Aryl boronic esters

The aryl tin compounds are better substrates for fluorination because they give high yields of fliiorinated aromatics and they may be fluorinated with acetyl hypofluorite, cesium fluoroxysulfate, or fluorine [52, 54 (equation 28). Aryl boronic esters react with cesium fluoroxysulfate to produce fluoroaromatics [55] (equation 29). 

Aryl boronic ester 389 was cross-coupled with 2-iodobenzimidazole 388 under Suzuki conditions to give 2-arylbenz-imidazole 390 in good yield (Scheme 93) <2003TL8967>. 

SAR studies were performed on compoimds containing the 9H-isothia-zolo[5,4-fc]quinoline-3,4-dione (ITQ) nucleus and it was found that some of them are potent antibacterial agents (see Scheme 101) [114,115]. They were prepared from compound 353, which was treated with cyclopropyl isothiocyanate in DMF and then with Mel. Compound 354 (94%) was obtained and treated with in NaH in DMF to give the isothiazolo[ 5,4-fo] quinoline compound 355 (93%). Its treatment with anhydrous NaSH gave the corresponding mercaptan (84%), which was directly cychsed without purification to 356 (85%) in the presence of hydroxylamine-O-sulfonic acid. Microwave-assisted Suzuki-Miyaura cross-coupling of the ITQ nucleus 356 with the desired aryl-boronic esters or acids afforded derivatives 357, typically, in 30-50% yield after HPLC purification (Scheme 87). 

PCy3 also proved to be the ligand of choice for a wide-ranging study of Suzuki couplings of heteroaryl chlorides and heteroarylboronic acids (Equation 2.18) where aryl boronate esters and aryl trifluoroborates could also be employed [33]. 

Primary alkyl arenesulfonates and halides react with aryl boronate esters in the presence of a Cul catalyst and f-BuOLi in A,A-dimethylformamide (DMF) to give the cross-coupling product in yields between 50 and 87%. Yields decrease from X = I to Cl and from tosylate (OTs) to mesylate (OMs). This reaction is thought to occur between the substrate and the organocopper intermediate formed from the borate ester,... 

An aryl boronate ester 2.279 was coupled with a heterocyclic bromide 2.278 to make a specialized kinase inhibitor 2.280 on a scale of 1.88 kg (Scheme 2.89). The inertness of the aryl fiuorides is as expected in this example. 

The proposed catalytic cycle is described in Scheme 4.23. Transmetallation of aryl-boronate esters to hydroxorhodium species, giving an arylrhodium intermediate, is followed by insertion of the norbomene derivative. Then, the alkylrhodium intermediate, which has no hydrogens for p-hydrogen elimination, undergoes insertion of... 

Chan and co-workers have demonstrated tiiat boronic esters can be used in place of boronic acids in both O- and N-arylations in the parent phenyl case (Scheme 5.26) [10]. In botii arylations, boronic esters 24-27 are even more efficient than the parent acid. However, catechol ester 28 and pinacolate 29 were less efficient, perhaps due to instability (possibility of catechol O-arylation) and steric hindrance respectively. The overall superior performance of the triphenylboroxine (30) is noteworthy since it is... 

Boronic esters will also react under appropriate circumstances. Petasis used bis(isopropyl) (2B)-bromoethenylboronic ester in a reaction with glyoicyUc acid and aminodiphenylmethane [34]. Scobie and co-workers have reported the coupbng of pinacolyl aryl and alkenylboronic esters with secondary amines (38). The reaction gave good yields with alkenylboronic esters (70-82%), but worked poorly with aryl-boronic esters (0-12%). In contrast to the above results, the reaction did not proceed with primary amines under the same conditions. 

Ir-catalyzed C—H borylation developed by Hartwig can be used in tandem with reactions of the resulting ArBPin as a two-step, one-pot route to the fluorination of arenes (Scheme 9.22) An aryl boronate ester obtained in situ from substituted arenes was shown to readily undergo trifluoromethylation using [(phen)CuCF3] in the presence of air. While the inherent selectivity is derived from the selectivity in the borylation, reagent compatability allows an expedient access to trifluoromethyl-ated arenes. 

A direct synthesis of substituted aryl boronic esters has been recently reported by Masuda [12,13]. Thus, coupling of pinacol borane 30 with aryl halides or triflates in the presence of a catalytic amount of PdCl2(dppf) and a base like triethylamine allows the preparation of aryl boronates having a variety of functional groups such as carbonyl, cyano, nitro, and acylammo of type 31 in high yields. The product distribution 31 versus 32 (reduced product) is strongly dependent on the choice of the base employed. In the presence of triethylamine as a base, selective formation of boronates 31 was observed with negligible amount of the reduced aromatic compound 32 (Scheme 3.8). 

R = 4-CI, 4-CN, 4-NM62, 4-NHAc, 4-CH2CN, 4-COMe, 4-C02Me, 3-COMe X = Br, I, OTf Scheme 3.8 Preparation of aryl boronic esters by palladium-catalyzed borylation. 

Scheme 3.9 Synthesis of aryl boronic esters by palladiumot-alyzed borylation with pinacolborane.

A novel macrocyclization procedure involving ttvo distinct cross-coupling manifolds in a domino fashion has been reported by Zhu for the synthesis of bipheno-mycin model 86 [56]. Thus, treatment oflinear feis-iodide with fois(pinacol)diborane (37) in the presence of Pd(dppf)2Cl2 under defined conditions affords the biphenyl macrocyclic compound 86 in 45% yield through a Miyaura aryl boronic ester formation followed by its intramolecular Suzuki cross-coupling. The diiodide containing a free phenol function (R=H) gave the macrocycle (R=H) in only 22-25% yield under these conditions (Scheme 3.37). 

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