Thiophenes 3-boronic acid

Temp. (°C) Benzeneboronic acid 8.5 MHClOt H0 = -4.69 Thiophene-2-boronic acid Thiophene-3-boronic acid 6.0 M HClOx Ho 2.83... 

Preparation of 5-isobutyl-2-[(Al- -butyl)sulfonamido]thiophene-3-boronic acid... 

A mixture consisting of the Step 4 product (0.773 mmol), thiophene-3-boronic acid (0.938 mmol), tetrakis(triphenylphosphine)palladium(0) (0.004 mmol), 276 mg sodium carbonate dissolved in 1.3 ml water, and 5 ml 1,4-dioxane was refluxed overnight under a nitrogen atmosphere. The reaction was quenched with water, extracted three times with 25 ml CH2C12, dried with Na2S04, filtered, and concentrated. The brown oily residue was purified by chromatography with silica gel using hexane/EtOAc, 1 1, and the product isolated in 48.4% yield. 

Thienylboronic acids are useful building blocks for preparing biaryls and heterobiaryls employing the Suzuki reaction. In one case, a Suzuki coupling between thiophene-3-boronic acid and iodocyclopropane 99 was promoted by cesium fluoride to furnish the adduct 100 with retention of configuration [74]. In another example, the union between thiophene-3-boronic acid and 5-bromo-2,2-dimethoxy-l,3-mdandione (101) provided ninhydrin derivative 102 [75]. 

Rate coefficients have been determined for protodeboronation of benzene- and thiophene-boronic acids in a range of aqueous perchloric acid mixtures at temperatures between 25 and 90 °C630. First-order rate coefficients are given in Table 204, but not all of the rates were measured at the acidities indicated (see Table footnote), but were corrected to these making use of the linear relationship which was found, in preliminary experiments, to exist between log rate and H0. Similarly, the relative reactivities to thiophene-2-, thiophene-3-, and benzene-boronic acid (8.5 x 10s, 7.1 x 103, and 1.0, respectively) were obtained at an H0... 

Rate coefficients and kinetic parameters for iododeboronation were determined for the benzene- and thiophene-boronic acids, and the results are given in Table 256. The relative reactivities derived from this work correlated well with those obtained in a number of other electrophilic substitutions572, which is perhaps surprising in view of the large variation in the entropies of activation. These differences were explained by Brown et al.132 in terms of the transition state for the phenyl compound occurring earlier along the reaction coordinate than for the... 

In the second example, optimization of a Suzuki coupling on SP was carried out. Two boronic acids were coupled with resin-bound iodide 6.56 (Fig. 6.24) at 90 °C for increasing reaction times of 1, 3, 6, and 10 h and the yields of the products 6.58 and 6.59 were calculated after cleavage of the product from the resin. The results are shown in Table 6.3. The less hindered thiophene boronic acid reacted completely after 1 h, while the more hindered tolyl derivative required 3 h to drive the reaction to completion. In this ease it was found that while 3 h was an optimal length of time for both substrates, longer reaction times tended to decrease the reaction yields. 

Another device for bringing thiophenes into reaction with Mannich intermediates is to utilise thiophene boronic acids - the Petasis reaction primary aromatic amines can also be used as the amine component. ... 

There are by now many examples involving palladium(0)-catalysed couplings using halothiophenes, thiophene boronic acids, thienylstannanes, and thienylzinc... 

Thiophene oligomers (up to six units) have been obtained by Barbarella et al. [73] under microwave conditions from 2-thiophene boronic acid and dibromo precursors with three thiophene units in the presence of a palladium catalyst and KF with KOH (Scheme 14.36). The reactions were run in a single-mode microwave reactor at 70 °C for 10 min. 

Thus, we decided to return to the concept of the original synthesis and couple the vinyl iodide 16 and thiophene boronic acid 17 to arrive to the same intermediate trisubstituted alcohol 18. 

