Acids boronic

The oxidation of rm-butylboronic acid by chromic acid has the stoichiometry 

The acidity dependence is complex and indicates that no extra proton to give H2Cr04 is required, but that H3Cr04 is an active oxidant in this reaction. The rate is very sensitive to the nature of the alkyl group, viz. 

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D Boronic acid coupling 10 l-(4-Methylphenylsulfonyl)indole- l-Benzyl-3-trifluoromethanesulfonyloxy-l,2,5,6- 92 [10]... 

Vinylation can also be done by Pd-catalysed cross-coupling in which one component is used as a halide or triflate and the other as a stannane (Stille reaction) or boronic acid (Suzuki reaction). Entry 9, Table 11.3, is an example of the use of a vinylstannane with a haloindole. lndole-3-boronic acids, which can be prepared by mcrcuration/boration, undergo coupling with vinyl triflates (Entry 10). 

The Suzuki coupling of arylboronic acids and aryl halides has proven to be a useful method for preparing C-aryl indoles. The indole can be used either as the halide component or as the boronic acid. 6-Bromo and 7-bromoindolc were coupled with arylboronic acids using Pd(PPh3)4[5]. No protection of the indole NH was necessary. 4-Thallated indoles couple with aryl and vinyl boronic acides in the presence of Pd(OAc)j[6]. Stille coupling between an aryl stannane and a haloindole is another option (Entry 5, Table 14.3). 

A solution of 6-bromoindole (O.lOmol) in toluene (200 ml) was treated with Pd(PPh3)4 (5mol%) and stirred for 30 min. A solution of 4-fluorophenyl-boronic acid (0.25 M, 0.15 mol) in abs. EtOH was added, followed immediately by sal aq. NaHCOj (10 eq.). The biphasic mixture was refluxed for several hours and then cooled to room temperature. The reaction mixture was poured into sat. aq. NaCl (200 ml) and the layers separated. The aq. layer was extracted with additional EtOAc (200 ml) and the combined organic layers dried (Na2S04), filtered and concentrated in vacuo. The solution was filtered through silica gel using hexane-CHjCl -hexanc for elution and evaporated. Final purification by recrystallization gave the product (19 g, 90%). 

A number of less hindered monoalkylboranes is available by indirect methods, eg, by treatment of a thexylborane—amine complex with an olefin (69), the reduction of monohalogenoboranes or esters of boronic acids with metal hydrides (70—72), the redistribution of dialkylboranes with borane (64) or the displacement of an alkene from a dialkylborane by the addition of a tertiary amine (73). To avoid redistribution, monoalkylboranes are best used /V situ or freshly prepared. However, they can be stored as monoalkylborohydrides or complexes with tertiary amines. The free monoalkylboranes can be hberated from these derivatives when required (69,74—76). Methylborane, a remarkably unhindered monoalkylborane, exhibits extraordinary hydroboration characteristics. It hydroborates hindered and even unhindered olefins to give sequentially alkylmethyl- and dialkylmethylboranes (77—80). 

The iodination reaction can also be conducted with iodine monochloride in the presence of sodium acetate (240) or iodine in the presence of water or methanolic sodium acetate (241). Under these mild conditions functionalized alkenes can be transformed into the corresponding iodides. AppHcation of B-alkyl-9-BBN derivatives in the chlorination and dark bromination reactions allows better utilization of alkyl groups (235,242). An indirect stereoselective procedure for the conversion of alkynes into (H)-1-ha1o-1-alkenes is based on the mercuration reaction of boronic acids followed by in situ bromination or iodination of the intermediate mercuric salts (243). 

Moderate yields of acids and ketones can be obtained by paHadium-cataly2ed carbonylation of boronic acids and by carbonylation cross-coupling reactions (272,320,321). In an alternative procedure for the carbonylation reaction, potassium trialkylborohydride ia the presence of a catalytic amount of the free borane is utilized (322). FiaaHy, various tertiary alcohols including hindered and polycycHc stmctures become readily available by oxidation of the organoborane iatermediate produced after migration of three alkyl groups (312,313,323). 

Alternatively, radiohalogen-labeled compounds may be prepared by way of isotopic labeling from the unlabeled bromo or iodo derivatives by various two-step reaction sequences. Examples include the use of trialkylsilyl synthons as described in References 10—13, and the use of boronic acid synthons as described in References 14 and 15. 

Technetium-99m teboroxime is a myocardial imaging agent and is excreted primarily by the hepatobiliary system. It is rapidly taken up by the myocardium and mosdy washes out within 30 minutes. Imaging protocols are performed immediately after injection. The product is a lyopbili ed mixture of boronic acid, dioxine, and other excipients, and the agent is formed with a beating step. 

The reaction is proposed to proceed from the anion (9) of A/-aminocatbonylaspattic acid [923-37-5] to dehydrooranate (11) via the tetrahedral activated complex (10), which is a highly charged, unstable sp carbon species. In order to design a stable transition-state analogue, the carboxylic acid in dihydrooronate (hexahydro-2,6-dioxo-4-pyrimidinecarboxylic acid) [6202-10-4] was substituted with boronic acid the result is a competitive inhibitor of dibydroorotase witb a iC value of 5 ]lM. Its inhibitory function is supposedly due to tbe formation of tbe charged, but stable, tetrabedral transition-state intermediate (8) at tbe active site of tbe enzyme. 

