Aryl borates

Marcuccio etal, US Patent 6,559,310 (May 6, 2003) Assignee Commonwealth Scientific and Industrial Research Organization Utility Arylboron Intermediates 

Neopentanediol (0.093 mol), 100 ml diethyl ether and tetrakis(dimethylamino)diborane were mixed, cooled with an ice bath, and 76 ml 2.46 M anhydrous hydrogen chloride (0.187 mol) in ether added. The mixture came to ambient temperature and stirred overnight. The solution was filtered, the solvent evaporated and the product isolated in 23% yield. Residue precipitate was extracted twice with 200 ml benzene increasing the overall yield to 74%. The solid was re-crystallized in benzene/light petroleum and had a mp = 161-162°C. H-NMR data supplied. 

The product from Step 1 (1.66 mmol), 4-iodobenzonitrile (1.09 mmol) and PdCl2(dppf) (3.27 mmol) dissolved in 6 ml methyl alcohol were stirred at ambient temperature 3 days. The mixture was poured into 20 ml water and the product extracted with 75 ml and 50 ml diethyl ether. The solvent was evaporated, the product purified by distillation at 80-100°C at 0.001 mm Hg, and isolated in 72% yield. H-NMR data supplied. 

The product from Step 2 was dissolved in methyl alcohol and the reaction monitored by HPLC (Waters 600E) using a Zorbax column (ODS) under the conditions of L = 230 nm, 2ml/min, 20% CH3CN 80% water (initial) to 80% CH3CN 20% water, and changed linearly from 9-17 minutes. A single peak was isolated within 5.8 minutes. 

The author coupled the borane reagent in Step 1 with other diols including  

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The general formula for boric acid esters is B(OR)2. The lower molecular weight esters such as methyl, ethyl, and phenyl are most commonly referred to as methyl borate [121 -43-7] ethyl borate [130-46-9J, and phenyl borate [1095-03-0] respectively. Some of the most common boric acid esters used in industrial appHcations are Hsted in Table 1. The nomenclature in the boric acid ester series can be confusing. The lUPAC committee on boron chemistry has suggested using trialkoxy- and triaryloxyboranes (5) for compounds usually referred to as boric acid esters, trialkyl (or aryl) borates, trialkyl (or aryl) orthoborates, alkyl (or aryl) borates, alkyl (or aryl) orthoborates, and in the older Hterature as boron alkoxides and aryloxides. CycHc boric acid esters, which are trimeric derivatives of metaboric acid (HBO2), are known as boroxines (1). 

Procedures for shipping boric acid esters depend on the particular compound. Aryl borates produce phenols when in contact with water and are therefore subject to shipping regulations governing such materials and must carry a Corrosive Chemical label. Lower alkyl borates are flammable, flash points of methyl, ethyl, and butyl borates are 0, 32, and 94°C, respectively, and must be stored in approved areas. Other compounds are not hazardous, and may be shipped or stored in any convenient manner. Because borate esters are susceptible to hydrolysis, the more sensitive compounds should be stored and transferred in an inert atmosphere, such as nitrogen. 

A regioselective and highly syn-stereoselective catalyst-free intermolecular alkylation of aryl borates with aryl epoxides under mild, neutral conditions has been reported.27 The reaction of /ra .s-stilbene oxide with tri(3,5-dimethylphenyl)borate gave a 38% yield (>95% syn) of the C-alkylated product (13), easily separated from (g) the O-alkylated product(s). Triflic anhydride has been used to activate enones to nucleophilic attack by electron-rich arenes in the presence of a sterically hindered base.28 Resorcinol dimethyl ether, for example, reacted with cyclohex-2-en-l-one to... 

Fluorinated aryl borates, in organometallic synthesis, 1, 72 Fluorinated heteroaromatics, fast oxidative addition,... 

Aryl borates such as catechol butylborate and triphenyl borate undergo a syn -stereoselective reaction with arylazirines.41 The syn-stereoselectivity was attributed to a transition state where the phenoxide tethered to the boron is transferred intramolec-ularly to the most substituted carbon. The reaction is completed when the phenoxide anion tethered to the boron reacts with the most substituted carbon of the substrate in an intramolecular reaction. 

