplings. The arylboronic ester was derived from 1-benzyl-5-iodo-1/-/-benzimidazole using the Miyaura boration. 

In 2010, Radi and coworkers reported the synthesis of isozaleplon, which is a regioisomer of the therapeutic drug Zaleplon to treat insomnia. The synthesis of isozaleplon featured the key C-C bond formation via direct arylation of the tautomerizable heterocycle with the arylboronic ester using PyBroP in the presence of PdCl2(PPh3)2 catalyst (10H1359). 

Ready availability of arylboronic esters from aryl halides or triflates (Eqs. 13 and 14) now offers a one-pot, two-step procedure for synthesizing unsymmetrical biaryls. The cross-coupling reaction of bis(pinaco-lato)diboron with triflate in dioxane is followed by a subsequent coupling with another triflate in the presence of K3PO4 to furnish an unsymmetrical biaryl from two triflates (Eq. 63). The synthesis from two different... 

Isolation of free boronic acids using an aqueous work up may lead to low yields, especially for small or polar ones, which tend to be water-soluble even at a low pH (Section 1.4). In such cases, it is often better to isolate the desired boronic acid as an ester. In an improved procedure that does not involve an aqueous work-up. Brown and Cole reported that the reaction of several types of organolithium intermediates with triisopropylborate was very effective for the synthesis of arylboronic esters [180]. To help minimize the possible formation of borinic acids and boranes by multiple displacements (i.e.. Equation 28 in Figure 1.19), the reaction protocol involves the slow addition of the organolithium to a solution of triisopropylborate in diethyl ether cooled to -78 °C. The use of smaller borate esters such as trimethylborate gave large proportions of multiple addition products (i.e., borinic acid and borane). With triiso-... 

The ready availability of arylboronates by an aromatic C-H borylation provides a synthetic link to the well-established palladium-catalyzed cross-coupling reactions, rhodium-catalyzed 1,4-addition to a,p-unsaturated carbonyl compounds, and other bond forming reactions using arylboronic esters (Scheme 2.12). Borylation of 1,3-dichlorobenzene with pinacolborane is followed directly by a cross-coupling reaction with methyl p-bromobenzoate for the synthesis of a biaryl product in 91% yield [60]. Pinacol esters of arylboronic acids react much slower than the free acids [62], but both derivatives achieve high isolated yields and comparable enantioselectivities (91% ee) in asymmetric 1,4-addition to N-benzyl crotonamides [63]. Borylation of arenes followed by oxidation of the C-B bond is synthetically equivalent to an aromatic C-H oxidation to phenols [64]. Oxidation of the resulting arylboronates with Oxone in a 1 1 acetone-water solution is completed within 10 min at room temperature. 

The same year, Gandon et al. reported the synthesis of fused arylboronic esters 36 via cobalt(0)-mediated cycloaddition of alkynylboronates 33 with diynes 35 (Scheme 1.11) [22], The boronate is first reacted with Co2(CO)g at room temperature for 4 h to generate the corresponding dicobaltatetrahedrane 34. The diyne is then added and the mixture is refluxed for 2 h. To show the utility of the products, one of them was treated with phenyl iodide under Pd catalysis to give 37. Complementary to these investigations, Ru-catalyzed [2 - - 2 - - 2] cycloaddition of tethered alkynyl-boronic esters with alkynes was reported [23]. In this case, the borylated arene could not be isolated but was converted directly in situ by Suzuki-Miyaura coupling. 

This procedure allows the synthesis of arylboronic esters in good yields while tolerating various ftinctional groups. A by-product is the homocoupling product (see 4.18). In Scheme 5-164, some successful substrates are depicted. 

In another publication, the Miyaura group described the cross-coupling of aryl triflates to arylboronic esters as well as the synthesis of unsymmetrical biaryls using a modified protocol. In both cases, the authors used KOAc as base since stronger bases such as K2CO3 afforded symmetrical biaryls (see also 4.18) as by-products. The proposed mechanism of this reaction is depicted in Scheme 5-166. Oxidative addition of the catalyst to haloarene followed by displacement of the halide leads to the corresponding pentacoordinated palladium(II) species. Transmetalation with bis(pinacolato)diboron followed by reductive elimination yields the arylboronic ester. 

Scheme 2.50 Synthesis of fused arylboronic esters via cobalt(0)-mediated cycloaddition of alkynyiboronates with diynes.

Gandom, V., Leca, D., Aechtner, T., Vollhardt, K.P., Malacria, M. and Aubert, C. (2004) Synthesis of fused arylboronic esters via cobalt(0)-mediated cycloaddition of alkynylboronates with ct,w-diynes. Organic Letters, 6(19), 3405-3407. 

Arylboron Formation Investigated in Micro Reactors Organic synthesis 40 [OS 40] Formation of phenyl esters of boronic add... 

Trialkylaryltin derivatives 30 are converted into fluoro-substituted derivatives 31. 37-38 (4-Mcth-oxyphenyl)trimethylsilane (32) in acetonitrile gives 4-fluoroanisole and (3-fluoro-4-meth-oxyphenyl)trimethylsilane in the ratio 1 2. A -Methyldiethanol esters of arylboronic acids 33 (l-aryl-5-methyl-2,8-dioxa-5-azonia-l-boranuidabicyclo[3.3.0]octanes) are converted into tluoroaromatic compounds with cesium fluoroxysulfate in acetonitrile in the presence of 1,3-dinitrobenzene at room temperature.39-40 Regiospecific synthesis of 2-fluoro-3-0-methyles-trone in 27 % yield occurs upon fluorination of the corresponding arylboronic acid with cesium fluoroxysulfate.41... 

Watanabe, T. Miyaura, N. Suzuki, A. Synthesis of sterically hindered biaryls via the Pd-cat-alyzed cross-coupling reaction of arylboronic acids or their esters with haloarenes. Synlett 1992, 207-210. 

Synthesis of arylboronates via the palladium(0)-catalyzed cross-coupling reaction of tetra(alkoxy)diboranes with aryl triflates has been reported.114 The cross-coupling reaction of (RO)2B-B(OR)2 (OR = methoxy and pinacolato) with aryl triflates to give arylboronates 178-189 was carried out at 80 °C in the presence of PdCl2(dppf) (3 mol%), and KOAc (three equivalents) in dioxane. The reaction was generalized to various functional groups such as nitro, cyano, ester, and carbonyl groups (Scheme 30). 

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