Acylation, vinylation, and ethinylation involving Pd(0)-catalyzed coupling reactions can be performed with halothiophenes, thiophene boronic acids, or thienyl stannanes following the classical Suzuki-Miyaura, Stille, or Sonogashira protocols [64]. 

The regioisomeric 4,4 -dipentoxy-2,2 -bithiophene 327 bearing the pentoxy groups in the outer /3-positions was synthesized in 70% yield by oxidative coupling of lithiated 3-pentoxythiophene 321 with copper chloride. 4-Pentoxy-2-thiophene-boronic acid 326 which was synthesized from 3-pentoxythiophene 321, lithiumdiiso-propylamid and trimethylborate was coupled with I-Tj-I 54 and I-T2—I 306,... 

In the area of ion sensing, cation recognition by electrodes containing functionalized redox-active polymers has been an area of considerable interest. Fabre and co-workers have reported the development of a boronate-functionalized polypyrrole as a fluoride anion-responsive electroactive polymer film. The electropolymerizable polypyrrole precursor (11) (Fig. 11) was synthesized by the hydroboration reaction of l-(phenylsulfonyl)-3-vinylpyrrole with diisopinocampheylborane followed by treatment with pinacol and the deprotection of the pyrrole ring.33 The same methodology was utilized for the production of several electropolymerizable aromatic compounds (of pyrrole (12) (Fig. 11), thiophene (13 and 14) (Fig. 11), and aniline) bearing boronic acid and boronate substituents as precursors of fluoride- and/or chloride-responsive conjugated polymer.34... 

This gives tautomeric mixtures119 when the tert-butyl group is removed. The methyl ether has been used to obtain 3-hydroxy-2-carbonyl derivatives in the selenophene series.120 The unsubstituted 2-hydroxyselenophene system has been prepared by hydrogen peroxide oxidation of 2-selenophene-boronic acid.121 However, in the 5-methyl-substituted system deboronation became such an important side reaction that 5-methyl-2-hydroxyselenophene had to be prepared by acid-catalyzed dealkylation of 5-methyl-2-fert-butoxy-selenophene. Both 2-hydroxy- and 5-methyl-2-hydroxyselenophene exist mainly as 3-selenolene-2-ones (93) and for the 5-methyl derivative it was possible to isolate the / ,y-unsaturated form (92) and follow the tautomeric isomerization. The activation parameters thus obtained were compared with those for the corresponding furan and thiophene systems. 

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

The coupling of the same boronic acid was also achieved with 4-chlorobenzoyl chloride (6.5.), Running the reaction under anhydrous conditions the desired 2-(4 chlorobenzoyl)thiophene was obtained in good yield.7 The opening step in this process is the selective oxidative addition of the palladium into the carbonyl-chlorine bond giving an acylpalladium complex, which on subsequent transmetalation and reductive elimination gives the observed product. 

In the alternate approach arylboronic acids were coupled with A-aryhhio-succinimides. In the process the aryl group of the boronic acid replaces the succinimide moiety in the coupling partner. In the example presented (6.85.) the 2-thiothiophene derivative was converted to 2-(4 -fluorophenylthio)-thiophene in 76% yield. The procedure was successfully extended to benzothiazoles too.115... 

The introduction of a uracil moiety onto thiophene was achieved by the use of a similar boronic acid, bearing /erz-butoxydc substituents in positions 2 and 4 (7.13.), This compound was reacted with a bromothiophene to give the Suzuki coupling product in 63% yield, which on treatment with... 

Cross-coupling reactions between organoboranes and heteroaryl halides are effectively catalyzed by Pd(0) in the presence of a base. Couplings in simple pyrimidines are illustrated by the reaction between 2-chloropyrimidine and 2- or 3-thiophene- and selenophene-boronic acids which give the corresponding 2-substituted pyrimidines (921) (Scheme 72). In 2,4-dichloro- or 2,4-dibromo-pyrimidine it is the 4-halo substituent which is the more reactive. 

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