Although boronates are quite susceptible to hydrolysis, they have been useful for the protection of carbohydrates. Note that as the steric demands of the diol increase, the rate of hydrolysis decreases. For example, pinacol boronates are rather difficult to hydrolyze in fact, they can be isolated from aqueous systems with no hydrolysis. The section on the protection of boronic acids should be consulted. 

Boronic esters are easily prepared from a diol and the boronic acid with removal of water, either chemically or azeotropically. (See Chapter 2 on the protection of diols.) Sterically hindered boronic esters, such as those of pinacol, can be prepared in the presence of water. Boronic esters of simple unhindered diols are quite sensitive to water and hydrolyze readily. On the other hand, very hindered esters, such as the pinacol and pinanediol derivatives, are exceedingly difficult to hydrolyze and often require rather harsh conditions to achieve cleavage. 

Boronic acids readily dehydrate at moderate temperatures (or over P4O10 at room temperature) to give trimeric cyclic anhydrides known as trialkyl(aryl)boroxines ... 

Boronic acids RB(OH)2 were first made over a century ago by the unlikely route of slow partial oxidation of the spontaneously flammable trialkyl boranes followed by hydrolysis of the ester so formed (E. Frankland, 1862) ... 

The methylenebis(boronic acid) 122 may be deprotonated and alkylated at the central position and may thus behave as an acyl anion equivalent. Monoalkylation of 122 followed by hydrolysis gives aldehydes in good yield, and a second alkylation led to a ketone in one case (77JA3196). 

Cyclic esters of a-halo boronic acids in asymmetric synthesis 98T10555. 

The first total synthesis of 87 was published in 1990 (90TL1523). 5-Hydroxyindole (88) was mesylated and then reduced with sodium cyanoborohydride to give an indoline which was brominated to afford the bromoindoline 89 in good yield (Scheme 33). Cross-coupling with ortho-formyl boronic acid under Suzuki conditions, followed by air oxidation of the resulting cyclized product, followed by reduction of the lactam formed with excess Red-Al gave the target compound 87. 

Bromoquinolines behave in the Suzuki reaction similarly to simple carbocyclic aryl bromides and the reaction is straightforward. Examples include 3-(3-pyridyl)quinoline (72) from 3-bromoquinoline (70) and 3-pyridylboronic acid (71) (91JOC6787) and 3-phenyl-quinoline 75 from substituted 3,7-dibromoquinoline 73 and (2-pivaloylaminophenyl)boronic acid 74 (95SC4011). Notice that the combination of potassium carbonate and ethanol resulted in debromination at the C(7) position (but the... 

Palladium-catalyzed carbon-carbon bond forming reactions like the Suzuki reac-tion as well as the Heck reaction and the Stille reaction, have in recent years gained increased importance in synthetic organic chemistry. In case of the Suzuki reaction, an organoboron compound—usually a boronic acid—is reacted with an aryl (or alkenyl, or alkynyl) halide in the presence of a palladium catalyst. 

The boronic acid 2 is first converted to an activated species 8 containing a tetravalent boron center by reaction with a base. Halides or triflates (OTf = trilluoromethanesulfonate) are used as coupling partners R-X for the boronic acids. In many cases the rate-limiting step is the oxidative addition. With respect to the leaving group X, the rate decreases in the order ... 

An alkyl- or alkenylboron compound, as a suitable organoboron component (a borane, boronic acid or ester) can be prepared through hydroboration of an... 

Palladium-mediated catalysis has only been exploited relatively recently in the synthesis of substituted PPV derivatives. The use of aryl dibromides as monomers is particularly useful as it allows the synthesis of PPVs substituted with alkyl rather than alkoxy sidechains. The Suzuki [53, 54], Heck [55], and Stille [56] reactions have been used in the synthesis of new PPV derivatives, but attaining high molecular weight PPV derivatives by these methodologies has proved problematic. A phenyl-subslilutcd PPV material PPPV 31 was synthesized by a Suzuki coupling (Scheme 1-10) of dibromoethene and fo/.v-boronic acid 30. Its absorption (2ni ix=385 nm) and emission (2max=475 nm) maxima were strongly... 

The authors used a synthesis of 9,9-spirobitluorenes 32 which was developed by Clarksen and Gomberg [60] and which includes the addition of biphenyl-2-yl-magnesium iodide to fluorenone and subsequent cyclization with protic acids. To obtain 2,2,, 7,7 -arylated 9,9-spirobifluorenes 33, 9,9-spirobifluorene (32) was tetrabrominated [58] to yield 34 followed by a Suzuki-type aryl-aryl cross-coupling with various oligoaryl and oligoheteroaryl boronic acids to obtain the 2,2, 7,7 -tetraarylated derivatives 33. 

Kim and Webster [57] were the first to show that trifunctional benzene-based monomers can also be used to synthesize poly(phenylene)s, in this case hyperbranched structures 31 based on 1,3,5-trisubstituled benzene cores. They self-condensed l,3-dibromophenyl-5-boronic acid leading to the formation of soluble, hyperbranched PPP-type macromolecule 31. 

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