Pinacol boronates

The Suzuki-Miyaura tactic carried out on solid support (Scheme 28) [52] provides routes to small libraries of condensed heterocycles. Thus, Merrifield resin with the LeznofF-linked bromobenzene derivative 78 undergoes cross-coupling under normal solution-phase conditions with boron pinacolate 79 or boronic acid 80, prepared by DoM, to afford phenan-thridines 81 or, via 82 and some manipulation, dibenzopyranones 83 in good yields and with high purities. The Stille solid-support reaction has also been successfully executed [53]. 

Owing to fast protodeboronation and slow transmetaUation, direct cross-coupling reactions of secondary alkyl boronic acids are notoriously difficult. In order to enhance the stability of boronic acids, various diols can be used to react with boronic acids to form more stable boronic esters. Unfortunately, boron s Lewis acidity dramatically decreases in this case mainly due to the increased steric bulk surrounding the boron atom, making the transmetaUation more difficult. Toward this end, Shibata and coworkers [123] in 2010 designed a system where one of the carbon substituents is another boron pinacolate (Eq. (44), Scheme 2.41). As boron atoms are known to stabilize a-anions due to the empty p orbitals on the boron atom... 

Harrity and co-workers described the application of 2-substituted 1-alkynylboronic esters in the Dotz cycloaddition of Fisher chromium carbene complexes, affording in a highly regioselective fashion a novel class of hydroxy-naphthyl boron pinacolates (entry 18, Table 1.3) [217]. These reaction products also provided, upon treatment with ceric ammonium nitrate, the corresponding quinone boronic esters. 

The Pd-catalyzed reaction of such polyfunctional boronic esters like 21b with various aryl halides provides the desired cross-coupling products like 22 in high yields [10,11]. Interestingly, a one-pot reaction allowing the selective reaction with two electrophiles is possible. Thus, the treatment of the meta-iodophenyl boronic pinacol ester 18 with i-PrMgCl LiCl followed by a transmetallation to the copper derivative and subsequent reaction with 2-methyl-3-iodocyclohexenone provides the intermediate boronic ester 23 that after a Suzuki-Miyaura cross-coupling, furnishes the heterocyclic product 24 in 52% yield (Scheme 3.6) [11]. 

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. 

Boron trifluoride-acetic acid complex Harshaw Chemical Co., Allied Chemical Co. 1,5-Cyclooctadiene A, MCB Sulfur dichloride MCB Boron trifluoride etherate EK, MCB Mercuric acetate MCB Norbornene MCB Calcium carbide MCB Pinacol EK, MCB... 

Allylboronates prepared from simple diols display appreciable reactivity, but eyelie boronate derivatives prepared from 1,2- or 1,3-diols display considerably less. The commonly employed pinacol esters are among the least reactive members of this class. 2-Allyl-3-methyl-l,3,2-oxaza-... 

Boronic Ester Relative Retention Minimum Detectable Quantity (pg of pinacol) Optimum Detector Temperature ( C)... 

We have broadened the scope of this reverse addition protocol to prepare a variety of boronic acids bearing different functional groups for use in Suzuki coupling reactions. The yield and quality of the boronic acid prepared by this reverse addition protocol is usually better than the sequential approach. The boronic acids can be used without further purification (formation of pinacols) in Suzuki coupling reactions. 

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... 

Another useful method for generating various IV-allylhydroxylamines is the reaction between vinyl boronic ester of pinacol and nitrone in the presence of dimethylzinc (655). 

Addition of a boron-boron bond across a carbon-carbon triple bond is known for some 40 years since the finding that diboron tetrahalides add to alkenes and alkynes in the absence of catalysts.36 Although the reaction seemed to be potentially attractive, the instability of diboron tetrahalides was the critical drawback for the practical use in synthesis. In 1993, much more stable pinacol ester derivative of diboron was found to add to alkynes in the presence of platinum catalysts such as Pt(PPh3)4, Pt(CH2=CH2)(PPh3)2, and Pt(CO)2(PPh3)2 (Figure 1, Scheme 2).37,38 Other... 

Instead of the borohydrido pinacol ester one can also use the boron dimer. Several metals, intermediates as the one shown in Figure 19.10 have been isolated. They may contain 1-3 Bpin units and 3-1 hydrides. For the mechanism... 

As a conseqnence of their superior stability, many types of allylic boronates can be isolated and purified. It should be noted that most pinacol allylic boronic esters and other bnlky esters are stable to hydrolysis and can be conveniently pnrified by chromatography on silica gel. A potential pitfall of all allylic boron componnds is their stereochemical integrity, and snbstituted allylic boranes are known to nndergo reversible borotropic rearrangements at temperatures above —45° (see Eq. 12, M = Eor this reason, allylic boranes are nor-... 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

The use of chiral Br0nsted acids is illustrated in Eq. 93 as a method for catalyst-controlled double diastereoselective additions of pinacol allylic boronates. Aside from circumventing the need for a chiral boronate, these additions can lead to very good amplification of facial stereoselectivity. For example, compared to both non-catalyzed (room temperature, Eq. 90) and SnCU-catalyzed variants, the use of the matched diol-SnCU enantiomer at a low temperature leads to a significant improvement in the proportion of the desired anti-syn diastereomer in the crotylation of aldehyde 117 with pinacolate reagent (Z)-7 (Eq. 93). Moreover, unlike reagent (Z)-ll (Eq. 91) none of the other diastereomers arising from Z- to E-isomerization is observed. 

As described above in Eq. 43, simple allylboronates can be transformed into more elaborated ones using olefin cross-metathesis. " Treatment of pinacol allylboronate 31 with a variety of olefin partners in the presence of Grubbs second-generation catalyst 142 smoothly leads to formation of 3-substituted allylboronates 143 as cross-metathesis products (Eq. 104). Unfortunately, these new allylic boronates are formed as mixtures of geometrical isomers with modest E/Z selectivity. They are not isolated but rather are treated directly with benzaldehyde to give the corresponding homoallylic alcohol products in good yields (Table A). 

The excess of trimethylamine was removed by washing the pinacol (R)-( )-2-(3-trimethylsiloxy-l-butene)boronate (5.0 g) in petroleum ether (50 mL) using 5% aqueous AcOH (10 mL), 4% aqueous NaHCOs (10 mL), and saturated aqueous Na2S04 solution. The aqueous phases were back extracted each time with petroleum ether (10 mL). The combined organic layers were dried over anhydrous MgS04, filtered, and the solvent was removed under reduced pressure to afford pure pinacol ( )-2-(3-trimethylsiloxy-l-butene)boronate (4.84 g). Co(N03)2 6H20 (20 mg, 0.069 mmol) was added to a stirred solution of pinacol (R)-( )-2-(3-trimethylsiloxy-l-butene)boronate (5.70 g, 21.1 mmol) in petroleum ether (130 mL). Freshly distilled SOCI2 (2.75 g, 23.1 mmol) was added, and... 

Addition of Pinacol (l/ )-2-[l-Chloro-2-(Z )-butenyl]boronate to Aldehydes]. ... 

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