Some of the most useful organoboron compounds are ethers of boric acid, trialkyl(aryl)borates. There are several techniques for producing these ethers ... 

Of practical interest are the last two techniques for producing trialkylbo-rates. It should be noted however, that the industrial reaction of boric anhydride with alcohols is fraught with difficulties. E.g., when powderlike boric anhydride is introduced into alcohol, clumps should be broken lest they kill the reaction. If boric anhydride is used in the form of pieces, the reaction should be conducted under an increased pressure and alcohol should be dehydrated beforehand. Thus, the most technological method is to obtain trialkyl(aryl)borates by the interaction of boric acid with alcohols. 

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. 

Aryl borates can provide both C-alkylation and O-alkylation products upon reaction with epoxides <07JOC7761>. The reaction shown below exemplifies a general reaction of arylborates with vinyl epoxides <07SL3011>. A number of examples were reported, the yield shown is typical. The ratio of SN2 to SN2 is generally >95 5 and the ratio of C-alkylation O-alkylation is also excellent (usually >95 5). 

The oxidation of carbon-boron bond converts boranes into alkyl or aryl borates, which may be hydrolyzed subsequently to alcohols and boric acid [991], The oxidation is carried out with hydrogen peroxide [183,1201, 1202] or trimethyiamine oxide [991, 992]. Phenylboronic acids are oxidized to phenols biochemically [1034]. 

Aqueous Derivatization with Tetraalkyl(aryl)borates... 

Tetracoordinated borate complexes are usually formed as intermediates, which are not always isolated. Convenient methods for the synthesis of aryl borates consist of the reaction of boron halides with an appropriate organometallic compound or the complexation of boranes with a nucleophile (76JOM281 78JCS(P2)1225 79MI2). Application of the former... 

Aryl borate esters are usually produced from the corresponding aryl halide by first metalating the carbon bearing the halide (typically with R-Li) and then treating the metalated arene with B (O-alky 1)3 (equation 12.70). 

More recently, a protocol was elucidated by Malezcka and Smith to produce aryl borate esters directly without first producing aryl halides.144 The reaction involves an Ir-catalyzed C-H activation (Section 7-2-1) to yield the aryl borate, which can then be used directly in Suzuki cross-coupling (equation 12.71). This new development adds another green aspect to Suzuki cross-coupling, which is already a relatively green synthesis tool. 

Fluorinated aryl borates have emerged as versatile organometaiiic WGA reagents in the last decade. Their availability through reliable preparative procedures, or commercial sources, as well as their excellent solubility and stability properties, has made fluorinated aryl borates the anion of choice in many organometaiiic research programs. Two derivatives, in particular, are extremely common tris(pentafluorophenyl)borane derivatives and tetrakis(3,5-trifluoro-methylphenyl)borate (see Figure 18). 

Non-metallic stractures of boron, silicon, phosphorus, and bromine can be bonded to phenolics. In most cases, these resins show an improved thermal stability in comparison to the nonmodified ones [1], Boron modified phenolics are prepared from aryl borates that are synthesized from phenol and boric acid (Scheme 26). The aryl borates react with methanal or 1,3,5-trioxane as shown in Scheme 26 to give boron modified prepolymers [167,168],... 

The Suzuki-Miyaura coupling joins an alkenyl or aryl borate with an alkenyl or aryl halide in the presence of a palladium catalyst. The stereochemistry of alkenyl reactants is preserved in the coupling. 

Buchwald and co-authors reported synthesis of biaryls by a lithiation/ borylation/Suzuki-Miyaura cross coupling sequence in continuous flow [53]. Aryl bromides could be lithiated at room temperature with 2 s-10 min residence time by mixing with n-BuLi, which then reacted with B(OiPr)3 at room temperature with 1 min residence time to afford aryl borates, ArB(OiPr)3Li. The reactor was sonicated to avoid blocking by precipitated ArB(OiPr)3Li. The reaction mixture was then mixed with Pd catalyst/THF solution and reacted at 60 °C (4—10 min residence time) to give biaryls in good yields. For example, 2-fluoro-4 -methoxy-[l,l -biphenyl]-4-carbonitrile was obtained in 94% yield (4 min residence time) (Scheme 5.38). 

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